FI109130B - Menetelmä, laite ja laitteen käyttö polynukleotidi- tai aminohapposekvenssin tutkimiseksi - Google Patents

Menetelmä, laite ja laitteen käyttö polynukleotidi- tai aminohapposekvenssin tutkimiseksi Download PDF

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Publication number
FI109130B
FI109130B FI915723A FI915723A FI109130B FI 109130 B FI109130 B FI 109130B FI 915723 A FI915723 A FI 915723A FI 915723 A FI915723 A FI 915723A FI 109130 B FI109130 B FI 109130B
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substrate
sequence
amino acid
light
sequences
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FI915723A
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English (en)
Swedish (sv)
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FI915723A0 (fi
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Michael C Pirrung
J Leighton Read
Stephen P A Fodor
Lubert Stryer
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Affymetrix Inc Delaware Corp
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    • C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
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Description

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Menetelmä, laite ja laitteen käyttö polynukleotidi- tai aminohapposekvenssin tutkimiseksi
Keksinnön ala 5 Keksinnön kohteena on menetelmä ja laite polynukleotidi- tai ami nohapposekvenssin tutkimiseksi reseptori/ligandi sitoutumisella. Keksinnön kohteena on edelleen laitteen käyttö edellä mainittuun tarkoitukseen.
Keksinnön tausta
Esillä oleva keksintö liittyy materiaalien synteesiin ja sijoittamiseen 10 tunnettuihin sijaintikohtiin. Erityisesti tässä kuvataan menetelmä ja liittyvä laite erilaisten kemiallisten sekvenssien valmistamiseksi tunnettuihin sijaintikohtiin yksittäisellä substraattipinnalla. Keksintöä voidaan soveltaa esimerkiksi oligo-meeri-, peptidi-, nukleiinihappo-, oligosakkaridi-, fosfolipidi-, polymeerivalmis-tuksen tai lääkeanalogivalmistuksen alalla, etenkin kemiallisesti vaihtelevien 15 lähteiden luomiseksi käytettäviksi seulonnassa biologisen aktiivisuuden suhteen.
Molekyylien rakenteen ja aktiivisuuden välinen suhde on olennainen seikka biologisten systeemien tutkimuksessa. Rakenne-aktiivisuussuhteet ovat tärkeitä esimerkiksi entsyymien funktion, tapojen, joilla solut ovat yhteydessä .20 toisiinsa sekä solusäätely- ja feedback-systeemien ymmärtämiseksi.
• · : Tiettyjen makromolekyylien tiedetään olevan vuorovaikutuksessa ja ’ sitoutuvan toisiin molekyyleihin, joilla on hyvin spesifinen 3-ulotteinen avaruus- ! . ja elektronijakauma. Mikä tahansa suuri molekyyli, jolla on tällaista spesifi- j syyttä, voidaan katsoa reseptoriksi riippumatta siitä, onko se aineenvaihdunta- 25 välituotteen hydrolyysiä katalysoiva entsyymi, solupintaproteiini, joka toimii vä-v : littäjänä ionien membraanikuljetuksessa, glykoproteiini, jonka tehtävänä on tunnistaa tietty solu sen naapureille, plasmassa kiertävä IgG-luokan vas-: ta-aine, DNA-oligonukleotidisekvenssi tumassa tai vastaava. Eri molekyylit, • ’' *: joita reseptorit selektiivisesti sitovat, tunnetaan ligandeina.
♦ * · ;.\ 30 Monia määrityksiä on saatavana tunnettujen reseptorien ja ligandi- en sitoutumisaffiniteetin mittaamiseksi, mutta tällaisista kokeista saavutettavis-’·;· sa olevaa tietoa rajoittaa usein saatavana olevien ligandien lukumäärä ja tyyp- : pi. Uusia ligandeja löydetään joskus sattumalta tai käyttämällä uusia teknii- koita molekyylirakenteen selvittämiseksi, mukaan lukien röntgensädekristallo-35 grafinen analyysi ja yhdistelmä-DNA-geenitekniikat proteiineille.
2 109130
Pienet peptidit ovat mallisysteemi rakenteen ja funktion välisen suhteen tutkimiseksi biologiassa. Peptidi on aminohappojen muodostama sekvenssi. Kun 20 luontaisesti esiintyvää aminohappoa kondensoidaan polymee-rimolekyyleiksi, ne muodostavat laajan valikoiman 3-ulotteisia konfiguraatioita, 5 joista kukin syntyy tietyissä aminohapposekvenssi- ja liuotinolosuhteissa. 20:stä luontaisesti esiintyvästä aminohaposta muodostettavien mahdollisten pentapeptidien lukumäärä on esimerkiksi 205 tai 3,2 miljoonaa erilaista peptidiä. Sen todennäköisyyttä, että tämän kokoiset molekyylit saattaisivat olla käyttökelpoisia reseptorisitoutumistutkimuksissa, tukevat epitooppianalyysitut-10 kimukset, jotka osoittavat, että jotkut vasta-aineet tunnistavat niinkin lyhyitä kuin muutaman aminohapon mittaisia sekvenssejä hyvin spesifisesti. Lisäksi aminohappojen keskimääräinen molekyylipaino sijoittaa pienet peptidit monien tällä hetkellä käyttökelpoisten farmaseuttisten tuotteiden kokoalueelle.
Farmaseuttisten lääkeaineiden etsintä on yksi tutkimustyyppi, joka 15 nojaa tällaiseen rakenne-aktiivisuussuhteiden tutkimiseen. Useimmissa tapauksissa nykyaikaista farmaseuttista tutkimusta voidaan kuvata prosessiksi, jossa biologisesti tärkeille reseptoreille etsitään uusia ligandeja, joilla on halutun mukaisia spesifisyyskuvioita. Toinen esimerkki on tutkimus uusien yhdisteiden, esimerkiksi pestisidien ja herbisidien, löytämiseksi maataloudessa 20 käytettäviksi.
: Toisinaan ligandien suunnittelun ja rakentamisen rationaalisen pro- . ' sessin ratkaiseminen on vaikeata tai mahdotonta. Aiemmat menetelmät suuri- ; " en lukumäärien erilaisia polymeerejä valmistamiseksi ovat olleet tuskastutta- : : ; van hitaita käytettyinä mittakaavassa, joka on riittävä mahdollistaakseen te- 25 hokkaan suunnitelmallisen tai satunnaisen seulonnan. Esimerkiksi v : "MerrifiekT-menetelmää (J.Am.Chem.Soc. 85 (1963) 2149 - 2154, joka sisäl lytetään tähän viitteeksi kaikissa tarkoituksissa) on käytetty peptidien synteti-soimiseksi kiinteälle tuelle. Merrifield-menetelmässä aminohappo sidotaan ko-valenttisesti tukeen, joka on valmistettu liukenemattomasta polymeeristä. Toi-30 nen aminohappo, jonka α-ryhmä on suojattu, saatetaan reagoimaan kovalent-tisesti sidotun aminohapon kanssa dipeptidin muodostamiseksi. Pesun jälkeen '*;· suojaryhmä poistetaan ja kolmas aminohappo, jonka α-ryhmä on suojattu, li- : sätään dipeptidiin. Tätä prosessia jatketaan, kunnes saadaan pituudeltaan ja : sekvenssiltään halutun mukainen peptidi. Merrifield-menetelmää käyttäen ei 35 ole taloudellisesti käytännöllistä syntetisoida useampia kuin kourallinen pepti- disekvenssejä päivässä.
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Suurien lukumäärien polymeerisekvenssejä syntetisoimiseksi on samoin ehdotettu käytettäväksi sarjaa reaktioastioita polymeerien syntetisoimiseksi. Esimerkiksi putkireaktorisysteemiä voidaan käyttää lineaarisen polymeerin syntetisoimiseksi kiinteäfaasituelle lisäämällä reagensseja automati-5 soidusti peräkkäin. Tämäkään menetelmä ei silti mahdollista riittävän suurien lukumäärien polymeerisekvenssejä synteesiä silmällä pitäen tehokasta taloudellista seulontaa.
Tunnetaan samoin menetelmiä ison joukon polymeerisekvenssejä valmistamiseksi, joissa rei'itetty säiliö sisältää tunnetun määrän reaktiivisia 10 hiukkasia, jolloin hiukkaset ovat kooltaan suurempia kuin rei'ät säiliössä. Säiliöt voidaan saattaa selektiivisesti reagoimaan haluttujen materiaalien kanssa haluttujen sekvenssien tuotemolekyylejä syntetisoimiseksi. Kuten muitakaan alalla tunnettuja menetelmiä tätäkään menetelmää ei voida käytännöllisesti käyttää riittävän moninaisuuden polypeptidejä syntetisoimiseksi tehokkaaseen 15 seulontaan.
Muitakin tekniikoita on kuvattu. Näihin menetelmiin lukeutuu peptidien synteesi 96 muovinupissa, jotka sopivat standardimikrotiitterilevyjen muotoon. Valitettavasti vaikkakin nämä tekniikat ovat olleet jossain määrin käyttökelpoisia, huomattavia ongelmia on yhä. Esimerkiksi näissä menetelmis-;.·. 20 sä on edelleen rajoituksena sekvenssien moninaisuus, joka on taloudellisesti ’ ·. : syntetisoitavissa ja seulottavissa.
.! ' Edeltävästä voidaan nähdä, että aiempaa parempi menetelmä ja ; .** laite erilaisten kemiallisten sekvenssien syntetisoimiseksi tunnettuihin sijainti- : ; ; kohtiin on toivottava.
25 Yhteenveto keksinnöstä ·’ Julkistetaan aiempaa parempi menetelmä ja laite erilaisten poly meerien tutkimiseksi. Menetelmälle ja laitteelle on tunnusomaista se, mitä pa-tenttivaatimuksessa 1 ja vastaavasti 7 esitetään. Keksintöön kuuluu lisäksi ky-•seisen laitteen käyttö tutkittaessa polynukleotidi- tai aminohapposekvenssiä 30 reseptori/ligandi-sitoutumisella.
Yhdessä edullisessa suoritusmuodossa liittomolekyylejä sijoitetaan substraatille. Liittomolekyylien ääripää on varustettu reaktiivisella funktionaali-: ;': sella ryhmällä, joka on suojattu valolla poistettavalla suojaryhmällä. Litografisia menetelmiä käyttäen valolla poistettava suojaryhmä altistetaan valolle ja 35 poistetaan liittomolekyyleistä ensimmäisiksi valituilla alueilla. Sitten substraatti pestään ensimmäisellä monomeerillä tai saatetaan muuten kosketuksiin mai- 4 109130 nitun kanssa, joka reagoi liittomolekyylien paljaana olevien funktionaalisten ryhmien kanssa. Edullisessa suoritusmuodossa monomeeri on aminohappo, joka sisältää valolla poistettavan suojaryhmän amino- tai karboksipäässään, ja liittomolekyyli päättyy amino- tai karboksyylihappoon, joka käsittää valolla 5 poistettavan suojaryhmän.
Sen jälkeen toiseksi valittu aluesarja altistetaan valolle ja valolla poistettava suojaryhmä poistetaan liittomolekyylistä/suojatusta aminohaposta toisella aluesarjalla. Sitten substraatti saatetaan kosketuksiin toisen mono-meerin kanssa, joka sisältää valolla poistettavan suojaryhmän, silmällä pitäen 10 reaktiota paljaana olevien funktionaalisten ryhmien kanssa. Tätä prosessia toistetaan monomeerien selektiiviseksi lisäämiseksi, kunnes saadaan polymeerejä, jotka ovat halutun mittaisia ja joilla on haluttu kemiallinen sekvenssi. Valolabiilit ryhmät poistetaan sitten mahdollisesti, minkä jälkeen sekvenssi mahdollisesti varustetaan salparyhmällä. Jos sivuketjun suojaryhmiä on läsnä, 15 myös ne poistetaan.
Käyttämällä tässä julkistettuja litografisia tekniikoita on mahdollista ohjata valo suhteellisen pieniin ja täsmällisesti tunnettuihin sijaintikohtiin substraatilla. Tämän vuoksi on mahdollista syntetisoida polymeerejä, joilla on tunnettu kemiallinen sekvenssi, tunnettuihin sijaintikohtiin substraatilla.
20 Saadulla substraatilla on erilaisia käyttöjä mukaan lukien esimerkik- : si suurien lukumäärien polymeerejä seulonta biologisen aktiivisuuden suhteen.
·*, ' Biologisen aktiivisuuden suhteen seulomiseksi substraatti saatetaan kosketuk- ! . siin yhden tai useamman reseptorin kanssa kuten vasta-aine, kokonaiset so- | lut, reseptorit rakkuloiden pinnalla, lipidit, tai mikä tahansa erilaisista muista 25 reseptoreista. Reseptorit leimataan edullisesti esimerkiksi fluoresoivalla mer-v ; kiliä, radioaktiivisella merkillä tai leimatulla vasta-aineella, joka reagoi resepto rin kanssa. Merkin sijaintikohta substraatilla todetaan esimerkiksi fotonidetek-tietekniikoilla tai autoradiografisilla tekniikoilla. Koska materiaalin sekvenssi kohdassa, jossa sitoutumista todetaan, tunnetaan, on mahdollista määrittää 30 nopeasti, mikä sekvenssi sitoutuu reseptoriin, minkä vuoksi tekniikkaa voidaan käyttää suurien lukumäärien peptidejä seulomiseksi. Näiden keksintöjen mui-’·;·* hin kyseeseen tuleviin sovellutuksiin kuuluu diagnostiikka, jossa nimenomais- : ten reseptorien vastaisia erilaisia vasta-aineita sijoitettaisiin substraatille ja seulottaisiin esimerkiksi veriseerumia immuunivajeiden suhteen. Edelleen 35 muita sovellutuksia ovat esimerkiksi orgaanisten materiaalien selektiivinen "doping" puolijohdelaitteissa ja vastaavat.
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Keksinnön yhteen näkökohtaan liittyen julkistetaan myös aiempaa parempi reaktorisysteemi polymeerien syntetisoimiseksi. Reaktorisysteemiin kuuluu substraattialusta, joka sitoo substraatin ääripinnalleen. Substraatti-alusta on varustettu substraatin ja alustan välisellä reaktoritilalla, jonka kautta 5 tai johon reaktionesteitä pumpataan tai virratetaan. Substraatille asetetaan tai fokusoidaan maski, jota valotetaan substraatin valikoitujen alueiden vapauttamiseksi suojaryhmistä reaktoritilassa. Monomeeriä pumpataan reaktoritilan läpi tai se saatetaan muutoin kosketuksiin substraatin kanssa, jolloin se reagoi | suojaryhmiä vailla olevien alueiden kanssa. Vapauttamalla selektiivisesti 10 substraatin alueita suojaryhmistä ja virrattamalla ennalta määrättyjä mono-meerejä reaktoritilan läpi voidaan syntetisoida haluttuja polymeerejä tunnettuihin sijaintikohtiin.
Julkistetaan myös aiempaa parempi laite ja aiempaa parempia menetelmiä detektoinnin suorittamiseksi. Detektiomenetelmä ja -laite käyttävät 15 substraattia, jolla on pinnallaan suuri valikoima polymeerisekvenssejä tunnetuissa sijaintikohdissa. Substraatti saatetaan kosketuksiin fluoresoivasti leimatun reseptorin kanssa, joka sitoutuu yhteen tai useampaan polymeerisek-venssiin. Substraatti sijoitetaan mikroskooppidetektiolaitteeseen niiden sijainti-kohtien tunnistamiseksi, joissa sitoutumista tapahtuu. Mikroskooppidetektio-y. 20 laitteeseen kuuluu monokromaattinen tai polykromaattinen valolähde valon ohjaamiseksi substraatille, laite fluoresoivan valon substraatista toteamiseksi ’ sekä laite fluoresoivan valon sijaintikohdan määrittämiseksi. Laite substraatin ; . fluoresoiman valon toteamiseksi voi joissakin suoritusmuodoissa käsittää foto- ; nilaskijan. Laite fluoresoivan valon sijaintikohdan määrittämiseksi voi käsittää * ‘ 25 x/y-siirtopöydän substraatille. Levyn siirrot ja kerätyt tiedot rekisteröidään ja v : käsitellään sopivasti ohjelmoidulla digitaalitietokoneella.
Näiden keksintöjen luonne ja edut voidaan ymmärtää selvemmin : ·.: tutustumalla selitysosuuden jäljellä oleviin osiin sekä oheisiin piirroksiin.
Suppea kuvaus kuvioista 30 Kuvio 1 esittää substraatin peittämistä ja säteilyttämistä ensimmäi- sessä kohdassa. Substraatti esitetään poikkileikkauksena; ‘ ' kuvio 2 esittää substraattia monomeerin "A" käytön jälkeen; : kuvio 3 esittää substraatin säteilyttämistä toisessa kohdassa; ' ’ ‘; kuvio 4 esittää substraattia monomeerin "B" käytön jälkeen; 35 kuvio 5 esittää "A"-monomeerin säteilyttämistä; kuvio 6 esittää substraattia "B":n toisen käytön jälkeen; 6 109130 i ! j kuvio 7 esittää valmista substraattia; kuviot 8A ja 8B esittävät reaktorisysteemin vaihtoehtoisia suoritusmuotoja monolukuisen määrän polymeerejä muodostamiseksi substraatille; i | kuvio 9 esittää detektiolaitetta fluoresoivien merkkien paikantami- 5 seksi substraatilta; kuviot 10A - 10M esittävät menetelmää käytettäessä sitä trimeerien valmistamiseksi monomeereistä "A" ja "B"; kuviot 11 A, 11B ja 11C ovat fluoresenssiajoja fluoresoivista stan-dardihelmistä; 10 kuviot 12A ja 12B ovat fluoresenssikäyriä NVOC-levyille, joita ei ole altistettu tai jotka vastaavasti on altistettu valolle; kuviot 13A ja 13B esittävät levyn muodostusta, jossa on shakkilau-takuvio YGGFL:ää ja GGFL:ää ja joka saatetaan kosketuksiin leimatun Herz-vasta-aineen kanssa; ja 15 kuviot 14A ja 14B esittävät karttoja 16 sekvenssistä, jotka synteti soitiin kahdella eri lasilevyllä.
Yksityiskohtainen kuvaus edullisista suoritusmuodoista Sisältö y. 20 I. Sanasto II. Yleistä ‘ III. Polymeerisynteesi ; ’ IV. Yksityiskohtia reaktorisysteemin yhdestä suoritusmuodosta j V. Yksityiskohtia fluoresenssidetektiolaitteen yhdestä suoritusmuo- ' * 25 dosta v ; VI. Reseptorien suhteellisen sitoutumisvoimakkuuden määritys VII. Esimerkkejä '.‘A A. Objektilasin valmistus **”: B. Kahdeksan (8) trimeerien synteesi "A":sta ja "B":stä 30 C. Dimeerin synteesi aminopropyyliryhmästä ja fluoresoivasta ryh- mästä ' ·;·' D. Signaalintuottokyvyn osoittaminen : E. Molekyylien lukumäärän alueyksikköä kohden määritys F. NVOC:n poistaminen ja fluoresoivan merkin kiinnitys 35 G. Maskin käyttö NVOC:n poistossa 7 109130 H. YGGFLn kiinnitys ja sitten seuraava saattaminen kosketuksiin Herz-vasta-aineen ja vuohen anti-hiirivasta-aineen kanssa I. Monomeeri-monomeerimuodostus YGGFL:stä ja sitten seuraava saattaminen kosketuksiin leimatun vasta-aineen kanssa 5 J. Monomeeri-monomeerisynteesi YGGFL:stä ja PGGFL:stä K. Monomeeri-monomeerisynteesi YGGFLstä ja YPGGFLstä L. 16 erilaisen aminohapposekvenssin sarjan synteesi sekä suhteellisen sitoutumisaffiniteetin Herz-vasta- aineeseen arviointi
Vili. Havainnollistava vaihtoehtoinen suoritusmuoto 10 IX. Päätös I. Sanasto
Seuraavilla termeillä tarkoitetaan olevan seuraavat yleiset merkitykset niitä tässä käytettäessä: 1. Komplementaarinen: Viittaa ligandimolekyylin ja sen reseptorin 15 vuorovaikutuksessa olevien pintojen topologiseen yhteensopivuuteen tai sopimiseen yhteen. Täten reseptoria ja sen ligandia voidaan kuvata komplementaarisiksi ja edelleen kontaktipintaominaisuudet ovat toisilleen komplementaarisia.
2. Epitooppi: Se osa antigeenimolekyylistä, jonka rajaa vuorovai-20 kutuksen alue vasta-aineina tunnettujen reseptorien alaluokan kanssa.
. : 3. Liqandi: Ligandi on molekyyli, jonka nimenomainen reseptori tun- ’ ‘ nistaa. Esimerkkejä ligandeista, joita voidaan tutkia tällä keksinnöllä, ovat mai- ; , nittuihin kuitenkaan rajoittumatta solumembraanireseptorien agonistit ja anta- ; gonistit, toksiinit ja (käärme)myrkyt, virusepitoopit, hormonit (esim. opiaatit, 25 steroidit jne.), hormonireseptorit, peptidit, entsyymit, entsyymisubstraatit, ko-v : faktorit, lääkkeet, lektiinit, sokerit, oligonukleotidit, nukleiinihapot, oligosakkari dit, proteiinit ja monoklonaaliset vasta-aineet.
: 4. Monomeeri: Jäsen sarjassa pieniä molekyylejä, jotka voidaan liittää yhteen polymeerin muodostamiseksi. Monomeerien sarjaan kuuluvat 30 mainittuihin kuitenkaan rajoittumatta esimerkiksi tavallisten L-aminohappojen sarja, D-aminohappojen sarja, synteettisten aminohappojen sarja, nukleotidien '· ·’ sarja ja pentoosien ja heksoosien sarjat. Tässä käytettynä monomeereillä tar- : koitetaan mitä tahansa jäsentä perussarjasta polymeerin syntetisoimiseksi.
Esimerkiksi L-aminohappojen dimeerit muodostavat 400 monomeerin perus-35 sarjan polypeptidien syntetisoimiseksi. Erilaisia monomeerien perussarjoja voidaan käyttää peräkkäisissä vaiheissa polymeerin synteesissä.
β 109130 5. Peptidi: Polymeeri, jossa monomeerit ovat α-aminohappoja, joita liittävät yhteen amidisidokset, ja jota vaihtoehtoisesti kutsutaan polypeptidiksi. Tämän patenttiselityksen asianyhteydessä tulkoon huomatuksi, että aminohapot voivat olla L-optisia isomeerejä tai D-optisia isomeerejä. Peptidit ovat yli 2 5 aminohappomonomeeriä pitkiä, ja usein yli 20 aminohappomonomeerin pituisia. Aminohapoista käytetään vakiolyhenteitä (esim. P proliinista). Nämä lyhenteet on sisällytetty kirjaan Stryer, "Biochemistry", 3. painos, 1988, joka sisällytetään tähän viitteeksi kaikissa tarkoituksissa.
6. Säteily: Energia, jota voidaan käyttää selektiivisesti, mukaan luki-10 en energia, jonka aallonpituus on 10'14 - 104 metriä, mukaan lukien esimerkiksi elektronisädesäteily, gamma-säteily, röntgensädesäteily, ultraviolettisäteily, näkyvä valo, infrapunasäteily, mikroaaltosäteily ja radioaallot. ’’Säteilyttäminen” viittaa säteilyn kohdistamiseen pinnalle.
7. Reseptori: Molekyyli, jolla on affiniteettia tietyn ligandin suhteen. 15 Reseptorit voivat olla luontaisesti esiintyviä tai ihmisen tekemiä molekyylejä.
Samoin niitä voidaan käyttää niiden ei-muutetussa tilassa tai aggregaatteina muiden lajien kanssa. Reseptorit voidaan kiinnittää, kovalenttisesti tai ei-kovalenttisesti, sitoutumisjäseneen, joko suoraan tai spesifisen sidosaineen välityksellä. Esimerkkejä reseptoreista, joita voidaan käyttää tässä keksinnös- 20 sä, ovat mainittuihin kuitenkaan rajoittumatta vasta-aineet, solumembraanire- \ septorit, monoklonaaliset vasta-aineet ja vastaseerumit, jotka ovat reaktiivisia : spesifisten antigeenimääreiden suhteen (kuten virukset, solut tai muut materi- ; ” aalit), lääkkeet, polynukleotidit, nukleiinihapot, peptidit, kofaktorit, lektiinit, so- • * · : kerit, polysakkaridit, solut, solumembraanit ja soluelimet. Reseptoreita kutsu- 25 taan alalla joskus antiligandeiksi. Käytettäessä tässä termiä reseptorit ei pyritä ♦ I · v : mihinkään merkityseroon. "Ligandi-reseptoripari" muodostuu, kun kaksi mak romolekyyliä on yhdistynyt molekyylitunnistuksen välityksellä muodostamaan kompleksin.
·*·; Muita esimerkkejä reseptoreista, joita voidaan tutkia tällä keksin- i > * 30 nöllä, ovat mainittuihin kuitenkaan rajoittumatta: • » · a) Mikro-orqanismireseptorit: Sen kaltaisiin reseptoreihin kuten spe-sifiset kuljetusproteiinit tai entsyymit, jotka ovat oleellisia mikro-organismien : i‘i eloonjäännille, sitoutuvien ligandien määritys on käyttökelpoista uudessa anti- ;. bioottiluokassa. Erityisen arvokkaita olisivat antibiootit vastaan opportunistisia 35 sieniä, alkueläimiä ja niitä bakteereja, jotka ovat resistenttejä tämänhetkisessä käytössä oleville antibiooteille.
9 109130 b) Entsyymit: Esimerkiksi sellaisten entsyymien sitoutumiskeskus kuten entsyymien, jotka ovat vastuussa hermojen välittäjäaineiden pilkkomisesta; ligandien määritys, jotka sitoutuvat tiettyihin reseptoreihin entsyymien vaikutuksen moduloimiseksi, jotka pilkkovat erilaisia hermojen välittäjäaineita, 5 on käyttökelpoista lääkkeiden kehityksessä, joita voidaan käyttää hermosiirto-funktion häiriöiden hoidossa.
c) Vasta-aineet: Esimerkiksi keksintö voi olla käyttökelpoinen tutkittaessa ligandisitoutumiskeskusta vasta-ainemolekyylin pinnalla, joka liittyy kiinnostavan antigeenin epitooppiin; antigeeniepitooppia jäljittelevän sekvens- 10 sin määritys voi johtaa rokotteiden kehitykseen, joiden immunogeeni perustuu yhteen tai useampaan tällaiseen sekvenssiin, tai johtaa muiden liittyvien diagnostisten aineiden tai yhdisteiden kehitykseen, jotka ovat käyttökelpoisia esimerkiksi autoimmuunisairauksien terapeuttisissa hoidoissa (esim. salpaamalla "itse"-vasta-aineiden sitoutuminen).
15 d) Nukleiinihapot: Nukleiinihappojen sekvenssejä voidaan synteti soida DNA- tai RNA-sitoutumissekvenssien määrittämiseksi.
e) Katalyyttiset polvpeptidit: Polymeerejä, edullisesti polypeptidejä, jotka kykenevät edistämään kemiallista reaktiota, jossa tapahtuu yhden tai useamman reagoivan aineen konversio yhdeksi tai useammaksi tuotteeksi.
20 Tällaisissa polypeptideissä on yleensä sitoutumiskeskus, joka on spesifinen ainakin yhdelle reagoivalle aineelle tai reaktiovälituotteelle, sekä lähellä sitou-' tumiskeskusta sijaitseva aktiivinen funktionaalisuus, joka funktionaalisuus ky- ; kenee kemiallisesti modifioimaan sitoutunutta reagoivaa ainetta. Katalyyttisiä ί,: ; polypeptidejä kuvataan esimerkiksi US-patenttihakemuksessa sarjanro 404 25 920, joka sisällytetään tähän viitteeksi kaikissa tarkoituksissa.
* · · v ; f) Hormonireseptorit: Esimerkiksi insuliinin ja kasvuhormonin re septorit. Ligandien määritys, jotka sitoutuvat korkealla affiniteetilla reseptoriin, :\i on käyttökelpoista esimerkiksi suun kautta otettavan korvikkeen kehittämiseksi päivittäisille ruiskeille, joita diabeetikkojen on otettava sokeritaudin oireiden lie- 30 vittämiseksi, ja toisessa tapauksessa korvikkeen (kehittämiseksi) niukasti esiintyvälle ihmisen kasvuhormonille, jota voidaan saada vain ruumiista tai yh-distelmä-DNA-teknisesti. Muita esimerkkejä ovat verisuonia supistavien hor-: monien reseptorit; reseptoriin sitoutuvien ligandien määritys voi johtaa lääkkei- * t» den kehitykseen verenpaineen kontrolloimiseksi.
10 109130 g) Qpiaattireseptorit: Ligandien määritys, jotka sitoutuvat opiaattire-septoreihin aivoissa, on käyttökelpoista vähemmän addiktiivisten korvikkeiden kehittämiseksi morfiinille ja samankaltaisille lääkkeille.
8. Substraatti: Materiaali, jolla on jäykkä tai puolijäykkä pinta. Mo-5 nissa suoritusmuodoissa substraatin ainakin yksi pinta on oleellisesti tasainen, vaikka joissakin suoritusmuodoissa voi olla toivottavaa erottaa fyysisesti eri polymeerien synteesialueet esimerkiksi kuopilla, kohollaan olevilla alueilla, syövytetyillä ojilla tai vastaavilla. Muiden suoritusmuotojen mukaan pinta voidaan varustaa pienillä helmillä, jotka voidaan vapauttaa synteesin päätteeksi. 10 9. Suoiarvhmä: Materiaali, joka on sidottu monomeeriyksikköön ja joka voidaan tilan suhteen poistaa altistamalla selektiivisesti aktivaattorille kuten elektromagneettiselle säteilylle. Esimerkkejä suojaryhmistä, jotka ovat tässä käyttökelpoisia, ovat nitroveratryylioksikarbonyyli, nitrobentsyylioksikar-bonyyli, dimetyylidimetoksibentsyylioksikarbonyyli, 5-bromi-7-nitroindolinyyli, 15 o-hydroksi-a-metyylisinnamoyyli ja 2-oksimetyleeniantrakinoni. Muita esimerkkejä aktivaattoreista ovat ionisuihkut, sähkökentät, magneettikentät, elektroni-suihkut, röntgensäteet ja vastaavat.
10. Ennaltamäärättv alue: Ennaltamäärätty alue on pinnalla paikannettu alue, joka aktivoidaan, aktivoitiin tai on tarkoitus aktivoida polymeerin 20 muodostamiseksi. Ennalta määrätty alue voi olla minkä tahansa kätevän t · · muotoinen, esim. ympyränmuotoinen, nelikulmainen, ellipsinmuotoinen, kii- > I * ’ lanmuotoinen jne. Tässä lyhyyden vuoksi "ennalta määrättyjä" alueita kutsu- ; taan toisinaan yksinkertaisesti "alueiksi".
• tt : 11. Oleellisesti puhdas: Polymeerin katsotaan olevan "oleellisesti 25 puhdas" substraatin ennaltamäärätyllä alueella, kun se osoittaa ominaisuuk- I I « v ; siä, jotka erottavat sen muista ennaltamäärätyistä alueista. Tyypillisesti puhta us mitataan biologisena aktiivisuutena tai funktiona, joka on tulosta yhtenäi-sestä sekvenssistä. Tällaiset ominaisuudet mitataan tyypillisesti sitomalla va- • littuun ligandiin tai reseptoriin.
, , 30 II. Yleistä :Esillä oleva keksintö antaa käyttöön menetelmiä ja laitteen substraatin valmistamiseksi ja käyttämiseksi, jossa on monilukuinen määrä ! polymeerisekvenssejä ennalta määrätyillä alueilla. Keksintöä kuvataan tässä pääasiassa suhteessa molekyylien valmistukseen, jotka sisältävät aminohap- 35 posekvenssejä, mutta sitä voitaisiin vaikeuksitta käyttää muiden polymeerien valmistukseen. Tällaisia polymeerejä ovat esimerkiksi sekä lineaariset että
* I
11 109130 sykliset polymeerit nukleiinihappoja, polysakkarideja, fosfolipidejä ja peptidejä, joissa on joko α-, β- tai gamma-aminohappoja, heteropolymeerit, joissa tunnettu lääke on kovalenttisesti sidottu johonkin edeltävistä, polyuretaanit, polyesterit, polykarbonaatit, polyureat, polyamidit, polyetyleeni-imiinit, polyarylee-5 nisulfidit, polysiloksaanit, polyimidit, polyasetaatit tai muut polymeerit, jotka ovat ilmeisiä tutustuttaessa tähän julkistukseen. Edullisessa suoritusmuodossa tätä keksintöä käytetään peptidien synteesissä.
Valmistettua substraattia voidaan käyttää esimerkiksi erilaisten polymeerien seulomiseksi ligandeiksi reseptoriin sidottaviksi, vaikka ilmeistä on-10 kin, että keksintöä voitaisiin käyttää reseptorin syntetisoimiseksi ligandiin sidottavaksi. Tässä julkistetulla substraatilla on laaja valikoima muita käyttöjä. Pelkästään esimerkiksi tätä keksintöä voidaan käyttää proteiineihin sitoutuvien peptidi- ja nukleiinihapposekvenssien määrityksessä, sekvenssispesifisesti sitoutuvien lääkkeiden löytämiseksi, vasta-aineiden tunnistamien epitooppien 15 tunnistamiseksi sekä erilaisten lääkkeiden arvioimiseksi kliinisiin ja diagnostisiin käyttöihin, sekä edeltävien yhdistelmissä.
Keksintö antaa edullisesti käyttöön substraatin "S", jossa on pinta. Substraatin pinta on mahdollisesti varustettu liittomolekyyleillä "L". Liittomole-kyylien tarkoitus joissakin suoritusmuodoissa on helpottaa syntetisoitujen po-·' 20 lymeerien reseptoritunnistusta.
:: Mahdollisesti liittomolekyylit on voitu suojata kemiallisesti varastoin- I *
: '·· titarkoituksissa. Kemiallista varastointisuojaryhmää kuten t-BOC
: : (t-butyylioksikarbonyyli) voidaan käyttää joissakin suoritusmuodoissa. Tällaiset ·:·: kemialliset suojaryhmät poistettaisiin kemiallisesti saattamalla kosketuksiin 25 esimerkiksi happaman liuoksen kanssa ja niiden tehtävänä olisi suojata pintaa varastoinnin aikana ja ne poistettaisiin ennen polymeerin valmistusta.
; Liittomolekyylien substraatti- tai distaalipää on varustettu funktio- !,.[ naalisella ryhmällä, jossa on suojaryhmä P0. Suojaryhmä PQ voidaan poistaa ·;* altistamalla säteilylle, sähkökentille, sähkövirroille tai muille aktivaattoreille j 30 funktionaalisen ryhmän paljastamiseksi.
Edullisessa suoritusmuodossa säteily on ultravioletti- (UV-), infra-puna- (IR-) valoa tai näkyvää valoa. Kuten alla tarkemmin kuvataan, suoja-ryhmä voi vaihtoehtoisesti olla sähkökemiallisesti herkkä ryhmä, joka voidaan '· ·' poistaa sähkökentän läsnä ollessa. Edelleen muissa vaihtoehtoisissa suori- 35 tusmuodoissa suojaryhmän poistossa voidaan käyttää ionisuihkuja, elektroni-suihkuja tai vastaavia.
12 109130
Joissakin suoritusmuodoissa altistetut alueet ovat pienempiä ja siksi alue, jolle kukin erillinen polymeerisekvenssi syntetisoidaan on pienempi, kuin noin 1 cm2 tai alle 1 mm2. Edullisissa suoritusmuodoissa altistettu alue on alle noin 10 000 pm2 tai edullisemmin alle 100 pm2 ja voi joissakin suoritusmuo-5 doissa käsittää sitoutumiskeskuksen niinkin vähälle kuin yksittäiselle molekyylille. Näillä alueilla kukin polymeeri syntetisoidaan edullisesti oleellisesti puhtaassa muodossa.
Substraatin tunnetun alueen altistamisen valolle kanssa samanaikaisesti tai sen jälkeen pinta saatetaan kosketuksiin ensimmäisen monomee-10 riyksikön M! kanssa, joka reagoi funktionaalisen ryhmän kanssa, jolle on suoritettu suojaryhmänpoistovaihe. Ensimmäinen monomeeri käsittää suojaryh-män Pv P., voi olla tai voi olla olematta sama kuin P0.
Täten ensimmäisen kierroksen jälkeen pinnan tunnetut ensimmäiset alueet voivat käsittää sekvenssin: 15 S-L-Μ,-Ρ, kun taas pinnan jäljellä olevat alueet käsittävät sekvenssin: 20 S-L-P0.
• «
Sitten pinnan toiset alueet (jotka voivat käsittää ensimmäisen alu- • een) altistetaan valolle ja saatetaan kosketuksiin toisen monomeerin M2 kans-sa (joka voi olla tai voi olla olematta sama kuin M.,), jossa on suojaryhmä P2. P2 ·:·. 25 voi olla tai voi olla olematta sama kuin P0 ja Pv Tämän toisen kierroksen jäl keen substraatin eri alueet voivat käsittää yhden tai useamman seuraavan . . sekvenssin:
• I
S-L-M^M^P, 30 S-L-M2-P2 S-L-Μ,-Ρ, ja/tai ..·. S-L-P0.
Edeltävää menetelmää toistetaan kunnes substraatti käsittää halu-35 tun mittaisina halutut polymeerit. Kontrolloimalla valolle altistettuja substraatin 13 109130 kohtia sekä altistuksen jälkeen substraatin kanssa kosketuksiin saatettuja rea-gensseja kunkin sekvenssin sijaintikohta tullaan tietämään.
Tämän jälkeen suojaryhmät poistetaan osasta substraattia tai siitä kokonaisuudessaan ja sekvenssit mahdollisesti salvataan salpayksiköllä C.
5 Menetelmästä saadaan substraatti, joka pinnallaan käsittää monilukuisen määrän polymeerejä, joiden yleinen kaava on seuraava: S—[L]—(Mj)—(Mj)—(Mk)... (MX)-[C] 10 jossa hakasulut osoittavat valinnaisia ryhmiä ja Mj...Mx osoittaa jo tain monomeerien sekvenssiä. Monomeerien lukumäärä saattaisia kattaa laajan valikoiman arvoja, mutta edullisessa suoritusmuodossa niitä on 2-100.
Joissakin suoritusmuodoissa monilukuisen määrän kohtia substraattipolymeereillä on määrä sisältää yhteinen monomeerialasekvenssi. 15 Esimerkiksi voi olla toivottavaa syntetisoida sekvenssi S-M1-M2-M3 ensimmäisiin kohtiin ja sekvenssi S-M4-M2-M3 toisiin kohtiin. Menetelmä aloitettaisiin säteilyttämällä ensimmäisiä kohtia, minkä jälkeen ne saatettaisiin kosketuksiin Μ,-Ριη kanssa, jolloin saataisiin sekvenssi S-Μ,-Ρ ensimmäisiin kohtiin. Sitten toiset kohdat säteilytettäisiin ja saatettaisiin kosketuksiin M4-P:n kanssa, 20 jolloin saataisiin sekvenssi S-M4-P toisiin kohtiin. Sen jälkeen sekä ensimmäi-:.’-i set että toiset kohdat säteilytettäisiin ja saatettaisiin kosketuksiin dimeerin M2-M3 kanssa, jolloin saataisiin sekvenssi S-M1-M2-M3 ensimmäisiin kohtiin ja l S—M4-M2-M3 toisiin kohtiin. Luonnollisesti minkä tahansa mittaisia yhteisiä alasekvenssejä voitaisiin käyttää mukaan lukien kahdesta useampaan mono-25 meerin mittaisia, 2-100 monomeerin, 2-20 monomeerin mittaisia ja edullisimmin 2-3 monomeerin mittaisia.
. . Muiden suoritusmuotojen mukaan käytetään maskisarjaa ensim- mäiselle monomeerikerrokselle, minkä jälkeen käytetään vaihtelevia valon ·;·' aallonpituuksia suojaryhmien selektiiviseksi poistamiseksi. Esimerkiksi edellä 30 käsitellyssä menetelmässä ensimmäiset alueet altistetaan ensin maskin läpi ja ‘: saatetaan reagoimaan ensimmäisen monomeerin kanssa, jossa on ensimmäi nen suojaryhmä P,, joka voidaan poistaa altistamalla ensimmäiselle valon aallonpituudelle (esim. IR). Toisilla alueilla käytetään maskia ja ne saatetaan '··· reagoimaan toisen monomeerin kanssa, jossa on toinen suojaryhmä P2, joka 35 voidaan poistaa altistamalla toiselle valon aallonpituudelle (esim. UV). Tämän jälkeen maskit tulevat synteesissä tarpeettomiksi, koska substraatti kokonai- 14 109130 suudessaan voidaan altistaa vaihtoehtoisesti valon ensimmäiselle ja toiselle aallonpituudelle suojaryhmien poistokierroksella.
Edeltävien menetelmien mukaan substraatille valmistetuilla polymeereillä on erilaisia käyttöjä mukaan lukien esimerkiksi biologisen aktiivisuu-5 den suhteen seulominen. Tällaisissa seulontatoiminnoissa sekvenssit sisältävä substraatti saatetaan kosketuksiin leimaa vailla olevan tai leimatun reseptorin kanssa, joka voi olla vasta-aine, solureseptori, fosfolipidirakkula tai mikä tahansa erilaisista muista reseptoreista. Yhdessä edullisessa suoritusmuodossa polymeerit saatetaan kosketuksiin ensimmäisen leimaa vailla olevan kiinnos-10 tavan reseptorin kanssa, minkä jälkeen ne saatetaan kosketuksiin leimatun re-septorispesifisen tunnistusyksikön kanssa, joka on esimerkiksi vasta-aine. Tämä menetelmä tuottaa signaalin vahvistuksen detektiovaiheessa.
Reseptorimolekyylit voivat sitoutua yhteen tai useampaan polymeeriin substraatilla. Leimatun reseptorin läsnäolo ja siten reseptoriin sitoutuvan 15 sekvenssin läsnäolo todetaan edullisessa suoritusmuodossa käyttämällä auto-radiografiaa, fluoresenssin detektiota varauskytketyllä laitteella, fluoresenssi-mikroskopiaa tai vastaavia. Polymeerin sekvenssiä kohdissa, joissa reseptori-sitoutumista todetaan, voidaan käyttää reseptorille komplementaarisen sekvenssin määrittämiseksi kokonaisuudessaan tai osittain.
20 Tämän keksinnön käyttöä havainnollistetaan ensisijaisesti viittaa- maila seulontaan biologisen aktiivisuuden suhteen. Keksinnöllä on kuitenkin monia muitakin käyttöjä. Esimerkiksi keksintöä voidaan käyttää tietojen tallen-nuksessa (esim. optisille levyille), molekyylielektronisten laitteiden valmistuk-sessa, stationaarifaasien valmistuksessa erotustieteissä, värien ja kirkastimien :·. 25 tuotannossa, valokuvauksessa sekä solujen, proteiinien, lektiinien, nukleiini happojen, polysakkaridien ja vastaavien immobilisoinnissa kuvioiksi pinnalle spesifisten polymeerisekvenssien molekyylitunnistuksen välityksellä. Synteti-,/ soimalla sama yhdiste vierekkäisissä, progressiivisesti poikkeavissa pitoisuuk- ;·' sissa muodostetaan gradientti kemotaksis-ilmiön kontrolloimiseksi tai diagnos- : 30 tisten "upotustikkujen" kehittämiseksi, jotka esimerkiksi titraavat vasta-aineen kasvavaa antigeenin määrää vastaan. Syntetisoimalla useita katalysaattori-molekyylejä lähelle toisiaan voidaan päästä tehokkaampiin monivaihekonver-sioihin "koordinoidun immobilisaation" välityksellä. Koordinoitua immobilisaa-tiota voidaan käyttää myös elektronisiirtosysteemeissä ja sekä rakenteellisen 35 yhtenäisyyden että muiden haluttujen ominaisuuksien saamiseksi esim. voitelu-, kostustus-jne. materiaaleihin.
15 109130
Vaihtoehtoisten suoritusmuotojen mukaan voidaan tutkia molekyylien biojakaumaa tai farmakokineettisiä ominaisuuksia. Esimerkiksi vastustuksen suoli- tai seerumiproteaaseille määrittämiseksi polymeerit voidaan salvata fluoresoivalla tarralla ja saattaa kosketuksiin kiinnostavien biologisten nestei-5 den kanssa.
III. Polymeerisynteesi
Kuviossa 1 havainnollistetaan yhtä tässä julkistetun keksinnön suoritusmuotoa, jossa substraatti 2 on esitetty poikkileikkauksena. Oleellisesti keksinnössä voidaan käyttää mitä tahansa kuviteltavissa olevaa substraattia. 10 Substraatti voi olla biologinen, ei-biologinen, orgaaninen, epäorgaaninen tai minkä tahansa näistä yhdistelmä, jota on hiukkasina, säikeinä, sakkoina, geeleinä, levynä, putkena, palloina, astioina, kapillaareina, tuppoina, viipaleina, kalvoina, levyinä, objektilaseina jne. Substraatti voi olla minkä tahansa kätevän muotoinen, kuten kiekko, neliö, pallo, ympyrä jne. Substraatti on edulli-15 sesti tasainen, mutta sen pinta voi olla jossain erilaisista vaihtoehtoisista kon-figuraatioista. Esimerkiksi substraatti voi sisältää kohotettuja tai painettuja alueita, joissa synteesi tapahtuu. Substraatti ja sen pinta muodostavat edullisesti jäykän tuen, jolla suorittaa tässä kuvatut reaktiot. Substraatti ja sen pinta valitaan myös tuottamaan tarkoituksenmukaiset valoabsorptio-ominaisuudet. Esi-:·.·’ 20 merkiksi substraatti voi olla polymeroitu Langmuir Blodgett-kalvo, funktionaali- • j seksi tehty lasi, Si, Ge, GaAs, GaP, Si02, SiN4, modifioitua piitä tai jotain laa- jasta valikoimasta geelejä tai polymeerejä kuten (polyjtetrafluorietyleeni, (poly)vinylideenidifluoridi, polystyreeni, polykarbonaatti tai mainittujen yhdis-telmät. Muita substraattimateriaaleja tulee helposti ilmeiseksi alan ammattilai-25 sille heidän tutustuessaan tähän julkistukseen. Edullisessa suoritusmuodossa substraatti on tasainen lasi tai yksikidepiitä, jonka pintamuodostelmapiirteet . . ovat alle 10 A.
i i « / Joittenkin suoritusmuotojen mukaan substraatin pintaa syövytetään ···* käyttäen hyvin tunnettuja tekniikoita haluttujen pintapiirteiden saamiseksi.
30 Esimerkiksi muodostamalla ojia, v-vakoja, mesa-rakenteita tai vastaavia syn-
» I
teesialueet voidaan sijoittaa likeisemmin törmäävän valon polttopisteeseen, varustaa heijastavilla "peili"-rakenteilla valon keräämisen maksimoiseksi fluo-';; · ’ resoivista lähteistä tai vastaavaa.
Kiinteän substraatin pinnat koostuvat tavallisesti mutta eivät aina 35 samasta materiaalista kuin substraatti. Täten pinta voi koostua mistä tahansa laajasta valikoimasta materiaaleja, esimerkiksi polymeerit, muovit, hartsit, po- 16 109130 lysakkaridit, piidioksidi tai piidioksidipohjaiset materiaalit, hiili, metallit, epäorgaaniset lasit, membraanit, tai mistä tahansa edellä luetelluista substraatti-materiaaleista. Joissakin suoritusmuodoissa pinnalla voi olla mahdollista j käyttää koteloituja sitoutumisjäseniä, jotka on kiinnitetty tiukasti substraatin 5 pintaan avoinna olevan patenttihakemuksen sarjanro 404 920 oppien mukaisesti, joka hakemus aiemmin sisällytettiin tähän viitteeksi. Edullisesti pinta sisältää reaktiivisia ryhmiä, jotka voisivat olla karboksyylejä, aminoja, hydrok-syylejä tai vastaavia. Edullisimmin pinta on optisesti läpinäkyvä ja sillä on pin-ta-Si-OH-funktionaalisuuksia, kuten tavataan piidioksidipinnoilla.
10 Substraatin pinta 4 on edullisesti varustettu kerroksella liittomole- kyylejä 6, vaikka tulee ymmärtää, että liittomolekyylit eivät ole keksinnön edellyttämiä yksiköitä. Liittomolekyylit ovat edullisesti riittävän pituisia mahdollistaakseen polymeerien valmiissa substraatissa vapaan vuorovaikutuksen substraatin kanssa kosketuksiin saatettujen molekyylien kanssa. Liittomole-15 kyylien tulisi olla 6-50 atomin mittaisia riittävän altistuksen saamiseksi. Liitto-molekyylit voivat olla esimerkiksi aryyliasetyleeni-, etyleeniglykolioligomeerejä, jotka sisältävät 2-10 monomeeriyksikköä, diamiineja, dihappoja, aminohappoja tai mainittujen yhdistelmiä. Muita liittomolekyylejä voidaan käyttää tämä julkistus huomioon ottaen.
20 Vaihtoehtoisten suoritusmuotojen mukaan liittomolekyylit valitaan niiden hydrofiilisten/hydrofobisten ominaisuuksien mukaan syntetisoitujen po-; lymeerien esityksen tietyille reseptoreille parantamiseksi. Esimerkiksi hydrofiili- : .·. sen reseptorin kyseessä ollen hydrofiiliset liittomolekyylit ovat edullisia, jotta ....: reseptorin on mahdollista mennä lähemmäs syntetisoitua polymeeriä.
...t 25 Toisen vaihtoehtoisen suoritusmuodon mukaan liittomolekyylit on samoin varustettu valolla pilkottavalla ryhmällä väliasemassa. Valolla pilkottava ryhmä voidaan edullisesti pilkkoa jollain muulla aallonpituudella kuin suoja-ryhmä. Tällöin on mahdollista poistaa eri polymeerit synteesin päätyttyä altis-’...: tamalla valon erilaisille aallonpituuksille.
• 30 Liittomolekyylit voidaan kiinnittää substraattiin hiili-hiilisidoksilla .···. käyttäen esimerkiksi (poly)trifluorikloorietyleenipintoja, tai edullisesti siloksaa- nisidoksia (käyttäen esimerkiksi lasi- tai piioksidipintoja). Siloksaanisidoksia - ·' substraatin pinnan kanssa voidaan muodostaa yhdessä suoritusmuodossa trikloorisilyyliryhmiä sisältävien liittomolekyylien reaktioissa. Liittomolekyylit 35 voidaan mahdollisesti kiinnittää järjestäytyneeksi joukoksi, eli osiksi pääryhmiä 17 109130 polymeroidussa Langmuir Blodgett-kalvossa. Vaihtoehtoisissa suoritusmuodoissa liittomolekyylit on adsorboitu substraatin pintaan.
Liittomolekyylit ja monomeerit, joita tässä käytetään, on varustettu funktionaalisella ryhmällä, johon on sidottu suojaryhmä. Edullisesti suojaryhmä 5 on liittomolekyylin distaali- tai ääripäässä substraattiin nähden vastakkaisella puolella. Suojaryhmä voi olla joko negatiivinen suojaryhmä (eli suojaryhmä te-I kee liittomolekyyleistä vähemmän reaktiivisia monomeerin kanssa kosketuksiin saatettaessa) tai positiivinen suojaryhmä (eli suojaryhmä tekee liittomolekyyleistä reaktiivisempia monomeerin kanssa kosketuksiin saatettaessa). Negatii-10 visten suojaryhmien kohdalla vaaditaan lisävaiheena reaktivaatio. Joissakin suoritusmuodoissa tämä suoritetaan kuumentamalla.
Liittomolekyylien suojaryhmä voidaan valita laajasta valikoimasta positiivisia, valon vaikutuksesta reaktiivisia ryhmiä, edullisesti mukaan sisällyttäen aromaattiset nitroyhdisteet kuten o-nitrobentsyylijohdannaiset tai bent-15 syylisulfonyyli. Edullisessa suoritusmuodossa käytetään 6-nitroveratryylioksi-karbonyylia (NVOC), 2-nitrobentsyylioksikarbonyylia (NBOC) tai α,α-dimetyylidimetoksibentsyylioksikarbonyylia (DDZ). Yhdessä suoritusmuodossa käytetään aromaattista nitroyhdistettä, joka sisältää bentsyylivedyn or-to-asemassa nitroryhmään nähden, eli kemikaalia, joka on muotoa: ' 20 R, R. o
1 aXA A
·;· 3UA° ···
: : n02 •i R
:·. 25 1 jossa R, on alkoksi, alkyyli, halogeeni, aryyli, alkenyyli tai vety; R2 on alkoksi, alkyyli, halogeeni, aryyli, nitro tai vety; R3 on alkoksi, alkyyli, halo-• geeni, nitro, aryyli tai vety; R4 on alkoksi, alkyyli, vety, aryyli, halogeeni tai nit- ro; ja R5 on alkyyli, alkynyyli, syaani, alkoksi, vety, halogeeni, aryyli tai alke-.·. 30 nyyli. Muita materiaaleja, joita voidaan käyttää, ovat o-hydroxi-a-metyylisinna- moyylijohdannaiset. Valolla poistettavia suojaryhmiä kuvataan esimerkiksi jul-·* kaisuissa Patchornik, J.Am.Chem.Soc. 92 (1970) 6333, ja Amie et aL, .:.: J.Ora.Chem. 39 (1974) 192, jotka kummatkin sisällytetään tähän viitteiksi.
Vaihtoehtoisessa suoritusmuodossa positiivinen reaktiivinen ryhmä 35 aktivoidaan reaktiota varten reagensseilla liuoksessa. Esimerkiksi 5-bromi-7- ie 109130 nitroindoliiniryhmä karbonyyliin sidottuna reagoi altistettaessa valolle 420 nm:ssä.
Toisessa vaihtoehtoisessa suoritusmuodossa liittomolekyylin reaktiivinen ryhmä valitaan laajasta valikoimasta negatiivisia, valon vaikutuksesta 5 reaktiivisia ryhmiä mukaan lukien sinnamaattiryhmä.
Vaihtoehtoisesti reaktiivinen ryhmä aktivoidaan tai deaktivoidaan käyttäen elektronisuihkulitografiaa, röntgensädelitografiaa tai mitä tahansa muuta säteilyä. Sopiviin reaktiivisiin ryhmiin elektronisuihkulitografiaan kuuluu sulfonyyli. Muita menetelmiä voidaan käyttää mukaan lukien esimerkiksi altis-10 taminen virtalähteelle. Muita reaktiivisia ryhmiä ja aktivaatiomenetelmiä voidaan käyttää tämä julkistus huomioon ottaen.
Kuten esitetään kuviossa 1, liittomolekyylit altistetaan edullisesti esimerkiksi valolle sopivan maskin 8 läpi käyttäen fotolitografisia tekniikoita, jotka edustavat tyyppiä, joka tunnetaan puolijohdeteollisuudessa ja jota kuva-15 taan esimerkiksi kirjoissa Sze, "VLSI Technology", McGraw-Hill, 1983, ja Mead et aL, "Introduction to VLSI SYstems", Addison-Wesley, 1980, jotka sisällytetään tähän viitteiksi kaikissa tarkoituksissa. Valo voidaan ohjata joko pinnalle, joka sisältää suojaryhmät, tai substraatin taakse, kunhan substraatti on läpinäkyvä valon aallonpituudella, jota tarvitaan suojaryhmien poistamiseksi. Kuvios-20 sa 1 esitetyssä suoritusmuodossa valo ohjataan substraatin sille pinnalle, joka sisältää suojaryhmät. Kuviossa 1 havainnollistetaan tällaisten maskitekniikoi-den käyttöä käytettäessä niitä positiiviseen reaktiiviseen ryhmään liittomole-.·. kyylien aktivoimiseksi ja funktionaalisten ryhmien paljastamiseksi alueilla 10a ’ ’.: ja 10b.
25 Maski 8 on yhdessä suoritusmuodossa läpinäkyvä tukimateriaali, ·' ’ joka on selektiivisesti päällystetty kerroksella himmeää materiaalia. Osia him- meästä materiaalista on poistettu, jolloin himmeä materiaali on jäänyt täsmälli- • # sesti siihen kuvioon, joka halutaan substraatin pinnalle. Maski tuodaan lähelle ,,. '· tai kuvannetaan substraatin pinnalle tai saatetaan sen kanssa suoraan kos- • ’ , 30 ketukseen kuten esitetään kuviossa 1. "Aukot" maskissa vastaavat substraatin kohtia, joista halutaan poistaa valolla poistettavat suojaryhmät substraatista. Kohdalleen asettelu voidaan suorittaa käyttäen tavanomaisia kohdentamistek-niikoita, joissa käytetään kohdennusmerkkejä (ei esitetty) peräkkäisten maski-,,/ en asettamiseksi tarkasti päällekkäin edeltävien kuvioitusvaiheiden mukaan, 35 tai hienostuneempia tekniikoita voidaan käyttää. Esimerkiksi voidaan käyttää interferometrisiä tekniikoita kuten sitä, jota kuvataan julkaisussa Flanders et 19 109130 aL, "A New Interferometric Alignment Technique" (suom. "Uusi interferometri-nen kohdennustekniikka"), App.Phvs.Lett. 31 (1977) 426 428, joka sisällytetään tähän viitteeksi.
Substraatille kohdistetun valon kontrastin parantamiseksi kontrastia 5 tehostavia materiaaleja on toivottavaa sijoittaa maskin ja substraatin väliin joittenkin suoritusmuotojen mukaan. Tämä kontrastintehostuskerros voi käsittää molekyylin, joka hajoaa valon vaikutuksesta, kuten kinonidiatsidi, tai materiaalin, joka tilapäisesti menettää värinsä kiinnostavalla aallonpituudella. Materiaalien tilapäinen värinmenetys mahdollistaa suuremman tunkeutumisen valo loa käyttökohdissa, mikä tehostaa kontrastia. Vaihtoehtoisesti kontrastin tehostuminen voidaan saada käyttämällä päällystetyistä kuiduista koostuvaa optista nippua.
Valo voi olla peräisin tavanomaisesta hehkulähteestä, laserista, la-serdiodista tai vastaavasta. Jos käytetään ei-kollimoituja valolähteitä, paksun 15 tai monikerroksisen maskin käyttäminen voi olla toivottavaa valon leviämisen substraatille estämiseksi. Joissakin suoritusmuodoissa voi edelleen olla toivottavaa käyttää ryhmiä, jotka ovat herkkiä eri aallonpituuksille, synteesin kontrolloimiseksi. Esimerkiksi käyttämällä ryhmiä, jotka ovat herkkiä eri aallonpituuksille, on mahdollista valita haarautumisasemia polymeerin synteesissä 20 tai eliminoida tiettyjä maskinkäyttövaiheita. Useita reaktiivisia ryhmiä vastaavi-:ne aallonpituuksineen suojaryhmän poistamiseksi esitetään taulukossa 1.
I
Taulukko 1 • Likimääräinen dll 25 Ryhmä suojaryhmäpoiston aallonpituus nitroveratryylioksikarbonyyli (NVOC) UV (300 - 400 nm) ', nitrobentsyylioksikarbonyyli (NBOC) UV (300 - 350 nm) " 30 dimetyylidimetoksibentsyylioksi- UV (280 - 300 nm) *, karbonyyli 5-bromi-7-nitroindolinyyli UV (420 nm) .: o-hydroksi-a-metyylisinnamoyyli UV (300 - 350 nm) 2-oksimetyleeniantrakinoni UV (350 nm) 35 20 109130
Vaikka keksintöä havainnollistetaan tässä Pääasiassa käyttämällä maskia substraatin valittujen alueiden valaisemiseksi, muitakin tekniikoita voidaan käyttää. Esimerkiksi substraattia voidaan siirtää moduloidun laser- tai diodivalolähteen alla. Tällaisia tekniikoita käsitellään esimerkiksi 5 US-patenttijulkaisussa nro 4 719 615 (Feyrer et ai.), joka sisällytetään tähän viitteeksi. Vaihtoehtoisissa suoritusmuodoissa käytetään galvanometristä la-serpyyhkäisijää. Muissa suoritusmuodoissa synteesi voi tapahtua tavanomaisella nestekiteellä tai kosketuksissa mainittuun Gota kutsutaan tässä "valoventtiiliksi") tai kuituoptiikkavalolähteillä. Tarkoituksenmukaisesti modu-10 loimalla nestekiteitä valoa voidaan selektiivisesti kontrolloida, jotta valo voi koskettaa valittuja alueita substraatilla. Vaihtoehtoisesti synteesi voi tapahtua sarjan optisia kuituja päässä, johon valoa kohdistetaan selektiivisesti. Muut tavat valoaltistuksen kohdan kontrolloimiseksi ovat ilmeisiä alan ammattilaisille.
Substraattia voidaan säteilyttää joko kosketuksissa tai ei kosketuk-15 sissa liuokseen (ei esitetty) ja sitä säteilytetään edullisesti kosketuksissa liuokseen. Liuos sisältää reagensseja säteilytyksessä muodostuneiden sivutuotteiden estämiseksi häiritsemästä polymeerin synteesiä joittenkin suoritusmuotojen mukaan. Tällaisia sivutuotteita saattaisivat olla esimerkiksi hiilidioksidi, nit-rosokarbonyyliyhdisteet, styreenijohdannaiset, indolijohdannaiset ja tuotteet ·’: 20 niiden valokemiallisista reaktioista. Vaihtoehtoisesti liuos voi sisältää reagens- ·,: seja, joita käytetään substraatin taitekertoimen saamiseksi. Liuokseen lisättyi- . # hin reagensseihin voi edelleen sisältyä esimerkiksi happamia tai emäksisiä ,·, puskureita, tioleja, substituoituja hydratsiineja tai hydroksyyliamiineja, pelkisti- ‘ I miä (esim. NADH) tai reagensseja, joiden tiedetään reagoivan tietyn funktio- 25 naalisen ryhmän kanssa (esim. aryylinitroso + glyoksyylihappo aryyli-'·* ’ formhydroksamaatti + C02).
Joko säteilytysvaiheen kanssa samanaikaisesti tai sen jälkeen liit-:‘: tomolekyylit pestään ensimmäisellä monomeerillä tai saatetaan muutoin kos- ‘...: ketuksiin mainitun kanssa, jota havainnollistaa "A" alueilla 12a ja 12b kuviossa V, 30 2. Ensimmäinen monomeeri reagoi valolle altistettujen liittomolekyylien akti- ·, voitujen funktionaalisten ryhmien kanssa. Ensimmäinen monomeeri, joka on ' edullisesti aminohappo, on samoin varustettu valosuojaryhmällä. Valosuoja- ryhmä monomeerissä voi olla sama tai erilainen kuin liittomolekyyleissä käy-tetty suojaryhmä, ja se voidaan valita mistä tahansa edellä kuvatuista suoja-35 ryhmistä. Yhdessä suoritusmuodossa suojaryhmät A-monomeerille valitaan ryhmistä NBOC ja NVOC.
21 109130
Kuten esitetään kuviossa 3, säteilytysmenetelmä toistetaan sen jälkeen, jolloin maski on uudelleen asemoitu sidossuojaryhmien poistamiseksi ja funktionaalisten ryhmien paljastamiseksi alueilla 14a ja 14b, jotka on esitetty alueiksi, jotka olivat suojattuja edeltävässä maskinkäyttövaiheessa. Ensimmäi-5 sen maskin uudelleen asemoinnin vaihtoehtona monissa suoritusmuodoissa käytetään toista maskia. Muissa vaihtoehtoisissa suoritusmuodoissa joittenkin i vaiheitten tarkoitus voi olla yhteisen alueen valaiseminen peräkkäisissä vai heissa. Kuten esitetään kuviossa 3, voi olla toivottaa saada erotus säteilytet-tyjen alueiden välille. Esimerkiksi noin I - 5 pm:n erotus voi olla tarkoituksen-10 mukainen kohdistustoleranssien huomioon ottamiseksi.
Kuten esitetään kuviossa 4, substraatti saatetaan sitten kosketuksiin toisen suojatun monomeerin "B" kanssa, jolloin saadaan B-alueet 16a ja 16b. Sen jälkeen substraatilla käytetään taas maskia suojaryhmien poistamiseksi ja reaktiivisten ryhmien paljastamiseksi A-alueella 12a ja B-alueella 16b. 15 Substraatti saatetaan taas kosketuksiin monomeerin B kanssa, jolloin muodostuu kuviossa 6 esitetty rakenne. Substraatille on tuotettu dimeerit B-A ja B-B.
Seuraavassa sarjassa maskinkäyttö- ja kosketuksiinsaattovaiheita, jotka ovat samankaltaisia kuin edellä A:lla kuvatut, (ei esitetty) saadaan kuvi-. 20 ossa 7 esitetty rakenne. Menetelmässä saadaan kaikki mahdolliset B:n ja A:n • dimeerit, eli B-A, A-B, A-Aja B-B.
Substraatti, synteesin alue ja kunkin yksittäisen polymeerin syntee-,·. sin alue voisivat olla minkä tahansa kokoisia tai muotoisia. Esimerkiksi voidaan ' ! käyttää neliöitä, ellipsoideja, nelikulmioita, kolmioita, ympyröitä tai niiden osia, 25 sekä epäsäännöllisiä geometrisia muotoja. Yhdellä substraatilla voidaan niinikään käyttää kaksinkertaisia synteesialueita runsaussyistä.
Yhdessä suoritusmuodossa alueiden 12 ja 16 substraatilla pinta-ala : on noin 1 cm2 - 10'10 cm2. Joissakin suoritusmuodoissa alueiden 12 ja 16 pin- ta-alat ovat alle noin 10‘1 cm2, 10'2 cm2, ΙΟ"3 cm2, 10-4 cm2, 10'5 cm2, 10-6 cm2, v. 30 10-7 cm2, 10'8 cm2 tai 10'10 cm2. Edullisessa suoritusmuodossa alueet 12 ja 16 ovat noin 10 x 10 pm - 500 x 500 pm.
*; Joissakin suoritusmuodoissa yksittäinen substraatti kantaa enem- män kuin noin 10 erilaista monomeerisekvenssiä ja edullisesti enemmän kuin noin 100 erilaista monomeerisekvenssiä, vaikka joissakin suoritusmuodoissa 35 substraatille muodostetaan enemmän kuin noin 103, 104, 105, 106, 107 tai 108 erilaista sekvenssiä. Luonnollisesti substraatin alueen puitteissa, jolle mono- 22 109130 meerisekvenssi syntetisoidaan, on edullista, että monomeerisekvenssi on oleellisesti puhdas. Joissakin suoritusmuodoissa substraatin alueet sisältävät polymeerisekvenssejä, joiden puhtausaste on ainakin noin 1 %, 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, 50 %, 60 %, 70 %, 80 %, 90 %, 95 5 %, 96 %, 97 %, 98 % tai 99 %.
Joittenkin suoritusmuotojen mukaan useita sekvenssejä sijoitetaan tarkoituksellisesti yhdelle alueelle alustavan seulonnan biologisen aktiivisuuden suhteen saamiseksi, minkä jälkeen materiaaleja alueilla, jotka osoittavat merkittävää sitoutumista, arvioidaan edelleen.
10 IV. Yksityiskohtia reaktorisysteemin yhdestä suoritusmuodosta
Kuviossa 8A esitetään kaaviollisesti reaktorisysteemin 100 edullinen suoritusmuoto polymeerien syntetisoimiseksi valmistetulle substraatille keksinnön yhden näkökohdan mukaan. Reaktorisysteemi käsittää rungon 102, jonka pinnalla on ontelo 104. Edullisissa suoritusmuodoissa ontelo 104 on noin 50 -15 1 000 pm syvä, jolloin edullinen syvyys on noin 500 pm.
Ontelon pohja on edullisesti varustettu joukolla harjanteita 106, jotka ulkonevat sekä kuvion tasossa että kuvion tasoon nähden samansuuntaisina. Harjanteet ovat edullisesti noin 50 - 200 pm syviä ja ne on sijoitettu 2-3 mm:n päähän toisistaan. Harjanteiden tarkoituksena on muodostaa turbulentti 20 virtaus paremman sekoituksen saamiseksi. Ontelon pohjapinta on edullisesti . . : valoa absorboiva törmäävän valon heijastumisen estämiseksi.
’ Substraatti 112 sijoitetaan ontelon 104 yläpuolelle. Substraatin
pohjapinta 114 on varustettu valolla poistettavalla suojaryhmällä kuten NVOC
“ ; käyttäen tai käyttämättä välissä liittomolekyyliä. Substraatti on edullisesti läpi- * » # · | 25 näkyvä laajalla valospektrillä, mutta joissakin suoritusmuodoissa se on läpinä-
·* ‘ kyvä vain aallonpituudella, jolla suojaryhmä voidaan poistaa (kuten UV
NVOG:n kohdalla). Substraatti on joissakin suoritusmuodoissa tavanomainen .‘•j mikroskoopin objektilasi tai peiteliuska. Substraatti on edullisesti niin ohut kuin mahdollista, samalla kun se yhä tarjoaa riittävän fyysisen tuen. Edullisesti 30 substraatti on alle noin 1 mm:n paksuinen, edullisemmin alle 0,5 mm:n paksui- » nen, edullisemmin alle 0,1 mm:n paksuinen ja edullisimmin alle 0,05 mm:n ;· paksuinen. Vaihtoehtoisissa edullisissa suoritusmuodoissa substraattia on kvartsia tai piitä.
Substraatti ja runko sulkevat onkalon lukuunottamatta tuloaukkoa 35 108 ja poistoaukkoa 110. Runko ja substraatti on voitu sovittaa sinetöitäviksi joissakin suoritusmuodoissa yhdellä tai useammalla tiivisteellä. Edullisen suo- 23 109130 ritusmuodon mukaan runko on varustettu kahdella samankeskisellä tiivisteellä, joiden välinen tila pidetään tyhjössä substraatin liittymisen tiivisteisiin varmistamiseksi.
Nestettä pumpataan tuloaukon kautta onteloon pumpulla 116, joka 5 voi olla esimerkiksi malli nro B-120-S, jota valmistaa Eldex Laboratories. Valittuja nesteitä kierrätetään pumpulla onteloon, ontelon läpi ja ulos poistoau-kosta uudelleenkierrätystä tai poisheittoa silmällä pitäen. Reaktoriin voidaan kohdistaa ultraäänisäteilyä ja/tai sitä voidaan kuumentaa sekoituksen helpottamiseksi joissakin suoritusmuodoissa.
10 Substraatin 112 päällä on linssi 120, joka voi olla esimerkiksi 2" 100 mm:n fokaalipituusfuusiopiilinssi. Kompaktin systeemin saamiseksi voidaan käyttää heijastavaa peiliä 122 valon ohjaamiseksi valolähteestä 124 substraatille. Valolähde 124 voi olla esimerkiksi Xe(Hg)-valolähde, jota valmistaa Oriel ja jonka mallinro on 66024. Toista linssiä 126 voidaan käyttää maskikuvan 15 projisoimiseksi substraatille yhdessä linssin 112 kanssa. Tätä litografian muotoa kutsutaan tässä projektiopainamiseksi. Kuten tästä julkistuksesta selvästi ilmenee, proksimiteettipainatusta ja vastaavia voidaan samoin käyttää joittenkin suoritusmuotojen mukaan.
Valo valolähteestä voi saavuttaa vain valitut kohdat substraatilla 20 maskin 128 johdosta. Maski 128 voi olla esimerkiksi lasilevy, jolla on kromiet-saus. Maski 128 on yhdessä suoritusmuodossa varustettu ristikolla läpinäkyviä kohtia ja himmeitä kohtia. Tällaiset maskit voivat olla esimerkiksi Photo Sciences, Inc. -valmistajalta. Valo kulkee vapaasti maskin läpinäkyvien alueiden lä-: ; pi, mutta heijastuu muista alueista tai absorboituu niihin. Tämän vuoksi vain 25 valitut alueet substraatista altistuvat valolle, v ; Kuten edellä esitettiin, valoventtiilejä (LCD:t) voidaan käyttää ta vanomaisten maskien vaihtoehtona alueiden substraatista selektiiviseksi al-: tistamiseksi. Vaihtoehtoisesti kuituoptisia päälilevyjä kuten niitä, joita on saa- tavana valmistajalta Schott Glass, Inc., voidaan käyttää maskin kontrastin te-30 hostamistarkoituksessa tai ainoana keinona alueen rajaamiseksi, jolle valoa ; kohdistetaan. Tällaiset päälilevyt asetettaisiin suoraan substraatin yläpuolelle ;·’ tai sille kuviossa 8A esitetyssä reaktorissa. Edelleen muissa suoritusmuodois- sa kontrastin tehostamiseksi voidaan käyttää "kärpässilmä"-linssejä, reunois-‘ ’: taan ohuempia kuituoptiikkapäälilevyjä tai vastaavia.
35 Valaistuksen saamiseksi alueille, jotka ovat pienempiä kuin valon aallonpituus, voidaan käyttää mutkikkaampia tekniikoita. Esimerkiksi yhden 24 109130 edullisen suoritusmuodon mukaan valoa ohjataan substraatille käyttämällä molekyylimikrokiteitä esimerkiksi mikropipettien kärjessä. Tällaisia laitteita julkistetaan julkaisussa Lieberman et ah, "Light Source Smaller Than the Optical Wavelength" (suom. "Optista aallonpituutta pienempi valolähde"), Science 247 5 (1990) 59 - 61, joka sisällytetään tähän viitteeksi kaikissa tarkoituksissa.
Käytännössä substraatti sijoitetaan onteloon ja sinetöidään siihen. Kaikki menettelyt menetelmässä substraatin valmistamiseksi suoritetaan huoneessa, joka on valaistu pääasiassa tai kokonaisuudessaan valolla, jonka aallonpituus on ulkopuolella valoalueen, jolla suojaryhmä poistetaan. Esimer-10 kiksi NVOC:n kohdalla huoneen tulisi olla valaistu tavanomaisella pimeä huone -valolla, jossa on vain vähän tai ei lainkaan UV-valoa. Kaikki menettelyt suoritetaan edullisesti noin huoneenlämpötilassa.
Ensiksi suojaryhmänpoistonestettä (ilman monomeeriä) kierrätetään ontelon läpi. Liuos on edullisesti 5 mM rikkihappoa dioksaaniliuoksessa, jonka 15 tehtävänä on pitää paljaana olevat aminoryhmät protonoituina sekä vähentää niiden reaktiivisuutta fotolyysin sivutuotteiden kanssa. Absorptiivisia materiaaleja kuten N,N-dietyyliamino-2,4-dinitrobentseeniä esimerkiksi voidaan sisällyttää suojaryhmänpoistonesteeseen valon absorboimiseksi sekä heijastumisen ja epätoivottavan fotolyysin estämiseksi.
20 Sen jälkeen levy asetetaan valosädereitille maskista siten, että en- ·,*: simmäiset kohdat substraatilla tulevat valaistuksi, jolloin niistä siten suojaryh- .! ’ mät poistuvat. Edullisissa suoritusmuodoissa substraattia valaistaan noin 1 - ’’ 15 minuutin ajan, jolloin edullinen valaisuaika on noin 10 minuuttia 10 - 20 ; mW:lla/cm2 365 nm:n valoa käyttäen. Levyt neutraloidaan (eli saatetaan ' * 25 pH:hon noin 7) fotolyysin jälkeen käyttämällä esimerkiksi liuosta, jossa on v : di-isopropyylietyyliamiinia (DIEA) metyleenikloridissa, noin 5 minuutin ajan.
Ensimmäinen monomeeri sijoitetaan sitten ensimmäisiin kohtiin f substraatilla. Säteilytyksen jälkeen levy poistetaan, käsitellään kokonaisuutena ja sijoitetaan sitten takaisin virtauskennoon. Vaihtoehtoisesti nestettä, joka si-30 sältää ensimmäisen monomeerin, edullisesti myös suojattuna suojaryhmällä, kierrätetään ontelon läpi pumpulla 116. Jos esimerkiksi halutaan kiinnittää » ;·’ aminohappo Y substraattiin ensimmäisissä kohdissa, aminohappoa Y (joka : käsittää suojaryhmän α-typessään) sekä reagensseja, joita käytetään mono- meerin tekemiseksi reaktiiviseksi, ja/tai kantajaa kierrätetään varastosäiliöstä 35 118 pumpun välityksellä ontelon läpi ja takaisin pumpun tuloaukkoon.
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Monomeerikantajaliuos muodostetaan edullisessa suoritusmuodossa sekoittamalla ensimmäistä liuosta Göta kutsutaan tässä liuokseksi "A") ja toista liuosta Göta kutsutaan tässä liuokseksi "B"). Taulukossa 2 esitetään esimerkkinä seos, jota voidaan käyttää liuoksena A.
5
Taulukko 2
Edustava monomeerikantajaliuos "A" 100 mg NVOC-aminosuojattua aminohappoa 10 37 mg HOBT:tä (1-hydroksibentsotriatsoli) 250 μΙ DMF:ää (dimetyyliformamidi) 86 μΙ DIEA:ta (di-isopropyylietyyliamiinia)
Liuoksen B koostumusta havainnollistetaan taulukosssa 3. Liuokset 15 A ja B sekoitetaan ja niiden annetaan reagoida huoneenlämpötilassa noin 8 minuutin ajan, minkä jälkeen niitä laimennetaan lisäämällä 2 ml DMF:ää ja 500 μΙ sijoitetaan levyn pinnalle tai liuosta kierrätetään reaktorisysteemissä ja sen annetaan reagoida noin 2 tunnin ajan huoneenlämpötilassa. Sitten levy pestään DMF:llä, metyleenikloridilla ja etanolilla.
20 t . Taulukko 3 * i ; ' Edustava monomeerikantajaliuos "B" 250 μΙ DMF:ää I · *: 111 mg BOP:tä bentsotrlatsolyyli-n-oksitris(dimetyyliamino)- « : 25 fosfoniumheksafluorifosfaatti) · · Kun liuosta, joka sisältää kiinnitettävän monomeerin, kierrätetään ontelon läpi, aminohappo tai muu monomeeri reagoi karboksyylipäästään * aminoryhmien kanssa substraatin alueilla, joista on suojaryhmä poistettu.
‘ Luonnollisesti vaikka keksintöä havainnollistetaan kierrättäen monomeeriä » 30 ontelon läpi, keksintöä voitaisiin harjoittaa poistaen levy reaktorista ja upottaen ; * se tarkoituksenmukaiseen monomeeriliuokseen.
• : Kun ensimmäinen monomeeri on lisätty, ensimmäisen aminohapon sisältävä liuos huuhdotaan sitten pois systeemistä. Kun riittävää määrää DMF:ää/metyleenikloridia on kierrätetty siten, että aminohapon poistumisesta 35 voidaan olla varmoja (esim. noin 50 kertaa ontelon ja kantajaliitäntöjen tilavuus), maski tai substraatti uudelleen asemoidaan, tai käytetään uutta maskia 26 109130 siten, että toiset alueet substraatilla altistuvat valolle ja valoa 124 käytetään toiseen altistukseen. Tällöin suojaryhmät poistuvat substraatin toisilta alueilta ja menetelmää toistetaan kunnes halutut polymeerisekvenssit on syntetisoitu.
Sen jälkeen substraattijohdannainen kokonaisuudessaan saatetaan 5 kosketuksiin kiinnostavan reseptorin kanssa, joka on edullisesti leimattu esimerkiksi fluoresoivalla merkillä, kierrättämällä reseptorin liuosta tai lietettä ontelon läpi tai saattamalla levyn pinta kontaktiin kokonaisuudessaan. Reseptori sitoutuu ensisijaisesti substraatin tiettyihin alueisiin, jotka sisältävät komplementaarisia sekvenssejä.
10 Vasta-aineet lietetään tyypillisesti nesteeseen, jota yleisesti kutsu taan "superkoktailiksi", joka voi olla esimerkiksi liuos, jossa on noin 1 % BSA:ta (nautaseerumialbumiinia), 0,5 % Tween-valmistetta PBS- (fosfaattipuskuroitu suolaliuos-) puskurissa. Vasta-aineet laimennetaan super-koktail-puskuriin loppupitoisuudeksi esimerkiksi noin 0,1-4 pg/ml.
15 Kuviossa 8B esitetään vaihtoehtoinen edullinen suoritusmuoto ku viossa 8A esitetystä reaktorista. Tämän suoritusmuodon mukaan maski 128 sijoitetaan suoraan kosketuksiin substraatin kanssa. Edullisesti maskin syövytetty osa asetetaan alaspäin valon dispergoitumisen vaikutusten vähentämiseksi. Tämän suoritusmuodon mukaan kuvannuslinssit 120 ja 126 eivät ole 20 välttämättömiä, koska maski viedään hyvin lähelle substraattia.
* · **f> Tekniikan signaali-häiriösuhteen nostamiseksi keksinnön joissakin suoritusmuodoissa substraatti saatetaan kosketuksiin ensimmäisen leimatun ► · .,’,j tai ei-leimatun reseptorin kanssa, minkä jälkeen se saatetaan kosketuksiin ... leimatun toisen reseptorin kanssa (esim. vasta-aine), joka sitoutuu moniin 25 kohtiin ensimmäisellä reseptorilla. Jos esimerkiksi ensimmäinen reseptori on vasta-aine, joka on saatu ensimmäisestä eläinlajista, toinen reseptori on vas-ta-aine, joka on saatu toisesta lajista ja joka kohdistuu vastaan ensimmäiseen
I | I
lajiin liittyviä epitooppeja. Esimerkiksi hiirivasta-aineen kyseessä ollen fluore-soivasti leimattua vuohivasta-ainetta tai vastaseerumia, joka on hiirivastaista, .*··. 30 voidaan käyttää sitoutumassa useihin kohtiin hiirivasta-aineella, jolloin saa daan moninkertainen fluoresenssi verrattuna yhden hiirivasta-aineen kiinnittä-miseen kuhunkin sitoutumiskohtaan. Tämä menetelmä voidaan toistaa uudel-leen käyttäen muita vasta-aineita (esim. vuohi-hiiri-vuohi jne.) signaalin lisä-vahvistuksen saamiseksi.
35 Edullisissa suoritusmuodoissa käytetään järjestettyä maskisarjaa.
Joissakin suoritusmuodoissa on mahdollista käyttää niinkin vähää kuin yhtä 27 109130 j maskia kaikkien mahdollisten polymeerien tietystä monomeerisarjasta synteti-| soimiseksi.
! Jos esimerkiksi halutaan syntetisoida kaikki 16 dinukleotidia 4 emäksestä, 1 cm2:n synteesialue jaetaan käsitteellisesti 16 laatikoksi, joista 5 kukin on 0,25 cm:n levyinen. 4 monomeeriyksikköä merkitään A:ksi, B:ksi, C:ksi ja D:ksi. Ensimmäiset reaktiot suoritetaan 4 pystysuorassa kolonnissa, joista kukin on 0,25 cm:n levyinen. Ensimmäinen maski altistaa laatikoista va-semmanpuoleisimman kolonnin, jossa A kytketään. Toinen maski altistaa seu-raavan kolonnin, jossa B kytketään; minkä jälkeen seuraa kolmas maski 10 C-kolonnille; ja viimeinen maski, joka altistaa oikeanpuoleisimman kolonnin D:lle. Ensimmäinen, toinen, kolmas ja neljäs maski voivat olla yksi maski, jota siirretään eri kohtiin.
Menetelmä toistetaan vaakasuorassa suunnassa dimeerin toiselle yksikölle. Tällä kertaa maskit mahdollistavat vaakasuorien rivien, jälleen 0,25 15 cm:n levyisten, altistuksen. A, B, C ja D kytketään sarjassa käyttäen maskeja, jotka altistavat reaktioalueen vaakaneljännekset. Saatu substraatti sisältää neljän emäksen kaikki 16 dinukleotidia.
Kahdeksan maskia, joita käytetään dinukleotidin syntetisoimiseksi, ;.v: liittyvät toisiinsa siirtämällä tai kiertämällä. Itse asiassa yhtä maskia voidaan 20 käyttää kussakin 8 vaiheessa, jos sitä sopivasti kierretään tai siirretään. Esi- * t merkiksi edeltävässä esimerkissä maskia jossa on yksi läpinäkyvä alue, voitai-: siin käyttää sarjassa kunkin pystysuorista kolonneista altistamiseksi, siirtää 90° '" J ja sitten käyttää sarjassa vaakasuorien rivien altistuksen saamiseksi.
Taulukoissa 4 ja 5 esitetään yksinkertainen tietokoneohjelma Quick 25 Basic -kielellä maskinkäyttöohjelman ja vastaavasti näytteenkäytön suunnittelemiseksi polymeeriketjun syntetisoimiseksi 3 monomeeristä ("tähteestä"), jos-sa on 3 erilaista monomeeriä ensimmäisellä tasolla, 4 erilaista monomeeriä » * · toisella tasolla ja 5 erilaista monomeeriä 3. tasolla juovikkaassa kuviossa. Oh-jelman tulostus on kennojen lukumäärä, "juovien" (valoalueiden) lukumäärä [···, 30 kullakin maskilla ja siirtämisen määrä, joka tarvitaan maskin kullekin altistuk selle.
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Taulukko 4
Maskistrategiaohjelma
DEFINT A-Z
5 DIM b(20), w(20), 1(500) F$ = "LPTI:" OPEN f$ FOR OUTPUT AS #1
jmax = 3 'tähteiden lukumäärä 10 b(l) = 3: b(2) = 4: b(3) = 5 'rakennusosien lukumäärä tähteille 1,2,3 g = I: lmax(1) = I
FOR j = I TO jmax: g= g * b(j): NEXT j 15 w(0) = 0: w(l) = g / b(l) PRINT #l, "MASK2.BAS ", DATE$ TIME$: PRINT #l, PRINT #l, USING "tähteiden lukumäärä=##"; jmax FORj = ITOjmax : . : 20 PRINT#l, USING" tähde## ## rakennusosa"; j; b(j) : .·. NEXT j ;;;! print #i, " PRINT #l, USING "kennojen lukumäärä=####"; g: PRINT #l, ‘ ‘ ‘ 25 FOR j = 2 TO jmax '·· lmax(j) = lmax(j -1)* b(j -1) wG) = wQ -1) / b(j) NEXT j 30 FORj=ITOjmax PRINT #l, USING "maski tähteelle ##"; j: PRINT #l, PRINT #l, USING " juovien lukumäärä=###"; ImaxG) PRINT #l, USING " kunkin juovan leveys=###"; wG) FOR I = I TO ImaxG) 35 29 109130 a = I + (I -1) * w(j -1) j ae = a + w(j) -1 ' PRINT #l, USING " juova ## alkaa kohdasta ### ja päättyy kohtaan ###"; I; a; ae NEXT I 5 PRINT #l, PRINT #\, USING " kullekin ## rakennusosalle siirrä maskia ## kennoa"; b(j); w(j).
PRINT #l, : PRINT #l : PRINT #l, NEXT j 10 Copyright 1990, Affymax N.V.
Taulukko 5
Maskistrategiatulostus 15 Tähteiden lukumäärä= 3 tähde 1 3 rakennusosaa tähde 2 4 rakennusosaa tähde 3 5 rakennusosaa : 20 Kennojen lukumäärä= 60 ··, Maski tähteelle 1 '· ; juovien lukumäärä= 1 kunkin juovan leveys= 20 *·' * 25 juova 1 alkaa kohdasta 1 ja päättyy kohtaan 20 kullekin 3 rakennusosalle siirrä maskia 20 kennoa • '*: Maski tähteelle 2 30 juovien lukumäärä= 3 kunkin juovan leveys= 5 : juova 1 alkaa kohdasta 1 ja päättyy kohtaan 5 : juova 2 alkaa kohdasta 21 ja päättyy kohtaan 25 juova 3 alkaa kohdasta 41 ja päättyy kohtaan 45 30 109130
Kullekin 4 rakennusosalle siirrä maskia 5 kennoa Maski tähteelle 3 5 juovien lukumäärä= 12 kunkin juovan leveys= 1 juova 1 alkaa kohdasta 1 ja päättyy kohtaan 1 juova 2 alkaa kohdasta 6 ja päättyy kohtaan 6 juova 3 alkaa kohdasta 11 ja päättyy kohtaan 11 10 juova 4 alkaa kohdasta 16 ja päättyy kohtaan 16 juova 5 alkaa kohdasta 21 ja päättyy kohtaan 21 juova 6 alkaa kohdasta 26 ja päättyy kohtaan 26 juova 7 alkaa kohdasta 31 ja päättyy kohtaan 31 juova 8 alkaa kohdasta 36 ja päättyy kohtaan 36 15 juova 9 alkaa kohdasta 41 ja päättyy kohtaan 41 juova 10 alkaa kohdasta 46 ja päättyy kohtaan 46 juova 11 alkaa kohdasta 51 ja päättyy kohtaan 51 juova 12 alkaa kohdasta 56 ja päättyy kohtaan 56 20 Kullekin 5 rakennusosalle siirrä maskia 1 kennolla
Copyright 1990, Affymax N.V.
< · V. Yksityiskohtia fluoresenssidetektiolaitteen yh v ·’ 25 destä suoritusmuodosta
Kuviossa 9 esitetään fluoresenssidetektiolaite fluoresoivasti leimat-tujen reseptorien toteamiseksi substraatilla. Substraatti 112 on sijoitettu * ’' *: x/y-siirtopöydälle 202. Edullisessa suoritusmuodossa x/y-siirtopöytä on malli nro PM500-A1, jota valmistaa Newport Corporation, x/y-siirtopöytä on kytketty 30 tarkoituksenmukaisesti ohjelmoituun digitaalitietokoneeseen 204, jolla sitä kontrolloidaan ja joka voi olla esimerkiksi tarkoituksenmukaisesti ohjelmoitu : IBM PC/AT tai AT-yhteensopiva tietokone. Luonnollisesti tässä havainnollis- tamistarkoituksessa käytetty AT-tietokone voitaisiin vaikeuksitta korvata muillakin tietokonejärjestelmillä, erityiskäyttölaitteilla tai vastaavilla. Tietokoneoh-35 jelmia tässä kuvattuja siirto- ja tiedonkeräysfunktioita varten voidaan saada kaupallisesti saatavana olevien ohjelmien perusteella, mukaan lukien esimer- 31 109130 kiksi "Lab Windows", jolle myöntää lisenssin National Instruments, ja joka sisällytetään tähän viitteeksi kaikissa tarkoituksissa.
Substraatti ja x/y-siirtopöytä sijoitetaan mikroskoopin 206 alle, joka käsittää yhden tai useamman objektiivin 208. Valoa (noin 488 nm) laserista 5 210, joka joissakin suoritusmuodoissa on malli nro 2020-05 argonionilaser, jota valmistaa Spectraphysics, ohjataan substraatille dikroisella peilillä 207, joka päästää lävitseen yli noin 520 nm:n valon mutta heijastaa 488 nm:n valon. Dikroinen peili 207 voi olla esimerkiksi malli nro FT510, jota valmistaa Carl Zeiss. Peilistä heijastunut valo saapuu sitten mikroskooppiin 206, joka voi olla 10 esimerkiksi malli nro Axioscop 20, jota valmistaa Carl Zeiss. Fluoreseiinilla merkityt materiaalit substraatilla fluoresoivat > 488 nm:n valoa ja fluoresoitu valo kerätään mikroskooppiin ja käytetään peilin läpi. Fluoresoiva valo substraatista ohjataan sitten aallonpituussuodattimen 209 läpi ja sitten aper-tuurin rajoittimen 211 kautta. Aallonpituussuodatin 209 voi olla esimerkiksi 15 malli nro OG530, jota valmistaa Melles Griot ja apertuurin rajoitin 211 voi olla esimerkiksi malli nro 477352/477380, jota valmistaa Carl Zeiss.
Fluoresoitu valo menee sitten valomonistinputkeen 212, joka joissakin suoritusmuodoissa on malli nro R94302, jota valmistaa Hamamatsu, signaali vahvistetaan esivahvistimessa 214 ja fotonit lasketaan fotonilaskijalla ’/. 20 216. Fotonien lukumäärä rekisteröidään sijaintikohdan funktiona tietokonee- * · ' seen 204. Esivahvistin 214 voi olla esimerkiksi malli nro SR440, jota valmistaa : ’’ Stanford Research Systems, ja fotonilaskija 216 voi olla malli nro SR400, jota : valmistaa Stanford Research Systems. Substraatti siirretään sitten seuraavaan ’ : kohtaan ja menetelmä toistetaan. Edullisissa suoritusmuodoissa tietoja saa- ν' ·' 25 daan joka 1.-100. pm, jolloin tietokeräyshalkaisija noin 0,8 - 10 pm on edulli nen. Suoritusmuodoissa, joissa fluoresenssi on riittävän voimakasta, käyte-: *·, i tään CCD-detektoria, jossa on laajakenttävalaistus.
Laskemalla vastineena laserille tietyllä alueella muodostuneiden fotonien lukumäärä on mahdollista määrittää, missä fluoresoivasti merkityt •>t;‘ 30 molekyylit sijaitsevat substraatilla. Siten objektilasille, jonka pinnalle on synte- '···' tisoitu esimerkiksi polypeptidimatriisi, on mahdollista määrittää, mikä polypep- tideistä on komplementaarinen fluoresoivasti merkitylle reseptorille.
Edullisten suoritusmuotojen mukaan substraatille kohdistetun valon intensiteettiä ja kestoa kontrolloidaan vaihtelemalla laserin voimakkuutta ja 35 pyyhkäisyvaihenopeutta paremman signaali-häiriösuhteen saamiseksi maksimoimalla fluoresoiva emissio ja minimoimalla taustahäiriöt.
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Vaikka detektiolaitetta on havainnollistettu tässä pääasiassa suhteessa merkittyjen reseptorien detektioon, keksinnöllä on käyttöä muilla alueilla. Esimerkiksi tässä julkistettua detektiolaitetta voitaisiin käyttää katalyysin, DNA- tai proteiinigeelipyyhkäisyn ja vastaavilla aloilla.
5 VI. Reseptorien suhteellisen sitoutumisvoimakkuu- den määritys
Esillä olevan keksinnön mukainen signaali-häiriösuhde on riittävän korkea, että ei ainoastaan kyetä toteamaan reseptorin ligandissa läsnäoloa tai puuttumista vaan myös voidaan määrittää reseptorien suhteellinen sitoutumi-10 saffiniteetti erilaisten sekvenssien suhteen.
Käytännössä todetaan, että reseptori sitoutuu useihin peptidisek-vensseihin joukosta, mutta sitoutuu huomattavasti voimakkaammin joihinkin sekvensseihin kuin toisiin. Tässä voimakasta sitoutumisaffiniteettia osoittaa voimakas fluoresoiva tai radiografinen signaali, koska monet reseptorimole-15 kyylit sitoutuvat voimakkaasti sitoutuneen ligandin alueelle. Päinvastoin heikkoa sitoutumisaffiniteettia osoittaa heikko fluoresoiva tai radiografinen signaali, joka johtuu niiden reseptorimolekyylien suhteellisen alhaisesta lukumäärästä, jotka sitoutuvat substraatin tietylle alueelle, joka käsittää ligandin, jonka sitou-tumisaffiniteetti reseptorin suhteen on heikko. Näinmuodoin tässä tulee mah- ♦ · · . 20 dolliseksi määrittää ligandin suhteellinen sitoutumishalukkuus (tai affiniteetti yksivalenssisten vuorovaikutusten kohdalla) fluoresoivan tai radiografisen signaalin intensiteetistä ligandin sisältävällä alueella.
··’ i Puolikvantitatiivista tietoa affiniteeteista voitaisiin samoin saada vaihtelemalla reseptorin pesuolosuhteita ja pitoisuuksia. Tämä tehtäisiin esi- * * » 25 merkiksi vertaamalla tunnettuihin ligandi-reseptoripareihin.
VII. Esimerkkejä
Seuraavat esimerkit esitetään näiden keksintöjen tehokkuuden ha- * · . vainnollistamiseksi. Kaikki menettelyt suoritettiin noin ympäristön lämpötiloissa ja paineissa ellei vastakkaisesti ole mainittu.
* · ·' 30 A. Objektilasin valmistus
Ennen reaktiivisten ryhmien kiinnitystä edullisesti puhdistetaan ; substraatti, joka on edullisessa suoritusmuodossa lasisubstraatti kuten mikro- ."·. skoopin objektilasi tai peiteliuska. Yhden suoritusmuodon mukaan objektilasia liuotetaan alkalisessa kylvyssä, joka koostuu esimerkiksi 1 litrasta 95-%:ista 35 etanolia, jossa on 120 ml vettä ja 120 g natriumhydroksidia, 12 tunnin ajan.
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Sitten objektilasit pestään juoksevalla vedellä ja niiden annetaan kuivaa ilmassa, minkä jälkeen ne huuhdotaan kerran 95-%:isella etanoliliuoksella.
Sitten objektilasit aminoidaan esimerkiksi aminopropyylitrietoksisi-laanilla aminoryhmien kiinnittämiseksi lasipintaan liittomolekyyleihin, vaikka 5 tässä tarkoituksessa voitaisiin samoin käyttää mitä tahansa omega-funktion käsittävää silaania. Yhdessä suoritusmuodossa käytetään 0,1-%:ista amino-propyylitrietoksisilaaniliuosta, vaikka liuoksia, joissa pitoisuudet ovat 10-7 % -10 % voidaan käyttää, jolloin edullinen on noin 10-3 % - 2 %. 0,1-%:inen seos valmistetaan lisäämällä 100 ml:aan 95 % etanolia/5 % vettä -seosta 100 μΙ 10 aminopropyylitrietoksisilaania. Seosta sekoitetaan noin ympäristön lämpötilassa kiertävässä sekoittajassa noin 5 minuutin ajan. 500 μΙ tätä seosta levitetään sitten kunkin puhdistetun objektilasin yhden puolen pinnalle. 4 minuutin kuluttua tämä liuos kaadetaan pois objektilaseilta, jotka huuhdotaan kolmeen kertaan upottamalla esimerkiksi 100-%:iseen etanoliin.
15 Kun objektilasit ovat kuivaneet, ne sijoitetaan 110 - 120 °C:n tyhjö- uuniin noin 20 minuutiksi, minkä jälkeen niiden annetaan kovettua huoneenlämpötilassa noin 12 tunnin ajan argon-ympäristössä. Sitten objektilasit upotetaan DMF- (dimetyyliformamidi-) liuokseen, minkä jälkeen ne pestään pe-V, rusteellisesti metyleenikloridilla.
20 Objektilasin aminoitu pinta saatetaan sitten kosketuksiin noin 500 μΙ kanssa esimerkiksi NVOC-GABA(gamma-aminovoihappo-) NHS:n ; *' (N-hydroksisukkinimidi) 30 mM liuosta DMF:ssä NVOC-GABA:n kiinnittämi- : : seksi kuhunkin aminoryhmään.
Pinta pestään sitten esimerkiksi DMF:llä, metyleenikloridilla ja eta- v * 25 nolilla.
Pinnan käsittämä mahdollinen reagoimatta jäänyt aminopropyylisi-lääni - eli ne aminoryhmät, joihin NVOC- GABA ei ole kiinnittynyt - salvataan
I I
nyt asetyyliryhmillä (edelleenreagoinnin estämiseksi) saattamalla kosketuksiin 1:3-seoksen kanssa, jossa on asetanhydridiä pyridiinissä, 1 tunnin ajaksi. 30 Muita materiaaleja, jotka voivat suorittaa tämän loppuvaiheen salpausfunktion, . : ovat trifluoriasetanhydridi, muurahaishappo-etikkahappoanhydridi, tai muut re- ; aktiiviset asyloivat aineet. Lopuksi objektilasit pestään taas DMF:llä, metylee nikloridilla ja etanolilla.
34 109130 B. Kahdeksan (8) trimeerien synteesi "A":sta ja "B":stä
Kuviossa 10 esitetään 8 trimeerin mahdollinen synteesi kahden monomeerin sarjasta: gly, phe (joita edustavat "A" ja vastaavasti "B").
5 Substraatiksi valmistetaan objektilasi, joka käsittää 6-nitroveratryylioksikarboksamidi- (NVOC-NH-) tähteisiin päättyviä silaaniryh-miä. Reagensseiksi valmistetaan gly:n ja phe:n aktiivisia estereitä j (pentafluorifenyyli-, OBt-, jne.), joiden aminoryhmä on suojattu NVOC:llä.
Vaikkei se olekaan tässä esimerkissä oleellista, jos sivuketjun suojaryhmiä 10 tarvitaan monomeerisarjalle, nämä eivät saa olla valoreaktiivisia valon sillä aallonpituudella, jota käytetään primaariketjun suojaamiseksi.
Monomeerisarjalle, jonka koko on n, tarvitaan n x 1 kierrosta kaikkien mahdollisten sekvenssien syntetisoimiseksi, joiden pituus on 1. Kierros käsittää seuraavat vaiheet: 15 1. Säteilyttäminen tarkoituksenmukaisen maskin läpi aminoryhmien paljastamiseksi kohdissa, joihin seuraava tähde on määrä lisätä, jolloin käytetään tarkoituksenmukaisia pesuja suojaryhmänpoiston sivutuotteiden poistamiseksi.
2. Yhden aktivoidun ja suojatun (sama valokemiallisesti poistettava , \ 20 ryhmä) monomeerin lisääminen, joka reagoi vain vaiheessa 1 käsitellyissä t t ; '* kohdissa, jolloin käytetään tarkoituksenmukaisia pesuja reagenssiylimäärän poistamiseksi pinnalta.
! Edeltävä kierros toistetaan monomeerisarjan kullekin jäsenelle, t r"· kunnes kutakin kohtaa pinnalla on laajennettu yhdellä tähteellä yhdessä suo- 25 ritusmuodossa. Muissa suoritusmuodoissa useita tähteitä lisätään peräkkäin yhteen kohtaan ennen kuin siirrytään seuraavaan kohtaan. Kierroskertoja ra-joittaa yleensä kytkentäreaktion nopeus, joka nyt on niinkin lyhyt kuin 20 minuuttia automatisoiduissa peptidisyntetisaattoreissa. Tätä vaihetta seuraa t mahdollisesti suojaryhmän lisääminen joukon stabiloimiseksi myöhempää • : 30 testausta silmällä pitäen. Joillekin polymeerityypeille (esim. peptideille) voi- daan tarvita koko pinnan viimeinen suojaryhmien poistaminen .'. (valosuojasivuketjuryhmien poistaminen).
. , Tarkemmin ottaen kuten esitetään kuviossa 10A lasi 20 käsittää alueet 22, 24, 26, 28, 30, 32, 34 ja 36. Alueet 30, 32, 34 ja 36 varustetaan 35 maskilla kuten esitetään kuviossa 10B, minkä jälkeen lasia säteilytetään ja se saatetaan kosketuksiin reagenssin kanssa, joka sisältää "A":n (esim. gly), joi- 109130 oo loin saatu rakenne esitetään kuviossa 10C. Sen jälkeen alueet 22, 24, 26 ja 28 varustetaan maskilla, lasia säteilytetään (kuten esitetään kuviossa 10D) ja se saatetaan kosketuksiin reagenssin kanssa, joka sisältää "B":n (esim. phe), jolloin saatu rakenne esitetään kuviossa 10E. Menetelmä etenee peräkkäin 5 varustamalla maskilla ja altistamalla osia esitetyn mukaisesti kunnes saadaan kuviossa 10M esitetty rakenne. Lasia säteilytetään ja pääryhmät salvataan mahdollisesti asetyloimalla. Kuten esitetään saadaan kaikki mahdolliset tri-meerit gly/phe.
Tässä esimerkissä ei tarvita sivuketjun suojaryhmän poistamista. 10 Jos se on toivottavaa, sivuketjun suojaryhmät voidaan poistaa käsittelemällä etaanidiolilla ja trifluorietikkahapolla.
Yleensä ottaen vaiheiden lukumäärän, joka tarvitaan nimenomaisen polymeeriketjun saamiseksi, määrittelee: 15 nxl (1) jossa n = monomeerien lukumäärä monomeerien perussarjassa; ja I = monomeeriyksiköiden lukumäärä polymeeriketjussa.
Vastakkaisesti l:n pituisten syntetisoitujen sekvenssien lukumäärä : 20 on: n1 (2).
Luonnollisesti enemmän vaihtelua saadaan käyttämällä maskistra-25 tegioita, joihin sisältyy myös polymeerien synteesi, joiden pituus on alle I. Jos . . ääritapauksessa syntetisoidaan kaikki polymeerit, joiden pituus on pienempi tai sama kuin I, syntetisoitujen polymeerien lukumäärä on « · n'+ n1'1 + ... + n1 (3).
30
Tarvittavien litografisten vaiheiden maksimilukumäärä on yleensä n kullekin monomeeri-"kerrokselle", eli tarvittavien maskien kokonaislukumäärä (ja siten litografisten vaiheiden lukumäärä) on n x I. Läpinäkyvien maskialuei-den koko vaihtelee substraattipinta-alan mukaan, joka on käytettävissä syn-35 teesiin, ja muodostettavien sekvenssien lukumäärän mukaan. Yleensä ottaen synteesipintaalojen koko on: 36 109130 synteesipinta-alojen koko = (A)/(S) jossa: A on synteesiin käytettävissä oleva kokonaispinta-ala; ja 5 S on pinta-alalle haluttujen sekvenssien lukumäärä.
Alan ammattilaiset ymmärtävät, että edeltävää menetelmää voitaisiin vaikeuksitta käyttää tuhansien tai miljoonien oligomeerien tuottamiseksi j samanaikaisesti substraatille tässä julkistettuja fotolitografisia tekniikoita käyt täen. Täten menetelmä tuottaa kyvyn käytännöllisesti testata suuria lukumää-10 riä esimerkiksi di-, tri-, tetra-, penta-, heksa-, hepta-, oktapeptidejä, dodeka-peptidejä tai suurempia polypeptidejä (tai vastaavasti polynukleotideja).
Edeltävä esimerkki on havainnollistanut menetelmää käsin suoritettavan esimerkin välityksellä. Huomataan luonnollisesti, että voitaisiin käyttää automatisoituja tai puoliautomatisoituja menetelmiä. Substraatti sijoitettaisiin 15 virtauskennoon reagenssien automatisoiduksi lisäämiseksi ja poistamiseksi, tarvittavien reagenssien tilavuuden minimoimiseksi sekä reaktio-olosuhteiden huolellisemmaksi kontrolloimiseksi. Peräkkäisiä maskeja käytettäisiin käsin tai automaattisesti.
C. Dimeerin synteesi aminopropyyliryhmästä ja 20 fluoresoivasta ryhmästä
Dimeerin synteesissä aminopropyyliryhmästä ja fluoresoivasta ryh-mästä substraattina käytettiin funktionaaliseksi tehtyä Durapore-membraania. Durapore-membraani oli polyvinylidiinidifluoridia, jossa oli aminopropyyliryh-miä. Aminopropyyliryhmät suojattiin DDZ-ryhmällä saattamalla karbonyyliklori-25 di reagoimaan aminoryhmien kanssa, jonka reaktion alan ammattilaiset vai-, , keuksitta tunnistavat. Nämä ryhmät käsittävä pinta sijoitettiin THF-liuokseen ja *; / saatettiin kosketuksiin maskin kanssa, joka käsitti shakkilautakuviona 1 mm:n himmeitä ja läpinäkyviä alueita. Maskiin kohdistettiin ultraviolettivalo, jonka aallonpituus oli laskettu ainakin noin 280 nm:iin, noin 5 minuutin ajan ympä-30 ristön lämpötilassa, vaikka laaja valikoima altistusaikoja ja -lämpötiloja voi olla tarkoituksenmukainen keksinnön eri suoritusmuodoissa. Esimerkiksi yhdessä suoritusmuodossa voidaan käyttää noin 1 - 5 000 sekunnin altistusaikaa me-netelmälämpötiloissa -70 - +50 °C.
Yhdessä edullisessa suoritusmuodossa käytetään altistusaikoja 35 noin 1 - 500 sekuntia noin ympäristön paineessa. Joissakin edullisissa suori- 37 109130 tusmuodoissa käytetään haihtumisen estämiseksi ympäristön paineen ylittäviä paineita.
Sitten membraanin pintaa pestiin noin 1 tunnin ajan fluoresoivalla leimalla, joka käsitti aktiivisen esterin sidottuna lantanidikelaattiin. Pesuajat 5 vaihtelevat suurissa arvorajoissa noin muutamasta minuutista muutamaan tuntiin. Nämä materiaalit fluoresoivat punaisella ja vihreällä näkyvällä alueella. Sitten kun reaktio aktiivisen esterin kanssa fluoroforissa oli mennyt loppuun, kohdat, johon fluorofori oli sitoutunut, voitiin saada näkyviin altistamalla ne ultraviolettivalolle ja tarkkaamalla punaista ja vihreää fluoresenssia. Havaittiin, 10 että substraattijohdannaisen muotoon saatetut alueet vastasivat likeisesti maskin alkuperäistä kuviota.
D. Signaalintuottokyvyn osoittaminen
Signaalidetektiokyky osoitettiin käyttäen alhaisen tason vakiofluore-senssihelmiä käsittävää pakkausta, jota valmistaa Flow Cytometry Standarda 15 ja jonka mallinro on 824. Tämä pakkaus sisältää helmiä, joiden halkaisija on 5,8 μητη ja joista kuhunkin on imeytetty tunnettu lukumäärä fluoreseiinimole-kyylejä.
Yksi helmistä sijoitettiin valaistuskenttään pyyhkäisypöydälle kuten esitetään kuviossa 9 laser-lampun kenttään, jolla lampulla oli aluksi suojus. 20 Fotonidetektiolaite sijoitettiin valaistuskenttään, minkä jälkeen se kytkettiin päälle. Laser-säde oli ei-salvattu ja se oli vuorovaikutuksessa helmihiukkasen kanssa, joka sitten fluoresoi. Kuvioissa 11A ja 11B esitetään fluoresenssiku-vaajat helmille, joihin on imeytetty 7 000 ja vastaavasti 29 000 fluoreseiinimo-... lekyyliä. Kummallakin käyrällä on esitetty myös ajot helmille, jotka eivät sisällä 25 fluoreseiinimolekyylejä. Nämä kokeet suoritettiin viritysaallonpituudella 488 nm käyttäen 100 μ\Λ/:η laser-tehoa. Valo fokusoitiin 40 tehon 0,75 NA objektiivin t · · ’· " läpi.
• i t
Fluoresenssi-intensiteetti kaikissa tapauksissa lähti korkeasta ar-vosta ja aleni sitten eksponentiaalisesti. Intensiteetin lasku johtuu fluoreseiini-.···. 30 molekyylien valovalkaisusta. Fluoreseiinimolekyylejä sisältämättömien helmien ajoja käytetään taustan vähentämiseksi. Ero alkuperäisessä eksponentiaali-sessa vaimennuksessa leimattujen ja ei-leimattujen helmien välillä integroi-:: daan fotonilukujen kokonaislukumäärän saamiseksi ja tämä luku on suhteessa molekyylien lukumäärään helmeä kohden. Tämän vuoksi on mahdollista pää-35 teliä fluoreseiinimolekyyliä kohden fotonien lukumäärä, joka voidaan todeta.
38 109130
Kuviossa 11 esitetyille kuvaajille tämä laskelma osoittaa, että todetaan noin 40 - 50 fotonin säteily fluoreseiinimolekyyliä kohden.
E. Molekyylien lukumäärän alueyksikköä kohden määritys 5 Aminopropyloituja mikroskoopin objektilaseja, jotka valmistettiin edellä käsiteltyjen menetelmien mukaan, käytettiin objektilasien leimauksen tiheyden määrittämiseksi. Objektilasien vapaat aminopäät saatettiin reagoimaan FITC:n (fluoreseiini-isotiosyanaatti) kanssa, joka muodostaa aminoryh-män kanssa kovalenttisen sidoksen. Sen jälkeen objektilasi pyyhkäistään 10 muodostuneiden fluoresoivien fotonien lukumäärän laskemiseksi joltain alueelta, jolloin käyttäen arviota 40 - 50 fotonia fluoresoivaa molekyyliä kohden kyetään laskemaan pinnalta molekyylien lukumäärä yksikköalaa kohden.
Objektilasi, joka käsitti pinnallaan aminopropyylisilaania, upotettiin FITC:n 1 mM liuokseen DMF:ssä 1 tunniksi noin ympäristön lämpötilassa. Re-15 aktion jälkeen objektilasi pestiin kahdesti DMF:llä, minkä jälkeen se pestiin etanolilla, vedellä ja sitten taas etanolilla. Sitten se kuivattiin ja varastoitiin pimeään kunnes se oli valmis tarkasteltavaksi.
Käyttämällä samankaltaisia kuvaajia kuin kuviossa 11 esitetyt sekä integroimalla fluoresenssiluvut eksponentiaalisesti vaimenevan signaalin alle 20 määritettiin vapaiden aminoryhmien lukumäärä pinnalla johdannaismuodos-tuksen jälkeen. Määritettiin, että objektilaseja, joiden leimaustiheydet olivat 1 .·. fluoreseiini kohden 103 x 103 noin 2x2 nm, voitiin valmistaa toistettavasi! ami- ,’,',Ι nopropyylitrietoksisilaanin pitoisuuden vaihdellessa 10'5 % -10‘1 % F. NVOC:n poistaminen ja fluoresoivan merkin kiin- 25 nitys NVOC-GABA-ryhmät kiinnitettiin kuten kuvattiin edellä. Yhden ob-'.'•i jektilasin pinta kokonaisuudessaan altistettiin valolle vapaan aminoryhmän * · a gamma-aminovoihapon päässä altistamiseksi. Tämä objektilasi ja rinnakkais- kappale, jota ei altistettu, saatettiin sitten kosketuksiin fluoreseii- .···. 30 ni-isotiosyanaatin (FITC) kanssa.
* ·
Kuviossa 12A esitetään objektilasi, jota ei altistettu valolle, mutta jo-ka saatettiin kosketuksiin FITC:n kanssa. Yksiköt x-akselilla ovat aika ja yksi-köt y-akselilla ovat lukuja. Ajo sisältää tietyn määrän taustafluoresenssia. Rin-nakkaisobjektilasi altistettiin 350 nm:n leveänauhavalaistukselle noin 1 minuu-35 tiksi (12 mW/cm2, noin 350 nm:n valaistus), pestiin ja saatettiin reagoimaan FITC:n kanssa. Tämän objektilasin fluoresenssikuvaajat on esitetty kuviossa 39 109130 12B. Havaitaan suuri nousu fluoresenssin tasossa, mikä osoittaa, että fotolyysi on paljastanut lukuisia aminoryhmiä objektilasien pinnalla fluoresoivan merkin kiinnittämiseksi.
G. Maskin käyttö NVOC:n poistossa 5 Seuraava koe suoritettiin käyttäen 0,1 %:n aminopropyloitua objek- tilasia. Valoa Hg-Xe-kaarilampusta kuvannettiin substraatille la-ser-ablaatio-kromi-lasillamaskin läpi, joka oli suorassa kosketuksessa substraattiin.
Tätä objektilasia valaistiin noin 5 minuutin ajan käyttäen 12 mW:n 10 350 nm:n leveänauhavaloa, minkä jälkeen se saatettiin reagoimaan 1 mM
FITC-liuoksen kanssa. Se sijoitettiin laser-detektio-pyyhkäisypöydälle ja piirrettiin kuvaaja kaksidimensionaalisena esityksenä asemasta värikoodattuna fluoresenssi-intensiteetille. Koe toistettiin lukuisia kertoja käyttäen erilaisia maskeja. Fluoresenssikuviot 100 x 100 μητη maskille, 50 μητη maskille, 20 15 μητη maskille ja 10 μηι:η maskille osoittavat, että maskikuvio on selvä ainakin noin 10 μητη neliöihin tätä litografista tekniikkaa käytettäessä.
H. YGGFLrn kiinnitys ja sitten seuraava saattaminen kosketuksiin Herz-vasta-aineen ja vuohen anti-hiirivasta-aineen kanssa i . : 20 Sen osoittamiseksi, että nimenomaisen polypeptidisekvenssin re septorit sitoutuivat pintaan sidottuun peptidiin ja voitiin todeta, Leu-enkefaliinia kytkettiin pintaan ja se tunnistettiin vasta-aineella. Objektilasi saatettiin joh-! dannaismuotoon käyttäen 0,1 -%:ista aminopropyylitrietoksisilaania ja suojat tiin NVOC:llä. 500 μητη shakkilautamaskia käytettiin objektilasin altistamiseksi 25 virtauskennossa käyttäen taustapuolen kontaktipainatusta. Leu-enkefaliinisek-venssi (H2N-tyrosiini, glysiini, glysiini, fenyylialaniini, leusiini-C02H, jota muu-toin kutsutaan tässä YGGFL:ksi) kiinnitettiin karboksipäästään paljastettuihin aminoryhmiin objektilasin pinnalla. Peptidi lisättiin DMF-liuoksessa BOP/HOBT/DIEA-kytkentäreagensseja käyttäen ja sitä uudelleen kierrätettiin 30 virtauskennossa 2 tunnin ajan huoneenlämpötilassa.
Ensimmäinen vasta-aine, joka tunnetaan Herz-vasta-aineena, saavi, ·' tettiin kosketuksiin objektilasin pinnan kanssa 45 minuutiksi pitoisuutena 2 pg/ml superkoktailissa (joka sisälsi 1 %:n BSA:ta ja tässä tapauksessa myös 1 %:n muna-albumiinia). Toinen vasta-aine, vuohen antihiirifluoreseiinikonju-35 gaatti, lisättiin sitten pitoisuutena 2 pg/ml superkoktailpuskurissa, ja inkuboitiin 2 tunnin ajan.
40 109130 Tämän kokeen tuloksista piirrettiin kuvaaja, jossa oli fluoresenssi-intensiteetti aseman funktiona. Tämä kuva otettiin 10 pm:n askelein, ja osoitettiin ei ainoastaan, että suojaryhmät kyetään poistamaan hyvin määritellyn kuvion mukaan, vaan myös, että (1) menetelmällä saatiin peptidien me-5 nestyksekäs kytkentä substraatin pintaan, (2) sidotun peptidin pinta oli käytettävissä sidottavaksi vasta-aineeseen, ja (3) detektiolaitekapasiteetit olivat riittävät reseptorin sitoutumisen toteamiseksi.
I. Monomeeri-monomeerimuodostus YGGFL:stä ja sitten seuraava saattaminen kosketuksiin leimatun 10 vasta-aineen kanssa
Monomeeri-monomeerisynteesi YGGFL:stä ja GGFLstä vuoroneli-öinä suoritettiin objektilasilla shakkilautakuviossa ja saatu objektilasi saatettiin kosketuksiin Herz-vasta-aineen kanssa. Tätä koetta havainnollistetaan kuvioissa 13A ja 13B.
15 Kuviossa 13A esitetään objektilasi, joka on saatettu johdannais- muotoon aminopropyyliryhmällä, joka on suojattu tässä tapauksessa t-BOC:llä (t-butoksikarbonyyli). Objektilasia käsiteltiin TFA:lla t-BOC-suojaryhmän poistamiseksi. E-aminokapronihappo, jonka aminoryhmä oli suojattu t-BOC:llä, kytkettiin sitten aminopropyyliryhmiin. Aminokapronihappo toimii välikkeenä ·.: 20 aminopropyyliryhmän ja syntetisoitavan peptidin välillä. Välikkeen amino- päästä poistettiin suojaryhmä ja se kytkettiin NVOC-leusiiniin. Sitten objektila-,·. siä kokonaisuudessaan valaistiin 12 mW:n 325 nm:n leveänauhavalaistuksel- ' i la. Sitten objektilasi kytkettiin NVOC-fenyylialaniiniin ja pestiin. Objektilasi ko konaisuudessaan valaistiin taas, minkä jälkeen se kytkettiin NVOC-glysiiniin ja ’·’ 25 pestiin. Objektilasi valaistiin taas ja kytkettiin NVOC-glysiiniin sekvenssin muo dostamiseksi, joka esitetään kuvion 13A viimeisessä osassa.
Kuten esitetään kuviossa 13B vuorottelevia alueita objektilasilla valaistiin sitten käyttäen projektiopainatusta ja 500 x 500 μητη shakkilauta-maskia; täten glysiinin aminoryhmä paljastui vain valaistuilla alueilla. Suoritet-,···. 30 taessa seuraava kytkentäkemiallinen vaihe lisättiin NVOC-tyrosiini ja se tuli kytketyksi vain niissä kohdissa, jotka olivat vastaanottaneet valaistusta. Sitten objektilasi kokonaisuudessaan valaistiin kaikkien NVOC-ryhmien poistamisek-si, jolloin saatiin shakkilauta, jossa oli YGGFL valaistuilla alueilla ja GGFL muilla alueilla. Sitten lisättiin Herz-vasta-aine (joka tunnistaa YGGFL:n mutta 35 ei GGFL:ää) ja sen jälkeen vuohen anti-hiirifluoreseiinikonjugaatti.
41 109130
Saadussa fluoresenssipyyhkäisyssä oli tummia alueita, jotka sisälsivät tetrapeptidin GGFL, jota Herz-vasta-aine ei tunnista (jolloin ei tapahdu fluoreseiinikonjugaatin käsittävän anti-hiirivasta-aineen sitoutumista), ja punaisia alueita, joissa oli YGGFL. Herz-vasta-aine tunnistaa YGGFL-pentapeptidin, 5 jolloin valaistuilla alueilla on vasta-ainetta fluoreseiiniin konjugoidun vuohen anti-hiirivasta-aineen tunnistettavaksi.
Samankaltaiset kuviot 50 μηη:η maskilla, jota käytettiin suorassa kosketuksessa ("proksimiteettipainatus") substraattiin, antoivat kuvion, joka oli selvempi ja jossa shakkilautakuvion nurkat koskettivat tuloksena siitä, että 10 maski sijoitettiin suoraan kosketukseen substraatin kanssa (mikä heijastaa erotuksen paranemista tätä tekniikkaa käytettäessä).
J. Monomeeri-monomeerisynteesi YGGFL:stä ja PGGFL:stä
Suoritettiin synteesi käyttäen 50 μητη shakkilautamaskia, joka oli 15 samankaltainen kuin kuviossa 13 esitetty. Kuitenkin P lisättiin substraatin GGFL-kohtiin käyttämällä ylimääräistä kytkentävaihetta. P lisättiin altistamalla suojattu GGFL valolle maskin läpi ja saattamalla kosketuksiin P:n kanssa edellä esitettyyn tapaan. Tämän vuoksi puolet alueista substraatilla sisälsivät YGGFL:n ja loppupuoli sisälsi PGGFL:n.
: 20 Fluoresenssikuvaaja tästä kokeesta osoitti, että alueet olivat jälleen helposti erotettavissa niihin, joissa sitoutumista tapahtui, ja niihin, joissa sitä ei tapahtunut. Tämä koe osoitti, että vasta-aineet kykenevät tunnistamaan spesi-" ; fisen sekvenssin ja ettei tunnistus ole pituudesta riippuvainen.
K. Monomeeri-monomeerisynteesi YGGFL:stä ja : 25 YPGGFL:stä
Keksinnön käytettävyyden edelleen osoittamiseksi syntetisoitiin 50 μητη shakkilautakuvio vuorottelevia YGGFL:ää ja YPGGFL:ää substraatille ' käyttäen edellä esitettyjen kaltaisia tekniikoita. Saatu fluoresenssikuvaaja osoitti, että vasta-aine kykeni selvästi tunnistamaan YGGFL-sekvenssin eikä 30 sitoutunut merkittävästi YPGGFLalueisiin.
L. 16 erilaisen aminohapposekvenssin sarjan syn- teesi sekä suhteellisen sitoutumisaffiniteetin
Herz-vasta-aineeseen arviointi Käyttäen edellä esitettyihin nähden samankaltaisia tekniikoita syn-35 tetisoitiin 16 erilaisen aminohapposekvenssin joukko (toistettiin 4 kertaa) kummallakin kahdesta lasisubstraatista. Sekvenssit syntetisoitiin kiinnittämällä 42 109130 sekvenssi NVOC-GFL objektilasien koko pinnan poikki. Käyttäen maskisarjaa substraatille vietiin sitten selektiivisesti kaksi kerrosta aminohappoja. Kunkin alueen mitat olivat 0,25 cm x 0,0625 cm. Ensimmäinen objektilasi sisälsi aminohapposekvenssejä, jotka sisälsivät vain L-aminohappoja, kun puolestaan 5 toinen objektilasi sisälsi valittuja D-aminohappoja. Kuvioissa 14A ja 14B esitetään kartta eri alueista ensimmäisellä ja vastaavasti toisella objektilasilla. Kuvioissa 14A ja 14B esitetyt kuviot toistettiin 4 kertaan kummallakin objektilasilla. Sitten objektilasit saatettiin kosketuksiin Herz-vasta-aineen ja fluoreseii-nilla leimatun vuohi-anti-hiirivasta-aineen kanssa.
10 Fluoresenssikuvaajassa ensimmäisestä objektilasista, joka sisälsi vain L-aminohappoja, oli punaisia alueita (mikä osoittaa voimakasta sitoutumista, eli lukua 149 000 tai enemmän) ja mustia alueita (mikä osoittaa Herz-vasta-aineen vähäistä tai ei lainkaan tapahtunutta sitoutumista, eli lukua 20 000 tai alle). Sekvenssi YGGFL tuli selvästi voimakkaammin tunnistetuksi.
15 Sekvenssit YAGFL ja YSGFL osoittivat myös voimakasta vasta-aineen tunnistamista. Sitä vastoin useimmat jäljellä olevista sekvensseistä osoittivat vain vähäistä tai ei lainkaan tapahtuvaa sitoutumista. Neljä rinnakkaisosaa objekti-laseja olivat varsin yhtäpitäviä osoittamassaan sitoutumisen määrässä.
Fluoresenssikuvaaja D-aminohappo-objektilasista osoitti, että voi-: 20 makkainta sitoutumista osoitti YGGFL-sekvenssi. Merkittävää sitoutumista to- , * dettiin myös YaGFL:ään, YsGFL:ään ja YpGFL:ään. Loput sekvenssit osoitti- vat vähemmän sitoutumista vasta-aineeseen. Todettiin sekvenssin yGGFL alhainen sitoutumisteho.
• · ·
Taulukossa 6 luetellaan testatut eri sekvenssit suhteellisen fluore-1 ·' ' 25 senssin mukaan, joka antaa tietoa suhteellisesta sitoutumisaffiniteetista.
. ·; » 43 109130
Taulukko 6 Näennäinen sitoutuminen Herz-vasta-aineeseen L-aminohapposarja D-aminohapposarja
5 YGGFL YGGFL
YAGFL YaGFL
YSGFL YsGFL
LGGFL YpGFL
FGGFL fGGFL
10 YPGFL yGGFL
LAG FL faGFL
FAGFL wGGFL
WGGFL yaGFL
fpGFL
15 waGFL
Vili. Havainnollistava vaihtoehtoinen suoritusmuoto
Keksinnön vaihtoehtoisen suoritusmuodon mukaan menetelmien ·. : 20 mukaan pintaan voidaan kiinnittää koteloitu sitoutumisjäsen, jolla koteloidussa «· ! ‘ muodossaan on suhteellisen alhainen affiniteetti muiden potentiaalisesti si toutuvien lajien suhteen, kuten reseptorien ja spesifisten sidosaineiden. Tällai-: ; siä tekniikoita kuvataan perusteellisemmin avoinna olevassa patenttihakemuk- ' ‘ sessa sarja nro 404 920, joka jätettiin 8. syyskuuta 1989 ja joka sisällytetään v ; 25 tähän viitteeksi kaikissa tarkoituksissa.
Tämän vaihtoehtoisen suoritusmuodon mukaan keksintö antaa •.: käyttöön menetelmiä ennalta määrättyjen alueiden muodostamiseksi kiinteän tuen pinnalle, jotka ennalta määrätyt alueet kykenevät immobilisoimaan re-septoreja. Menetelmissä käytetään hyväksi pintaan kiinnitettyjä koteloituja si-30 toutumisjäseniä, jolloin kyetään selektiivisesti aktivoimaan ennalta määrättyjä » alueita. Koteloidut sitoutumisjäsenet vapautetaan toimimaan sitoutumisjäseni-\· nä, jotka lopulta kykenevät sitomaan reseptoreita aktivoitaessa selektiivisesti *: ennalta määrätyt alueet. Aktivoituja sitoutumisjäseniä käytetään sitten spesi fisten molekyylien kuten reseptorien immobilisoimiseksi pinnan ennalta mää-35 rätylle alueelle. Edeltävä menettely toistetaan pinnan samoissa tai eri kohdissa pinnan saamiseksi, jolle on valmistettu monilukuinen määrä alueita, jotka si- 44 109130 sältävät esimerkiksi saman tai erilaisia reseptoreita. Kun tällä tavalla immobili-soiduilla reseptoreilla on erilainen affiniteetti yhden tai useamman ligandin suhteen, voidaan suorittaa ligandien seulontoja ja määrityksiä reseptoreita sisältävillä pinnan alueilla.
5 Vaihtoehtoisessa suoritusmuodossa voidaan käyttää substraattiin kiinnitettyjä uusia koteloituja sitoutumisjäseniä. Koteloiduilla (ei-aktivoiduilla) jäsenillä on suhteellisen alhainen affiniteetti aineiden reseptorien suhteen, jotka spesifisesti sitoutuvat ei-koteloituihin sitoutumisjäseniin, verrattuna aktivoitujen sitoutumisjäsenien vastaaviin affiniteetteihin. Täten sitoutumisjäsenet on 10 suojattu reagoimasta kunnes sopivaa energialähdettä käytetään niillä pinnan alueilla, jotka halutaan aktivoida. Sopivaa energialähdettä käytettäessä kotelo-ryhmät muuttuvat labiileiksi, jolloin aktivoitu sitoutumisjäsen paljastuu. Tyypillinen energialähde on valo.
Sitten kun sitoutumisjäsenet pinnalla on aktivoitu, ne voidaan kiin-15 nittää reseptoriin. Valittu reseptori voi olla monoklonaalinen vasta-aine, nukle-iinihapposekvenssi, lääkereseptori jne. Reseptori valmistellaan tavallisesti vaikkakaan ei aina siten, että se voidaan kiinnittää suoraan tai epäsuorasti si-toutumisjäseneen. Esimerkiksi spesifistä sidosainetta, jolla on voimakas si-toutumisaffiniteetti sitoutumisjäsenen suhteen ja voimakas affiniteetti resepto-: 20 rin tai reseptorin konjugaatin suhteen, voidaan käyttää haluttaessa siltana si- • »t ‘ toutumisjäsenien ja reseptorien välissä. Menetelmässä käytetään reseptoria, •· joka on valmisteltu siten, että reseptorilla on tallella aktiivisuutensa jonkin ni- ; menomaisen ligandin suhteen.
* · ·»
Edullisesti kiinteään substraattiin kiinnitetty koteloitu sitoutumisjäsen v ; 25 on valolla aktivoitava biotiinikompleksi, eli biotiinimolekyyli, jota on kemiallisesti modifioitu valolla aktivoitavilla suojaryhmillä siten, että sillä on merkittävästi \i alempi sitoutumisaffiniteetti avidiinille tai avidiinianalogeille kuin luontaisella biotiinilla. Edullisessa suoritusmuodossa suojaryhmät, jotka sijaitsevat pinnan
t ) I
Λ ennaltamäärätyllä alueella, poistetaan käyttämällä sopivaa säteilylähdettä si- ',30 toutumisjäsenien saamiseksi, jotka ovat biotiini tai funktionaalisesti analoginen » yhdiste, jolla on oleellisesti sama sitoutumisaffiniteetti avidiinille tai avidiinia-nalogeille kuin biotiinilla.
Toisessa edullisessa suoritusmuodossa avidiinia tai avidiinianalogia inkuboidaan aktivoitujen sitoutumisjäsenien kanssa pinnalla, kunnes avidiini 35 sitoutuu voimakkaasti sitoutumisjäseniin. Avidiinia, joka näin on immobilisoitu pinnan ennaltamäärätyille alueille, voidaan sitten inkuboida halutun reseptorin 45 109130 tai halutun reseptorin konjugaatin kanssa. Reseptori on edullisesti biotinyloitu, esim. biotinyloitu vasta-aine, kun avidiini on immobilisoitu pinnan ennaltamää-rätyille alueille. Vaihtoehtoisesti edullisessa suoritusmuodossa avidii-ni/biotinyloitu reseptori -kompleksi, joka on valmistettu etukäteen, tarjotaan 5 pinnan aktivoiduille sitoutumisjäsenille.
IX. Päätös
Esillä olevat keksinnöt antavat käyttöön paljon aiempaa parempia menetelmiä ja laitteita polymeerien syntetisoimiseksi substraateilla. Huomattakoon, että edeltävän kuvauksen on tarkoitus olla havainnollistava eikä rajoitta-10 va. Monet suoritusmuodot tulevat alan ammattilaisille ilmeisiksi heidän tutustuessaan edeltävään kuvaukseen. Esimerkin vuoksi keksintöä on kuvattu pääasiassa viitaten valolla poistettavien suojaryhmien käyttöön, mutta alan ammattilaiset havainnevat vaikeuksitta, että muitakin säteilylähteitä kuin valoa voitaisiin käyttää. Esimerkiksi joissakin suoritusmuodoissa saattaa olla toivot-15 tavaa käyttää suojaryhmiä, jotka ovat herkkiä elektronisädesäteilytykselle, röntgensädesäteilytykselle, yhdessä elektronisädelitografisten tai röntgensä-delitografisten tekniikoiden kanssa. Vaihtoehtoisesti ryhmä voitaisiin poistaa altistamalla se sähkövirralle. Keksinnön laajuutta ei tulisi siksi määrittää edeltävän kuvauksen perusteella, vaan se tulisi sen sijaan määrittää oheisten pa-'/. 20 tenttivaatimusten perusteella sekä niiden ekvivalenttien täyden laajuuden pe rusteella, joihin nämä vaatimukset oikeuttavat.
► » ·

Claims (12)

46 109130
1. Menetelmä polynukleotidi- tai aminohapposekvenssin tutkimiseksi reseptori/ligandi sitoutumisella tunnettu siitä, että käytetään substraat-5 tia pinnalla, jolla on vähintään 103 erilaista tunnettua nukleotidi- tai aminohapposekvenssiä alueella, joka on vähemmän kuin 1 cm2, jolloin mainitut erilaiset nukleotidi- tai aminohapposekvenssit miehittävät kukin eri tunnetun kohdan, menetelmässä leimataan tutkittava sekvenssi ja identifioidaan mikä mainituista erilaisista sekvensseistä sitoutuu analysoitavaan sekvenssiin.
2. Patenttivaatimuksen 1 mukainen menetelmä, tunnettu siitä, että jokaisen eri tunnetun kohdan ala on vähemmän kuin 10 000 pm2, mahdollisesti vähemmän kuin noin 100 pm2.
3. Patenttivaatimuksen 1 tai 2 mukainen menetelmä, tunnettu siitä, että pinnalla on 104 tai useampia, mahdollisesti 105 tai useampia, erilaisia 15 monomeerisekvenssejä ja ennalta määrättyjä alueita.
4. Jonkin patenttivaatimuksista 1-3 mukainen menetelmä, tunnettu siitä, että leima on fluoresoiva leima, radioaktiivinen leima tai leimattu vasta-aine.
5. Jonkin patenttivaatimuksista 1 - 4 mukainen menetelmä, t u n - \ 20 n e 11 u siitä, että tietyissä kohdissa olevia monomeerisekvenssejä, joissa si- : toutuminen havaitaan, käytetään määrittämään koko sekvenssi tai osa sek- ' " venssistä, joka on komplementaarista analysoitavalle sekvenssille.
: : 6. Jonkin patenttivaatimuksista 1-5 mukainen menetelmä, t u n - n e 11 u siitä, että monomeerisekvens- sien pituus on 2 -100 monomeeriä. : j’: 25
7. Laite polynukleotidi- tai aminohapposekvenssien tutkimiseksi re- septori/ligandi-sitoutumisella, tunnettu siitä, että laitteessa on substraatti pinnalla, joka pinta sisältää vähintään 103 erilaista tunnettua nukleotidi- tai t ·. aminohapposekvenssiä alueella, joka on vähemmän kuin 1 cm2 ja kukin erilai- >’ nen tunnettu nukleotidi- tai amoniohapposekvenssi miehittää oman kohtansa. * 30
8. Patenttivaatimuksen 7 mukainen laite, tunnettu siitä, että laitetta määrittelevät edelleen yhden tai useamman vaatimuksista 2, 3 ja 6 spesifinen piirre/spesifiset piirteet.
·. 9. Patenttivaatimuksen 7 tai 8 mukainen laite, tunnettu siitä, että substraatti on alle 0,5 mm paksu, mahdollisesti alle 0,05 mm paksu. „ 109130 47
10. Jonkin patenttivaatimuksista 7-9 mukainen laite, tunnettu siitä, että ennalta määrättyjen alueiden pinta-ala on vähemmän kuin noin 10'5 cm2.
11. Jonkin patenttivaatimuksista 7-10 mukainen laite, tunnet- 5. u siitä, että kukin nukleotidi- tai aminohappomonomeerisekvenssi ennalta määrätyllä alueella on vähintään 50%:sti, edullisesti vähintään 90%:sti puh-i das.
12. Patenttivaatimuksissa 7-11 määritellyn laitteen käyttö tutkittaessa polynukleotidi- tai aminohapposekvenssiä reseptori/ligandi-sitoutumisella. • · • · • · » · · * I ! · t » * I « t 48 109130
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Families Citing this family (3539)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5866363A (en) * 1985-08-28 1999-02-02 Pieczenik; George Method and means for sorting and identifying biological information
US6270961B1 (en) * 1987-04-01 2001-08-07 Hyseq, Inc. Methods and apparatus for DNA sequencing and DNA identification
GB8810400D0 (en) 1988-05-03 1988-06-08 Southern E Analysing polynucleotide sequences
US7811751B2 (en) 1988-05-03 2010-10-12 Oxford Gene Technology Limited Analysing polynucleotide sequences
US6054270A (en) * 1988-05-03 2000-04-25 Oxford Gene Technology Limited Analying polynucleotide sequences
US5547839A (en) * 1989-06-07 1996-08-20 Affymax Technologies N.V. Sequencing of surface immobilized polymers utilizing microflourescence detection
US6955915B2 (en) * 1989-06-07 2005-10-18 Affymetrix, Inc. Apparatus comprising polymers
US5527681A (en) * 1989-06-07 1996-06-18 Affymax Technologies N.V. Immobilized molecular synthesis of systematically substituted compounds
US6309822B1 (en) 1989-06-07 2001-10-30 Affymetrix, Inc. Method for comparing copy number of nucleic acid sequences
US6406844B1 (en) 1989-06-07 2002-06-18 Affymetrix, Inc. Very large scale immobilized polymer synthesis
US5424186A (en) * 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
US6379895B1 (en) 1989-06-07 2002-04-30 Affymetrix, Inc. Photolithographic and other means for manufacturing arrays
US5925525A (en) * 1989-06-07 1999-07-20 Affymetrix, Inc. Method of identifying nucleotide differences
US6346413B1 (en) 1989-06-07 2002-02-12 Affymetrix, Inc. Polymer arrays
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5744101A (en) 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US6919211B1 (en) * 1989-06-07 2005-07-19 Affymetrix, Inc. Polypeptide arrays
US5871928A (en) * 1989-06-07 1999-02-16 Fodor; Stephen P. A. Methods for nucleic acid analysis
US5800992A (en) 1989-06-07 1998-09-01 Fodor; Stephen P.A. Method of detecting nucleic acids
US6040138A (en) 1995-09-15 2000-03-21 Affymetrix, Inc. Expression monitoring by hybridization to high density oligonucleotide arrays
US5242974A (en) * 1991-11-22 1993-09-07 Affymax Technologies N.V. Polymer reversal on solid surfaces
US6551784B2 (en) 1989-06-07 2003-04-22 Affymetrix Inc Method of comparing nucleic acid sequences
US7049102B1 (en) 1989-09-22 2006-05-23 Board Of Trustees Of Leland Stanford University Multi-gene expression profile
US5545522A (en) 1989-09-22 1996-08-13 Van Gelder; Russell N. Process for amplifying a target polynucleotide sequence using a single primer-promoter complex
US5252743A (en) * 1989-11-13 1993-10-12 Affymax Technologies N.V. Spatially-addressable immobilization of anti-ligands on surfaces
US6506558B1 (en) 1990-03-07 2003-01-14 Affymetrix Inc. Very large scale immobilized polymer synthesis
US5252296A (en) * 1990-05-15 1993-10-12 Chiron Corporation Method and apparatus for biopolymer synthesis
US6040423A (en) * 1990-08-31 2000-03-21 Gsellschaft Fur Biotechnologische Forschung Mbh (Gbf) Process for synthesis of peptides
EP0562025B1 (en) * 1990-12-06 2001-02-07 Affymetrix, Inc. (a Delaware Corporation) Compounds and their use in a binary synthesis strategy
DK0834575T3 (da) * 1990-12-06 2002-04-02 Affymetrix Inc A Delaware Corp Identifikation af nucleinsyrer i prøver
US5658728A (en) * 1991-06-19 1997-08-19 Gosney, Jr.; William Milton Templates for nucleic acid molecules
GB2258236B (en) * 1991-07-30 1995-03-22 Hitachi Europ Ltd Molecular synthesis
WO1993002992A1 (en) * 1991-08-07 1993-02-18 H & N Instruments, Inc. Synthesis of chain chemical compounds
US5449754A (en) * 1991-08-07 1995-09-12 H & N Instruments, Inc. Generation of combinatorial libraries
JPH05206017A (ja) * 1991-08-09 1993-08-13 Internatl Business Mach Corp <Ibm> リソグラフイ露光システム及びその方法
US6921636B1 (en) * 1991-09-04 2005-07-26 Metrigen, Inc. Method and apparatus for conducting an array of chemical reactions on a support surface
US5474796A (en) * 1991-09-04 1995-12-12 Protogene Laboratories, Inc. Method and apparatus for conducting an array of chemical reactions on a support surface
US6589726B1 (en) 1991-09-04 2003-07-08 Metrigen, Inc. Method and apparatus for in situ synthesis on a solid support
US5846717A (en) 1996-01-24 1998-12-08 Third Wave Technologies, Inc. Detection of nucleic acid sequences by invader-directed cleavage
ES2097925T3 (es) * 1991-09-18 1997-04-16 Affymax Tech Nv Metodo para sintetizar diversas colecciones de oligomeros.
US5639603A (en) * 1991-09-18 1997-06-17 Affymax Technologies N.V. Synthesizing and screening molecular diversity
US5733731A (en) * 1991-10-16 1998-03-31 Affymax Technologies N.V. Peptide library and screening method
US5270170A (en) * 1991-10-16 1993-12-14 Affymax Technologies N.V. Peptide library and screening method
US6051380A (en) * 1993-11-01 2000-04-18 Nanogen, Inc. Methods and procedures for molecular biological analysis and diagnostics
US5632957A (en) 1993-11-01 1997-05-27 Nanogen Molecular biological diagnostic systems including electrodes
US5605662A (en) * 1993-11-01 1997-02-25 Nanogen, Inc. Active programmable electronic devices for molecular biological analysis and diagnostics
US5849486A (en) * 1993-11-01 1998-12-15 Nanogen, Inc. Methods for hybridization analysis utilizing electrically controlled hybridization
US6569382B1 (en) 1991-11-07 2003-05-27 Nanogen, Inc. Methods apparatus for the electronic, homogeneous assembly and fabrication of devices
US6652808B1 (en) * 1991-11-07 2003-11-25 Nanotronics, Inc. Methods for the electronic assembly and fabrication of devices
US6048690A (en) * 1991-11-07 2000-04-11 Nanogen, Inc. Methods for electronic fluorescent perturbation for analysis and electronic perturbation catalysis for synthesis
US6017696A (en) 1993-11-01 2000-01-25 Nanogen, Inc. Methods for electronic stringency control for molecular biological analysis and diagnostics
US5556961A (en) * 1991-11-15 1996-09-17 Foote; Robert S. Nucleosides with 5'-O-photolabile protecting groups
US5846708A (en) * 1991-11-19 1998-12-08 Massachusetts Institiute Of Technology Optical and electrical methods and apparatus for molecule detection
IL103674A0 (en) * 1991-11-19 1993-04-04 Houston Advanced Res Center Method and apparatus for molecule detection
ATE241426T1 (de) * 1991-11-22 2003-06-15 Affymetrix Inc A Delaware Corp Verfahren zur herstellung von polymerarrays
US5324633A (en) * 1991-11-22 1994-06-28 Affymax Technologies N.V. Method and apparatus for measuring binding affinity
US5412087A (en) * 1992-04-24 1995-05-02 Affymax Technologies N.V. Spatially-addressable immobilization of oligonucleotides and other biological polymers on surfaces
US5550215A (en) * 1991-11-22 1996-08-27 Holmes; Christopher P. Polymer reversal on solid surfaces
US5384261A (en) * 1991-11-22 1995-01-24 Affymax Technologies N.V. Very large scale immobilized polymer synthesis using mechanically directed flow paths
US6468740B1 (en) 1992-11-05 2002-10-22 Affymetrix, Inc. Cyclic and substituted immobilized molecular synthesis
US6943034B1 (en) 1991-11-22 2005-09-13 Affymetrix, Inc. Combinatorial strategies for polymer synthesis
EP1382386A3 (en) * 1992-02-19 2004-12-01 The Public Health Research Institute Of The City Of New York, Inc. Novel oligonucleotide arrays and their use for sorting, isolating, sequencing, and manipulating nucleic acids
US5359115A (en) * 1992-03-26 1994-10-25 Affymax Technologies, N.V. Methods for the synthesis of phosphonate esters
US5541061A (en) * 1992-04-29 1996-07-30 Affymax Technologies N.V. Methods for screening factorial chemical libraries
US5728802A (en) * 1992-05-06 1998-03-17 Affymax Technologies N.V. Peptides and compounds that bind selectins including endothelium leukocyte adhesion molecule 1 (ELAM-1)
US5643873A (en) * 1992-05-06 1997-07-01 Affymax Technologies N.V. Peptides and compounds that bind selectins including endothelial leukocyte adhesion molecule 1
US5648458A (en) * 1992-05-06 1997-07-15 Affymax Technologies N.V. Peptides and compounds that bind to ELAM-1
US5849545A (en) * 1992-05-11 1998-12-15 Evotec Biosystems Gmbh Substrate material for simultaneously binding genotypic and phenotypic substances
JPH0622798A (ja) * 1992-07-07 1994-02-01 Hitachi Ltd 塩基配列決定法
US5585275A (en) * 1992-09-02 1996-12-17 Arris Pharmaceutical Corporation Pilot apparatus for peptide synthesis and screening
US5591646A (en) * 1992-09-02 1997-01-07 Arris Pharmaceutical Method and apparatus for peptide synthesis and screening
US5420328A (en) * 1992-09-11 1995-05-30 Affymax Technologies, N.V. Methods for the synthesis of phosphonate esters
US5288514A (en) * 1992-09-14 1994-02-22 The Regents Of The University Of California Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support
US5877278A (en) * 1992-09-24 1999-03-02 Chiron Corporation Synthesis of N-substituted oligomers
US5567391A (en) * 1992-10-08 1996-10-22 Warner-Lambert Company Apparatus for multiple simultaneous synthesis
US5714127A (en) * 1992-10-08 1998-02-03 Warner-Lambert Company System for multiple simultaneous synthesis
US5324483B1 (en) * 1992-10-08 1996-09-24 Warner Lambert Co Apparatus for multiple simultaneous synthesis
US5702672A (en) * 1992-10-08 1997-12-30 Warner-Lambert Company Apparatus and method for multiple simultaneous synthesis
US5554501A (en) * 1992-10-29 1996-09-10 Beckman Instruments, Inc. Biopolymer synthesis using surface activated biaxially oriented polypropylene
WO1994010128A1 (en) * 1992-11-02 1994-05-11 Affymax Technologies N.V. Novel photoreactive protecting groups
HUT73150A (en) * 1992-11-06 1996-06-28 Chiron Mimotopes Pty Ltd Modular polymer and support for the synthesis thereof
US5605798A (en) 1993-01-07 1997-02-25 Sequenom, Inc. DNA diagnostic based on mass spectrometry
JPH08511234A (ja) * 1993-02-23 1996-11-26 ザ トラスティーズ オブ プリンストン ユニヴァーシティー グリコシド結合の溶液及び固相形成
US6864048B2 (en) * 1993-04-28 2005-03-08 Affymetrix, Inc. Factorial chemical libraries
US6632613B1 (en) * 1993-06-02 2003-10-14 University Of Utah Research Foundation Compositions and kits for fluorescence polarization assay of large molecules
US6008058A (en) * 1993-06-18 1999-12-28 University Of Louisville Cyclic peptide mixtures via side chain or backbone attachment and solid phase synthesis
US6153379A (en) * 1993-06-22 2000-11-28 Baylor College Of Medicine Parallel primer extension approach to nucleic acid sequence analysis
US7001722B1 (en) 1993-06-22 2006-02-21 Baylor College Of Medicine Parallel primer extension approach to nucleic acid sequence analysis
US5858659A (en) * 1995-11-29 1999-01-12 Affymetrix, Inc. Polymorphism detection
US7115364B1 (en) 1993-10-26 2006-10-03 Affymetrix, Inc. Arrays of nucleic acid probes on biological chips
US20030134291A1 (en) * 1993-06-25 2003-07-17 Affymetrix, Inc. Polymorphism detection
US5837832A (en) * 1993-06-25 1998-11-17 Affymetrix, Inc. Arrays of nucleic acid probes on biological chips
WO1995000530A1 (en) 1993-06-25 1995-01-05 Affymax Technologies N.V. Hybridization and sequencing of nucleic acids
US6027880A (en) * 1995-08-02 2000-02-22 Affymetrix, Inc. Arrays of nucleic acid probes and methods of using the same for detecting cystic fibrosis
US5861242A (en) * 1993-06-25 1999-01-19 Affymetrix, Inc. Array of nucleic acid probes on biological chips for diagnosis of HIV and methods of using the same
EP0787183A4 (en) * 1993-07-23 1998-05-27 Hyseq Inc METHOD FOR DETECTION OF UNKNOWN ORGANISMS
US6401267B1 (en) 1993-09-27 2002-06-11 Radoje Drmanac Methods and compositions for efficient nucleic acid sequencing
JPH0798276A (ja) * 1993-09-28 1995-04-11 Hitachi Electron Eng Co Ltd Ｄｎａ塩基配列決定装置
US5900160A (en) * 1993-10-04 1999-05-04 President And Fellows Of Harvard College Methods of etching articles via microcontact printing
US5776748A (en) 1993-10-04 1998-07-07 President And Fellows Of Harvard College Method of formation of microstamped patterns on plates for adhesion of cells and other biological materials, devices and uses therefor
US5512131A (en) * 1993-10-04 1996-04-30 President And Fellows Of Harvard College Formation of microstamped patterns on surfaces and derivative articles
US6180239B1 (en) 1993-10-04 2001-01-30 President And Fellows Of Harvard College Microcontact printing on surfaces and derivative articles
US6776094B1 (en) * 1993-10-04 2004-08-17 President & Fellows Of Harvard College Kit For Microcontact Printing
CA2173990A1 (en) * 1993-10-12 1995-04-20 Narasinga Rao A library of glyco-peptides useful for identification of cell adhesion inhibitors
US20060229824A1 (en) * 1993-10-26 2006-10-12 Affymetrix, Inc. Arrays of nucleic acid probes for analyzing biotransformation genes
US7097839B1 (en) * 1993-10-26 2006-08-29 Thomas Jefferson University ST receptor binding compounds and methods of using the same
US6156501A (en) * 1993-10-26 2000-12-05 Affymetrix, Inc. Arrays of modified nucleic acid probes and methods of use
US6045996A (en) 1993-10-26 2000-04-04 Affymetrix, Inc. Hybridization assays on oligonucleotide arrays
US20030232361A1 (en) * 1993-10-26 2003-12-18 Affymetrix, Inc. Nucleic acid array preparation using purified phosphoramidites
US5879656A (en) * 1993-10-26 1999-03-09 Thomas Jefferson University Methods of treating metastatic colorectal cancer with ST receptor binding compounds
US7375198B2 (en) * 1993-10-26 2008-05-20 Affymetrix, Inc. Modified nucleic acid probes
US6309823B1 (en) 1993-10-26 2001-10-30 Affymetrix, Inc. Arrays of nucleic acid probes for analyzing biotransformation genes and methods of using the same
US20120329677A9 (en) * 1993-10-26 2012-12-27 Cronin Maureen T Arrays of nucleic acid probes for detecting cystic fibrosis
US5429807A (en) * 1993-10-28 1995-07-04 Beckman Instruments, Inc. Method and apparatus for creating biopolymer arrays on a solid support surface
ES2176308T3 (es) * 1993-10-28 2002-12-01 Houston Advanced Res Ct Dispositivo de microestructura porosa que permite un flujo.
US6893816B1 (en) * 1993-10-28 2005-05-17 Houston Advanced Research Center Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions
US5922545A (en) * 1993-10-29 1999-07-13 Affymax Technologies N.V. In vitro peptide and antibody display libraries
US6306348B1 (en) * 1993-11-01 2001-10-23 Nanogen, Inc. Inorganic permeation layer for micro-electric device
US6315953B1 (en) 1993-11-01 2001-11-13 Nanogen, Inc. Devices for molecular biological analysis and diagnostics including waveguides
US20040077074A1 (en) * 1993-11-01 2004-04-22 Nanogen, Inc. Multi-chambered analysis device
US6225059B1 (en) 1993-11-01 2001-05-01 Nanogen, Inc. Advanced active electronic devices including collection electrodes for molecular biological analysis and diagnostics
US6375899B1 (en) 1993-11-01 2002-04-23 Nanogen, Inc. Electrophoretic buss for transport of charged materials in a multi-chamber system
US7582421B2 (en) * 1993-11-01 2009-09-01 Nanogen, Inc. Methods for determination of single nucleic acid polymorphisms using a bioelectronic microchip
US6287517B1 (en) 1993-11-01 2001-09-11 Nanogen, Inc. Laminated assembly for active bioelectronic devices
US6254827B1 (en) 1993-11-01 2001-07-03 Nanogen, Inc. Methods for fabricating multi-component devices for molecular biological analysis and diagnostics
US6726880B1 (en) 1993-11-01 2004-04-27 Nanogen, Inc. Electronic device for performing active biological operations and method of using same
US6331274B1 (en) 1993-11-01 2001-12-18 Nanogen, Inc. Advanced active circuits and devices for molecular biological analysis and diagnostics
US7172864B1 (en) 1993-11-01 2007-02-06 Nanogen Methods for electronically-controlled enzymatic reactions
US5965452A (en) * 1996-07-09 1999-10-12 Nanogen, Inc. Multiplexed active biologic array
US6638482B1 (en) 1993-11-01 2003-10-28 Nanogen, Inc. Reconfigurable detection and analysis apparatus and method
US6309602B1 (en) 1993-11-01 2001-10-30 Nanogen, Inc. Stacked, reconfigurable system for electrophoretic transport of charged materials
US6068818A (en) 1993-11-01 2000-05-30 Nanogen, Inc. Multicomponent devices for molecular biological analysis and diagnostics
US6319472B1 (en) 1993-11-01 2001-11-20 Nanogen, Inc. System including functionally separated regions in electrophoretic system
US6129828A (en) 1996-09-06 2000-10-10 Nanogen, Inc. Apparatus and methods for active biological sample preparation
US7314708B1 (en) * 1998-08-04 2008-01-01 Nanogen, Inc. Method and apparatus for electronic synthesis of molecular structures
US7101661B1 (en) 1993-11-01 2006-09-05 Nanogen, Inc. Apparatus for active programmable matrix devices
US6165778A (en) * 1993-11-02 2000-12-26 Affymax Technologies N.V. Reaction vessel agitation apparatus
US5503805A (en) * 1993-11-02 1996-04-02 Affymax Technologies N.V. Apparatus and method for parallel coupling reactions
US7034110B2 (en) * 1994-01-05 2006-04-25 Arqule, Inc. Method of identifying chemical compounds having selected properties for a particular application
GB9401833D0 (en) * 1994-02-01 1994-03-30 Isis Innovation Method for discovering ligands
US5631734A (en) * 1994-02-10 1997-05-20 Affymetrix, Inc. Method and apparatus for detection of fluorescently labeled materials
US6741344B1 (en) * 1994-02-10 2004-05-25 Affymetrix, Inc. Method and apparatus for detection of fluorescently labeled materials
US6090555A (en) * 1997-12-11 2000-07-18 Affymetrix, Inc. Scanned image alignment systems and methods
US20030017081A1 (en) * 1994-02-10 2003-01-23 Affymetrix, Inc. Method and apparatus for imaging a sample on a device
US5578832A (en) * 1994-09-02 1996-11-26 Affymetrix, Inc. Method and apparatus for imaging a sample on a device
GB9404709D0 (en) * 1994-03-11 1994-04-27 Multilyte Ltd Binding assay
US6015880A (en) * 1994-03-16 2000-01-18 California Institute Of Technology Method and substrate for performing multiple sequential reactions on a matrix
US5502246A (en) * 1994-03-22 1996-03-26 Eli Lilly And Company Solid-phase synthesis utilizing photochemical carbon-sulfur bond cleavage of thioethers
ATE197156T1 (de) * 1994-03-23 2000-11-15 Penn State Res Found Verfahren zum nachweis von verbindungen einer konbinatorischen bibliothek.
US5871918A (en) * 1996-06-20 1999-02-16 The University Of North Carolina At Chapel Hill Electrochemical detection of nucleic acid hybridization
US5571639A (en) * 1994-05-24 1996-11-05 Affymax Technologies N.V. Computer-aided engineering system for design of sequence arrays and lithographic masks
US6287850B1 (en) * 1995-06-07 2001-09-11 Affymetrix, Inc. Bioarray chip reaction apparatus and its manufacture
EP0695941B1 (en) * 1994-06-08 2002-07-31 Affymetrix, Inc. Method and apparatus for packaging a chip
US7323298B1 (en) 1994-06-17 2008-01-29 The Board Of Trustees Of The Leland Stanford Junior University Microarray for determining the relative abundances of polynuceotide sequences
US7615368B1 (en) 1994-06-17 2009-11-10 The Board Of Trustees Of The Leland Stanford Junior University Microarrays of polypeptides
US7625697B2 (en) * 1994-06-17 2009-12-01 The Board Of Trustees Of The Leland Stanford Junior University Methods for constructing subarrays and subarrays made thereby
US7378236B1 (en) 1994-06-17 2008-05-27 The Board Of Trustees Of The Leland Stanford Junior University Method for analyzing gene expression patterns
US5807522A (en) * 1994-06-17 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods for fabricating microarrays of biological samples
US5525735A (en) * 1994-06-22 1996-06-11 Affymax Technologies Nv Methods for synthesizing diverse collections of pyrrolidine compounds
US5525734A (en) * 1994-06-22 1996-06-11 Affymax Technologies N.V. Methods for synthesizing diverse collections of pyrrolidine compounds
US5679773A (en) * 1995-01-17 1997-10-21 Affymax Technologies N.V Reagants and methods for immobilized polymer synthesis and display
WO1996000378A1 (en) * 1994-06-23 1996-01-04 Affymax Technologies N.V. Photolabile compounds and methods for their use
US6403367B1 (en) 1994-07-07 2002-06-11 Nanogen, Inc. Integrated portable biological detection system
US6071394A (en) * 1996-09-06 2000-06-06 Nanogen, Inc. Channel-less separation of bioparticles on a bioelectronic chip by dielectrophoresis
US6379897B1 (en) * 2000-11-09 2002-04-30 Nanogen, Inc. Methods for gene expression monitoring on electronic microarrays
US7857957B2 (en) 1994-07-07 2010-12-28 Gamida For Life B.V. Integrated portable biological detection system
US5710000A (en) * 1994-09-16 1998-01-20 Affymetrix, Inc. Capturing sequences adjacent to Type-IIs restriction sites for genomic library mapping
US6327031B1 (en) * 1998-09-18 2001-12-04 Burstein Technologies, Inc. Apparatus and semi-reflective optical system for carrying out analysis of samples
US6558633B1 (en) * 1994-09-21 2003-05-06 Isis Pharmaceuticals, Inc. Chemical reaction apparatus and methods
US5604097A (en) 1994-10-13 1997-02-18 Spectragen, Inc. Methods for sorting polynucleotides using oligonucleotide tags
USRE43097E1 (en) 1994-10-13 2012-01-10 Illumina, Inc. Massively parallel signature sequencing by ligation of encoded adaptors
US5695934A (en) * 1994-10-13 1997-12-09 Lynx Therapeutics, Inc. Massively parallel sequencing of sorted polynucleotides
US6004617A (en) * 1994-10-18 1999-12-21 The Regents Of The University Of California Combinatorial synthesis of novel materials
US6121048A (en) * 1994-10-18 2000-09-19 Zaffaroni; Alejandro C. Method of conducting a plurality of reactions
US7767627B1 (en) 1994-10-18 2010-08-03 Symyx Solutions, Inc. Combinatorial synthesis of inorganic or composite materials
US5985356A (en) * 1994-10-18 1999-11-16 The Regents Of The University Of California Combinatorial synthesis of novel materials
US5556752A (en) * 1994-10-24 1996-09-17 Affymetrix, Inc. Surface-bound, unimolecular, double-stranded DNA
US6600996B2 (en) 1994-10-21 2003-07-29 Affymetrix, Inc. Computer-aided techniques for analyzing biological sequences
US8236493B2 (en) 1994-10-21 2012-08-07 Affymetrix, Inc. Methods of enzymatic discrimination enhancement and surface-bound double-stranded DNA
US5795716A (en) 1994-10-21 1998-08-18 Chee; Mark S. Computer-aided visualization and analysis system for sequence evaluation
US6974666B1 (en) * 1994-10-21 2005-12-13 Appymetric, Inc. Methods of enzymatic discrimination enhancement and surface-bound double-stranded DNA
US5585069A (en) * 1994-11-10 1996-12-17 David Sarnoff Research Center, Inc. Partitioned microelectronic and fluidic device array for clinical diagnostics and chemical synthesis
US5603351A (en) 1995-06-07 1997-02-18 David Sarnoff Research Center, Inc. Method and system for inhibiting cross-contamination in fluids of combinatorial chemistry device
ATE277450T1 (de) * 1994-11-10 2004-10-15 Orchid Biosciences Inc Flüssigkeitsverteilungssystem
US5486633A (en) * 1994-11-10 1996-01-23 Duke University Photochemically-removable silyl protecting groups
SE9404166D0 (sv) * 1994-11-30 1994-11-30 Pharmacia Biotech Ab Multifunctional surfaces
US5830645A (en) * 1994-12-09 1998-11-03 The Regents Of The University Of California Comparative fluorescence hybridization to nucleic acid arrays
US5622826A (en) * 1994-12-22 1997-04-22 Houston Advanced Research Center Method for immobilization of molecules on platinum solid support surfaces
US5712171A (en) 1995-01-20 1998-01-27 Arqule, Inc. Method of generating a plurality of chemical compounds in a spatially arranged array
US5959098A (en) 1996-04-17 1999-09-28 Affymetrix, Inc. Substrate preparation process
US5599695A (en) * 1995-02-27 1997-02-04 Affymetrix, Inc. Printing molecular library arrays using deprotection agents solely in the vapor phase
US6239273B1 (en) 1995-02-27 2001-05-29 Affymetrix, Inc. Printing molecular library arrays
US5908926A (en) * 1995-03-16 1999-06-01 Duke University 5'to 3' nucleic acid synthesis using 3'-photoremovable protecting group
US6428955B1 (en) 1995-03-17 2002-08-06 Sequenom, Inc. DNA diagnostics based on mass spectrometry
US7803529B1 (en) * 1995-04-11 2010-09-28 Sequenom, Inc. Solid phase sequencing of biopolymers
US6284459B1 (en) 1995-04-25 2001-09-04 Discovery Partners International Solid support matrices with memories and combinatorial libraries therefrom
US6416714B1 (en) * 1995-04-25 2002-07-09 Discovery Partners International, Inc. Remotely programmable matrices with memories
US5961923A (en) * 1995-04-25 1999-10-05 Irori Matrices with memories and uses thereof
US6331273B1 (en) 1995-04-25 2001-12-18 Discovery Partners International Remotely programmable matrices with memories
US6100026A (en) * 1995-04-25 2000-08-08 Irori Matrices with memories and uses thereof
US5925562A (en) * 1995-04-25 1999-07-20 Irori Remotely programmable matrices with memories
US5741462A (en) * 1995-04-25 1998-04-21 Irori Remotely programmable matrices with memories
US6329139B1 (en) 1995-04-25 2001-12-11 Discovery Partners International Automated sorting system for matrices with memory
US6017496A (en) 1995-06-07 2000-01-25 Irori Matrices with memories and uses thereof
US5874214A (en) 1995-04-25 1999-02-23 Irori Remotely programmable matrices with memories
US6025129A (en) * 1995-04-25 2000-02-15 Irori Remotely programmable matrices with memories and uses thereof
US5751629A (en) 1995-04-25 1998-05-12 Irori Remotely programmable matrices with memories
US5624711A (en) * 1995-04-27 1997-04-29 Affymax Technologies, N.V. Derivatization of solid supports and methods for oligomer synthesis
US5830655A (en) 1995-05-22 1998-11-03 Sri International Oligonucleotide sizing using cleavable primers
US5683983A (en) * 1995-06-07 1997-11-04 Glaxo Group Limited Peptides and compounds that bind to the IL-5 receptor
CN1315870C (zh) 1995-06-07 2007-05-16 葛兰素集团有限公司 结合血小板生成素受体的肽和化合物
US5668110A (en) * 1995-06-07 1997-09-16 Affymax Technologies N.V. Peptides and compounds that bind to the IL-5 receptor
US5545531A (en) * 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US5869451A (en) * 1995-06-07 1999-02-09 Glaxo Group Limited Peptides and compounds that bind to a receptor
US5677280A (en) * 1995-06-07 1997-10-14 Glaxo Group Limited Peptides and compounds that bind to the IL-5 receptor
US6720149B1 (en) * 1995-06-07 2004-04-13 Affymetrix, Inc. Methods for concurrently processing multiple biological chip assays
US5654276A (en) * 1995-06-07 1997-08-05 Affymax Technologies N.V. Peptides and compounds that bind to the IL-5 receptor
US5958792A (en) * 1995-06-07 1999-09-28 Chiron Corporation Combinatorial libraries of substrate-bound cyclic organic compounds
US6251864B1 (en) 1995-06-07 2001-06-26 Glaxo Group Limited Peptides and compounds that bind to a receptor
US6387625B1 (en) 1995-06-27 2002-05-14 The University Of North Carolina At Chapel Hill Monolayer and electrode for detecting a label-bearing target and method of use thereof
US6127127A (en) * 1995-06-27 2000-10-03 The University Of North Carolina At Chapel Hill Monolayer and electrode for detecting a label-bearing target and method of use thereof
US5968745A (en) * 1995-06-27 1999-10-19 The University Of North Carolina At Chapel Hill Polymer-electrodes for detecting nucleic acid hybridization and method of use thereof
US6132971A (en) * 1995-06-27 2000-10-17 The University Of North Carolina At Chapel Hill Microelectronic device
US6180346B1 (en) 1995-06-27 2001-01-30 The Universtiy Of North Carolina At Chapel Hill Electropolymerizable film, and method of making and use thereof
US6346387B1 (en) * 1995-06-27 2002-02-12 Xanthon, Inc. Detection of binding reactions using labels detected by mediated catalytic electrochemistry
US6361951B1 (en) 1995-06-27 2002-03-26 The University Of North Carolina At Chapel Hill Electrochemical detection of nucleic acid hybridization
US20020022261A1 (en) * 1995-06-29 2002-02-21 Anderson Rolfe C. Miniaturized genetic analysis systems and methods
US6168948B1 (en) 1995-06-29 2001-01-02 Affymetrix, Inc. Miniaturized genetic analysis systems and methods
US5856174A (en) * 1995-06-29 1999-01-05 Affymetrix, Inc. Integrated nucleic acid diagnostic device
US20050100946A1 (en) * 1995-06-29 2005-05-12 Affymetrix, Inc. Integrated nucleic acid diagnostic device and method for in-situ confocal microscopy
US5968740A (en) * 1995-07-24 1999-10-19 Affymetrix, Inc. Method of Identifying a Base in a Nucleic Acid
US6326140B1 (en) 1995-08-09 2001-12-04 Regents Of The University Of California Systems for generating and analyzing stimulus-response output signal matrices
US5759779A (en) * 1995-08-29 1998-06-02 Dehlinger; Peter J. Polynucleotide-array assay and methods
US5633724A (en) * 1995-08-29 1997-05-27 Hewlett-Packard Company Evanescent scanning of biochemical array
US7026114B1 (en) 1995-09-13 2006-04-11 Affymetrix, Inc. Methods and compositions for monitoring polymer array synthesis
US5733729A (en) 1995-09-14 1998-03-31 Affymetrix, Inc. Computer-aided probability base calling for arrays of nucleic acid probes on chips
US5843655A (en) 1995-09-18 1998-12-01 Affymetrix, Inc. Methods for testing oligonucleotide arrays
US20040086917A1 (en) * 1995-09-27 2004-05-06 Nanogen, Inc. Methods for electronic fluorescent perturbation for analysis and electronic perturbation catalysis for synthesis
US6132580A (en) * 1995-09-28 2000-10-17 The Regents Of The University Of California Miniature reaction chamber and devices incorporating same
US20020068357A1 (en) * 1995-09-28 2002-06-06 Mathies Richard A. Miniaturized integrated nucleic acid processing and analysis device and method
US20040175718A1 (en) * 1995-10-16 2004-09-09 Affymetrix, Inc. Computer-aided visualization and analysis system for sequence evaluation
US5658734A (en) * 1995-10-17 1997-08-19 International Business Machines Corporation Process for synthesizing chemical compounds
US7455964B1 (en) 1996-07-15 2008-11-25 The Hospital For Sick Children Genes from the 20q13 amplicon and their uses
US5854033A (en) 1995-11-21 1998-12-29 Yale University Rolling circle replication reporter systems
US5763263A (en) * 1995-11-27 1998-06-09 Dehlinger; Peter J. Method and apparatus for producing position addressable combinatorial libraries
US6953663B1 (en) * 1995-11-29 2005-10-11 Affymetrix, Inc. Polymorphism detection
US6300063B1 (en) 1995-11-29 2001-10-09 Affymetrix, Inc. Polymorphism detection
US6022963A (en) * 1995-12-15 2000-02-08 Affymetrix, Inc. Synthesis of oligonucleotide arrays using photocleavable protecting groups
US6147205A (en) 1995-12-15 2000-11-14 Affymetrix, Inc. Photocleavable protecting groups and methods for their use
US20110028350A1 (en) * 1995-12-15 2011-02-03 Affymetrix, Inc. Photocleavable protecting groups
US6660233B1 (en) * 1996-01-16 2003-12-09 Beckman Coulter, Inc. Analytical biochemistry system with robotically carried bioarray
US20010018514A1 (en) * 1998-07-31 2001-08-30 Mcgall Glenn H. Nucleic acid labeling compounds
US6864059B2 (en) * 1996-01-23 2005-03-08 Affymetrix, Inc. Biotin containing C-glycoside nucleic acid labeling compounds
EP0880598A4 (en) * 1996-01-23 2005-02-23 Affymetrix Inc RAPID EVALUATION OF NUCLEIC ACID ABUNDANCE DIFFERENCE, WITH A HIGH-DENSITY OLIGONUCLEOTIDE SYSTEM
US7291463B2 (en) * 1996-01-23 2007-11-06 Affymetrix, Inc. Nucleic acid labeling compounds
US7423143B2 (en) * 1996-01-23 2008-09-09 Affymetrix. Inc. Nucleic acid labeling compounds
US6965020B2 (en) 1996-01-23 2005-11-15 Affymetrix, Inc. Nucleic acid labeling compounds
US20040210045A1 (en) * 1996-01-23 2004-10-21 Mcgall Glenn Nucleic acid labeling compounds
US7282327B2 (en) * 1996-01-23 2007-10-16 Affymetrix, Inc. Nucleic acid labeling compounds
US7527928B2 (en) * 1996-11-29 2009-05-05 Third Wave Technologies, Inc. Reactions on a solid surface
WO1997029212A1 (en) 1996-02-08 1997-08-14 Affymetrix, Inc. Chip-based speciation and phenotypic characterization of microorganisms
EP1728875A3 (en) 1996-02-08 2007-05-09 Affymetrix, Inc. Chip-based speciation and phenotypic characterization of microorganisms
US6924094B1 (en) * 1996-02-08 2005-08-02 Affymetrix, Inc. Chip-based species identification and phenotypic characterization of microorganisms
US6852487B1 (en) 1996-02-09 2005-02-08 Cornell Research Foundation, Inc. Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays
EP2332958B1 (en) 1996-02-09 2016-04-20 Cornell Research Foundation, Inc. Detection of nucleic and sequence differences using the ligase detection reaction with addressable arrays
US20020150921A1 (en) * 1996-02-09 2002-10-17 Francis Barany Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays
US6838256B2 (en) 1996-02-12 2005-01-04 Gene Logic Inc. Coding sequences of the human BRCA1 gene
US6130322A (en) * 1996-02-12 2000-10-10 Gene Logic, Inc. Coding sequences of the human BRCA1 gene
US20030022184A1 (en) * 1996-02-12 2003-01-30 Oncormed. Inc. Coding sequences of the human BRCA1 gene
DE19609272C2 (de) * 1996-02-27 2000-05-25 Schering Ag Verfahren zur Parallelsynthese großer Zahlen von 2,6-disubstituierten Chinolinderivaten
US6063633A (en) 1996-02-28 2000-05-16 The University Of Houston Catalyst testing process and apparatus
EP0886681A1 (en) 1996-03-04 1998-12-30 Genetrace Systems, Inc. Methods of screening nucleic acids using mass spectrometry
WO1997033169A1 (en) * 1996-03-08 1997-09-12 Smithkline Beecham Corporation A method for determining the affinity of proteins for chemical agents during screening of combinatorial libraries
FR2775984B1 (fr) 1998-03-11 2006-09-15 Bioscreen Therapeutics Sa Criblage differentiel qualitatif
US6013440A (en) 1996-03-11 2000-01-11 Affymetrix, Inc. Nucleic acid affinity columns
US6881571B1 (en) 1998-03-11 2005-04-19 Exonhit Therapeutics S.A. Qualitative differential screening
US20030165931A1 (en) * 1998-03-11 2003-09-04 Bruno Tocque Qualitative differential screening
WO1997035033A1 (en) 1996-03-19 1997-09-25 Molecular Tool, Inc. Method for determining the nucleotide sequence of a polynucleotide
US6361937B1 (en) * 1996-03-19 2002-03-26 Affymetrix, Incorporated Computer-aided nucleic acid sequencing
US6528324B1 (en) * 1996-03-22 2003-03-04 Ontogen Corporation Apparatus for pre-determined mass sorting of positional-encoded solid phase synthesis supports
US6777217B1 (en) 1996-03-26 2004-08-17 President And Fellows Of Harvard College Histone deacetylases, and uses related thereto
US6114122A (en) 1996-03-26 2000-09-05 Affymetrix, Inc. Fluidics station with a mounting system and method of using
DE19612356B4 (de) * 1996-03-28 2007-04-26 Clondiag Chip Technologies Gmbh Optischer Nachweis von Hybridisierungs-Signalen
US6458530B1 (en) 1996-04-04 2002-10-01 Affymetrix Inc. Selecting tag nucleic acids
WO1997041139A2 (en) 1996-04-17 1997-11-06 Koester Hubert A combinatorial protecting group strategy for multifunctional molecules
US5733509A (en) * 1996-04-17 1998-03-31 Motorola, Inc. Method and system for synthesizing oligonucleotides using nucleotide-specific dispensing bars
US6706875B1 (en) * 1996-04-17 2004-03-16 Affyemtrix, Inc. Substrate preparation process
US6958245B2 (en) 1996-04-25 2005-10-25 Bioarray Solutions Ltd. Array cytometry
US7144119B2 (en) * 1996-04-25 2006-12-05 Bioarray Solutions Ltd. System and method for programmable illumination pattern generation
ATE366418T1 (de) 1996-04-25 2007-07-15 Bioarray Solutions Ltd Licht-regulierte, elektrokinetische zusammensetzung von partikeln an oberflächen
US6165335A (en) 1996-04-25 2000-12-26 Pence And Mcgill University Biosensor device and method
JP2000512744A (ja) 1996-05-16 2000-09-26 アフィメトリックス，インコーポレイテッド 標識材料を検出するシステムおよび方法
US5958342A (en) * 1996-05-17 1999-09-28 Incyte Pharmaceuticals, Inc. Jet droplet device
CA2255774C (en) 1996-05-29 2008-03-18 Cornell Research Foundation, Inc. Detection of nucleic acid sequence differences using coupled ligase detection and polymerase chain reactions
US20060141539A1 (en) * 1996-05-30 2006-06-29 Taylor D L Miniaturized cell array methods and apparatus for cell-based screening
US6103479A (en) * 1996-05-30 2000-08-15 Cellomics, Inc. Miniaturized cell array methods and apparatus for cell-based screening
US5989835A (en) 1997-02-27 1999-11-23 Cellomics, Inc. System for cell-based screening
US6057100A (en) * 1996-06-07 2000-05-02 Eos Biotechnology, Inc. Oligonucleotide arrays
US7091311B2 (en) * 1996-06-07 2006-08-15 Smithkline Beecham Corporation Peptides and compounds that bind to a receptor
US5912124A (en) * 1996-06-14 1999-06-15 Sarnoff Corporation Padlock probe detection
US5770370A (en) * 1996-06-14 1998-06-23 David Sarnoff Research Center, Inc. Nuclease protection assays
WO1997047761A1 (en) * 1996-06-14 1997-12-18 Sarnoff Corporation Method for polynucleotide sequencing
US5914229A (en) * 1996-06-14 1999-06-22 Sarnoff Corporation Method for amplifying a polynucleotide
SE9602545L (sv) 1996-06-25 1997-12-26 Michael Mecklenburg Metod för att diskriminera komplexa biologiska prover
BR9710702A (pt) 1996-07-08 2000-01-11 Burstein Lab Inc Dispositivo de elemento de sinal clivável e método.
US20050214827A1 (en) * 1996-07-08 2005-09-29 Burstein Technologies, Inc. Assay device and method
US6331275B1 (en) 1996-07-08 2001-12-18 Burstein Technologies, Inc. Spatially addressable, cleavable reflective signal elements, assay device and method
US6342349B1 (en) 1996-07-08 2002-01-29 Burstein Technologies, Inc. Optical disk-based assay devices and methods
US20050069923A1 (en) * 1996-07-08 2005-03-31 Mullis Kary Banks Dual bead assays using cleavable spacers and/or ligation to improve specificity and sensitivity including related methods and apparatus
DE19629141A1 (de) * 1996-07-19 1998-04-16 Bayer Ag Verfahren und Vorrichtung zum Screening von Molekülen bezüglich ihres individuellen Bindungsverhaltens zu mindestens einem vorgegebenen Ligand
US5798360A (en) * 1996-08-01 1998-08-25 Isis Pharmaceuticals, Inc. N-(aminoalkyl)- and/or N-(amidoalkyl)- dinitrogen heterocyclic compositions
US5922872A (en) * 1996-08-01 1999-07-13 Isis Pharmaceuticals, Inc. Meta-benzylic and alpha-amido compositions and methods for preparing same
US5817489A (en) * 1996-08-01 1998-10-06 Isis Pharmaceuticals, Inc. Di-nitrogen heterocycle compositions
US5731438A (en) * 1996-08-01 1998-03-24 Isis Pharmaceuticals, Inc. N-(aminoalkyl)-and/or N-(amidoalkyl)-dinitrogen heterocycles
US5858666A (en) * 1996-08-29 1999-01-12 Biotechnology Research And Development Corporation Apparatus and method of detection employing an AC frequency sensor array
US6020047A (en) * 1996-09-04 2000-02-01 Kimberly-Clark Worldwide, Inc. Polymer films having a printed self-assembling monolayer
US5965363A (en) 1996-09-19 1999-10-12 Genetrace Systems Inc. Methods of preparing nucleic acids for mass spectrometric analysis
US6391550B1 (en) 1996-09-19 2002-05-21 Affymetrix, Inc. Identification of molecular sequence signatures and methods involving the same
WO1998012559A1 (en) * 1996-09-20 1998-03-26 Demers James P Spatially addressable combinatorial chemical arrays in cd-rom format
EP1783139B8 (en) 1996-10-01 2009-09-23 Geron Corporation Human telomerase catalytic subunit
US6468806B1 (en) 1996-10-02 2002-10-22 Symyx Technologies, Inc. Potential masking systems and methods for combinatorial library synthesis
US5932546A (en) * 1996-10-04 1999-08-03 Glaxo Wellcome Inc. Peptides and compounds that bind to the thrombopoietin receptor
US6136274A (en) * 1996-10-07 2000-10-24 Irori Matrices with memories in automated drug discovery and units therefor
US6738529B1 (en) 1996-10-09 2004-05-18 Symyx Technologies, Inc. Analysis of chemical data from images
US5762881A (en) * 1996-10-29 1998-06-09 Bohdan Automation, Inc. Apparatus for multiple, simultaneous synthesis of organic compounds
US6875620B1 (en) 1996-10-31 2005-04-05 Agilent Technologies, Inc. Tiling process for constructing a chemical array
US5780241A (en) 1996-11-05 1998-07-14 Isis Pharmaceuticals, Inc. Complex chemical libraries
EP0937096B1 (en) 1996-11-06 2004-02-04 Sequenom, Inc. Method of mass spectrometry analysis
US6140053A (en) * 1996-11-06 2000-10-31 Sequenom, Inc. DNA sequencing by mass spectrometry via exonuclease degradation
US6133436A (en) 1996-11-06 2000-10-17 Sequenom, Inc. Beads bound to a solid support and to nucleic acids
US6024925A (en) 1997-01-23 2000-02-15 Sequenom, Inc. Systems and methods for preparing low volume analyte array elements
US20030129589A1 (en) * 1996-11-06 2003-07-10 Hubert Koster Dna diagnostics based on mass spectrometry
US7285422B1 (en) * 1997-01-23 2007-10-23 Sequenom, Inc. Systems and methods for preparing and analyzing low volume analyte array elements
US6441172B1 (en) * 1996-11-07 2002-08-27 Torrey Pines Institute For Molecular Studies Diketodiazacyclic compounds, diazacyclic compounds and combinatorial libraries thereof
US6887665B2 (en) * 1996-11-14 2005-05-03 Affymetrix, Inc. Methods of array synthesis
WO1998020967A1 (en) * 1996-11-14 1998-05-22 Affymetrix, Inc. Chemical amplification for the synthesis of patterned arrays
US5965719A (en) * 1996-11-15 1999-10-12 Sunsorb Biotech, Inc. Combinatorial synthesis of carbohydrate libraries
US5780603A (en) * 1996-11-15 1998-07-14 Synsorb Biotech, Inc. Combinatorial synthesis of carbohydrate libraries
US6706473B1 (en) 1996-12-06 2004-03-16 Nanogen, Inc. Systems and devices for photoelectrophoretic transport and hybridization of oligonucleotides
CA2274587A1 (en) 1996-12-10 1998-06-18 Genetrace Systems Inc. Releasable nonvolatile mass-label molecules
US5942397A (en) * 1996-12-11 1999-08-24 Tarlov; Michael J. Surface immobilization of biopolymers
US6458547B1 (en) 1996-12-12 2002-10-01 Prolume, Ltd. Apparatus and method for detecting and identifying infectious agents
EP1007969A4 (en) * 1996-12-17 2006-12-13 Affymetrix Inc DESIGN OF LITHOGRAPHIC MASKS AND SYNTHESIS OF VARIOUS PROBES ON A SUBSTRATE
US5922550A (en) * 1996-12-18 1999-07-13 Kimberly-Clark Worldwide, Inc. Biosensing devices which produce diffraction images
US6048623A (en) * 1996-12-18 2000-04-11 Kimberly-Clark Worldwide, Inc. Method of contact printing on gold coated films
EP0958303A4 (en) 1996-12-19 2004-03-31 Univ Yale BIOREACTIVE ALLOSTERIC POLYNUCLEOTIDES
WO1998029736A1 (en) * 1996-12-31 1998-07-09 Genometrix Incorporated Multiplexed molecular analysis apparatus and method
US6277563B1 (en) 1997-01-16 2001-08-21 The Regents Of The University Of California Genetic alterations associated with cancer
US7670767B1 (en) 1997-01-16 2010-03-02 The Regents Of The University Of California Genetic alterations associated with cancer
DE69835143T2 (de) 1997-01-21 2007-06-06 The General Hospital Corp., Boston Selektion von proteinen mittels rns-protein fusionen
US5837475A (en) * 1997-01-30 1998-11-17 Hewlett-Packard Co. Apparatus and method for scanning a chemical array
US5812272A (en) * 1997-01-30 1998-09-22 Hewlett-Packard Company Apparatus and method with tiled light source array for integrated assay sensing
US6262269B1 (en) 1997-02-04 2001-07-17 Trega Biosciences, Inc. 4-Substituted-quinoline derivatives and 4-substituted-quinoline combinatorial libraries
US5773308A (en) * 1997-02-10 1998-06-30 The United States Of America As Represented By The Secretary Of The Navy Photoactivatable o-nitrobenzyl polyethylene glycol-silane for the production of patterned biomolecular arrays
EP1009802B1 (en) 1997-02-12 2004-08-11 Eugene Y. Chan Methods for analyzimg polymers
WO1998035707A1 (en) 1997-02-18 1998-08-20 Thomas Jefferson University Compositions that bind to pancreatic cancer cells and methods of using the same
US6727071B1 (en) 1997-02-27 2004-04-27 Cellomics, Inc. System for cell-based screening
AU730100B2 (en) 1997-02-27 2001-02-22 Cellomics, Inc. A system for cell-based screening
US7117098B1 (en) 1997-02-27 2006-10-03 Cellomics, Inc. Machine-readable storage medium for analyzing distribution of macromolecules between the cell membrane and the cell cytoplasm
US6165709A (en) 1997-02-28 2000-12-26 Fred Hutchinson Cancer Research Center Methods for drug target screening
US7622294B2 (en) 1997-03-14 2009-11-24 Trustees Of Tufts College Methods for detecting target analytes and enzymatic reactions
US20030027126A1 (en) 1997-03-14 2003-02-06 Walt David R. Methods for detecting target analytes and enzymatic reactions
US6028189A (en) * 1997-03-20 2000-02-22 University Of Washington Solvent for oligonucleotide synthesis and methods of use
US6419883B1 (en) 1998-01-16 2002-07-16 University Of Washington Chemical synthesis using solvent microdroplets
EP0970101A2 (en) 1997-03-20 2000-01-12 University Of Washington Solvent for biopolymer synthesis, solvent microdroplets and methods of use
US6180288B1 (en) 1997-03-21 2001-01-30 Kimberly-Clark Worldwide, Inc. Gel sensors and method of use thereof
US6753161B2 (en) * 1997-03-27 2004-06-22 Oncosis Llc Optoinjection methods
CA2284612A1 (en) 1997-04-04 1998-10-15 Michael Knapp Closed-loop biochemical analyzers
US5772855A (en) * 1997-04-17 1998-06-30 Bend Research, Inc. Preparation of bioactive compounds by plasma synthesis
US6143496A (en) * 1997-04-17 2000-11-07 Cytonix Corporation Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly
US6558901B1 (en) * 1997-05-02 2003-05-06 Biomerieux Vitek Nucleic acid assays
WO1998050403A1 (en) 1997-05-05 1998-11-12 Third Wave Technologies,Inc. Target-dependent reactions using structure-bridging oligonucleotides
US6194149B1 (en) 1998-03-03 2001-02-27 Third Wave Technologies, Inc. Target-dependent reactions using structure-bridging oligonucleotides
US7101672B2 (en) * 1998-05-05 2006-09-05 Third Wave Technologies, Inc. Target-dependent reactions using structure-bridging oligonucleotides
US6214545B1 (en) 1997-05-05 2001-04-10 Third Wave Technologies, Inc Polymorphism analysis by nucleic acid structure probing
US6210880B1 (en) 1997-09-19 2001-04-03 Third Wave Technologies, Inc. Polymorphism analysis by nucleic acid structure probing with structure-bridging oligonucleotides
US6159681A (en) * 1997-05-28 2000-12-12 Syntrix Biochip, Inc. Light-mediated method and apparatus for the regional analysis of biologic material
JP4433100B2 (ja) * 1997-06-20 2010-03-17 ニューヨーク ユニヴァーシティ チップ及びライブラリの大量製造における物質溶液の静電噴霧
NZ516848A (en) 1997-06-20 2004-03-26 Ciphergen Biosystems Inc Retentate chromatography apparatus with applications in biology and medicine
US6368877B1 (en) * 1997-06-25 2002-04-09 Massachusetts Institute Of Technology Self-assembling peptide surfaces for cell patterning and interactions
DE69824586T2 (de) * 1997-06-26 2005-06-23 PerSeptive Biosystems, Inc., Framingham Probenträger hoher dichte für die analyse biologischer proben
IL121312A (en) * 1997-07-14 2001-09-13 Technion Res & Dev Foundation Microelectronic components, their manufacture and electronic networks containing them
US6151123A (en) * 1997-07-14 2000-11-21 Symyx Technologies, Inc. Systems and methods for employing optical probes to characterize material properties
EP0996500A1 (en) 1997-07-22 2000-05-03 Rapigene, Inc. Apparatus and methods for arraying solution onto a solid support
EP1000176A1 (en) 1997-07-22 2000-05-17 Rapigene, Inc. Computer method and system for correlating sequencing data by ms
CA2297661A1 (en) 1997-07-22 1999-02-04 Darwin Molecular Corp. Amplification and other enzymatic reactions performed on nucleic acid arrays
JP2001515234A (ja) * 1997-07-25 2001-09-18 アフィメトリックス インコーポレイテッド 多型性データベースを提供するためのシステム
US7068830B2 (en) * 1997-07-25 2006-06-27 Affymetrix, Inc. Method and system for providing a probe array chip design database
US6826296B2 (en) 1997-07-25 2004-11-30 Affymetrix, Inc. Method and system for providing a probe array chip design database
US6420108B2 (en) * 1998-02-09 2002-07-16 Affymetrix, Inc. Computer-aided display for comparative gene expression
CA2338865A1 (en) * 1997-07-29 1999-02-11 James S. Huston Methods for detecting binding events using multiple binding partners and muliple targets
US6391655B1 (en) * 1997-07-30 2002-05-21 Corning Incorporated Oxidized styrenic polymers for DNA binding
US6290685B1 (en) 1998-06-18 2001-09-18 3M Innovative Properties Company Microchanneled active fluid transport devices
US6375871B1 (en) 1998-06-18 2002-04-23 3M Innovative Properties Company Methods of manufacturing microfluidic articles
JP4313861B2 (ja) 1997-08-01 2009-08-12 キヤノン株式会社 プローブアレイの製造方法
US6548020B2 (en) * 1997-08-01 2003-04-15 Canon Kabushiki Kaisha Reaction site array with a black matrix to decrease cross-contamination between reaction regions
US6326489B1 (en) 1997-08-05 2001-12-04 Howard Hughes Medical Institute Surface-bound, bimolecular, double-stranded DNA arrays
US6120995A (en) * 1997-08-07 2000-09-19 Thomas Jefferson University Compositions that specifically bind to colorectal cancer cells and methods of using the same
US7135333B1 (en) 1997-08-07 2006-11-14 Thomas Jefferson University Compositions that specifically bind to colorectal cancer cells and methods of using the same
US20090269814A1 (en) * 1998-05-22 2009-10-29 Murphy Patricia D Method of Analyzing a BRCA2 Gene in a Human Subject
EP2275574B1 (en) 1997-08-15 2015-06-03 Gene Logic Inc. Coding sequence haplotypes of the human BRCA2 gene
US6410342B1 (en) * 1997-08-19 2002-06-25 Pharmacopeia, Inc. Method and apparatus for controlled photoelution
US7252950B1 (en) 1997-09-04 2007-08-07 The Regents Of The University Of California Assays for detecting modulators of cytoskeletal function
US6432639B1 (en) 1997-09-10 2002-08-13 Dna Sciences Laboratories, Inc. Isolated CYP3A4 nucleic acid molecules and detection methods
ATE319986T1 (de) * 1997-09-11 2006-03-15 Bioventures Inc Verfahren zur herstellung von arrays hoher dichte
US7745142B2 (en) 1997-09-15 2010-06-29 Molecular Devices Corporation Molecular modification assays
DE19741715A1 (de) * 1997-09-22 1999-03-25 Hoechst Ag Pentopyranosyl-Nucleosid, seine Herstellung und Verwendung
US6492109B1 (en) 1997-09-23 2002-12-10 Gene Logic, Inc. Susceptibility mutation 6495delGC of BRCA2
US7214298B2 (en) * 1997-09-23 2007-05-08 California Institute Of Technology Microfabricated cell sorter
US20030104481A1 (en) * 1997-09-30 2003-06-05 Symyx Technologies Potential masking systems and methods for combinatorial library synthesis
US6607878B2 (en) 1997-10-06 2003-08-19 Stratagene Collections of uniquely tagged molecules
WO1999019510A1 (en) * 1997-10-10 1999-04-22 President And Fellows Of Harvard College Surface-bound, double-stranded dna protein arrays
US6511803B1 (en) * 1997-10-10 2003-01-28 President And Fellows Of Harvard College Replica amplification of nucleic acid arrays
JP2001519538A (ja) 1997-10-10 2001-10-23 プレジデント・アンド・フェローズ・オブ・ハーバード・カレッジ 核酸アレイのレプリカ増幅
US6485944B1 (en) 1997-10-10 2002-11-26 President And Fellows Of Harvard College Replica amplification of nucleic acid arrays
US20020155495A1 (en) * 2000-04-17 2002-10-24 Millstein Larry S. Method for producing arrays and devices relating thereto
US6348322B1 (en) 1997-10-17 2002-02-19 Duke University Method of screening for specific binding interactions
GB9722131D0 (en) * 1997-10-20 1997-12-17 Medical Res Council Method
US7351578B2 (en) 1999-12-10 2008-04-01 Invitrogen Corp. Use of multiple recombination sites with unique specificity in recombinational cloning
US6156494A (en) * 1997-10-28 2000-12-05 Mosaic Technologies Serially directed combinatorial synthesis on fiber optic arrays
AU753505B2 (en) * 1997-10-30 2002-10-17 Cold Spring Harbor Laboratory Probe arrays and methods of using probe arrays for distinguishing DNA
US6101946A (en) * 1997-11-21 2000-08-15 Telechem International Inc. Microarray printing device including printing pins with flat tips and exterior channel and method of manufacture
US6322968B1 (en) 1997-11-21 2001-11-27 Orchid Biosciences, Inc. De novo or “universal” sequencing array
US6794133B1 (en) 1997-12-11 2004-09-21 The General Hospital Corporation Broad range PCR amplification techniques
US6184377B1 (en) 1997-12-15 2001-02-06 Sepracor Inc. Compositions containing N-amino- and N-hydroxy-quinazolinones and methods for preparing libraries thereof
WO2003070984A1 (en) * 2002-02-15 2003-08-28 Somalogic, Inc. Methods and reagents for detecting target binding by nucleic acid ligands
US20070166741A1 (en) * 1998-12-14 2007-07-19 Somalogic, Incorporated Multiplexed analyses of test samples
US6242246B1 (en) 1997-12-15 2001-06-05 Somalogic, Inc. Nucleic acid ligand diagnostic Biochip
US6274383B1 (en) 1997-12-15 2001-08-14 Sepracor Inc. Methods for synthesizing libraries of dihydro-quinazolinones
US6060256A (en) * 1997-12-16 2000-05-09 Kimberly-Clark Worldwide, Inc. Optical diffraction biosensor
US6458533B1 (en) 1997-12-19 2002-10-01 High Throughput Genomics, Inc. High throughput assay system for monitoring ESTs
US20030039967A1 (en) * 1997-12-19 2003-02-27 Kris Richard M. High throughput assay system using mass spectrometry
US6238869B1 (en) 1997-12-19 2001-05-29 High Throughput Genomics, Inc. High throughput assay system
US20030096232A1 (en) * 1997-12-19 2003-05-22 Kris Richard M. High throughput assay system
US20100105572A1 (en) * 1997-12-19 2010-04-29 Kris Richard M High throughput assay system
US6232066B1 (en) 1997-12-19 2001-05-15 Neogen, Inc. High throughput assay system
US6093302A (en) 1998-01-05 2000-07-25 Combimatrix Corporation Electrochemical solid phase synthesis
US6087102A (en) 1998-01-07 2000-07-11 Clontech Laboratories, Inc. Polymeric arrays and methods for their use in binding assays
US6265163B1 (en) 1998-01-09 2001-07-24 Lynx Therapeutics, Inc. Solid phase selection of differentially expressed genes
WO1999034920A1 (en) * 1998-01-12 1999-07-15 Massachusetts Institute Of Technology Method and apparatus for performing microassays
US6893877B2 (en) 1998-01-12 2005-05-17 Massachusetts Institute Of Technology Methods for screening substances in a microwell array
US6201639B1 (en) 1998-03-20 2001-03-13 James W. Overbeck Wide field of view and high speed scanning microscopy
US20030166169A1 (en) * 1998-01-16 2003-09-04 Padgett Hal S. Method for constructing viral nucleic acids in a cell-free manner
US20020164585A1 (en) * 1998-01-16 2002-11-07 Sean Chapman Method for enhancing RNA or protein production using non-native 5' untranslated sequences in recombinant viral nucleic acids
US6426185B1 (en) 1998-01-16 2002-07-30 Large Scale Biology Corporation Method of compiling a functional gene profile in a plant by transfecting a nucleic acid sequence of a donor plant into a different host plant in an anti-sense orientation
US6303848B1 (en) 1998-01-16 2001-10-16 Large Scale Biology Corporation Method for conferring herbicide, pest, or disease resistance in plant hosts
WO1999036576A1 (en) * 1998-01-20 1999-07-22 Packard Bioscience Company Gel pad arrays and methods and systems for making them
US6289229B1 (en) 1998-01-20 2001-09-11 Scimed Life Systems, Inc. Readable probe array for in vivo use
DE19802576B4 (de) * 1998-01-23 2004-10-28 Xerion Pharmaceuticals Ag Verfahren zur gleichzeitigen Identifizierung von Proteinen und ihren Bindungspartnern
US6043294A (en) * 1998-01-29 2000-03-28 Gate Technologies International, Inc. Method of and apparatus for optically enhancing chemical reactions
US6741956B1 (en) 1998-02-03 2004-05-25 Lucent Technologies Inc. Analog computation using hybridization-capable oligomers
US6150102A (en) * 1998-02-03 2000-11-21 Lucent Technologies Inc. Method of generating nucleic acid oligomers of known composition
US6537747B1 (en) 1998-02-03 2003-03-25 Lucent Technologies Inc. Data transmission using DNA oligomers
EP0947246B1 (en) * 1998-02-04 2004-08-18 Corning Incorporated Substrate for array printing
ATE393912T1 (de) 1998-02-04 2008-05-15 Invitrogen Corp Microarrays und ihre verwendungen
US5994079A (en) 1998-02-06 1999-11-30 Digene Corporation Direct detection of RNA mediated by reverse transcriptase lacking RNAse H function
US20040265838A1 (en) * 1998-02-06 2004-12-30 Affymetrix, Inc. Method of manufacturing
US7399589B2 (en) * 1998-02-06 2008-07-15 Digene Corporation Immunological detection of RNA:DNA hybrids on microarrays
US20040035690A1 (en) * 1998-02-11 2004-02-26 The Regents Of The University Of Michigan Method and apparatus for chemical and biochemical reactions using photo-generated reagents
AU772531B2 (en) * 1998-02-11 2004-04-29 University Of Houston, The Method and apparatus for chemical and biochemical reactions using photo-generated reagents
EP1054726B1 (en) * 1998-02-11 2003-07-30 University of Houston, Office of Technology Transfer Apparatus for chemical and biochemical reactions using photo-generated reagents
US6537505B1 (en) 1998-02-20 2003-03-25 Bio Dot, Inc. Reagent dispensing valve
EP1056882A4 (en) * 1998-02-21 2002-04-17 Technology Foundation Wisys ONE-DIMENSIONAL CHEMICAL COMPOUND ARRAYS AND METHODS FOR ANALYZING THE SAME
WO1999042813A1 (en) * 1998-02-23 1999-08-26 Wisconsin Alumni Research Foundation Method and apparatus for synthesis of arrays of dna probes
US20020090639A1 (en) * 1998-02-26 2002-07-11 Mcginnis Ralph Evan Two dimensional linkage study methods and related inventions
US6087103A (en) * 1998-03-04 2000-07-11 Lifespan Biosciences, Inc. Tagged ligand arrays for identifying target-ligand interactions
EP1717249A1 (en) 1998-03-12 2006-11-02 Georgetown University Peptides containing a cholesterol recognition sequence and their uses
US6185030B1 (en) 1998-03-20 2001-02-06 James W. Overbeck Wide field of view and high speed scanning microscopy
WO1999049293A2 (en) * 1998-03-24 1999-09-30 Boston Probes, Inc. Methods, kits and compositions pertaining to detection complexes
US6218114B1 (en) 1998-03-27 2001-04-17 Academia Sinica Methods for detecting differentially expressed genes
JP2002507405A (ja) * 1998-03-27 2002-03-12 ザ ボード オブ トラスティーズ オブ ザ リーランド スタンフォード ジュニア ユニバーシティ 低酸素誘導ヒト遺伝子、タンパク質およびそれらの使用
EP1095183B1 (en) * 1998-03-31 2012-02-22 Esoterix Genetic Laboratories, LLC Methods for the diagnosis and treatment of lung cancer
US6077673A (en) * 1998-03-31 2000-06-20 Clontech Laboratories, Inc. Mouse arrays and kits comprising the same
US7108968B2 (en) * 1998-04-03 2006-09-19 Affymetrix, Inc. Mycobacterial rpoB sequences
ATE340870T1 (de) 1998-04-03 2006-10-15 Compound Therapeutics Inc Adressierbare protein arrays
US6284497B1 (en) * 1998-04-09 2001-09-04 Trustees Of Boston University Nucleic acid arrays and methods of synthesis
US6376619B1 (en) * 1998-04-13 2002-04-23 3M Innovative Properties Company High density, miniaturized arrays and methods of manufacturing same
AU3659199A (en) * 1998-04-20 1999-11-08 Affymetrix, Inc. Methods for reducing non-specific binding to a nucleic acid probe array
AU3572799A (en) * 1998-04-24 1999-11-16 Genova Pharmaceuticals Corporation Function-based gene discovery
US6884626B1 (en) 1998-04-27 2005-04-26 Corning Incorporated Redrawn capillary imaging reservoir
US6355419B1 (en) 1998-04-27 2002-03-12 Hyseq, Inc. Preparation of pools of nucleic acids based on representation in a sample
DE69835342T2 (de) 1998-04-27 2007-08-23 Corning Inc. Verfahren zur Ablage von biologischen Proben mit Hilfe eines nachgezogenen Kapillarspeichers
US6350618B1 (en) 1998-04-27 2002-02-26 Corning Incorporated Redrawn capillary imaging reservoir
US7617163B2 (en) * 1998-05-01 2009-11-10 Health Discovery Corporation Kernels and kernel methods for spectral data
US6780591B2 (en) 1998-05-01 2004-08-24 Arizona Board Of Regents Method of determining the nucleotide sequence of oligonucleotides and DNA molecules
US20080050836A1 (en) * 1998-05-01 2008-02-28 Isabelle Guyon Biomarkers for screening, predicting, and monitoring benign prostate hyperplasia
US7875440B2 (en) 1998-05-01 2011-01-25 Arizona Board Of Regents Method of determining the nucleotide sequence of oligonucleotides and DNA molecules
US6130046A (en) * 1998-05-04 2000-10-10 Affymetrix, Inc. Techniques for synthesis integrity evaluation utilizing cycle fidelity probes
US20030203394A1 (en) * 1998-05-04 2003-10-30 Yoav Eichen Detection of a target in a sample
US6979728B2 (en) * 1998-05-04 2005-12-27 Baylor College Of Medicine Articles of manufacture and methods for array based analysis of biological molecules
US6686163B2 (en) 1998-05-06 2004-02-03 Gene Logic Inc. Coding sequence haplotype of the human BRCA1 gene
US5965352A (en) 1998-05-08 1999-10-12 Rosetta Inpharmatics, Inc. Methods for identifying pathways of drug action
US5992226A (en) * 1998-05-08 1999-11-30 The United States Of America As Represented By The Secretary Of The Navy Apparatus and method for measuring intermolecular interactions by atomic force microscopy
US6324479B1 (en) 1998-05-08 2001-11-27 Rosetta Impharmatics, Inc. Methods of determining protein activity levels using gene expression profiles
US20030153023A1 (en) * 1999-05-13 2003-08-14 Starzl Timothy W. Enumeration method of analyte detection
DE19823454A1 (de) * 1998-05-18 1999-11-25 Epigenomics Gmbh Verfahren zur photolithographischen Herstellung von DNA, PNA und Protein Chips
DE19823660C1 (de) * 1998-05-20 1999-10-07 Nanomont Ges Fuer Nanotechnolo Verfahren und Vorrichtung zur Fixierung fester Mikro- und/oder Nanoobjekte
US6268210B1 (en) 1998-05-27 2001-07-31 Hyseq, Inc. Sandwich arrays of biological compounds
WO1999061653A2 (en) * 1998-05-27 1999-12-02 Syntrix Biochip Light-mediated regional analysis of biologic material
US6271957B1 (en) * 1998-05-29 2001-08-07 Affymetrix, Inc. Methods involving direct write optical lithography
US6086831A (en) * 1998-06-10 2000-07-11 Mettler-Toledo Bohdan, Inc. Modular reaction block assembly with thermoelectric cooling and heating
DE19826458A1 (de) * 1998-06-13 1999-12-16 Papst Motoren Gmbh & Co Kg Anordnung mit einem Elektromotor
US6872521B1 (en) 1998-06-16 2005-03-29 Beckman Coulter, Inc. Polymerase signaling assay
US6270730B1 (en) 1998-06-16 2001-08-07 Northwest Engineering Inc. Multi-well rotary synthesizer
US6251595B1 (en) 1998-06-18 2001-06-26 Agilent Technologies, Inc. Methods and devices for carrying out chemical reactions
US6218122B1 (en) * 1998-06-19 2001-04-17 Rosetta Inpharmatics, Inc. Methods of monitoring disease states and therapies using gene expression profiles
US6132969A (en) * 1998-06-19 2000-10-17 Rosetta Inpharmatics, Inc. Methods for testing biological network models
EP1632496A1 (en) * 1998-06-22 2006-03-08 Affymetrix, Inc. Reagents and methods for solid phase synthesis and display
US6235473B1 (en) 1998-07-02 2001-05-22 Orchid Biosciences, Inc. Gene pen devices for array printing
US6762061B1 (en) 1998-07-03 2004-07-13 Corning Incorporated Redrawn capillary imaging reservoir
US6593133B1 (en) 1998-07-06 2003-07-15 Nsgene A/S Neurotrophic factors
WO2000003037A1 (en) * 1998-07-10 2000-01-20 The Board Of Trustees Of The Leland Stanford Junior University Screening arrays of nucleotides to determine correspondence with both sequence and physical properties of a probe
US6171794B1 (en) 1998-07-13 2001-01-09 Rosetta Inpharmatics, Inc. Methods for determining cross-hybridization
US6406921B1 (en) * 1998-07-14 2002-06-18 Zyomyx, Incorporated Protein arrays for high-throughput screening
US20020119579A1 (en) * 1998-07-14 2002-08-29 Peter Wagner Arrays devices and methods of use thereof
US6897073B2 (en) * 1998-07-14 2005-05-24 Zyomyx, Inc. Non-specific binding resistant protein arrays and methods for making the same
US6576478B1 (en) 1998-07-14 2003-06-10 Zyomyx, Inc. Microdevices for high-throughput screening of biomolecules
US6682942B1 (en) 1998-07-14 2004-01-27 Zyomyx, Inc. Microdevices for screening biomolecules
US6780582B1 (en) * 1998-07-14 2004-08-24 Zyomyx, Inc. Arrays of protein-capture agents and methods of use thereof
US20030138973A1 (en) * 1998-07-14 2003-07-24 Peter Wagner Microdevices for screening biomolecules
WO2000004193A1 (en) 1998-07-20 2000-01-27 Yale University Method for detecting nucleic acids using target-mediated ligation of bipartite primers
JP2002521666A (ja) * 1998-07-21 2002-07-16 バースタイン テクノロジーズ，インコーポレイティド 光ディスクをベースとするアッセイ装置および方法
US20040029159A1 (en) * 1998-08-03 2004-02-12 Dreyer William J. Nucleic acid switch patterns as cell or tissue type identifiers
WO2000008468A1 (en) * 1998-08-03 2000-02-17 California Institute Of Technology Method of determining cell or tissue type by transmembrane receptor identifiers
US6528026B2 (en) 1998-08-13 2003-03-04 Symyx Technologies, Inc. Multi-temperature modular reactor and method of using same
US6864092B1 (en) 1998-08-13 2005-03-08 Symyx Technologies, Inc. Parallel reactor with internal sensing and method of using same
US6548026B1 (en) 1998-08-13 2003-04-15 Symyx Technologies, Inc. Parallel reactor with internal sensing and method of using same
US6306658B1 (en) 1998-08-13 2001-10-23 Symyx Technologies Parallel reactor with internal sensing
US6455316B1 (en) 1998-08-13 2002-09-24 Symyx Technologies, Inc. Parallel reactor with internal sensing and method of using same
DE19836882A1 (de) * 1998-08-14 2000-02-17 Papst Motoren Gmbh & Co Kg Anordnung mit einem Elektromotor
US6291190B1 (en) 1998-08-25 2001-09-18 The Board Of Trustees Of The Leland Stanford Junior University Molecular differences between species of the M. tuberculosis complex
US6271042B1 (en) * 1998-08-26 2001-08-07 Alpha Innotech Corporation Biochip detection system
AU757510C (en) * 1998-08-27 2003-09-11 Medimmune Limited Pyrrolobenzodiazepines
GB9818731D0 (en) * 1998-08-27 1998-10-21 Univ Portsmouth Compounds
GB9818730D0 (en) * 1998-08-27 1998-10-21 Univ Portsmouth Collections of compounds
GB9818732D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Collection of compounds
AU749884B2 (en) 1998-08-28 2002-07-04 Febit Ferrarius Biotechnology Gmbh Support for a method for determining an analyte and a method for producing the support
US6929912B2 (en) * 1998-08-31 2005-08-16 Genaissance Pharmaceuticals, Inc. Methods for evaluating the ability to metabolize pharmaceuticals
WO2000014197A1 (fr) * 1998-09-09 2000-03-16 Hitachi Software Engineering Co., Ltd. Biopuce et procede d'utilisation de la biopuce
US6461812B2 (en) * 1998-09-09 2002-10-08 Agilent Technologies, Inc. Method and multiple reservoir apparatus for fabrication of biomolecular arrays
EP1114184A2 (en) * 1998-09-15 2001-07-11 Yale University Molecular cloning using rolling circle amplification
US6255082B1 (en) 1998-09-15 2001-07-03 Yale University Artificial long terminal repeat vectors
US6475440B1 (en) 1998-09-16 2002-11-05 Clontech Laboratories, Inc. Applicator for use in deposition of fluid samples onto a substrate surface
US20070178475A1 (en) * 1998-09-17 2007-08-02 Nehls Michael C Novel human polynucleotides and polypeptides encoded thereby
US6821724B1 (en) 1998-09-17 2004-11-23 Affymetrix, Inc. Methods of genetic analysis using nucleic acid arrays
US6185561B1 (en) 1998-09-17 2001-02-06 Affymetrix, Inc. Method and apparatus for providing and expression data mining database
US20040199544A1 (en) * 2000-11-02 2004-10-07 Affymetrix, Inc. Method and apparatus for providing an expression data mining database
KR100369694B1 (ko) * 1998-09-17 2003-01-29 인터내셔널 비지네스 머신즈 코포레이션 화학적 태그의 합성 방법
US6146830A (en) 1998-09-23 2000-11-14 Rosetta Inpharmatics, Inc. Method for determining the presence of a number of primary targets of a drug
US20090119022A1 (en) * 1998-09-25 2009-05-07 Timberlake William E Emericella Nidulans Genome Sequence On Computer Readable Medium and Uses Thereof
US6703228B1 (en) 1998-09-25 2004-03-09 Massachusetts Institute Of Technology Methods and products related to genotyping and DNA analysis
EP1001037A3 (en) * 1998-09-28 2003-10-01 Whitehead Institute For Biomedical Research Pre-selection and isolation of single nucleotide polymorphisms
US6203989B1 (en) 1998-09-30 2001-03-20 Affymetrix, Inc. Methods and compositions for amplifying detectable signals in specific binding assays
US6682927B2 (en) * 1998-10-05 2004-01-27 Duke University Methods and apparatus for the high through-put detection of binding interactions in vivo
WO2000020859A1 (en) * 1998-10-05 2000-04-13 Duke University METHOD AND APPARATUS FOR DETECTING BINDING INTERACTIONS $i(IN VIVO)
US7071324B2 (en) * 1998-10-13 2006-07-04 Brown University Research Foundation Systems and methods for sequencing by hybridization
US6593084B2 (en) 1998-10-13 2003-07-15 Robert E. Bird Carcinogen assay
US6262216B1 (en) 1998-10-13 2001-07-17 Affymetrix, Inc. Functionalized silicon compounds and methods for their synthesis and use
US6489096B1 (en) * 1998-10-15 2002-12-03 Princeton University Quantitative analysis of hybridization patterns and intensities in oligonucleotide arrays
CA2347125A1 (en) * 1998-10-16 2000-04-27 Larry S. Millstein Methods of making patterned arrays of analyte-binding molecules
US7199809B1 (en) 1998-10-19 2007-04-03 Symyx Technologies, Inc. Graphic design of combinatorial material libraries
FR2784751B1 (fr) 1998-10-20 2001-02-02 Mesatronic Boitier de logement d'une puce electronique a sondes biologiques
WO2000023933A1 (en) * 1998-10-21 2000-04-27 Bios Group Lp Systems and methods for analysis of genetic networks
US7129043B1 (en) 1998-10-22 2006-10-31 Duke University Methods of screening for risk of proliferative disease and methods for the treatment of proliferative disease
US6667176B1 (en) 2000-01-11 2003-12-23 Geron Corporation cDNA libraries reflecting gene expression during growth and differentiation of human pluripotent stem cells
US6867289B1 (en) * 1998-10-26 2005-03-15 Board Of Regents, The University Of Texas Systems Thio-modified aptamer synthetic methods and compositions
US6203987B1 (en) 1998-10-27 2001-03-20 Rosetta Inpharmatics, Inc. Methods for using co-regulated genesets to enhance detection and classification of gene expression patterns
US6468476B1 (en) * 1998-10-27 2002-10-22 Rosetta Inpharmatics, Inc. Methods for using-co-regulated genesets to enhance detection and classification of gene expression patterns
FR2785052B1 (fr) * 1998-10-27 2000-12-01 Commissariat Energie Atomique Dispositif de determination de la concentration d'une substance melangee a un fluorophore et procede de mise en oeuvre de ce dispositif
US6950752B1 (en) 1998-10-27 2005-09-27 Rosetta Inpharmatics Llc Methods for removing artifact from biological profiles
IL126776A (en) 1998-10-27 2001-04-30 Technion Res & Dev Foundation A method of investing gold
AU6487899A (en) * 1998-10-30 2000-05-22 Takara Shuzo Co., Ltd. Method for detecting gene affected by endocrine disruptor
US6545264B1 (en) 1998-10-30 2003-04-08 Affymetrix, Inc. Systems and methods for high performance scanning
US6399299B1 (en) * 1998-11-02 2002-06-04 Perkinelmer Life Sciences, Inc. Amplified array analysis system
AU772243B2 (en) * 1998-11-04 2004-04-22 Genset Genomic and complete cDNA sequences of human adipocyte-specific APM1 and biallelic markers thereof
US6187540B1 (en) 1998-11-09 2001-02-13 Identigene, Inc. Method of newborn identification and tracking
US20110014706A2 (en) * 1998-12-14 2011-01-20 Monsanto Technology Llc Arabidopsis thaliana Genome Sequence and Uses Thereof
US7135283B1 (en) 1998-11-17 2006-11-14 Nanogen, Inc. Topoisomerase type II gene polymorphisms and their use in identifying drug resistance and pathogenic strains of microorganisms
US6309828B1 (en) 1998-11-18 2001-10-30 Agilent Technologies, Inc. Method and apparatus for fabricating replicate arrays of nucleic acid molecules
DE19853640C2 (de) * 1998-11-20 2002-01-31 Molecular Machines & Ind Gmbh Mehrgefäßanordnung mit verbesserter Empfindlichkeit für die optische Analytik, Verfahren zu ihrer Herstellung sowie ihre Verwendung in optischen Analyseverfahren
DE19854946C2 (de) 1998-11-27 2002-01-03 Guenter Von Kiedrowski Klonieren und Kopieren an Oberflächen
WO2000033084A2 (en) * 1998-12-01 2000-06-08 Syntrix Biochip, Inc. Arrays of organic compounds attached to surfaces
WO2000032678A1 (en) 1998-12-01 2000-06-08 Syntrix Biochip, Inc. Solvent resistant photosensitive compositions
US6951682B1 (en) * 1998-12-01 2005-10-04 Syntrix Biochip, Inc. Porous coatings bearing ligand arrays and use thereof
AU1742300A (en) * 1998-12-02 2000-06-19 Nanogen, Inc. Apparatus and methods for transport of charged biological materials
US6221579B1 (en) 1998-12-11 2001-04-24 Kimberly-Clark Worldwide, Inc. Patterned binding of functionalized microspheres for optical diffraction-based biosensors
US6245518B1 (en) 1998-12-11 2001-06-12 Hyseq, Inc. Polynucleotide arrays and methods of making and using the same
JP4471329B2 (ja) * 1998-12-14 2010-06-02 ドイチェス クレープスフォルシュングスツェントルム シュティフトゥング デス エッフェントリッヒェン レヒツ 分子ライブラリーをコンビナトリアル合成するための物質、とりわけモノマーを担体に付着させる方法と装置
US6579673B2 (en) 1998-12-17 2003-06-17 Kimberly-Clark Worldwide, Inc. Patterned deposition of antibody binding protein for optical diffraction-based biosensors
US20030032029A1 (en) * 1998-12-21 2003-02-13 Nanogen, Inc. Three dimensional apparatus and method for integrating sample preparation and multiplex assays
US6264891B1 (en) 1998-12-22 2001-07-24 Eos Biotechnology, Inc. Apparatus and method for concurrent chemical synthesis
US6453241B1 (en) 1998-12-23 2002-09-17 Rosetta Inpharmatics, Inc. Method and system for analyzing biological response signal data
DE19860547C1 (de) * 1998-12-23 2000-10-12 Genetrix B V I O Affinitätssensor für den Nachweis spezifischer molekularer Bindungsereignisse und dessen Verwendung
US6801859B1 (en) 1998-12-23 2004-10-05 Rosetta Inpharmatics Llc Methods of characterizing drug activities using consensus profiles
US6351712B1 (en) * 1998-12-28 2002-02-26 Rosetta Inpharmatics, Inc. Statistical combining of cell expression profiles
US7612020B2 (en) * 1998-12-28 2009-11-03 Illumina, Inc. Composite arrays utilizing microspheres with a hybridization chamber
US6429027B1 (en) 1998-12-28 2002-08-06 Illumina, Inc. Composite arrays utilizing microspheres
US6261431B1 (en) 1998-12-28 2001-07-17 Affymetrix, Inc. Process for microfabrication of an integrated PCR-CE device and products produced by the same
US6370478B1 (en) 1998-12-28 2002-04-09 Rosetta Inpharmatics, Inc. Methods for drug interaction prediction using biological response profiles
US6222093B1 (en) 1998-12-28 2001-04-24 Rosetta Inpharmatics, Inc. Methods for determining therapeutic index from gene expression profiles
US6087112A (en) 1998-12-30 2000-07-11 Oligos Etc. Inc. Arrays with modified oligonucleotide and polynucleotide compositions
US20030180789A1 (en) * 1998-12-30 2003-09-25 Dale Roderic M.K. Arrays with modified oligonucleotide and polynucleotide compositions
US20010034438A1 (en) * 2000-01-12 2001-10-25 Walke D. Wade Novel human membrane protein and polynucleotides encoding the same
US6570003B1 (en) * 2001-01-09 2003-05-27 Lexion Genetics Incorporated Human 7TM proteins and polynucleotides encoding the same
ATE277065T1 (de) 1999-01-05 2004-10-15 Bio Merieux Funktionalisierte verbindung, gegebenenfalls markierte polynukleotide und verfahren zur detektion einer ziel-nukleinsäure
JP4355384B2 (ja) 1999-01-14 2009-10-28 キヤノン株式会社 パターン露光方法、露光装置、核酸アレイの形成方法及びペプチドアレイの形成方法
US6312906B1 (en) 1999-01-15 2001-11-06 Imperial College Innovations, Ltd. Immobilized nucleic acid hybridization reagent and method
US6232068B1 (en) 1999-01-22 2001-05-15 Rosetta Inpharmatics, Inc. Monitoring of gene expression by detecting hybridization to nucleic acid arrays using anti-heteronucleic acid antibodies
EP1144677B1 (en) * 1999-01-25 2006-07-26 Micronas Holding GmbH Immobilization of molecules on surfaces via polymer brushes
US6320196B1 (en) 1999-01-28 2001-11-20 Agilent Technologies, Inc. Multichannel high dynamic range scanner
US6514768B1 (en) 1999-01-29 2003-02-04 Surmodics, Inc. Replicable probe array
US20030148360A1 (en) * 1999-01-29 2003-08-07 Surmodics, Inc. Replicable probe array
US20060234246A1 (en) * 1999-02-02 2006-10-19 Chiron Corporation Gene products differentially expressed in cancerous cells
US6429302B1 (en) 1999-02-02 2002-08-06 Chiron Corporation Polynucleotides related to pancreatic disease
US6605432B1 (en) * 1999-02-05 2003-08-12 Curators Of The University Of Missouri High-throughput methods for detecting DNA methylation
KR100497673B1 (ko) * 1999-02-10 2005-07-01 주식회사 마크로젠 광 변조기를 이용한 화학물질 라이브러리 제조 방법 및제조 장치
WO2000047598A1 (en) * 1999-02-10 2000-08-17 Macrogen Inc. Method and apparatus for compound library preparation using optical modulator
US6740875B1 (en) * 1999-02-11 2004-05-25 The Regents Of The University Of California Gamma watermarking
US6432719B1 (en) 1999-02-16 2002-08-13 Pe Corporation (Ny) Matrix storage and dispensing system
US7101510B2 (en) 1999-02-16 2006-09-05 Applera Corporation Matrix storage and dispensing system
AU762897B2 (en) * 1999-02-16 2003-07-10 Applera Corporation Bead dispensing system
US20030027214A1 (en) * 1999-02-17 2003-02-06 Kamb Carl Alexander Methods for substrate-ligand interaction screening
AU767606B2 (en) * 1999-02-19 2003-11-20 Synthetic Genomics, Inc. Method for producing polymers
US6142681A (en) 1999-02-22 2000-11-07 Vialogy Corporation Method and apparatus for interpreting hybridized bioelectronic DNA microarray patterns using self-scaling convergent reverberant dynamics
US20040111219A1 (en) * 1999-02-22 2004-06-10 Sandeep Gulati Active interferometric signal analysis in software
US6136541A (en) 1999-02-22 2000-10-24 Vialogy Corporation Method and apparatus for analyzing hybridized biochip patterns using resonance interactions employing quantum expressor functions
US6245511B1 (en) * 1999-02-22 2001-06-12 Vialogy Corp Method and apparatus for exponentially convergent therapy effectiveness monitoring using DNA microarray based viral load measurements
EP1586645A3 (en) * 1999-02-25 2006-02-22 Ceres Incorporated Sequence-determined DNA fragments and corresponding polypeptides encoded thereby
US6362907B1 (en) 1999-02-26 2002-03-26 Nec Research Institute, Inc. Apparatus and method for transmitting data between VLSI chips
AU5646800A (en) * 1999-03-02 2000-09-21 Helix Biopharma Corporation Card-based biosensor device
US6787368B1 (en) 1999-03-02 2004-09-07 Helix Biopharma Corporation Biosensor method for detecting analytes in a liquid
ATE431848T1 (de) 1999-03-05 2009-06-15 Mitsubishi Rayon Co Microarray mit einer biologischen substanz
US6716578B1 (en) 1999-03-08 2004-04-06 Bioforce Nanosciences, Inc. Method for solid state genome analysis
US7005256B1 (en) 1999-03-10 2006-02-28 Cold Spring Harbor Laboratory Gene chip technology for determining memory genes
CA2367925C (en) * 1999-03-11 2009-10-13 Combimatrix Corporation Self assembling arrays
US6296702B1 (en) 1999-03-15 2001-10-02 Pe Corporation (Ny) Apparatus and method for spotting a substrate
TW496775B (en) 1999-03-15 2002-08-01 Aviva Bioscience Corp Individually addressable micro-electromagnetic unit array chips
CN1185492C (zh) 1999-03-15 2005-01-19 清华大学 可单点选通式微电磁单元阵列芯片、电磁生物芯片及应用
CN1348396A (zh) * 1999-03-19 2002-05-08 金克克国际有限公司 用于高效筛选的多通孔测试板
US7014994B1 (en) 1999-03-19 2006-03-21 Cornell Research Foundation,Inc. Coupled polymerase chain reaction-restriction-endonuclease digestion-ligase detection reaction process
US6403309B1 (en) 1999-03-19 2002-06-11 Valigen (Us), Inc. Methods for detection of nucleic acid polymorphisms using peptide-labeled oligonucleotides and antibody arrays
US6506594B1 (en) 1999-03-19 2003-01-14 Cornell Res Foundation Inc Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays
WO2000056774A1 (en) * 1999-03-19 2000-09-28 Duke University Methods of using bioelastomers
US6764820B2 (en) 1999-03-26 2004-07-20 Ludwig Institute For Cancer Research Screening for lymphatic disorders involving the FLT4 receptor tyrosine kinase (VEGFR-3)
WO2000058511A1 (en) 1999-03-26 2000-10-05 Ludwig Institute For Cancer Research Screening and therapy for lymphatic disorders involving the flt4 receptor tyrosine kinase (vegfr-3)
AU4058500A (en) * 1999-03-30 2000-10-16 Nanogen, Inc. Single nucleotide polymorphic discrimination by electronic dot blot assay on semiconductor microchips
EP1041385A3 (en) * 1999-03-30 2004-01-02 Fuji Photo Film Co., Ltd. Method and apparatus for detecting an organism-originated substance
WO2000058521A2 (en) * 1999-03-31 2000-10-05 Rosetta Inpharmatics, Inc. Methods for the identification of reporter and target molecules using comprehensive gene expression profiles
US6582906B1 (en) 1999-04-05 2003-06-24 Affymetrix, Inc. Proportional amplification of nucleic acids
EP1196629A2 (en) 1999-04-07 2002-04-17 Dennis Michael Connolly High resolution dna detection methods and devices
US6824866B1 (en) * 1999-04-08 2004-11-30 Affymetrix, Inc. Porous silica substrates for polymer synthesis and assays
US20030133009A1 (en) * 1999-04-09 2003-07-17 Carl S Brown System and method for detecting with high resolution a large, high content field
EP1165832A2 (en) * 1999-04-09 2002-01-02 GPC Biotech AG Novel method for identifying antibacterial compounds
US6238868B1 (en) * 1999-04-12 2001-05-29 Nanogen/Becton Dickinson Partnership Multiplex amplification and separation of nucleic acid sequences using ligation-dependant strand displacement amplification and bioelectronic chip technology
US6531302B1 (en) * 1999-04-12 2003-03-11 Nanogen/Becton Dickinson Partnership Anchored strand displacement amplification on an electronically addressable microchip
EP1177423A4 (en) * 1999-04-12 2004-10-27 Nanogen Becton Dickinson Partn REINFORCEMENT AND SEPARATION OF NUCLEIC ACID SEQUENCES BY MEANS OF STRAND SHIFT REINFORCEMENT AND BIOELECTRONIC
US6326173B1 (en) * 1999-04-12 2001-12-04 Nanogen/Becton Dickinson Partnership Electronically mediated nucleic acid amplification in NASBA
US6235479B1 (en) 1999-04-13 2001-05-22 Bio Merieux, Inc. Methods and devices for performing analysis of a nucleic acid sample
DE19916867A1 (de) * 1999-04-14 2000-10-19 Fraunhofer Ges Forschung Anordnung und Verfahren zur Herstellung planarer Arrays mit immobilisierten Molekülen
US20030166015A1 (en) * 1999-04-15 2003-09-04 Zarowitz Michael A. Multiplexed analysis of cell-substrate interactions
KR20020026421A (ko) * 1999-04-15 2002-04-10 버츄얼 어레이즈 인코포레이티드 코딩 위치에 표시를 갖는 조합적인 화학 라이브러리지지체 및 이의 사용 방법
US20030207249A1 (en) * 1999-04-15 2003-11-06 Beske Oren E. Connection of cells to substrates using association pairs
US20030129654A1 (en) * 1999-04-15 2003-07-10 Ilya Ravkin Coded particles for multiplexed analysis of biological samples
US6908737B2 (en) * 1999-04-15 2005-06-21 Vitra Bioscience, Inc. Systems and methods of conducting multiplexed experiments
US20030134330A1 (en) * 1999-04-15 2003-07-17 Ilya Ravkin Chemical-library composition and method
US7253435B2 (en) 1999-04-15 2007-08-07 Millipore Corporation Particles with light-polarizing codes
US6171793B1 (en) 1999-04-19 2001-01-09 Affymetrix, Inc. Method for scanning gene probe array to produce data having dynamic range that exceeds that of scanner
US20060275782A1 (en) 1999-04-20 2006-12-07 Illumina, Inc. Detection of nucleic acid reactions on bead arrays
US20030207295A1 (en) * 1999-04-20 2003-11-06 Kevin Gunderson Detection of nucleic acid reactions on bead arrays
US20020177135A1 (en) * 1999-07-27 2002-11-28 Doung Hau H. Devices and methods for biochip multiplexing
US6174683B1 (en) 1999-04-26 2001-01-16 Biocept, Inc. Method of making biochips and the biochips resulting therefrom
US6518056B2 (en) * 1999-04-27 2003-02-11 Agilent Technologies Inc. Apparatus, systems and method for assaying biological materials using an annular format
DE19918956A1 (de) * 1999-04-27 2000-11-02 Studiengesellschaft Kohle Mbh Verfahren zur automatisierten Untersuchung katalytischer und spektroskopischer Eigenschaften der Komponenten kombinatorischer Bibliotheken
US6300137B1 (en) * 1999-04-28 2001-10-09 Agilent Technologies Inc. Method for synthesizing a specific, surface-bound polymer uniformly over an element of a molecular array
US20020110809A1 (en) * 1999-04-30 2002-08-15 Nehls Michael C. Novel human polynucleotides and polypeptides encoded thereby
US6395559B1 (en) * 1999-05-04 2002-05-28 Orchid Biosciences, Inc. Multiple fluid sample processor with single well addressability
US20020095031A1 (en) * 1999-05-04 2002-07-18 Nehls Michael C. Novel human polynucleotides and polypeptides encoded thereby
ATE442441T1 (de) * 1999-05-04 2009-09-15 Kentucky Bioproc Llc Virale expressionsvektoren für pflanzen
AU4698600A (en) * 1999-05-05 2000-11-17 Ut-Battelle, Llc Method and apparatus for combinatorial chemistry
DE19922941A1 (de) * 1999-05-14 2000-11-30 Epigenomics Gmbh Vorrichtung und Verfahren zur photolithographischen Belichtung von biologischen Stoffen
JP3957118B2 (ja) * 1999-05-18 2007-08-15 富士フイルム株式会社 試験片およびこの試験片からの画像情報読取装置
JP4598960B2 (ja) 1999-05-19 2010-12-15 エッペンドルフ アレイ テクノロジーズ エスアー （エーアーテー） 生物学的サンプルから得られた標的化合物のチップ上での同定及び／又は定量方法
US6638717B2 (en) 1999-05-19 2003-10-28 Aventis Pharmaceuticals, Inc. Microarray-based subtractive hybridzation
US20030096321A1 (en) * 1999-05-19 2003-05-22 Jose Remacle Method for the identification and/or the quantification of a target compound obtained from a biological sample upon chips
US6573369B2 (en) 1999-05-21 2003-06-03 Bioforce Nanosciences, Inc. Method and apparatus for solid state molecular analysis
CN1159454C (zh) * 1999-05-21 2004-07-28 陆祖宏 制备化合物微阵列芯片的方法及由该方法制备的化合物微阵列芯片
US20030073250A1 (en) * 1999-05-21 2003-04-17 Eric Henderson Method and apparatus for solid state molecular analysis
US20020042081A1 (en) * 2000-10-10 2002-04-11 Eric Henderson Evaluating binding affinities by force stratification and force panning
US6472141B2 (en) 1999-05-21 2002-10-29 Caliper Technologies Corp. Kinase assays using polycations
US6287774B1 (en) 1999-05-21 2001-09-11 Caliper Technologies Corp. Assay methods and system
US20030186311A1 (en) * 1999-05-21 2003-10-02 Bioforce Nanosciences, Inc. Parallel analysis of molecular interactions
CA2374515A1 (en) 1999-05-21 2000-11-30 Christian E. Gruber Compositions and methods for labeling of nucleic acid molecules
US6371370B2 (en) * 1999-05-24 2002-04-16 Agilent Technologies, Inc. Apparatus and method for scanning a surface
US6502039B1 (en) 2000-05-24 2002-12-31 Aventis Pharmaceuticals Mathematical analysis for the estimation of changes in the level of gene expression
ATE443295T1 (de) 1999-05-25 2009-10-15 Aventis Pharma Inc Mathematische analyse für die beurteilung von änderungen auf genexpressionsebene
US6485690B1 (en) 1999-05-27 2002-11-26 Orchid Biosciences, Inc. Multiple fluid sample processor and system
US6132686A (en) * 1999-05-28 2000-10-17 Mettler-Toledo Bohdan, Inc. Pressurized reaction block
JP2003501654A (ja) * 1999-06-05 2003-01-14 ツェプトゼンス アクチエンゲゼルシャフト 複数の分析対象物の測定のためのセンサプラットフォーム及び方法
KR20010001577A (ko) 1999-06-07 2001-01-05 윤종용 고분자 광산발생제를 이용한 올리고펩티드 핵산 탐침의 제조방법
US6660479B2 (en) 1999-06-07 2003-12-09 Samsung Electronics Co., Ltd. Process for preparing peptide nucleic acid probe using polymeric photoacid generator
US6716579B1 (en) 1999-06-11 2004-04-06 Narayan Baidya Gene specific arrays, preparation and use
US7485715B2 (en) * 1999-06-18 2009-02-03 Ceres, Inc. Sequence-determined DNA encoding AP2 domain polypeptides
WO2000079009A2 (en) 1999-06-22 2000-12-28 Invitrogen Corporation Improved primers and methods for the detection and discrimination of nucleic acids
US7501245B2 (en) 1999-06-28 2009-03-10 Helicos Biosciences Corp. Methods and apparatuses for analyzing polynucleotide sequences
KR100379411B1 (ko) 1999-06-28 2003-04-10 엘지전자 주식회사 바이오칩 및 그의 생체 물질 패터닝 및 측정 방법
US6818395B1 (en) 1999-06-28 2004-11-16 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences
US6399394B1 (en) 1999-06-30 2002-06-04 Agilent Technologies, Inc. Testing multiple fluid samples with multiple biopolymer arrays
US6258593B1 (en) 1999-06-30 2001-07-10 Agilent Technologies Inc. Apparatus for conducting chemical or biochemical reactions on a solid surface within an enclosed chamber
US6830902B1 (en) 1999-07-02 2004-12-14 Invitrogen Corporation Compositions and methods for enhanced sensitivity and specificity of nucleic acid synthesis
EP1208126B1 (en) 1999-07-02 2006-04-12 Symyx Technologies, Inc. Polymer brushes for immobilizing molecules to a surface or substrate, where the polymers have water-soluble or water-dispersible segments and probes bonded thereto
US6771376B2 (en) * 1999-07-05 2004-08-03 Novartis Ag Sensor platform, apparatus incorporating the platform, and process using the platform
ATE340996T1 (de) 1999-07-05 2006-10-15 Novartis Pharma Gmbh Verfahren zur anwendung einer sensoreinheit
US7223364B1 (en) 1999-07-07 2007-05-29 3M Innovative Properties Company Detection article having fluid control film
US6964847B1 (en) 1999-07-14 2005-11-15 Packard Biosciences Company Derivative nucleic acids and uses thereof
US7371516B1 (en) 1999-07-16 2008-05-13 Rosetta Inpharmatics Llc Methods for determining the specificity and sensitivity of oligonucleo tides for hybridization
US6346423B1 (en) 1999-07-16 2002-02-12 Agilent Technologies, Inc. Methods and compositions for producing biopolymeric arrays
US7013221B1 (en) 1999-07-16 2006-03-14 Rosetta Inpharmatics Llc Iterative probe design and detailed expression profiling with flexible in-situ synthesis arrays
US7479555B2 (en) * 1999-07-21 2009-01-20 Ceres, Inc. Polynucleotides having a nucleotide sequence that encodes a polypeptide having MOV34 family activity
US6692915B1 (en) 1999-07-22 2004-02-17 Girish N. Nallur Sequencing a polynucleotide on a generic chip
US7144700B1 (en) * 1999-07-23 2006-12-05 Affymetrix, Inc. Photolithographic solid-phase polymer synthesis
DE19935749C2 (de) * 1999-07-28 2003-06-26 Epigenomics Ag Verfahren zur Chrakterisierung von Nukleinsäurefragmenten
US6864050B2 (en) * 1999-07-30 2005-03-08 Affymetrix, Inc. Single-phase amplification of nucleic acids
EP1218545B1 (en) 1999-08-18 2012-01-25 Illumina, Inc. Methods for preparing oligonucleotide solutions
US6909006B1 (en) 1999-08-27 2005-06-21 Spirogen Limited Cyclopropylindole derivatives
US6942968B1 (en) 1999-08-30 2005-09-13 Illumina, Inc. Array compositions for improved signal detection
US7169553B1 (en) 1999-08-30 2007-01-30 Roche Diagnostics, Gmbh 2-Azapurine compounds and their use
US20050118618A1 (en) * 1999-08-30 2005-06-02 Dale Roderic M. Method for detecting nucleic acid sequences
CA2317179A1 (en) * 1999-09-01 2001-03-01 Affymetrix, Inc. Macromolecular arrays on polymeric brushes and methods for preparing the same
US20050153323A1 (en) * 2000-07-28 2005-07-14 Yi Hu Novel human proteases and polynucleotides encoding the same
US20080003673A1 (en) * 1999-09-02 2008-01-03 Alejandro Abuin Novel human proteases and polynucleotides encoding the same
US6395483B1 (en) 1999-09-02 2002-05-28 3M Innovative Properties Company Arrays with mask layers
US6716614B1 (en) 1999-09-02 2004-04-06 Lexicon Genetics Incorporated Human calcium dependent proteases, polynucleotides encoding the same, and uses thereof
US6448388B1 (en) 2000-08-16 2002-09-10 Lexicon Genetics Incorporated Human proteases and polynucleotides encoding the same
US20030050464A1 (en) * 2000-07-28 2003-03-13 Yi Hu Novel human proteases and polynucleotides encoding the same
US20020049312A1 (en) * 2000-05-23 2002-04-25 Turner C. Alexander Noel human thrombospondin-like proteins and polynucleotides encoding the same
US6358557B1 (en) * 1999-09-10 2002-03-19 Sts Biopolymers, Inc. Graft polymerization of substrate surfaces
KR100858465B1 (ko) 1999-09-10 2008-09-16 제론 코포레이션 올리고뉴클레오티드 엔3'→피5' 티오포스포라미데이트,이의 합성 및 용도
US6692918B2 (en) 1999-09-13 2004-02-17 Nugen Technologies, Inc. Methods and compositions for linear isothermal amplification of polynucleotide sequences
FR2798392B1 (fr) * 1999-09-13 2005-07-15 Exonhit Therapeutics Sa Marqueurs genetiques de la toxicite, preparation et utilisations
FR2798673B1 (fr) * 1999-09-16 2004-05-28 Exonhit Therapeutics Sa Methodes et compositions pour la detection d'evenements pathologiques
US6274320B1 (en) 1999-09-16 2001-08-14 Curagen Corporation Method of sequencing a nucleic acid
US6319674B1 (en) 1999-09-16 2001-11-20 Agilent Technologies, Inc. Methods for attaching substances to surfaces
US7244559B2 (en) * 1999-09-16 2007-07-17 454 Life Sciences Corporation Method of sequencing a nucleic acid
US6743585B2 (en) 1999-09-16 2004-06-01 Agilent Technologies, Inc. Methods for preparing conjugates
US7211390B2 (en) 1999-09-16 2007-05-01 454 Life Sciences Corporation Method of sequencing a nucleic acid
US20020006664A1 (en) * 1999-09-17 2002-01-17 Sabatini David M. Arrayed transfection method and uses related thereto
US7078167B2 (en) * 1999-09-17 2006-07-18 Agilent Technologies, Inc. Arrays having background features and methods for using the same
WO2001020015A1 (en) 1999-09-17 2001-03-22 Whitehead Institute For Biomedical Research Reverse transfection method
US7122303B2 (en) 1999-09-17 2006-10-17 Agilent Technologies, Inc. Arrays comprising background features that provide for a measure of a non-specific binding and methods for using the same
US6867291B1 (en) * 2000-09-15 2005-03-15 Lexicon Genetics Incorporated Human hemicentin proteins and polynucleotides encoding the same
US6790660B1 (en) * 2001-09-18 2004-09-14 Lexicon Genetics Incorporated Human kielin-like proteins and polynucleotides encoding the same
US6511840B1 (en) 2000-06-15 2003-01-28 Lexicon Genetics Incorporated Human kinase proteins and polynucleotides encoding the same
US20080050809A1 (en) * 1999-09-28 2008-02-28 Alejandro Abuin Novel human kinases and polynucleotides encoding the same
US6797510B1 (en) * 2001-05-24 2004-09-28 Lexicon Genetics Incorporated Human kinases and polynucleotides encoding the same
US6841377B1 (en) 2001-06-13 2005-01-11 Lexicon Genetics Incorporated Human kinase and polynucleotides encoding the same
US6541252B1 (en) 2000-05-19 2003-04-01 Lexicon Genetics Incorporated Human kinases and polynucleotides encoding the same
US6586230B1 (en) * 2000-10-27 2003-07-01 Lexicon Genetics Incorporated Human kinase and polynucleotides encoding the same
US6759527B2 (en) 2001-03-20 2004-07-06 Lexicon Genetics Incorporated Human kinase and polynucleotides encoding the same
US6844151B1 (en) 1999-09-29 2005-01-18 Oligos Etc. Inc. Methods for production of arrays with modified oligonucleotide and polynucleotide compositions
US6673536B1 (en) 1999-09-29 2004-01-06 Rosetta Inpharmatics Llc. Methods of ranking oligonucleotides for specificity using wash dissociation histories
JP5181157B2 (ja) * 1999-09-30 2013-04-10 ハミダ・フォー・ライフ・ベスローテン・フェンノートシャップ マイクロエレクトロニックアレイ上の生体分子付着部位
WO2001023426A2 (en) * 1999-09-30 2001-04-05 Varian Associates, Inc. Hypoxia-related human genes, proteins, and uses thereof
US7217573B1 (en) 1999-10-05 2007-05-15 Hitachi, Ltd. Method of inspecting a DNA chip
AU1075701A (en) 1999-10-08 2001-04-23 Protogene Laboratories, Inc. Method and apparatus for performing large numbers of reactions using array assembly
US20080213878A1 (en) * 1999-10-19 2008-09-04 Gregory Donoho Novel human membrane proteins and polynucleotides encoding the same
US6171797B1 (en) 1999-10-20 2001-01-09 Agilent Technologies Inc. Methods of making polymeric arrays
US7364920B2 (en) * 1999-10-27 2008-04-29 Technion Research And Development Foundation Ltd. Method for gold deposition
EP2357582A1 (en) 1999-10-27 2011-08-17 Health Discovery Corporation Methods and devices for identifying patterns in biological systems
US6958225B2 (en) 1999-10-27 2005-10-25 Affymetrix, Inc. Complexity management of genomic DNA
KR100339379B1 (ko) 1999-10-29 2002-06-03 구자홍 바이오칩과 그의 생체 물질 측정장치 및 측정방법
US6689319B1 (en) 1999-10-29 2004-02-10 Agilent Technologies, Ind. Apparatus for deposition and inspection of chemical and biological fluids
US8153367B2 (en) * 1999-10-29 2012-04-10 Perkinelmer Las, Inc. Amplified array analysis system
US6329210B1 (en) * 1999-10-29 2001-12-11 Agilent Technologies, Inc. Method and apparatus for high volume polymer synthesis
EP1230397A2 (en) * 1999-11-02 2002-08-14 Celine Hu Molecular microarrays and methods for production and use thereof
US7167615B1 (en) 1999-11-05 2007-01-23 Board Of Regents, The University Of Texas System Resonant waveguide-grating filters and sensors and methods for making and using same
US6569674B1 (en) 1999-12-15 2003-05-27 Amersham Biosciences Ab Method and apparatus for performing biological reactions on a substrate surface
US6642046B1 (en) 1999-12-09 2003-11-04 Motorola, Inc. Method and apparatus for performing biological reactions on a substrate surface
US6589778B1 (en) 1999-12-15 2003-07-08 Amersham Biosciences Ab Method and apparatus for performing biological reactions on a substrate surface
US7041445B2 (en) 1999-11-15 2006-05-09 Clontech Laboratories, Inc. Long oligonucleotide arrays
WO2001036442A1 (en) * 1999-11-17 2001-05-25 Jiuping Ji Simultaneous detection of hbv, hcv and hiv in plasma samples using a multiplex capture assay
US6583399B1 (en) 1999-11-22 2003-06-24 California Institute Of Technology Optical resonator microsphere sensor with altering Q-factor
US6446642B1 (en) * 1999-11-22 2002-09-10 Agilent Technologies, Inc. Method and apparatus to clean an inkjet reagent deposition device
EP1235939A2 (en) 1999-11-24 2002-09-04 Incyte Genomics, Inc. Normalization controls and duplex probes for quantitative hybridization reactions
US6423535B1 (en) 1999-11-24 2002-07-23 Incyte Genomics, Inc. Normalization control for hybridization reactions
WO2001038585A2 (en) * 1999-11-24 2001-05-31 The Regents Of The University Of California Polymer arrays and methods of using labeled probe molecules to identify and quantify target molecule expression
US6703480B1 (en) * 1999-11-24 2004-03-09 Palani Balu Peptide dimers as agonists of the erythropoientin (EPO) receptor, and associated methods of synthesis and use
EP1234026B1 (en) 1999-11-30 2011-08-17 Cyntellect, Inc. Method and apparatus for selectively targeting specific cells within a cell population
GB9928787D0 (en) * 1999-12-03 2000-02-02 Medical Res Council Direct screening method
GB9928789D0 (en) * 1999-12-03 2000-02-02 Medical Res Council Naive screening method
JP2004504005A (ja) * 1999-12-07 2004-02-12 レキシコン・ジェネティクス・インコーポレーテッド ヒト新規キナーゼタンパクおよびそれをコードするポリヌクレオチド
AU2070701A (en) * 1999-12-07 2001-06-18 Lexicon Genetics Incorporated Novel human membrane proteins and polynucleotides encoding the same
WO2001042786A2 (en) 1999-12-09 2001-06-14 Cellomics, Inc. System for cell based screening : cell spreading
AU784486B2 (en) 1999-12-09 2006-04-13 Lexicon Genetics Incorporated Novel human proteases and polynucleotides encoding the same
US6482638B1 (en) * 1999-12-09 2002-11-19 3M Innovative Properties Company Heat-relaxable substrates and arrays
CN1757724B (zh) 1999-12-10 2014-06-11 茵维特罗根公司 具有独特特异性的多个重组位点在重组克隆中的用途
WO2001042477A1 (en) * 1999-12-13 2001-06-14 Lexicon Genetics Incorporated Novel human transferase proteins and polynucleotides encoding the same
US6303082B1 (en) * 1999-12-15 2001-10-16 Nanogen, Inc. Permeation layer attachment chemistry and method
US7109299B1 (en) 1999-12-16 2006-09-19 Affymax, Inc. Peptides and compounds that bind to the IL-5 receptor
US6902891B2 (en) 1999-12-17 2005-06-07 Bio Merieux Process for labeling a nucleic acid
US20020197656A1 (en) * 1999-12-17 2002-12-26 Ronghao Li Cell arrays and the uses thereof
US6489114B2 (en) 1999-12-17 2002-12-03 Bio Merieux Process for labeling a ribonucleic acid, and labeled RNA fragments which are obtained thereby
US6406840B1 (en) 1999-12-17 2002-06-18 Biomosaic Systems, Inc. Cell arrays and the uses thereof
US6399295B1 (en) 1999-12-17 2002-06-04 Kimberly-Clark Worldwide, Inc. Use of wicking agent to eliminate wash steps for optical diffraction-based biosensors
US6670124B1 (en) 1999-12-20 2003-12-30 Stemcyte, Inc. High throughput methods of HLA typing
WO2001046417A2 (en) * 1999-12-22 2001-06-28 Lexicon Genetics Incorporated Human membrane proteins and polynucleotides encoding the same having homology to cd20 proteins and ige receptors
WO2001046407A1 (en) * 1999-12-22 2001-06-28 Lexicon Genetics Incorporated Polynucleotides encoding human protease homologs
DE19962803A1 (de) * 1999-12-23 2001-07-05 Basf Ag Verfahren und Vorrichtung zur maskenfreien Herstellung von Biopolymeren
US6929907B2 (en) 1999-12-31 2005-08-16 North Carolina State University Methods and compositions for determining the purity of chemically synthesized nucleic acids
CA2402360A1 (en) * 2000-01-06 2001-07-12 Lexicon Genetics Incorporated Novel human proteases and polynucleotides encoding the same
US6800439B1 (en) 2000-01-06 2004-10-05 Affymetrix, Inc. Methods for improved array preparation
US20050089923A9 (en) * 2000-01-07 2005-04-28 Levinson Douglas A. Method and system for planning, performing, and assessing high-throughput screening of multicomponent chemical compositions and solid forms of compounds
US20070020662A1 (en) * 2000-01-07 2007-01-25 Transform Pharmaceuticals, Inc. Computerized control of high-throughput experimental processing and digital analysis of comparative samples for a compound of interest
US20050118637A9 (en) * 2000-01-07 2005-06-02 Levinson Douglas A. Method and system for planning, performing, and assessing high-throughput screening of multicomponent chemical compositions and solid forms of compounds
US7108970B2 (en) * 2000-01-07 2006-09-19 Transform Pharmaceuticals, Inc. Rapid identification of conditions, compounds, or compositions that inhibit, prevent, induce, modify, or reverse transitions of physical state
KR20020071931A (ko) * 2000-01-07 2002-09-13 트렌스폼 파마수티컬스 인코퍼레이티드 다양한 고체-형태들의 고도의 자료 처리 편성, 확인 및분석
US20050095696A9 (en) * 2000-01-07 2005-05-05 Lemmo Anthony V. Apparatus and method for high-throughput preparation and characterization of compositions
US20070021929A1 (en) * 2000-01-07 2007-01-25 Transform Pharmaceuticals, Inc. Computing methods for control of high-throughput experimental processing, digital analysis, and re-arraying comparative samples in computer-designed arrays
US6977723B2 (en) * 2000-01-07 2005-12-20 Transform Pharmaceuticals, Inc. Apparatus and method for high-throughput preparation and spectroscopic classification and characterization of compositions
DE10000629C5 (de) * 2000-01-10 2010-06-02 november Aktiengesellschaft, Gesellschaft für Molekulare Medizin Verfahren zur Identifizierung einer auf einen festen Körper aufgebrachten Markierung
AU784540B2 (en) 2000-01-18 2006-04-27 Lexicon Pharmaceuticals, Inc. Novel human kinase protein and polynucleotides encoding the same
WO2003074738A1 (en) * 2000-01-18 2003-09-12 Quantom Dot Corporation Oligonucleotide-tagged semiconductor nanocrystals for microarray and fluorescence in situ hybridization
EP1254222A1 (en) * 2000-01-18 2002-11-06 Lexicon Genetics Incorporated Human gaba receptor proteins and polynucleotides encoding the same
US6728641B1 (en) 2000-01-21 2004-04-27 General Electric Company Method and system for selecting a best case set of factors for a chemical reaction
US7429466B2 (en) * 2000-01-24 2008-09-30 Hypromatrix, Inc Methods and arrays for detecting biological molecules
US8143195B2 (en) * 2000-01-24 2012-03-27 Yingjian Wang Arrays for bringing two or more reagents in contact with one or more biological targets and methods for making and using the arrays
US20030097222A1 (en) * 2000-01-25 2003-05-22 Craford David M. Method, system, and computer software for providing a genomic web portal
DE60118703T2 (de) * 2000-01-26 2006-12-14 Lexicon Genetics Inc., The Woodlands Menschliche neurexin-ähnliche proteine und dafür kodierende polynukleotide
EP1301600A2 (en) * 2000-01-28 2003-04-16 Lexicon Genetics Incorporated Human enzymes and polynucleotides encoding the same
US6618679B2 (en) 2000-01-28 2003-09-09 Althea Technologies, Inc. Methods for analysis of gene expression
CA2398791A1 (en) * 2000-01-28 2001-08-02 Lexicon Genetics Incorporated Human membrane proteins and polynucleotides encoding the same
US6489466B2 (en) 2000-01-28 2002-12-03 Linden Technologies, Inc. C-3′ protected monomeric nucleotides and synthesis of oligonucleotides on solid support
GB0002389D0 (en) * 2000-02-02 2000-03-22 Solexa Ltd Molecular arrays
US6625546B2 (en) * 2000-02-03 2003-09-23 Nanoscale Combinatorial Synthesis, Inc. Structure identification methods using mass measurements
ATE366315T1 (de) * 2000-02-04 2007-07-15 Lexicon Genetics Inc Menschliche enzyme und dafür kodierende polynukleotide
WO2001057086A2 (en) * 2000-02-04 2001-08-09 Lexicon Genetics Incorporated Novel human g protein coupled receptor proteins and polynucleotides encoding the same
US7955794B2 (en) 2000-09-21 2011-06-07 Illumina, Inc. Multiplex nucleic acid reactions
US20020006617A1 (en) * 2000-02-07 2002-01-17 Jian-Bing Fan Nucleic acid detection methods using universal priming
US8076063B2 (en) 2000-02-07 2011-12-13 Illumina, Inc. Multiplexed methylation detection methods
US7582420B2 (en) * 2001-07-12 2009-09-01 Illumina, Inc. Multiplex nucleic acid reactions
US20050214825A1 (en) * 2000-02-07 2005-09-29 John Stuelpnagel Multiplex sample analysis on universal arrays
US7611869B2 (en) 2000-02-07 2009-11-03 Illumina, Inc. Multiplexed methylation detection methods
US6770441B2 (en) * 2000-02-10 2004-08-03 Illumina, Inc. Array compositions and methods of making same
US6693033B2 (en) 2000-02-10 2004-02-17 Motorola, Inc. Method of removing an amorphous oxide from a monocrystalline surface
AU3690801A (en) 2000-02-11 2001-08-20 Lexicon Genetics Incorporated Human proteases and polynucleotides encoding the same
US20030176385A1 (en) * 2000-02-15 2003-09-18 Jingfang Ju Antisense modulation of protein expression
AU2001238503A1 (en) * 2000-02-17 2001-08-27 Lexicon Genetics Incorporated Novel human thrombospondin repeat proteins and polynucleotides encoding the same
US20030165987A1 (en) * 2000-02-18 2003-09-04 Aspira Biosystems, Inc. Compositions and methods for surface imprinting
US20020151040A1 (en) * 2000-02-18 2002-10-17 Matthew O' Keefe Apparatus and methods for parallel processing of microvolume liquid reactions
AU2001238606A1 (en) 2000-02-18 2001-08-27 Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for parallel processing of micro-volume liquid reactions
AU6291301A (en) 2000-02-22 2001-09-03 Genospectra, Inc. Microarray fabrication techniques and apparatus
US20040014102A1 (en) * 2000-02-22 2004-01-22 Shiping Chen High density parallel printing of microarrays
CN1404415A (zh) * 2000-02-22 2003-03-19 基因谱公司 微阵列制造技术及设备
US6515131B2 (en) 2000-02-22 2003-02-04 Biostream Therapeutics, Inc. Imagining agents for diagnosis of Parkinson's disease
CA2401118A1 (en) 2000-02-23 2001-08-30 Zyomyx, Inc. Microfluidic devices and methods
WO2001064903A2 (en) 2000-02-29 2001-09-07 Lexicon Genetics Incorporated Novel human transferase proteins and polynucleotides encoding the same
JP2003531582A (ja) * 2000-02-29 2003-10-28 レキシコン・ジェネティクス・インコーポレーテッド ヒトトランスポータータンパクおよびそれをコードするポリヌクレオチド
US6627571B1 (en) 2000-03-01 2003-09-30 Symyx Technologies, Inc. Method and system for the situ synthesis of a combinatorial library of supported catalyst materials
US20030129724A1 (en) 2000-03-03 2003-07-10 Grozinger Christina M. Class II human histone deacetylases, and uses related thereto
WO2001067369A2 (en) * 2000-03-03 2001-09-13 California Institute Of Technology Combinatorial array for nucleic acid analysis
US20020082405A1 (en) * 2000-03-06 2002-06-27 Gregory Donoho Novel human transporter proteins and polynucleotides encoding the same
DE10011022A1 (de) * 2000-03-07 2001-09-27 Meinhard Knoll Vorrichtung und Verfahren zur Durchführung von Synthesen, Analysen oder Transportvorgängen
US6897015B2 (en) * 2000-03-07 2005-05-24 Bioforce Nanosciences, Inc. Device and method of use for detection and characterization of pathogens and biological materials
AU4352101A (en) 2000-03-10 2001-09-24 Lexicon Genetics Inc Novel human g-coupled protein receptor kinases and polynucleotides encoding the same
JP2004500107A (ja) * 2000-03-13 2004-01-08 レキシコン・ジェネティクス・インコーポレーテッド 新規ヒトホスホリパーゼおよびそれをコードするポリヌクレオチド
US6489160B2 (en) 2000-03-16 2002-12-03 Kabushiki Kaisha Toshiba Method for producing nucleic acid strand immobilized carrier
US20050119473A1 (en) * 2000-03-17 2005-06-02 Affymetrix, Inc. Phosphite ester oxidation in nucleic acid array preparation
US6806361B1 (en) 2000-03-17 2004-10-19 Affymetrix, Inc. Methods of enhancing functional performance of nucleic acid arrays
US6833450B1 (en) 2000-03-17 2004-12-21 Affymetrix, Inc. Phosphite ester oxidation in nucleic acid array preparation
WO2001070806A2 (en) * 2000-03-20 2001-09-27 Lexicon Genetics Incorporated Human secreted proteins and polynucleotides encoding the same
US6413722B1 (en) 2000-03-22 2002-07-02 Incyte Genomics, Inc. Polymer coated surfaces for microarray applications
EP2365096A1 (en) 2000-03-22 2011-09-14 Life Technologies Corporation Methods of using semiconductor nanocrystals in bead-based nucleic acid assays
US7244572B1 (en) 2000-03-24 2007-07-17 Wisys Technology Foundation, Inc. One-dimensional arrays on optical fibers
US7202026B2 (en) * 2000-03-24 2007-04-10 Eppendorf Array Technologies Sa (Eat) Identification of a large number of biological (micro)organisms groups at different levels by their detection on a same array
US7205104B2 (en) 2000-03-24 2007-04-17 Eppendorf Array Technologies Sa (Eat) Identification of biological (micro) organisms by detection of their homologous nucleotide sequences on arrays
US7875442B2 (en) * 2000-03-24 2011-01-25 Eppendorf Array Technologies Identification and quantification of a plurality of biological (micro)organisms or their components
US7829313B2 (en) * 2000-03-24 2010-11-09 Eppendorf Array Technologies Identification and quantification of a plurality of biological (micro)organisms or their components
US20080085515A1 (en) * 2000-03-24 2008-04-10 Eppendorf Array Technologies Sa (Eat) Identification of multiple biological (micro) organisms by detection of their nucleotide sequences on arrays
CA2404431C (en) 2000-03-27 2011-06-07 Thomas Jefferson University Guanylyl cyclase c in the detection of stomach and esophageal cancers
EP1276702A2 (en) * 2000-03-31 2003-01-22 Genentech, Inc. Compositions and methods for detecting and quantifying gene expression
US6884578B2 (en) * 2000-03-31 2005-04-26 Affymetrix, Inc. Genes differentially expressed in secretory versus proliferative endometrium
US6767736B2 (en) 2000-04-03 2004-07-27 Lexicon Genetics Incorporated Human ion channel protein and polynucleotides encoding the same
US7157564B1 (en) 2000-04-06 2007-01-02 Affymetrix, Inc. Tag nucleic acids and probe arrays
GB0008563D0 (en) * 2000-04-07 2000-05-24 Cambridge Discovery Chemistry Investigating different physical and/or chemical forms of materials
CA2405729A1 (en) * 2000-04-12 2001-10-25 Lexicon Genetics Incorporated Human metalloprotease and polynucleotides encoding the same
US7455965B2 (en) 2000-04-14 2008-11-25 Cornell Research Foundation, Inc. Method of designing addressable array for detection of nucleic acid sequence differences using ligase detection reaction
JP2003530130A (ja) 2000-04-14 2003-10-14 メタボロン インコーポレイテッド メタボロミクスを使用した薬物発見、疾患の処置、及び診断のための方法
WO2001079821A1 (de) * 2000-04-14 2001-10-25 Zeptosens Ag Gitter-wellenleiter-struktur zur verstärkung eines anregungsfeldes und deren verwendung
US6983233B1 (en) 2000-04-19 2006-01-03 Symyx Technologies, Inc. Combinatorial parameter space experiment design
US6667287B2 (en) * 2000-04-20 2003-12-23 Colgate-Palmolive Company Light duty cleaning composition comprising an amine oxide and polyacrylic acid homopolymer
AU5719501A (en) 2000-04-25 2001-11-07 Lexicon Genetics Inc Novel human kinase proteins and polynucleotides encoding the same
US6458589B1 (en) 2000-04-27 2002-10-01 Geron Corporation Hepatocyte lineage cells derived from pluripotent stem cells
CA2406063A1 (en) 2000-05-03 2001-11-08 Caliper Technologies Corporation Multi depth substrate fabrication processes
CA2408291C (en) 2000-05-04 2014-07-15 Yale University High density protein arrays for screening of protein activity
US6690467B1 (en) 2000-05-05 2004-02-10 Pe Corporation Optical system and method for optically analyzing light from a sample
AU2001247853A1 (en) * 2000-05-08 2001-11-20 General Electric Company High throughput screening method and system
US7019129B1 (en) 2000-05-09 2006-03-28 Biosearch Technologies, Inc. Dark quenchers for donor-acceptor energy transfer
US6709840B1 (en) 2000-05-11 2004-03-23 The Board Of Trustees Of The Leland Stanford Junior University Anergy associated genes
US20020110843A1 (en) * 2000-05-12 2002-08-15 Dumas David P. Compositions and methods for epitope mapping
EP1280909A2 (en) * 2000-05-12 2003-02-05 Lexicon Genetics Incorporated Human lipocalin homologs and polynucleotides encoding the same
US6492458B1 (en) 2000-05-16 2002-12-10 Arizona Chemical Company Polyalkyleneoxydiamine polyamides useful for formulating inks for phase-change jet printing
WO2001088133A2 (en) 2000-05-18 2001-11-22 Lexicon Genetics Incorporated Human semaphorin homologs and polynucleotides encoding the same
US6656700B2 (en) 2000-05-26 2003-12-02 Amersham Plc Isoforms of human pregnancy-associated protein-E
US6686188B2 (en) * 2000-05-26 2004-02-03 Amersham Plc Polynucleotide encoding a human myosin-like polypeptide expressed predominantly in heart and muscle
US6790667B1 (en) * 2000-05-30 2004-09-14 Lexicon Genetics Incorporated Human mitochondrial proteins and polynucleotides encoding the same
US20020155471A1 (en) * 2000-05-31 2002-10-24 Nicolette Charles A. Compounds for therapy and diagnosis and methods for using same
US7005259B1 (en) * 2000-06-01 2006-02-28 Affymetrix, Inc. Methods for array preparation using substrate rotation
JP4644914B2 (ja) * 2000-06-02 2011-03-09 株式会社村田製作所 プローブアレイ用固相基材、およびプローブアレイ
US6994827B2 (en) 2000-06-03 2006-02-07 Symyx Technologies, Inc. Parallel semicontinuous or continuous reactors
US7351376B1 (en) 2000-06-05 2008-04-01 California Institute Of Technology Integrated active flux microfluidic devices and methods
AU2001275337A1 (en) * 2000-06-07 2001-12-17 Lexicon Genetics Incorporated Novel human transporter proteins and polynucleotides encoding the same
EP1162450A1 (en) * 2000-06-07 2001-12-12 F. Hoffmann-La Roche Ag Reference device for evaluating the performance of a confocal laser scanning microscope, and a method and system for performing that evaluation
US20040168209A1 (en) * 2000-06-12 2004-08-26 Alejandro Abuin Novel murine polynucleotide sequences and mutant cells and mutant animals defined thereby
EP1373561B1 (en) 2000-06-13 2009-02-18 The Trustees of Boston University Use of mass-matched nucleotides in the analysis of oligonucleotide mixtures and in highly multiplexed nucleic acid sequencing
US6455007B1 (en) * 2000-06-13 2002-09-24 Symyx Technologies, Inc. Apparatus and method for testing compositions in contact with a porous medium
EP1164201A1 (en) * 2000-06-14 2001-12-19 Facultés Universitaires Notre-Dame de la Paix Reverse detection for identification and/or quantification of nucleotide target sequences on biochips
US20060166227A1 (en) * 2000-06-20 2006-07-27 Stephen Kingsmore Protein expression profiling
US9709559B2 (en) 2000-06-21 2017-07-18 Bioarray Solutions, Ltd. Multianalyte molecular analysis using application-specific random particle arrays
US7892854B2 (en) 2000-06-21 2011-02-22 Bioarray Solutions, Ltd. Multianalyte molecular analysis using application-specific random particle arrays
EP1356094B1 (en) * 2000-06-26 2010-01-13 Nugen Technologies, Inc. Methods and compositions for transcription-based nucleic acid amplification
US7846733B2 (en) * 2000-06-26 2010-12-07 Nugen Technologies, Inc. Methods and compositions for transcription-based nucleic acid amplification
AU7151601A (en) * 2000-06-27 2002-01-08 Lexicon Genetics Inc Novel human gaba receptors and polynucleotides encoding the same
US6323009B1 (en) * 2000-06-28 2001-11-27 Molecular Staging, Inc. Multiply-primed amplification of nucleic acid sequences
DE10031587A1 (de) * 2000-06-29 2002-01-10 Basf Ag Dosierung von Suspensionen im Mikromaßstab zur Herstellung von Materialproben in der kombinatorischen Materialforschung sowie deren Prüfung
US20020012616A1 (en) * 2000-07-03 2002-01-31 Xiaochuan Zhou Fluidic methods and devices for parallel chemical reactions
US20030118486A1 (en) * 2000-07-03 2003-06-26 Xeotron Corporation Fluidic methods and devices for parallel chemical reactions
AU2001271720A1 (en) 2000-07-05 2002-01-14 Rosetta Inpharmatics, Inc. Methods and compositions for determining gene function
US20030219816A1 (en) * 2001-07-02 2003-11-27 Keith Solomon Composite microarray slides
AU2001271893A1 (en) * 2000-07-07 2002-01-21 Nimblegen Systems, Inc. Method and apparatus for synthesis of arrays of dna probes
US6913879B1 (en) 2000-07-10 2005-07-05 Telechem International Inc. Microarray method of genotyping multiple samples at multiple LOCI
US6511277B1 (en) * 2000-07-10 2003-01-28 Affymetrix, Inc. Cartridge loader and methods
US6380377B1 (en) 2000-07-14 2002-04-30 Applied Gene Technologies, Inc. Nucleic acid hairpin probes and uses thereof
US6596490B2 (en) * 2000-07-14 2003-07-22 Applied Gene Technologies, Inc. Nucleic acid hairpin probes and uses thereof
US7052659B1 (en) * 2000-07-18 2006-05-30 General Electric Company Sequential high throughput screening method and system
JP2004515220A (ja) * 2000-07-21 2004-05-27 インサイト・ゲノミックス・インコーポレイテッド プロテアーゼ
WO2002008453A2 (en) * 2000-07-21 2002-01-31 Phase-1 Molecular Toxicology Canine toxicity genes
US6590236B1 (en) 2000-07-24 2003-07-08 Motorola, Inc. Semiconductor structure for use with high-frequency signals
US6555946B1 (en) 2000-07-24 2003-04-29 Motorola, Inc. Acoustic wave device and process for forming the same
US6887685B1 (en) * 2000-07-25 2005-05-03 Lexicon Genetics Incorporated Human thymosin protein and polynucleotides encoding the same
DE10036174B4 (de) * 2000-07-25 2006-12-07 Axaron Bioscience Ag Verfahren und Vorrichtung zum Analysieren von chemischen oder biologischen Proben
DE10036457A1 (de) * 2000-07-26 2002-02-14 Giesing Michael Verwendung eines bildgebenden photoelektrischen Flächensensors zur Auswertung von Biochips und Bildgebungsverfahren hierfür
WO2002010750A2 (en) * 2000-07-31 2002-02-07 Maxygen, Inc. Biosensors, reagents and diagnostic applications of directed evolution
US6984522B2 (en) 2000-08-03 2006-01-10 Regents Of The University Of Michigan Isolation and use of solid tumor stem cells
US20050181421A1 (en) * 2000-08-03 2005-08-18 Affymetrix, Inc. Methods of array synthesis
EP1307469B1 (en) * 2000-08-03 2008-01-23 Boehringer Mannheim Gmbh Nucleic acid binding compounds containing pyrazolo¬3,4-d pyrimidine analogues of purin-2,6-diamine and their uses
WO2002052250A2 (en) 2000-08-03 2002-07-04 Perlegen Sciences Substrate scanning apparatus
US8463718B2 (en) * 2000-08-07 2013-06-11 Health Discovery Corporation Support vector machine-based method for analysis of spectral data
US6422249B1 (en) 2000-08-10 2002-07-23 Affymetrix Inc. Cartridge washing system and methods
US7476523B2 (en) 2000-08-14 2009-01-13 Surface Logix, Inc. Method of patterning a surface using a deformable stamp
ATE402760T1 (de) * 2000-08-15 2008-08-15 Bioforce Nanosciences Inc Vorrichtung zur bildung von nanomolekularen netzwerken
US6902702B1 (en) 2000-08-16 2005-06-07 University Health Network Devices and methods for producing microarrays of biological samples
US20050106621A1 (en) * 2000-08-16 2005-05-19 Winegarden Neil A. Devices and methods for producing microarrays of biological samples
US20020076780A1 (en) * 2000-08-16 2002-06-20 Turner C. Alexander Novel human ion channel proteins and polynucleotides encoding the same
US6680059B2 (en) * 2000-08-29 2004-01-20 Tripep Ab Vaccines containing ribavirin and methods of use thereof
AU9215101A (en) 2000-08-17 2002-02-25 Tripep Ab Vaccines containing ribavirin and methods of use thereof
US6858590B2 (en) * 2000-08-17 2005-02-22 Tripep Ab Vaccines containing ribavirin and methods of use thereof
US7022830B2 (en) * 2000-08-17 2006-04-04 Tripep Ab Hepatitis C virus codon optimized non-structural NS3/4A fusion gene
US7198924B2 (en) 2000-12-11 2007-04-03 Invitrogen Corporation Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites
ATE334208T1 (de) * 2000-08-22 2006-08-15 Lexicon Genetics Inc Menschliche proteasen und für diese kodierende polynukleotide
US6789040B2 (en) 2000-08-22 2004-09-07 Affymetrix, Inc. System, method, and computer software product for specifying a scanning area of a substrate
JP2004506447A (ja) * 2000-08-22 2004-03-04 レキシコン・ジェネティクス・インコーポレーテッド 新規ヒト７ｔｍタンパクおよびそれをコードするポリヌクレオチド
EP1573634A2 (en) 2000-08-22 2005-09-14 Affymetrix, Inc. System method, and computer software product for controlling biological microarray scanner
US6900013B1 (en) 2000-08-25 2005-05-31 Aviva Biosciences Corporation Methods and compositions for identifying nucleic acid molecules using nucleolytic activities and hybridization
EP1387894A4 (en) * 2000-08-24 2006-10-11 Aviva Biosciences Corp METHODS AND COMPOSITIONS FOR IDENTIFYING NUCLEIC ACID MOLECULES USING NUCLEOLYTIC ACTIVITIES AND HYBRIDIZATION
US6713257B2 (en) 2000-08-25 2004-03-30 Rosetta Inpharmatics Llc Gene discovery using microarrays
US7807447B1 (en) 2000-08-25 2010-10-05 Merck Sharp & Dohme Corp. Compositions and methods for exon profiling
US20020164634A1 (en) * 2000-08-26 2002-11-07 Perlegen Sciences, Inc. Methods for reducing complexity of nucleic acid samples
US20020055112A1 (en) * 2000-08-26 2002-05-09 Nila Patil Methods for reducing complexity of nucleic acid samples
US20030190612A1 (en) * 2000-08-31 2003-10-09 Nobuko Yamamoto Detecting method and detection substrate for use therein
AU2001285326A1 (en) * 2000-08-31 2002-03-13 Lexicon Genetics Incorporated Human kinase proteins and polynucleotides encoding the same
JP3467004B2 (ja) * 2000-08-31 2003-11-17 キヤノン株式会社 核酸の塩基配列の解析方法
JP2002071687A (ja) * 2000-08-31 2002-03-12 Canon Inc 変異遺伝子のスクリーニング方法
US7229790B2 (en) * 2000-09-01 2007-06-12 Lexicon Pharmaceuticals, Inc. Human GABA transporter protein and polynucleotides encoding the same
DE50115363D1 (de) * 2000-09-04 2010-04-08 Bayer Technology Services Gmbh System und verfahren zur multianalytbestimmung
US7108969B1 (en) 2000-09-08 2006-09-19 Affymetrix, Inc. Methods for detecting and diagnosing oral cancer
CA2421732A1 (en) * 2000-09-11 2002-03-14 Affymetrix, Inc. Photocleavable protecting groups
US20030176344A1 (en) * 2000-09-14 2003-09-18 Decode Genetics Ehf. Human osteoporosis gene
US20040185464A1 (en) * 2000-09-15 2004-09-23 Kris Richard M. High throughput assay system
US7057704B2 (en) * 2000-09-17 2006-06-06 Bioarray Solutions Ltd. System and method for programmable illumination pattern generation
US7829276B2 (en) * 2000-09-18 2010-11-09 Thomas Jefferson University Methods of using CRCA-1 as a stomach and esophageal cancer marker
WO2002024061A2 (en) 2000-09-20 2002-03-28 Case Western Reserve University Phyisological profiling
US6420178B1 (en) 2000-09-20 2002-07-16 General Electric Company High throughput screening method, array assembly and system
US6780648B1 (en) 2000-09-20 2004-08-24 General Electric Company Method and system for selectively distributing luminescence material precursors
AU2001292959A1 (en) * 2000-09-22 2002-04-02 Clontech Laboratories, Inc. Highly sensitive proteomic analysis methods and kits and systems for practicing the same
US20030077590A1 (en) * 2000-09-22 2003-04-24 Pedersen Finn Skou Methods for diagnosis and treatment of diseases associated with altered expression of neurogranin
US20020115058A1 (en) * 2000-09-22 2002-08-22 Pedersen Finn Skou Methods for diagnosis and treatment of diseases associated with altered expression of Pik3r1
US20030044803A1 (en) * 2000-09-22 2003-03-06 Pedersen Finn Skou Methods for diagnosis and treatment of diseases associated with altered expression of JAK1
US6806051B2 (en) * 2000-09-25 2004-10-19 Picoliter Inc. Arrays of partially nonhybridizing oligonucleotides and preparation thereof using focused acoustic energy
US20020037359A1 (en) 2000-09-25 2002-03-28 Mutz Mitchell W. Focused acoustic energy in the preparation of peptide arrays
US6613285B1 (en) 2000-09-25 2003-09-02 General Electric Company Reactor plate and method
US6808934B2 (en) 2000-09-25 2004-10-26 Picoliter Inc. High-throughput biomolecular crystallization and biomolecular crystal screening
JP4624644B2 (ja) 2000-09-25 2011-02-02 ピコリター インコーポレイテッド 複数のリザブワーからの流体の音響出射
US6493497B1 (en) 2000-09-26 2002-12-10 Motorola, Inc. Electro-optic structure and process for fabricating same
DE60119757T2 (de) 2000-09-27 2007-04-26 Lexicon Genetics Inc., The Woodlands Menschliche ionenaustauschproteine und dafür kodierende polynukleotiden
US6780584B1 (en) * 2000-09-27 2004-08-24 Nanogen, Inc. Electronic systems and component devices for macroscopic and microscopic molecular biological reactions, analyses and diagnostics
AU2001293084A1 (en) * 2000-09-27 2002-04-08 Lexicon Genetics Incorporated Human protease inhibitor proteins and polynucleotides encoding the same
US6496250B1 (en) 2000-09-29 2002-12-17 General Electric Company Combinatorial method foe development of optical ceramics
CN100495030C (zh) * 2000-09-30 2009-06-03 清华大学 多力操纵装置及其应用
US6777232B1 (en) * 2000-10-02 2004-08-17 Lexicon Genetics Incorporated Human membrane proteins and polynucleotides encoding the same
US6638838B1 (en) 2000-10-02 2003-10-28 Motorola, Inc. Semiconductor structure including a partially annealed layer and method of forming the same
US20020123474A1 (en) * 2000-10-04 2002-09-05 Shannon Mark E. Human GTP-Rho binding protein2
US20040091602A1 (en) * 2000-10-04 2004-05-13 Hwang Hyun Jin Method for immobilizing biologically active molecules
US20100261159A1 (en) * 2000-10-10 2010-10-14 Robert Hess Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof
WO2002031129A2 (en) 2000-10-12 2002-04-18 Lexicon Genetics Incorporated Human kinases and polynucleotides encoding the same
US6849409B2 (en) * 2000-10-16 2005-02-01 Axxima Pharmaceuticals Ag Cellular kinases involved in Cytomegalovirus infection and their inhibition
DE10051396A1 (de) 2000-10-17 2002-04-18 Febit Ferrarius Biotech Gmbh Verfahren und Vorrichtung zur integrierten Synthese und Analytbestimmung an einem Träger
US20030045005A1 (en) * 2000-10-17 2003-03-06 Michael Seul Light-controlled electrokinetic assembly of particles near surfaces
US7001763B1 (en) 2000-10-17 2006-02-21 Lexicon Genetics Incorporated Human semaphorin proteins and polynucleotides encoding the same
JP2004537712A (ja) * 2000-10-18 2004-12-16 バーチャル・アレイズ・インコーポレーテッド 多重細胞分析システム
WO2002033068A1 (fr) * 2000-10-18 2002-04-25 Canon Kabushiki Kaisha Procede d'analyse d'une sequence de base d'acide nucleique
CN1481441A (zh) * 2000-10-20 2004-03-10 斯坦福大学受托管理委员会 根据瞬时电信号表征样品中分子间相互作用和运动的方法和设备
US6861214B1 (en) 2000-10-23 2005-03-01 Beckman Coulter, Inc. Immobilization of biopolymers to aminated substrates by direct adsorption
US6804385B2 (en) 2000-10-24 2004-10-12 Oncosis Method and device for selectively targeting cells within a three-dimensional specimen
US6491967B1 (en) 2000-10-24 2002-12-10 General Electric Company Plasma spray high throughput screening method and system
DE10052823B4 (de) * 2000-10-24 2014-11-20 Ruprecht-Karls-Universität Heidelberg Verfahren zur lichtmikroskopischen Analyse der Topologie molekularer Strukturen in Rasteranordnungen
US7118908B2 (en) * 2000-10-25 2006-10-10 Bor-Iuan Jan On-spot selectively activated hydrophobic slide and preparation thereof
EP1203945B1 (en) * 2000-10-26 2006-12-20 Agilent Technologies, Inc. (a Delaware corporation) Microarray
WO2002070705A2 (en) * 2000-10-27 2002-09-12 Lexicon Genetics Incorporated Human 7tm proteins and polynucleotides encoding them
JP4015946B2 (ja) 2000-10-30 2007-11-28 シークエノム・インコーポレーテツド 基板上にサブマイクロリットルの体積を供給する方法及び装置
EP1330524A2 (en) * 2000-10-30 2003-07-30 Lexicon Genetics Incorporated Novel human 7tm proteins and polynucleotides encoding the same
EP1390477B1 (en) * 2000-11-01 2006-08-16 Lexicon Genetics Incorporated Polynucleotides encoding human meltrin beta (adam19) metalloendopeptidases
US6567751B1 (en) 2000-11-03 2003-05-20 General Electric Company Methods and computer system for combinatorial analysis of lighting phosphors
US7033821B2 (en) * 2000-11-08 2006-04-25 Surface Logix, Inc. Device for monitoring cell motility in real-time
US7374906B2 (en) 2000-11-08 2008-05-20 Surface Logix, Inc. Biological assays using gradients formed in microfluidic systems
US6844184B2 (en) * 2000-11-08 2005-01-18 Surface Logix, Inc. Device for arraying biomolecules and for monitoring cell motility in real-time
US6699665B1 (en) 2000-11-08 2004-03-02 Surface Logix, Inc. Multiple array system for integrating bioarrays
US6967074B2 (en) * 2000-11-08 2005-11-22 Surface Logix, Inc. Methods of detecting immobilized biomolecules
US6864065B2 (en) * 2000-11-08 2005-03-08 Surface Logix, Inc. Assays for monitoring cell motility in real-time
US7351575B2 (en) * 2000-11-08 2008-04-01 Surface Logix, Inc. Methods for processing biological materials using peelable and resealable devices
US7371563B2 (en) * 2000-11-08 2008-05-13 Surface Logix, Inc. Peelable and resealable devices for biochemical assays
US6893851B2 (en) 2000-11-08 2005-05-17 Surface Logix, Inc. Method for arraying biomolecules and for monitoring cell motility in real-time
US7439056B2 (en) 2000-11-08 2008-10-21 Surface Logix Inc. Peelable and resealable devices for arraying materials
US7001740B2 (en) * 2000-11-08 2006-02-21 Surface Logix, Inc. Methods of arraying biological materials using peelable and resealable devices
US6803205B2 (en) * 2000-11-08 2004-10-12 Surface Logix, Inc. Methods of measuring enzyme activity using peelable and resealable devices
EP1410044A2 (en) * 2000-11-08 2004-04-21 Burstein Technologies, Inc. Interactive system for analyzing biological samples and processing related information and the use thereof
US7033819B2 (en) 2000-11-08 2006-04-25 Surface Logix, Inc. System for monitoring cell motility in real-time
US7326563B2 (en) 2000-11-08 2008-02-05 Surface Logix, Inc. Device and method for monitoring leukocyte migration
US20020150887A1 (en) * 2000-11-09 2002-10-17 National Institute Of Advanced Industrial Science And Technology Methods and nucleic acid probes for molecular genetic analysis of polluted environments and environmental samples
US7061594B2 (en) * 2000-11-09 2006-06-13 Burstein Technologies, Inc. Disc drive system and methods for use with bio-discs
WO2002050278A2 (en) * 2000-11-15 2002-06-27 Lexicon Genetics Incorporated Novel human secreted proteins and polynucleotides encoding the same
WO2002040874A1 (en) 2000-11-16 2002-05-23 California Institute Of Technology Apparatus and methods for conducting assays and high throughput screening
WO2002044695A1 (en) * 2000-11-16 2002-06-06 Burstein Technologies, Inc. Methods and apparatus for detecting and quantifying lymphocytes with optical biodiscs
US7087203B2 (en) * 2000-11-17 2006-08-08 Nagaoka & Co., Ltd. Methods and apparatus for blood typing with optical bio-disc
US7026131B2 (en) * 2000-11-17 2006-04-11 Nagaoka & Co., Ltd. Methods and apparatus for blood typing with optical bio-discs
AU2002228633A1 (en) 2000-11-20 2002-06-03 Lexicon Genetics Incorporated Human kinases and polynucleotides encoding the same
US6905816B2 (en) * 2000-11-27 2005-06-14 Intelligent Medical Devices, Inc. Clinically intelligent diagnostic devices and methods
WO2002044425A2 (en) * 2000-12-01 2002-06-06 Visigen Biotechnologies, Inc. Enzymatic nucleic acid synthesis: compositions and methods for altering monomer incorporation fidelity
EP2336368A1 (en) 2000-12-07 2011-06-22 Novartis Vaccines and Diagnostics, Inc. Endogenous retroviruses up-regulated in prostate cancer
US7635571B2 (en) * 2000-12-07 2009-12-22 Siemens Healthcare Diagnostics Products Gmbh Amplified signal in binding assays
WO2002046762A2 (en) * 2000-12-08 2002-06-13 Burstein Technologies, Inc. Optical disc assemblies for performing assays
JP3778041B2 (ja) * 2000-12-08 2006-05-24 コニカミノルタホールディングス株式会社 粒子分離機構及び粒子分離装置
US6760298B2 (en) * 2000-12-08 2004-07-06 Nagaoka & Co., Ltd. Multiple data layer optical discs for detecting analytes
EP1341906A2 (en) * 2000-12-11 2003-09-10 Lexicon Genetics Incorporated Novel human kinase and polynucleotides encoding the same
US6596239B2 (en) * 2000-12-12 2003-07-22 Edc Biosystems, Inc. Acoustically mediated fluid transfer methods and uses thereof
WO2002048333A2 (en) * 2000-12-12 2002-06-20 Lexicon Genetics Incorporated Novel human kinases and uses thereof
CA2430329A1 (en) * 2000-12-13 2002-06-20 Nugen Technologies, Inc. Methods and compositions for generation of multiple copies of nucleic acid sequences and methods of detection thereof
WO2002048841A2 (en) * 2000-12-15 2002-06-20 Symyx Technologies, Inc. Methods and apparatus for designing high-dimensional combinatorial experiments
US6583269B1 (en) 2000-12-18 2003-06-24 Lexicon Genetics Incorporated Human protease inhibitor and polynucleotides encoding the same
US6448387B1 (en) * 2000-12-18 2002-09-10 Monsanto Technology, Llc Polymeric arrays adapted for high expressing polynucleotides
CA2432737A1 (en) * 2000-12-20 2002-06-27 Lexicon Genetics Incorporated Human ion channel protein and polynucleotides encoding the same
US6852844B1 (en) * 2000-12-20 2005-02-08 Lexicon Genetics Incorporated Human protocadherin proteins and polynucleotides encoding the same
US20030232334A1 (en) * 2000-12-22 2003-12-18 Morris David W. Novel compositions and methods for cancer
US20030099963A1 (en) * 2000-12-22 2003-05-29 Morris David W. Novel compositions and methods in cancer associated with altered expression of TBX21
US7645441B2 (en) 2000-12-22 2010-01-12 Sagres Discovery Inc. Compositions and methods in cancer associated with altered expression of PRLR
US7700274B2 (en) * 2000-12-22 2010-04-20 Sagres Discovery, Inc. Compositions and methods in cancer associated with altered expression of KCNJ9
US7820447B2 (en) 2000-12-22 2010-10-26 Sagres Discovery Inc. Compositions and methods for cancer
US20030087252A1 (en) * 2000-12-22 2003-05-08 Morris David W. Novel compositions and methods in cancer associated with altered expression of PRDM11
US7892730B2 (en) 2000-12-22 2011-02-22 Sagres Discovery, Inc. Compositions and methods for cancer
US20030165878A1 (en) * 2000-12-22 2003-09-04 Morris David W. Novel compositions and methods in cancer associated with altered expression of MCM3AP
WO2002052045A1 (en) * 2000-12-26 2002-07-04 Aviva Biosciences Active and biocompatible platforms prepared by polymerization of surface coating films
AU2002246858A1 (en) 2000-12-27 2002-08-06 Lexicon Genetics Incorporated Human kinases and polynucleotides encoding the same
WO2002053753A2 (en) * 2001-01-05 2002-07-11 Lexicon Genetics Incorporated Novel human lipase and polynucleotides encoding the same
AU2002236717A1 (en) * 2001-01-08 2002-07-16 Lexicon Genetics Incorporated Human protease and polynucleotides encoding the same
WO2003106964A2 (en) * 2001-01-10 2003-12-24 Dermal Systems International Inc. High throughput methods and devices for assaying analytes in a fluid sample
AU2002246978A1 (en) * 2001-01-10 2002-07-24 Symyx Technologies, Inc. Polymer brushes for immobilizing molecules to a surface
WO2002056311A2 (en) * 2001-01-11 2002-07-18 Burstein Technologies Inc Optical disc analysis system including related methods for biological and medical imaging
WO2002056057A2 (en) * 2001-01-12 2002-07-18 Nutec Sciences, Inc. Dotted micro-array data extraction method
KR100860291B1 (ko) * 2001-01-19 2008-09-25 에게아 바이오사이언시스, 인크. 표적 폴리펩티드를 암호화하는 폴리뉴클레오티드의 컴퓨터지시된 어셈블리
CA2434139C (en) * 2001-01-23 2014-05-27 President And Fellows Of Harvard College Nucleic-acid programmable protein arrays
EP1407029A2 (en) * 2001-01-23 2004-04-14 Lexicon Genetics Incorporated Novel human kinases and polynucleotides encoding the same
US6870011B2 (en) * 2001-01-24 2005-03-22 Arizona Chemical Company Hydrocarbon-terminated polyether-polyamide block copolymers and uses thereof
US6399713B1 (en) 2001-01-24 2002-06-04 Arizona Chemical Company Hydrocarbon-terminated polyether-polyamide block copolymers and uses thereof
US20090226915A1 (en) 2001-01-24 2009-09-10 Health Discovery Corporation Methods for Screening, Predicting and Monitoring Prostate Cancer
WO2002059328A1 (en) * 2001-01-24 2002-08-01 Lexicon Genetics Incorporated Human lipase and polynucleotides encoding the same
US20020169562A1 (en) * 2001-01-29 2002-11-14 Gregory Stephanopoulos Defining biological states and related genes, proteins and patterns
GB0102357D0 (en) * 2001-01-30 2001-03-14 Randox Lab Ltd Imaging method
US20030170148A1 (en) * 2001-01-31 2003-09-11 Mcentee John F. Reaction chamber roll pump
US7112305B2 (en) 2001-01-31 2006-09-26 Agilent Technologies, Inc. Automation-optimized microarray package
US7166258B2 (en) * 2001-01-31 2007-01-23 Agilent Technologies, Inc. Automation-optimized microarray package
US7442370B2 (en) 2001-02-01 2008-10-28 Biogen Idec Ma Inc. Polymer conjugates of mutated neublastin
WO2002063002A2 (en) * 2001-02-02 2002-08-15 Lexicon Genetics Incorporated Novel human transporter protein and polynucleotides encoding the same
AU2002255515A1 (en) * 2001-02-05 2002-08-19 Board Of Regents, The University Of Texas System The use of mesoscale self-assembly and recognition to effect delivery of sensing reagent for arrayed sensors
KR20030071854A (ko) * 2001-02-06 2003-09-06 다카라 바이오 가부시키가이샤 증폭 핵산 및 그의 고정화물
NZ527679A (en) * 2001-02-07 2005-07-29 Invitrogen Corp Nucleic acid Ter-(termination sequence) sites and Ter-binding proteins or RTPs in vitro and in vivo or combinations thereof
US6832163B2 (en) * 2001-02-09 2004-12-14 Agilent Technologies, Inc. Methods of identifying heterogeneous features in an image of an array
WO2002066624A2 (en) * 2001-02-20 2002-08-29 Lexicon Genetics Incorporated Novel human protease and polynucleotides encoding the same
US20020160527A1 (en) 2001-02-26 2002-10-31 3M Innovative Properties Company Combinatorial library comprising pouches as packages for library members and method therefor
US6673646B2 (en) 2001-02-28 2004-01-06 Motorola, Inc. Growth of compound semiconductor structures on patterned oxide films and process for fabricating same
CA2710031A1 (en) 2001-03-02 2002-09-12 University Of Western Ontario Polymer precursors of radiolabeled compounds, and methods of making and using the same
EP1364212B1 (en) 2001-03-02 2011-02-02 GPC Biotech AG Three hybrid assay system
EP1236804A1 (en) 2001-03-02 2002-09-04 Boehringer Mannheim Gmbh A method for determination of a nucleic acid using a control
US20050196785A1 (en) * 2001-03-05 2005-09-08 California Institute Of Technology Combinational array for nucleic acid analysis
JP3929250B2 (ja) * 2001-03-08 2007-06-13 株式会社ルネサステクノロジ 半導体装置
GB0105787D0 (en) * 2001-03-08 2001-04-25 Expresson Biosystems Ltd Complex element micro-array and methods of use
ATE361996T1 (de) * 2001-03-09 2007-06-15 Nugen Technologies Inc Methoden und zusammensetzungen zur vervielfältigung von rna sequenzen
EP1390537B1 (en) 2001-03-09 2013-11-13 Nugen Technologies, Inc. Methods and compositions for amplification of rna sequences
ES2593683T3 (es) * 2001-03-09 2016-12-12 Trovagene, Inc. Sondas conjugadas y detección óptica de analitos
CA2440754A1 (en) 2001-03-12 2002-09-19 Stephen Quake Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension
US20040076954A1 (en) * 2001-03-12 2004-04-22 Irm, Llc Genomics-driven high speed cellular assays, development thereof, and collections of cellular reporters
US7276580B2 (en) * 2001-03-12 2007-10-02 Biogen Idec Ma Inc. Neurotrophic factors
WO2002072774A2 (en) * 2001-03-12 2002-09-19 Lexicon Genetics Incorporated Novel human transporter proteins and polynucleotides encoding the same
US7252990B2 (en) * 2001-03-12 2007-08-07 Lexicon Genetics Incorporated Human dectin proteins and polynucleotides encoding the same
AU2002258502A1 (en) * 2001-03-12 2002-09-24 Affymetrix, Inc. Nucleic acid labeling compounds
AU2002306696B2 (en) * 2001-03-12 2007-12-20 Lexicon Pharmaceuticals, Inc. Novel human EGF-family proteins and polynucleotides encoding the same
AU2002254212A1 (en) * 2001-03-12 2002-09-24 Irm, Llc Identification of cellular targets for biologically active molecules
WO2002073673A1 (en) 2001-03-13 2002-09-19 Rochester Institute Of Technology A micro-electro-mechanical switch and a method of using and making thereof
US7211654B2 (en) 2001-03-14 2007-05-01 Regents Of The University Of Michigan Linkers and co-coupling agents for optimization of oligonucleotide synthesis and purification on solid supports
US20030104410A1 (en) * 2001-03-16 2003-06-05 Affymetrix, Inc. Human microarray
US6994995B1 (en) 2001-03-16 2006-02-07 Lexicon Genetics Incorporated Human synaptotagmin and polynucleotides encoding the same
US20030148295A1 (en) * 2001-03-20 2003-08-07 Wan Jackson Shek-Lam Expression profiles and methods of use
FR2822476B1 (fr) 2001-03-23 2004-04-02 Aventis Pharma Sa Procedes de purification et de detection de sequences cibles d'adn double brin par interaction triple helice
US7419958B2 (en) 2001-03-26 2008-09-02 Dana-Farber Cancer Institute, Inc. Method of attenuating reactions to skin irritants
US20020136772A1 (en) * 2001-03-26 2002-09-26 Tai-Nang Huang Polymer synthesis
US20040013573A1 (en) * 2001-03-26 2004-01-22 Tai-Nang Huang Polymer synthesis apparatus
US7115726B2 (en) * 2001-03-30 2006-10-03 Perlegen Sciences, Inc. Haplotype structures of chromosome 21
US6596489B2 (en) 2001-03-30 2003-07-22 Applied Gene Technologies Methods and compositions for analyzing nucleotide sequence mismatches using RNase H
AU785425B2 (en) * 2001-03-30 2007-05-17 Genetic Technologies Limited Methods of genomic analysis
US20040052489A1 (en) * 2001-04-02 2004-03-18 Duveneck Gert Ludwig Optical structure for multi-photon excitation and the use thereof
US7514263B2 (en) 2001-04-02 2009-04-07 3M Innovative Properties Company Continuous process for the production of combinatorial libraries of materials
US6960437B2 (en) 2001-04-06 2005-11-01 California Institute Of Technology Nucleic acid amplification utilizing microfluidic devices
JP2004528841A (ja) 2001-04-06 2004-09-24 レキシコン・ジェネティクス・インコーポレーテッド 新規ヒトキナーゼおよびそれをコードするポリヌクレオチド
EP1383879A4 (en) 2001-04-06 2005-05-11 Lexicon Genetics Inc HUMAN KINASES AND POLYNUCLEOTIDES ENCODING SAME
WO2002081086A1 (en) * 2001-04-09 2002-10-17 Dumas David P Transparent polymer support for organic synthesis
US20060129329A1 (en) * 2001-04-09 2006-06-15 Kobylecki Ryszard J Investigating different physical and/or chemical forms of materials
JP3885511B2 (ja) * 2001-04-11 2007-02-21 ソニー株式会社 レーザー光発生装置及び方法
US6644173B2 (en) * 2001-04-11 2003-11-11 Keuring, Incorporated Beverage filter cartridge holder
EP1493014A2 (en) 2001-04-11 2005-01-05 Burstein Technologies, Inc. Multi-parameter assays including analysis discs and methods relating thereto
US6607895B2 (en) 2001-04-16 2003-08-19 Lexicon Genetics Incorporated Human adenylsuccinate synthetase and polynucleotides encoding the same
EP1390526A4 (en) 2001-04-18 2005-02-02 Perlegen Sciences Inc METHOD FOR IDENTIFYING THE EVOLUTIONARY PRESERVED SEQUENCES
WO2002086095A2 (en) * 2001-04-23 2002-10-31 Chou Michael F Transcription factor network discovery methods
US6650411B2 (en) 2001-04-26 2003-11-18 Affymetrix, Inc. System, method, and product for pixel clocking in scanning of biological materials
US6643015B2 (en) 2001-04-26 2003-11-04 Affymetrix, Inc. System, method, and product for symmetrical filtering in scanning of biological materials
US6490533B2 (en) * 2001-04-26 2002-12-03 Affymetrix, Inc. System, method, and product for dynamic noise reduction in scanning of biological materials
US20020160427A1 (en) * 2001-04-27 2002-10-31 Febit Ag Methods and apparatuses for electronic determination of analytes
AU2002259011A1 (en) * 2001-04-30 2002-11-11 Lexicon Genetics Incorporated Novel human nuclear transporters and polynucleotides encoding the same
ES2400448T3 (es) * 2001-04-30 2013-04-10 Ventana Medical Systems, Inc. Reactivos y métodos para la hibridación automatizada in situ o para microarray
JP2004537986A (ja) * 2001-05-09 2004-12-24 レキシコン・ジェネティクス・インコーポレーテッド 新規キナーゼおよびそれをコードするポリヌクレオチド
US7244853B2 (en) 2001-05-09 2007-07-17 President And Fellows Of Harvard College Dioxanes and uses thereof
US7138506B2 (en) * 2001-05-09 2006-11-21 Genetic Id, Na, Inc. Universal microarray system
US20030119015A1 (en) * 2001-05-10 2003-06-26 Perlegen Sciences, Inc. Methods for nucleic acid analysis
US7695919B2 (en) * 2001-05-10 2010-04-13 Battelle Energy Alliance, Llc Antibody profiling sensitivity through increased reporter antibody layering
US6989276B2 (en) * 2001-05-10 2006-01-24 Battelle Energy Alliance, Llc Rapid classification of biological components
USRE46351E1 (en) 2001-05-10 2017-03-28 Battelle Energy Alliance, Llc Antibody profiling sensitivity through increased reporter antibody layering
USRE44031E1 (en) 2001-05-10 2013-02-26 Battelle Energy Alliance, Llc Antibody profiling sensitivity through increased reporter antibody layering
US6552160B2 (en) 2001-05-14 2003-04-22 Arizona Chemical Company Ester-terminated poly(ester-amides) useful for formulating transparent gels in low polarity fluids
US7183116B2 (en) 2001-05-14 2007-02-27 The Institute For Systems Biology Methods for isolation and labeling of sample molecules
AU2002368023A1 (en) * 2001-05-16 2004-03-04 Burstein Technologies, Inc. Variable sampling for rendering pixelization of analysis results in optical bio-disc assembly
US20080220441A1 (en) 2001-05-16 2008-09-11 Birnbaum Eva R Advanced drug development and manufacturing
US9157875B2 (en) * 2001-05-16 2015-10-13 Benjamin P. Warner Drug development and manufacturing
US7858385B2 (en) * 2001-05-16 2010-12-28 Los Alamos National Security, Llc Method for detecting binding events using micro-X-ray fluorescence spectrometry
US20050009101A1 (en) * 2001-05-17 2005-01-13 Motorola, Inc. Microfluidic devices comprising biochannels
US7083920B2 (en) * 2001-05-18 2006-08-01 Nagaoka & Co. Ltd. Surface assembly for immobilizing DNA capture probes in genetic assays using enzymatic reactions to generate signal in optical bio-discs and methods relating thereto
TW490783B (en) * 2001-05-22 2002-06-11 Hi Max Optoelectronics Corp Testing device and method built in the wafer scribe line
AU2002339853A1 (en) * 2001-05-24 2002-12-03 Genospectra, Inc. Pairs of nucleic acid probes with interactive signaling moieties and nucleic acid probes with enhanced hybridization efficiency and specificity
AU2002303827A1 (en) * 2001-05-25 2002-12-09 Invitrogen Corporation Compositions and methods for extension of nucleic acids
WO2002097095A1 (en) * 2001-05-25 2002-12-05 Lexicon Genetics Incorporated Novel human transporter proteins and polynucleotides encoding the same
US20070015144A9 (en) * 2001-05-25 2007-01-18 Genset, S.A. Human cDNAs and proteins and uses thereof
AU2002303879B2 (en) 2001-05-29 2007-08-09 Lexicon Pharmaceuticals, Inc. Novel human hydroxylases and polynucleotides encoding the same
AU2002303933A1 (en) 2001-05-31 2002-12-09 Rochester Institute Of Technology Fluidic valves, agitators, and pumps and methods thereof
US7294478B1 (en) 2001-06-06 2007-11-13 Rosetta Inpharmatics Llc Microarray reaction cartridge
WO2002099386A2 (en) * 2001-06-07 2002-12-12 Proligo Llc Microcalorimetric detection of analytes and binding events
US20070184436A1 (en) * 2001-06-07 2007-08-09 Joel Myerson Generic capture probe arrays
US7026121B1 (en) 2001-06-08 2006-04-11 Expression Diagnostics, Inc. Methods and compositions for diagnosing and monitoring transplant rejection
US7235358B2 (en) 2001-06-08 2007-06-26 Expression Diagnostics, Inc. Methods and compositions for diagnosing and monitoring transplant rejection
US6905827B2 (en) 2001-06-08 2005-06-14 Expression Diagnostics, Inc. Methods and compositions for diagnosing or monitoring auto immune and chronic inflammatory diseases
US20040048241A1 (en) * 2001-06-11 2004-03-11 Freeman Beverly Annette Methods for attaching molecules
US6824974B2 (en) * 2001-06-11 2004-11-30 Genorx, Inc. Electronic detection of biological molecules using thin layers
JP2004531268A (ja) * 2001-06-14 2004-10-14 レキシコン・ジェネティクス・インコーポレーテッド 新規ヒトトランスポータータンパクおよびそれをコードするポリヌクレオチド
US7171311B2 (en) * 2001-06-18 2007-01-30 Rosetta Inpharmatics Llc Methods of assigning treatment to breast cancer patients
US7514209B2 (en) * 2001-06-18 2009-04-07 Rosetta Inpharmatics Llc Diagnosis and prognosis of breast cancer patients
US20030096264A1 (en) * 2001-06-18 2003-05-22 Psychiatric Genomics, Inc. Multi-parameter high throughput screening assays (MPHTS)
US20030104426A1 (en) * 2001-06-18 2003-06-05 Linsley Peter S. Signature genes in chronic myelogenous leukemia
US20020198666A1 (en) * 2001-06-20 2002-12-26 Kabushikigaisha Dynacom System and method for computer-designing optimum oligo-nucleic acid sequences from nucleic acid base sequences, and oligo-nucleic acid array mounted with the designed oligo-nucleic acid sequences
US7262063B2 (en) 2001-06-21 2007-08-28 Bio Array Solutions, Ltd. Directed assembly of functional heterostructures
US6709989B2 (en) 2001-06-21 2004-03-23 Motorola, Inc. Method for fabricating a semiconductor structure including a metal oxide interface with silicon
DE60221987T2 (de) 2001-06-22 2008-05-15 Stemcells, Inc., Palo Alto Le-zellen (liver engrafting cells), assays und verwendungen davon
US20040166593A1 (en) * 2001-06-22 2004-08-26 Nolte David D. Adaptive interferometric multi-analyte high-speed biosensor
EP1925672A1 (en) 2001-06-22 2008-05-28 Syngeta Participations AG Abiotic stress responsive polynucleotides and polypeptides
US7402286B2 (en) * 2001-06-27 2008-07-22 The Regents Of The University Of California Capillary pins for high-efficiency microarray printing device
EP1402070B1 (en) 2001-06-27 2012-01-11 Cancer Research Technology Limited Methods for the diagnosis of cancer based on the obcam and ntm genes
US6855538B2 (en) * 2001-06-27 2005-02-15 The Regents Of The University Of California High-efficiency microarray printing device
JP4500540B2 (ja) * 2001-06-29 2010-07-14 ヴェリ‐キュー，インコーポレイテッド 化学的に合成された核酸の純度を決定し、かつ化学的に合成された核酸を精製するための方法および組成物
US9777312B2 (en) * 2001-06-30 2017-10-03 Enzo Life Sciences, Inc. Dual polarity analysis of nucleic acids
US9261460B2 (en) 2002-03-12 2016-02-16 Enzo Life Sciences, Inc. Real-time nucleic acid detection processes and compositions
US20040161741A1 (en) 2001-06-30 2004-08-19 Elazar Rabani Novel compositions and processes for analyte detection, quantification and amplification
US6691042B2 (en) 2001-07-02 2004-02-10 Rosetta Inpharmatics Llc Methods for generating differential profiles by combining data obtained in separate measurements
AU2002365177A1 (en) * 2001-07-02 2003-07-24 The Board Of Trustees Of The Leland Stanford Junior University Microarrays for cell phenotyping and manipulation
WO2003004609A2 (en) * 2001-07-03 2003-01-16 Lexicon Genetics Incorporated Novel human kielin-like proteins and polynucleotides encoding the same
US20030096268A1 (en) * 2001-07-06 2003-05-22 Michael Weiner Method for isolation of independent, parallel chemical micro-reactions using a porous filter
US7221632B2 (en) * 2001-07-12 2007-05-22 Burstein Technologies, Inc. Optical disc system and related detecting methods for analysis of microscopic structures
US20050287560A1 (en) * 2001-07-13 2005-12-29 Nanosphere, Inc. Method for preparing substrates having immobilized molecules and substrates
AU2002322458A1 (en) 2001-07-13 2003-01-29 Nanosphere, Inc. Method for immobilizing molecules onto surfaces
US7297553B2 (en) * 2002-05-28 2007-11-20 Nanosphere, Inc. Method for attachment of silylated molecules to glass surfaces
US20030013208A1 (en) * 2001-07-13 2003-01-16 Milagen, Inc. Information enhanced antibody arrays
CA2453434C (en) * 2001-07-16 2009-04-14 Hk Pharmaceuticals, Inc. Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions
US20030068691A1 (en) * 2001-07-16 2003-04-10 Applera Corporation Isolated human secreted proteins, nucleic acid molecules encoding human secreted proteins, and uses thereof
WO2003008941A2 (en) * 2001-07-17 2003-01-30 Bioforce Nanosciences, Inc. Combined molecular blinding detection through force microscopy and mass spectrometry
US6646293B2 (en) 2001-07-18 2003-11-11 Motorola, Inc. Structure for fabricating high electron mobility transistors utilizing the formation of complaint substrates
US20030143612A1 (en) * 2001-07-18 2003-07-31 Pointilliste, Inc. Collections of binding proteins and tags and uses thereof for nested sorting and high throughput screening
US6893822B2 (en) 2001-07-19 2005-05-17 Nanogen Recognomics Gmbh Enzymatic modification of a nucleic acid-synthetic binding unit conjugate
EP1417490A2 (en) * 2001-07-20 2004-05-12 Burstein Technologies, Inc. Optical analysis disc and related drive assembly for performing interactive centrifugation
US6693298B2 (en) 2001-07-20 2004-02-17 Motorola, Inc. Structure and method for fabricating epitaxial semiconductor on insulator (SOI) structures and devices utilizing the formation of a compliant substrate for materials used to form same
IL159768A0 (en) * 2001-07-24 2004-06-20 Genset Sa Polynucleotides encoding glycine transporter polypeptides, their preparation and use
US20030022150A1 (en) * 2001-07-24 2003-01-30 Sampson Jeffrey R. Methods for detecting a target molecule
US7348140B1 (en) 2001-07-25 2008-03-25 Acadia Pharmaceuticals, Inc. Clinical indications for genotyping polymorphic variants of G-protein coupled receptors
US6667196B2 (en) 2001-07-25 2003-12-23 Motorola, Inc. Method for real-time monitoring and controlling perovskite oxide film growth and semiconductor structure formed using the method
JP4265149B2 (ja) * 2001-07-25 2009-05-20 セイコーエプソン株式会社 電気光学装置、電気光学装置の製造方法
US20030022394A1 (en) * 2001-07-27 2003-01-30 Dumas David P. Biochips and methods of making same
WO2003083040A2 (en) * 2001-07-30 2003-10-09 Sts Biopolymers, Inc. Graft polymer matrices
US6833441B2 (en) * 2001-08-01 2004-12-21 Abmaxis, Inc. Compositions and methods for generating chimeric heteromultimers
US20030027258A1 (en) * 2001-08-02 2003-02-06 Chang Fang-Tseh Frank Methods and compositions for pearl oyster cultivation
US6589856B2 (en) 2001-08-06 2003-07-08 Motorola, Inc. Method and apparatus for controlling anti-phase domains in semiconductor structures and devices
US6639249B2 (en) 2001-08-06 2003-10-28 Motorola, Inc. Structure and method for fabrication for a solid-state lighting device
US20030082596A1 (en) * 2001-08-08 2003-05-01 Michael Mittmann Methods of genetic analysis of probes: test3
EP1414852A2 (en) 2001-08-10 2004-05-06 Genset S.A. Human secreted proteins, their encoding pulynucleotides, and uses thereof
KR100455284B1 (ko) * 2001-08-14 2004-11-12 삼성전자주식회사 탄소나노튜브를 이용한 고용량의 바이오분자 검출센서
EP1425382A4 (en) * 2001-08-14 2004-10-06 Lexicon Genetics Inc NEW HUMAN COLLAGEN PROTEINS AND THESE CODING POLYNUCLEOTIDS
US6673667B2 (en) 2001-08-15 2004-01-06 Motorola, Inc. Method for manufacturing a substantially integral monolithic apparatus including a plurality of semiconductor materials
WO2003016574A1 (en) * 2001-08-16 2003-02-27 Zhifeng Shao Analysis of gene expression profiles using sequential hybridization
US20080026367A9 (en) * 2001-08-17 2008-01-31 Perlegen Sciences, Inc. Methods for genomic analysis
WO2003018749A2 (en) * 2001-08-22 2003-03-06 Shengfeng Li Compositions and methods for generating antigen-binding units
WO2003020966A2 (de) * 2001-08-27 2003-03-13 Zeptosens Ag Oberfläche zur immobilisierung von nukleinsäuren
US20030129665A1 (en) * 2001-08-30 2003-07-10 Selvan Gowri Pyapali Methods for qualitative and quantitative analysis of cells and related optical bio-disc systems
US10539561B1 (en) 2001-08-30 2020-01-21 Customarray, Inc. Enzyme-amplified redox microarray detection process
US20050147984A1 (en) * 2001-08-31 2005-07-07 Clondiag Chip Technologies Gmbh Interaction detection on several probe arrays
WO2003021222A2 (en) * 2001-08-31 2003-03-13 Burstein Technologies, Inc. Capture layer assemblies for cellular assays including related optical analysis discs and methods
DE10142643A1 (de) * 2001-08-31 2003-04-24 Clondiag Chip Tech Gmbh Detektion von Wechselwirkungen auf Sonden-Arrays
US20050032060A1 (en) * 2001-08-31 2005-02-10 Shishir Shah Arrays comprising pre-labeled biological molecules and methods for making and using these arrays
US20030044798A1 (en) * 2001-08-31 2003-03-06 Lefkowitz Steven M. Methods for generating ligand arrays via deposition of ligands onto olefin displaying substrates, and arrays produced thereby
US20030108972A1 (en) * 2001-12-06 2003-06-12 Zweig Stephen Eliot Tethered receptor-ligand reagent and assay
AU2002335715A1 (en) * 2001-09-07 2003-03-24 Burstein Technologies, Inc. Optical bio-disc systems for nuclear morphology based identification
WO2003023409A2 (en) * 2001-09-07 2003-03-20 Transform Pharmaceuticals, Inc. Apparatus and method for high-throughput preparation and characterization of compositions
US20030054396A1 (en) * 2001-09-07 2003-03-20 Weiner Michael P. Enzymatic light amplification
US6974671B1 (en) 2001-09-12 2005-12-13 Salk Institute For Biological Studies Methods for indentifying compounds that modulate gluconeogenesis through the binding of CREB to the PGC-1 promoter
US20030096324A1 (en) * 2001-09-12 2003-05-22 Mikhail Matveev Methods for differential cell counts including related apparatus and software for performing same
US6900237B2 (en) * 2001-09-14 2005-05-31 Axys Pharmaceuticals, Inc. Sulfonamide compounds as protease inhibitors
US20040142325A1 (en) * 2001-09-14 2004-07-22 Liat Mintz Methods and systems for annotating biomolecular sequences
US20060188875A1 (en) * 2001-09-18 2006-08-24 Perlegen Sciences, Inc. Human genomic polymorphisms
US20070098728A1 (en) * 2001-09-24 2007-05-03 Pedersen Finn S Novel compositions and methods in cancer
US7202028B2 (en) * 2001-09-24 2007-04-10 The University Of North Carolina At Chapel Hill Methods for the electrochemical detection of multiple target compounds
US7042488B2 (en) 2001-09-27 2006-05-09 Fujinon Corporation Electronic endoscope for highlighting blood vessel
JP4754746B2 (ja) * 2001-09-28 2011-08-24 オリンパス株式会社 棒状担体およびこれを具備するシリンダー反応容器
US20030068621A1 (en) * 2001-10-04 2003-04-10 Jonathan Briggs Method and device for producing oligonucleotide arrays
US20040053232A1 (en) * 2001-10-05 2004-03-18 Perlegen Sciences, Inc. Haplotype structures of chromosome 21
DE10149684B4 (de) * 2001-10-09 2005-02-17 Clondiag Chip Technologies Gmbh Vorrichtung zur Halterung eines Substanzbibliothekenträgers
US6993173B2 (en) * 2001-10-12 2006-01-31 Duke University Methods for estimating probe cell locations in high-density synthetic DNA microarrays
US7439346B2 (en) 2001-10-12 2008-10-21 Perkinelmer Las Inc. Nucleic acids arrays and methods of use therefor
AU2002367886B8 (en) 2001-10-12 2008-08-14 Perkinelmer Las, Inc. Compilations of nucleic acids and arrays and methods of using them
AU2002334769A1 (en) * 2001-10-12 2003-04-28 Duke University Image analysis of high-density synthetic dna microarrays
CA2497740C (en) 2001-10-15 2011-06-21 Bioarray Solutions, Ltd. Multiplexed analysis of polymorphic loci by probe elongation-mediated detection
WO2003033718A1 (en) * 2001-10-17 2003-04-24 Global Genomics Ab Synthesis of oligonucleotides on solid support and assembly into doublestranded polynucleotides
US20030219800A1 (en) * 2001-10-18 2003-11-27 Beske Oren E. Multiplexed cell transfection using coded carriers
US20040126762A1 (en) * 2002-12-17 2004-07-01 Morris David W. Novel compositions and methods in cancer
US20040166490A1 (en) * 2002-12-17 2004-08-26 Morris David W. Novel therapeutic targets in cancer
US20030165859A1 (en) 2001-10-23 2003-09-04 Invitrogen Corporation Primers and methods for the detection and discrimination of nucleic acids
ITMI20010566U1 (it) * 2001-10-25 2003-04-25 Troletti Adriano Apparecchio asciugacapelli, ad elevata praticita' di impiego
ES2401425T3 (es) 2001-10-25 2013-04-19 Medical Research Council Moléculas
US7378775B2 (en) 2001-10-26 2008-05-27 Nth Tech Corporation Motion based, electrostatic power source and methods thereof
WO2003098661A2 (en) * 2001-10-26 2003-11-27 Integrated Nano-Technologies, Llc Chemical and biological hazard sensor system and methods thereof
EP1446634A4 (en) * 2001-10-26 2010-04-07 Univ Rochester BIOMOLECULAR DETECTION METHOD AND SYSTEM THEREFOR
US7211923B2 (en) 2001-10-26 2007-05-01 Nth Tech Corporation Rotational motion based, electrostatic power source and methods thereof
US20030082560A1 (en) * 2001-10-29 2003-05-01 Yingjian Wang Method of making interactive protein arrays
US6956114B2 (en) 2001-10-30 2005-10-18 '454 Corporation Sulfurylase-luciferase fusion proteins and thermostable sulfurylase
US20050124022A1 (en) * 2001-10-30 2005-06-09 Maithreyan Srinivasan Novel sulfurylase-luciferase fusion proteins and thermostable sulfurylase
WO2003053855A2 (en) * 2001-10-30 2003-07-03 University Of Delaware Rapid high-throughput screen for detecting biological species in ballast water
US6902921B2 (en) * 2001-10-30 2005-06-07 454 Corporation Sulfurylase-luciferase fusion proteins and thermostable sulfurylase
EP1446507A2 (en) * 2001-10-31 2004-08-18 Pfizer Products Inc. Therapeutics and diagnostics for disorders of erythropoiesis
US7175983B2 (en) * 2001-11-02 2007-02-13 Abmaxis, Inc. Adapter-directed display systems
ES2345329T3 (es) 2001-11-09 2010-09-21 Georgetown University Nueva isoforma del inhibidor del crecimiento celular endotelial vascular (vegi).
AU2002364894A1 (en) * 2001-11-09 2003-06-30 Neurogenetics, Inc. Single nucleotide polymorphisms and mutations on alpha-2-macroglobulin
US20040067512A1 (en) * 2001-11-09 2004-04-08 Neurogenetics, Inc. Single nucleotide polymorphisms and mutations on Alpha-2-Macroglobulin
US20080094974A1 (en) * 2001-11-09 2008-04-24 Burstein Technologies, Inc. Optical disc system and related detecting methods for analysis of microscopic structures
AU2002360361A1 (en) * 2001-11-09 2003-06-10 Biomicroarrays, Inc. High surface area substrates for microarrays and methods to make same
WO2003042697A1 (en) * 2001-11-14 2003-05-22 Genospectra, Inc. Biochemical analysis system with combinatorial chemistry applications
DE10156467A1 (de) * 2001-11-16 2003-06-05 Micronas Gmbh Träger zur Synthese sowie Verfahren zur Herstellung von Biopolymeren
WO2003044481A2 (en) * 2001-11-20 2003-05-30 Burstein Technologies, Inc. Optical bio-discs and microfluidic devices for analysis of cells
WO2003046144A2 (en) * 2001-11-26 2003-06-05 Molecular Reflections, Inc. Microscale immobilization of molecules using a hydrogel and methods of use thereof
US20040023237A1 (en) * 2001-11-26 2004-02-05 Perelegen Sciences Inc. Methods for genomic analysis
EP1463796B1 (en) 2001-11-30 2013-01-09 Fluidigm Corporation Microfluidic device and methods of using same
US20040180344A1 (en) * 2003-03-14 2004-09-16 Morris David W. Novel therapeutic targets in cancer
US20060040262A1 (en) * 2002-12-27 2006-02-23 Morris David W Novel compositions and methods in cancer
US20040197778A1 (en) * 2002-12-26 2004-10-07 Sagres Discovery, Inc. Novel compositions and methods in cancer
US20070037147A1 (en) * 2001-12-07 2007-02-15 Pablo Garcia Endogenous retrovirus polypeptides linked to oncogenic transformation
SI1458888T1 (sl) * 2001-12-10 2011-07-29 Novartis Ag Metode zdravljenja psihoze in shizofrenije na osnovi polimorfizmov gena cntf
US6960298B2 (en) * 2001-12-10 2005-11-01 Nanogen, Inc. Mesoporous permeation layers for use on active electronic matrix devices
US7098041B2 (en) 2001-12-11 2006-08-29 Kimberly-Clark Worldwide, Inc. Methods to view and analyze the results from diffraction-based diagnostics
US7102752B2 (en) 2001-12-11 2006-09-05 Kimberly-Clark Worldwide, Inc. Systems to view and analyze the results from diffraction-based diagnostics
US7858297B2 (en) 2001-12-18 2010-12-28 Centre National De La Recherche Scientifique Cnrs Chemokine-binding protein and methods of use
ATE451387T1 (de) * 2001-12-18 2009-12-15 Endocube Sas Neue mit dem zelltod assoziierte proteine aus der thap familie und par4 verwandte signalwege, die bei der kontrolle von apoptosis involviert sind
EP1321768A1 (en) * 2001-12-18 2003-06-25 Roche Diagnostics GmbH Diagnosis of endometriosis from menstrual blood
AU2002357368A1 (en) * 2001-12-19 2003-07-09 Affymetrix, Inc. Array plates and method for constructing array plates
KR20050008644A (ko) * 2001-12-21 2005-01-21 엘지 바이오메디컬 인스티튜트 위암에서의 유전자 발현 프로파일
US8367013B2 (en) 2001-12-24 2013-02-05 Kimberly-Clark Worldwide, Inc. Reading device, method, and system for conducting lateral flow assays
US20030119203A1 (en) 2001-12-24 2003-06-26 Kimberly-Clark Worldwide, Inc. Lateral flow assay devices and methods for conducting assays
CA2471658A1 (en) * 2001-12-26 2003-07-10 Canon Kabushiki Kaisha Probe medium and method for fixing probe on a substrate
US7335153B2 (en) 2001-12-28 2008-02-26 Bio Array Solutions Ltd. Arrays of microparticles and methods of preparation thereof
WO2003058201A2 (en) * 2001-12-31 2003-07-17 Quark Biotech, Inc. Methods for identifying marker genes for cancer
US6897025B2 (en) * 2002-01-07 2005-05-24 Perlegen Sciences, Inc. Genetic analysis systems and methods
US20030188343A1 (en) * 2002-01-09 2003-10-02 Lynx Therapeutics, Inc. Identification of genes associated with growth in plants
FR2834521B1 (fr) * 2002-01-10 2004-12-17 Bio Merieux Procede de detection et/ou d'identification de l'espece animale d'origine de la matiere animale contenue dans un echantillon
WO2003060668A2 (en) * 2002-01-14 2003-07-24 Burstein Technologies, Inc. Method and apparatus for visualizing data
DE10201463B4 (de) 2002-01-16 2005-07-21 Clondiag Chip Technologies Gmbh Reaktionsgefäß zur Durchführung von Array-Verfahren
US8008012B2 (en) 2002-01-24 2011-08-30 Health Discovery Corporation Biomarkers downregulated in prostate cancer
US20030148391A1 (en) * 2002-01-24 2003-08-07 Salafsky Joshua S. Method using a nonlinear optical technique for detection of interactions involving a conformational change
EP1470551A2 (en) * 2002-01-28 2004-10-27 Burstein Technologies, Inc. Methods and apparatus for logical triggering
US20050002827A1 (en) * 2002-01-29 2005-01-06 Mcintyre Kevin Robert Optical discs including equi-radial and/or spiral analysis zones and related disc drive systems and methods
US20050019901A1 (en) * 2002-01-31 2005-01-27 Evgenia Matveeva Methods for synthesis of bio-active nanoparticles and nanocapsules for use in optical bio-disc assays and disc assembly including same
US7418351B2 (en) * 2002-01-31 2008-08-26 Rosetta Inpharmatics Llc Methods for analysis of measurement errors in measured signals
US7083975B2 (en) * 2002-02-01 2006-08-01 Roland Green Microarray synthesis instrument and method
US7035739B2 (en) * 2002-02-01 2006-04-25 Rosetta Inpharmatics Llc Computer systems and methods for identifying genes and determining pathways associated with traits
US20030149933A1 (en) * 2002-02-01 2003-08-07 Marco Falcioni Graphical design of chemical discovery processes
US6887362B2 (en) * 2002-02-06 2005-05-03 Nanogen, Inc. Dielectrophoretic separation and immunoassay methods on active electronic matrix devices
US6861523B2 (en) 2002-02-08 2005-03-01 Torrey Pines Institute For Molecular Studies 1,3,5- trisubstituted-1,3,5-triazine-2,4,6-trione compounds and libraries
US7553619B2 (en) * 2002-02-08 2009-06-30 Qiagen Gmbh Detection method using dissociated rolling circle amplification
US20030156136A1 (en) * 2002-02-15 2003-08-21 Cattell Herbert F. Method and system for visualization of results of feature extraction from molecular array data
US20030162178A1 (en) * 2002-02-25 2003-08-28 O'hagan David Variable microarray and methods of detecting one or more anlaytes in a sample
NL1020066C2 (nl) * 2002-02-26 2003-08-27 Dutch Space B V Inrichting voor het vervaardigen van een DNA-testarray.
US20030161761A1 (en) * 2002-02-28 2003-08-28 Williams Roger O. Apparatus and method for composing high density materials onto target substrates by a rapid sequence
US6770892B2 (en) 2002-02-28 2004-08-03 Agilent Technologies, Inc. Method and system for automated focus-distance determination for molecular array scanners
US6929951B2 (en) * 2002-02-28 2005-08-16 Agilent Technologies, Inc. Method and system for molecular array scanner calibration
US6914229B2 (en) * 2002-02-28 2005-07-05 Agilent Technologies, Inc. Signal offset for prevention of data clipping in a molecular array scanner
US7504364B2 (en) * 2002-03-01 2009-03-17 Receptors Llc Methods of making arrays and artificial receptors
US20030203384A1 (en) * 2002-03-08 2003-10-30 Chafin David R. Multiplex detection of biological materials in a sample
WO2003077851A2 (en) * 2002-03-11 2003-09-25 Hk Pharmaceuticals, Inc. Compounds and methods for analyzing the proteome
ES2559764T3 (es) 2002-03-11 2016-02-15 Molecular Insight Pharmaceuticals, Inc. Complejos de tecnecio-dipiridina, y métodos de uso de los mismos
US9353405B2 (en) 2002-03-12 2016-05-31 Enzo Life Sciences, Inc. Optimized real time nucleic acid detection processes
US20060235200A1 (en) 2002-03-13 2006-10-19 Marie-Clair Grosjean-Cournoyer Mutagenesis of aspergillus fungi and identification of genes essential for growth
SE0200817D0 (sv) * 2002-03-15 2002-03-15 Ulf Gyllensten Method and kit for detection of mutations in mitochondrial DNA
US7689022B2 (en) 2002-03-15 2010-03-30 Affymetrix, Inc. System, method, and product for scanning of biological materials
US20030177380A1 (en) * 2002-03-18 2003-09-18 Woods Stanley P. Devices for storing array data and methods of using the same
AU2003220487A1 (en) * 2002-03-19 2003-10-08 Cengent Therapeutics, Inc. Discrete bayesian analysis of data
AU2003228348A1 (en) * 2002-03-20 2003-10-08 John T. Fassett Induction of hepatocyte proliferation in vitro by inhibition of cell cycle inhibitors
EP2093233A1 (en) 2002-03-21 2009-08-26 Sagres Discovery, Inc. Novel compositions and methods in cancer
US20040006431A1 (en) * 2002-03-21 2004-01-08 Affymetrix, Inc., A Corporation Organized Under The Laws Of Delaware System, method and computer software product for grid placement, alignment and analysis of images of biological probe arrays
US7193069B2 (en) * 2002-03-22 2007-03-20 Research Association For Biotechnology Full-length cDNA
US7935500B2 (en) * 2002-03-26 2011-05-03 Massachusetts Institute Of Technology Identifying calcineurin activators for treatment of schizophrenia
AR039102A1 (es) * 2002-03-26 2005-02-09 Lai Derhsing Chip de circuitos integrados para ensayos biologicos
US6916621B2 (en) 2002-03-27 2005-07-12 Spectral Genomics, Inc. Methods for array-based comparitive binding assays
US20030186279A1 (en) * 2002-03-28 2003-10-02 Affymetrix, Inc. Large scale genotyping methods
US20030186302A1 (en) * 2002-03-29 2003-10-02 Yixin Wang Colorectal cancer diagnostics
WO2003085379A2 (en) 2002-04-01 2003-10-16 Fluidigm Corporation Microfluidic particle-analysis systems
ES2734652T3 (es) 2002-04-04 2019-12-11 Zoetis Belgium S A Oligorribonucleótidos inmunoestimulantes que contienen G y U
US6773888B2 (en) * 2002-04-08 2004-08-10 Affymetrix, Inc. Photoactivatable silane compounds and methods for their synthesis and use
US20030194709A1 (en) * 2002-04-10 2003-10-16 Xing Yang Hydrophobic zone device
CA2480202A1 (en) * 2002-04-10 2003-10-23 Transtech Pharma, Inc. System and method for data analysis, manipulation, and visualization
US20030195431A1 (en) * 2002-04-10 2003-10-16 Sukhatme Vikas P. Observation of effects of body fluids on indicator cells for disease diagnosis
US7687256B2 (en) 2002-04-11 2010-03-30 Spire Corporation Surface activated biochip
AU2003224978A1 (en) 2002-04-12 2003-10-27 Curators Of The University Of Missouri ECIST microarrays for dual screening of DNA hypermethylation and gene silencing
WO2003087829A2 (en) * 2002-04-16 2003-10-23 Dot Diagnostics B.V. Human papilloma virus detection with dna microarray
ATE459880T1 (de) 2002-04-17 2010-03-15 Deutsches Krebsforsch Verfahren zum screening einer substanz zur modulierung der wnt -signalkaskade.
DE10217569A1 (de) * 2002-04-19 2003-11-13 Infineon Technologies Ag Vorrichtung auf Basis von partiell oxidiertem porösen Silizium
US7226771B2 (en) 2002-04-19 2007-06-05 Diversa Corporation Phospholipases, nucleic acids encoding them and methods for making and using them
CA2481411C (en) 2002-04-19 2016-06-14 Diversa Corporation Phospholipases, nucleic acids encoding them and methods for making and using them
WO2003091393A2 (en) * 2002-04-23 2003-11-06 Applera Corporation Nucleic “acid molecules encoding human proteins, and uses thereof”
US20030198967A1 (en) * 2002-04-23 2003-10-23 Matson Robert S. Multi-functional microarrays and methods
US6946285B2 (en) * 2002-04-29 2005-09-20 Agilent Technologies, Inc. Arrays with elongated features
US20040023275A1 (en) * 2002-04-29 2004-02-05 Perlegen Sciences, Inc. Methods for genomic analysis
CN1202266C (zh) * 2002-04-30 2005-05-18 欧姆龙株式会社 设置有光扫描装置的生物芯片和该生物芯片的读取方法
US6791690B2 (en) * 2002-04-30 2004-09-14 Agilent Technologies, Inc. Reading dry chemical arrays
US7118855B2 (en) * 2002-05-03 2006-10-10 Kimberly-Clark Worldwide, Inc. Diffraction-based diagnostic devices
US7485453B2 (en) * 2002-05-03 2009-02-03 Kimberly-Clark Worldwide, Inc. Diffraction-based diagnostic devices
US7771922B2 (en) 2002-05-03 2010-08-10 Kimberly-Clark Worldwide, Inc. Biomolecule diagnostic device
WO2003093810A1 (en) * 2002-05-03 2003-11-13 Vialogy Corporation System and method for characterizing microarray output data
US7214530B2 (en) 2002-05-03 2007-05-08 Kimberly-Clark Worldwide, Inc. Biomolecule diagnostic devices and method for producing biomolecule diagnostic devices
US7223368B2 (en) 2002-05-03 2007-05-29 Kimberly-Clark Worldwide, Inc. Diffraction-based diagnostic devices
US7223534B2 (en) 2002-05-03 2007-05-29 Kimberly-Clark Worldwide, Inc. Diffraction-based diagnostic devices
AU2003241359A1 (en) * 2002-05-06 2003-11-11 Functional Genetics, Inc. Mammalian genes involed in rapamycin resistance and tumorgenesis: annexin xiii genes
US20030216870A1 (en) * 2002-05-07 2003-11-20 Wolber Paul K. Method and system for normalization of micro array data based on local normalization of rank-ordered, globally normalized data
KR20120004544A (ko) 2002-05-08 2012-01-12 노쓰웨스트 바이오써라퓨틱스, 인크. 항원 제시 세포에 대한 정성적 검정법
US7217512B2 (en) * 2002-05-09 2007-05-15 Corning Incorporated Reagent and method for attaching target molecules to a surface
JP2006505256A (ja) * 2002-05-17 2006-02-16 ベイラー カレッジ オブ メディスン ドセタキセルの化学感受性および化学耐性を予測するための異なる遺伝子発現パターン
CA2486283A1 (en) * 2002-05-17 2004-02-05 Nugen Technologies, Inc. Methods for fragmentation, labeling and immobilization of nucleic acids
EP1514213A2 (en) * 2002-05-20 2005-03-16 Rosetta Inpharmactis LLC. Computer systems and methods for subdividing a complex disease into component diseases
US20050033525A1 (en) * 2002-05-21 2005-02-10 Corson John F. Method and system for computing and applying a user-defined, global, multi-channel background correction to a feature-based data set obtained from reading a microarray
US7221785B2 (en) * 2002-05-21 2007-05-22 Agilent Technologies, Inc. Method and system for measuring a molecular array background signal from a continuous background region of specified size
US20030220746A1 (en) * 2002-05-21 2003-11-27 Srinka Ghosh Method and system for computing and applying a global, multi-channel background correction to a feature-based data set obtained from scanning a molecular array
TWI221523B (en) * 2002-05-21 2004-10-01 Sony Corp Bioassay method, bioassay device, and bioassay substrate
US20040126773A1 (en) * 2002-05-23 2004-07-01 Beske Oren E. Assays with coded sensor particles to sense assay conditions
US20030219755A1 (en) * 2002-05-24 2003-11-27 Nanibhushan Dattagupta Compositions and methods for performing hybridization assays using target enhanced signal amplification (TESA)
US6763308B2 (en) 2002-05-28 2004-07-13 Sas Institute Inc. Statistical outlier detection for gene expression microarray data
US20050239193A1 (en) * 2002-05-30 2005-10-27 Bioforce Nanosciences, Inc. Device and method of use for detection and characterization of microorganisms and microparticles
US6806460B2 (en) * 2002-05-31 2004-10-19 Agilent Technologies, Inc. Fluorescence detection with increased dynamic range
US7537936B2 (en) * 2002-05-31 2009-05-26 Agilent Technologies, Inc. Method of testing multiple fluid samples with multiple biopolymer arrays
JP4193421B2 (ja) * 2002-06-06 2008-12-10 ソニー株式会社 バイオアッセイ装置及びその製造方法、並びにバイオアッセイ方法
EP1511569A1 (en) * 2002-06-13 2005-03-09 Millenium Biologix AG Reaction chamber
US8518694B2 (en) * 2002-06-13 2013-08-27 Novartis Vaccines And Diagnostics, Inc. Nucleic acid vector comprising a promoter and a sequence encoding a polypeptide from the endogenous retrovirus PCAV
US9388459B2 (en) * 2002-06-17 2016-07-12 Affymetrix, Inc. Methods for genotyping
US7108976B2 (en) * 2002-06-17 2006-09-19 Affymetrix, Inc. Complexity management of genomic DNA by locus specific amplification
US20030231986A1 (en) * 2002-06-18 2003-12-18 Eastman Kodak Company Micro-array identification means
US7332273B2 (en) 2002-06-20 2008-02-19 Affymetrix, Inc. Antireflective coatings for high-resolution photolithographic synthesis of DNA arrays
KR20050010956A (ko) 2002-06-20 2005-01-28 더 리전츠 오브 더 유니버시티 오브 캘리포니아 집광 다발색단을 사용하여 폴리뉴클레오티드를 검출 및분석하기 위한 방법 및 조성물
US7144950B2 (en) 2003-09-17 2006-12-05 The Regents Of The University Of California Conformationally flexible cationic conjugated polymers
US7091049B2 (en) 2002-06-26 2006-08-15 Kimberly-Clark Worldwide, Inc. Enhanced diffraction-based biosensor devices
US20040137491A1 (en) * 2002-06-28 2004-07-15 Tadashi Okamoto Method of analyzing probe carrier using time-of-flight secondary ion mass spectrometry
JP2004024203A (ja) * 2002-06-28 2004-01-29 Canon Inc 飛行時間型二次イオン質量分析法によるｒｎａの分析方法
CN1688716A (zh) * 2002-06-28 2005-10-26 罗斯塔英法美蒂克斯有限责任公司 评估微阵列质量的方法
JP3658397B2 (ja) * 2002-06-28 2005-06-08 キヤノン株式会社 飛行時間型二次イオン質量分析法による素子の情報取得方法、および、情報取得装置
JP4498132B2 (ja) * 2002-06-28 2010-07-07 キヤノン株式会社 プローブアレイの製造方法
US20040005769A1 (en) * 2002-07-03 2004-01-08 Cabot Microelectronics Corp. Method and apparatus for endpoint detection
DE10230320A1 (de) * 2002-07-05 2004-02-05 Marcel Rogalla Programmierbare Beleuchtungsvorrichtung zur hochauflösenden, massiv parallelen, räumlichen Systhese und Analyse von Microarrays
US20040009574A1 (en) * 2002-07-09 2004-01-15 Nanibhushan Dattagupta Compositions and methods for detecting streptococcus agalactiae capsular polysaccharide synthesis genes
USH2223H1 (en) 2002-07-11 2008-09-02 The United States Of America As Represented By The Secretary Of The Navy Patterned, micrometer-sized antibody features
US7504215B2 (en) 2002-07-12 2009-03-17 Affymetrix, Inc. Nucleic acid labeling methods
US20050185175A1 (en) * 2002-07-16 2005-08-25 Canos Avelino C. Rotary support and apparatus used for the multiple spectroscopic characterisation of samples of solid materials
AU2003261168A1 (en) * 2002-07-19 2004-02-09 Althea Technologies, Inc. Strategies for gene expression analysis
AU2003258472A1 (en) * 2002-07-23 2004-02-25 Universitat Leipzig Method for selective peptide labeling
JP2005533862A (ja) * 2002-07-25 2005-11-10 アーケミックス コーポレイション 調節されたアプタマー治療剤
US20040018497A1 (en) * 2002-07-26 2004-01-29 Warden Craig H Human obesity LIPIN3 polynucleotide and polypeptide sequences and methods of use thereof
US7601493B2 (en) * 2002-07-26 2009-10-13 Nanogen, Inc. Methods and apparatus for screening and detecting multiple genetic mutations
AU2003257040A1 (en) * 2002-07-29 2004-02-16 David P. Dumas Transparent polymer support for electrophoresis and electrochromatography and related methods
US7632916B2 (en) * 2002-08-02 2009-12-15 3M Innovative Properties Company Process to modify polymeric materials and resulting compositions
US7217518B2 (en) * 2002-08-02 2007-05-15 Applera Corporation Fluorescence polarization assay
AU2003257082A1 (en) * 2002-08-02 2004-02-23 Rosetta Inpharmatics Llc Computer systems and methods that use clinical and expression quantitative trait loci to associate genes with traits
AU2003257109A1 (en) * 2002-08-05 2004-02-23 Invitrogen Corporation Compositions and methods for molecular biology
US20060073475A1 (en) * 2002-08-09 2006-04-06 Nanibhushan Dattagupta Compositions and methods for detecting pathogenic bacteria expressing chaperonin proteins
US20060099676A1 (en) * 2002-08-15 2006-05-11 Limin Li Mammalian genes involved in rapamycin resistance and tumorgenesis: rapr6 genes
WO2004020581A2 (en) * 2002-08-15 2004-03-11 Functional Genetics, Inc. Mammalian genes involved in rapamycin resistance and tumorgenesis: rapr7 genes
US20050118616A1 (en) * 2002-08-16 2005-06-02 Kawashima Tadashi R. Amplification of target nucleotide sequence without polymerase chain reaction
US7118865B2 (en) * 2002-08-16 2006-10-10 Regents Of The University Of Minnesota Methods for diagnosing severe systemic lupus erythematosus
US20050233473A1 (en) * 2002-08-16 2005-10-20 Zyomyx, Inc. Methods and reagents for surface functionalization
US7267751B2 (en) * 2002-08-20 2007-09-11 Nanogen, Inc. Programmable multiplexed active biologic array
US7164533B2 (en) 2003-01-22 2007-01-16 Cyvera Corporation Hybrid random bead/chip based microarray
US7901630B2 (en) 2002-08-20 2011-03-08 Illumina, Inc. Diffraction grating-based encoded microparticle assay stick
US7508608B2 (en) 2004-11-17 2009-03-24 Illumina, Inc. Lithographically fabricated holographic optical identification element
US7473535B2 (en) * 2002-08-20 2009-01-06 The Institute For Systems Biology Chemical reagents and methods for detection and quantification of proteins in complex mixtures
US7900836B2 (en) 2002-08-20 2011-03-08 Illumina, Inc. Optical reader system for substrates having an optically readable code
US7872804B2 (en) 2002-08-20 2011-01-18 Illumina, Inc. Encoded particle having a grating with variations in the refractive index
US7923260B2 (en) 2002-08-20 2011-04-12 Illumina, Inc. Method of reading encoded particles
US8277753B2 (en) 2002-08-23 2012-10-02 Life Technologies Corporation Microfluidic transfer pin
US20040038214A1 (en) * 2002-08-23 2004-02-26 Corson John F. Method and system for reading a molecular array
WO2004092324A2 (en) 2002-08-26 2004-10-28 The Regents Of The University Of California Methods and compositions for detection and analysis of polynucleotides using light harvesting multichromophores
US7314763B2 (en) 2002-08-27 2008-01-01 Kimberly-Clark Worldwide, Inc. Fluidics-based assay devices
US7285424B2 (en) 2002-08-27 2007-10-23 Kimberly-Clark Worldwide, Inc. Membrane-based assay devices
US7432105B2 (en) 2002-08-27 2008-10-07 Kimberly-Clark Worldwide, Inc. Self-calibration system for a magnetic binding assay
AU2003298412A1 (en) * 2002-09-03 2004-03-29 Zeptosens Ag Analytical platform and identification method
JP2005537486A (ja) * 2002-09-03 2005-12-08 ツェプトゼンス　アクチエンゲゼルシャフト 分析対象物が試料中で固定化された特異的結合パートナーとして測定される分析プラットフォーム及び検出法
CN102516417B (zh) 2002-09-06 2014-12-10 天蓝制药公司 用于传递治疗剂的以环糊精为基础的聚合物
EP2161276A3 (en) * 2002-09-08 2010-05-26 Applera Corporation Methods, compositions and libraries pertaining PNA dimer and PNA oligomer systhesis
EP1546404A2 (en) * 2002-09-11 2005-06-29 Exiqon A/S A population of nucleic acids including a subpopulation of lna oligomers
US7092160B2 (en) 2002-09-12 2006-08-15 Illumina, Inc. Method of manufacturing of diffraction grating-based optical identification element
US20100255603A9 (en) 2002-09-12 2010-10-07 Putnam Martin A Method and apparatus for aligning microbeads in order to interrogate the same
US7563600B2 (en) 2002-09-12 2009-07-21 Combimatrix Corporation Microarray synthesis and assembly of gene-length polynucleotides
US6889143B2 (en) * 2002-09-12 2005-05-03 Intergrated Dna Technologies, Inc. Methods and systems for estimating the melting temperature (TM) for polynucleotide molecules
US7469076B2 (en) * 2003-09-03 2008-12-23 Receptors Llc Sensors employing combinatorial artificial receptors
US7595883B1 (en) * 2002-09-16 2009-09-29 The Board Of Trustees Of The Leland Stanford Junior University Biological analysis arrangement and approach therefor
US20050037381A1 (en) * 2002-09-16 2005-02-17 Receptors Llc Artificial receptors, building blocks, and methods
US20050136483A1 (en) * 2003-09-03 2005-06-23 Receptors Llc Nanodevices employing combinatorial artificial receptors
US20050170385A1 (en) * 2002-09-16 2005-08-04 Receptors Llc Artificial receptors including gradients
US20060057625A1 (en) * 2002-09-16 2006-03-16 Carlson Robert E Scaffold-based artificial receptors and methods
US20050037429A1 (en) * 2003-03-28 2005-02-17 Receptors Llc Artificial receptors including reversibly immobilized building blocks and methods
WO2005003326A2 (en) * 2003-03-28 2005-01-13 Receptors Llc. Artificial receptors including reversibly immobilized building blocks and methods
US20050037428A1 (en) * 2002-09-16 2005-02-17 Receptors Llc Artificial receptors including reversibly immobilized building blocks, the building blocks, and methods
CA2503905A1 (en) * 2002-09-16 2004-03-25 Plexxikon, Inc. Crystal structure of pim-1 kinase
US20040137481A1 (en) * 2002-09-16 2004-07-15 Receptors Llc Artificial receptor building blocks, components, and kits
ES2462916T3 (es) 2002-09-18 2014-05-26 Janssen Pharmaceuticals, Inc. Métodos para aumentar la producción de células madre hematopoyéticas y plaquetas
US7143785B2 (en) 2002-09-25 2006-12-05 California Institute Of Technology Microfluidic large scale integration
US7169550B2 (en) * 2002-09-26 2007-01-30 Kimberly-Clark Worldwide, Inc. Diffraction-based diagnostic devices
AU2003270898A1 (en) * 2002-09-27 2004-04-19 Nimblegen Systems, Inc. Microarray with hydrophobic barriers
DE10245432A1 (de) 2002-09-27 2004-04-08 Micronas Gmbh Verfahren und Vorrichtung zum Detektieren mindestens eines Lumineszenz-Stoffs
US7135288B2 (en) 2002-09-27 2006-11-14 Ut-Battelle, Llc Combinatorial synthesis of ceramic materials
WO2004031399A2 (en) 2002-09-30 2004-04-15 Nimblegen Systems, Inc. Parallel loading of arrays
US20040110212A1 (en) * 2002-09-30 2004-06-10 Mccormick Mark Microarrays with visual alignment marks
WO2004031351A2 (en) * 2002-10-01 2004-04-15 Nimblegen Systems, Inc. Microarrays having multiple oligonucleotides in single array features
WO2004040001A2 (en) 2002-10-02 2004-05-13 California Institute Of Technology Microfluidic nucleic acid analysis
US20040259105A1 (en) * 2002-10-03 2004-12-23 Jian-Bing Fan Multiplex nucleic acid analysis using archived or fixed samples
US20040067492A1 (en) * 2002-10-04 2004-04-08 Allan Peng Reverse transcription on microarrays
US7459273B2 (en) * 2002-10-04 2008-12-02 Affymetrix, Inc. Methods for genotyping selected polymorphism
US9453251B2 (en) 2002-10-08 2016-09-27 Pfenex Inc. Expression of mammalian proteins in Pseudomonas fluorescens
US20050003369A1 (en) * 2002-10-10 2005-01-06 Affymetrix, Inc. Method for depleting specific nucleic acids from a mixture
US20040120861A1 (en) * 2002-10-11 2004-06-24 Affymetrix, Inc. System and method for high-throughput processing of biological probe arrays
KR100508108B1 (ko) * 2002-10-14 2005-08-18 학교법인 포항공과대학교 중합체 패턴의 형성 방법
US20080293750A1 (en) * 2002-10-17 2008-11-27 Anna Helgadottir Susceptibility Gene for Myocardial Infarction, Stroke, Paod and Methods of Treatment
AU2003269557A1 (en) 2002-10-18 2004-05-04 Lg Life Sciences Ltd. Gene families associated with cancers
WO2004036188A2 (en) * 2002-10-18 2004-04-29 Cylene Pharmaceuticals, Inc. Processes for identifying quadruplex-targeted antiviral molecules
US20040076961A1 (en) * 2002-10-21 2004-04-22 Lewis Mark A. Biomolecule retaining material and methods for attaching biomolecules to a surface
US20040219565A1 (en) 2002-10-21 2004-11-04 Sakari Kauppinen Oligonucleotides useful for detecting and analyzing nucleic acids of interest
WO2004038042A1 (fr) * 2002-10-24 2004-05-06 Ben Gao Methode quadridimensionnelle et appareil de detection d'une paire hybride d'acides nucleiques sur une puce a adn
US6742843B2 (en) * 2002-10-25 2004-06-01 Knoll, Inc. Cable control with overload protection device
US7635564B2 (en) * 2002-10-25 2009-12-22 Agilent Technologies, Inc. Biopolymeric arrays having replicate elements
US20040115722A1 (en) * 2002-10-25 2004-06-17 Mel Kronick Biopolymeric arrays and methods of producing the same
EP1581654A4 (en) * 2002-10-28 2007-01-03 Invitrogen Corp SYNTHESIS AND USE OF MATRIX OLIGOMERS
JP3447009B1 (ja) * 2002-10-29 2003-09-16 實 平垣 構築物用構成体およびその製造方法
US7195908B2 (en) 2002-10-31 2007-03-27 Corning Incorporated Supports treated with triamine for immobilizing biomolecules
US20050037369A1 (en) * 2002-10-31 2005-02-17 Neote Kuldeep Singh Panels of molecular targets differentially expressed during CD8+ T cell priming, and methods for therapy and diagnosis utilizing the same
JP4571776B2 (ja) * 2002-11-05 2010-10-27 Ｊｘ日鉱日石エネルギー株式会社 潤滑油組成物
US20040086892A1 (en) * 2002-11-06 2004-05-06 Crothers Donald M. Universal tag assay
AU2002952696A0 (en) 2002-11-14 2002-11-28 Genomics Research Partners Pty Ltd Status determination
GB0226593D0 (en) * 2002-11-14 2002-12-24 Consultants Ltd Compounds
EP1579005A4 (en) * 2002-11-15 2007-07-25 Sangamo Biosciences Inc METHOD AND COMPOSITIONS FOR THE ANALYSIS OF REGULATORY SEQUENCES
AU2003298655A1 (en) 2002-11-15 2004-06-15 Bioarray Solutions, Ltd. Analysis, secure access to, and transmission of array images
EP1420248A3 (de) * 2002-11-18 2004-05-26 Schott Glas Validiertes Design für Mikroarrays
AU2003291104A1 (en) * 2002-11-18 2004-06-15 Genospectra, Inc. Uncaging devices
US7314750B2 (en) * 2002-11-20 2008-01-01 Affymetrix, Inc. Addressable oligonucleotide array of the rat genome
US7250289B2 (en) * 2002-11-20 2007-07-31 Affymetrix, Inc. Methods of genetic analysis of mouse
US7781172B2 (en) 2003-11-21 2010-08-24 Kimberly-Clark Worldwide, Inc. Method for extending the dynamic detection range of assay devices
KR20050083971A (ko) * 2002-11-22 2005-08-26 더 존스 홉킨스 유니버시티 인지능 손상의 치료를 위한 표적
EP2112229A3 (en) 2002-11-25 2009-12-02 Sequenom, Inc. Methods for identifying risk of breast cancer and treatments thereof
US20040101861A1 (en) * 2002-11-27 2004-05-27 Little Roger G. Resonant cavity photodiode array for rapid DNA microarray readout
TWI255971B (en) * 2002-11-29 2006-06-01 Asml Netherlands Bv Lithographic apparatus and device manufacturing method
EP1424599B1 (en) * 2002-11-29 2008-03-12 ASML Netherlands B.V. Lithographic apparatus and device manufacturing method
US20040109045A1 (en) * 2002-12-06 2004-06-10 Eastman Kodak Company Print head for micro-deposition of bio-molecules
WO2004052939A2 (en) 2002-12-09 2004-06-24 Massachusetts Institute Of Technology Ligands for metals and improved metal-catalyzed processes based thereon
US20040259111A1 (en) * 2002-12-10 2004-12-23 Rosetta Inpharmatics Llc Automated system and method for preparing an assay ready biological sample
US20040115654A1 (en) * 2002-12-16 2004-06-17 Intel Corporation Laser exposure of photosensitive masks for DNA microarray fabrication
WO2004056868A2 (en) * 2002-12-19 2004-07-08 Endocube Sas Nf-hev compositions and methods of use
US7247500B2 (en) 2002-12-19 2007-07-24 Kimberly-Clark Worldwide, Inc. Reduction of the hook effect in membrane-based assay devices
US20040120859A1 (en) * 2002-12-20 2004-06-24 Kocher Thomas E. Biomolecular micro-deposition system
US9487823B2 (en) 2002-12-20 2016-11-08 Qiagen Gmbh Nucleic acid amplification
AU2003302264A1 (en) * 2002-12-20 2004-09-09 Biotrove, Inc. Assay apparatus and method using microfluidic arrays
US20060094108A1 (en) * 2002-12-20 2006-05-04 Karl Yoder Thermal cycler for microfluidic array assays
EP1583816A4 (en) * 2002-12-22 2007-06-13 Scripps Research Inst PROTEIN NETWORKS
US20040180368A1 (en) * 2002-12-23 2004-09-16 Affymetrix, Inc. Method for producing a high density nucleic acid array using activators
US7541152B2 (en) * 2002-12-24 2009-06-02 Agilent Technologies, Inc. Integrated light source for diagnostic arrays
US20040126766A1 (en) * 2002-12-26 2004-07-01 Amorese Douglas A. Breakaway seal for processing a subarray of an array
WO2004061616A2 (en) 2002-12-27 2004-07-22 Rosetta Inpharmatics Llc Computer systems and methods for associating genes with traits using cross species data
US6977153B2 (en) * 2002-12-31 2005-12-20 Qiagen Gmbh Rolling circle amplification of RNA
KR20050100367A (ko) * 2003-01-02 2005-10-18 바이오포스 나노사이언스, 인크. 소용적 샘플 내의 분자 분석용 방법 및 장치
ATE405592T1 (de) * 2003-01-13 2008-09-15 Univ Michigan Verfahren zur bildung eines protein- mikroarraysystems
US20060051879A9 (en) * 2003-01-16 2006-03-09 Hubert Koster Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions
KR100994566B1 (ko) * 2003-01-20 2010-11-15 삼성전자주식회사 고정화 영역을 갖는 포토레지스트 막을 포함하는 어레이장치 및 이를 이용한 표적 물질 검출방법
US7996155B2 (en) 2003-01-22 2011-08-09 Microsoft Corporation ANOVA method for data analysis
WO2004067191A2 (en) 2003-01-29 2004-08-12 President And Fellows Of Harward College Alteration of surface affinities
EP2159285B1 (en) 2003-01-29 2012-09-26 454 Life Sciences Corporation Methods of amplifying and sequencing nucleic acids
US7575865B2 (en) * 2003-01-29 2009-08-18 454 Life Sciences Corporation Methods of amplifying and sequencing nucleic acids
US20050048573A1 (en) * 2003-02-03 2005-03-03 Plexxikon, Inc. PDE5A crystal structure and uses
EP1599165A4 (en) 2003-02-10 2010-09-08 Univ Jefferson THE USE OF GCC LIGANDS
US20040157220A1 (en) 2003-02-10 2004-08-12 Purnima Kurnool Methods and apparatus for sample tracking
AU2004215006A1 (en) 2003-02-13 2004-09-10 The Regents Of The University Of California Methods and compositions for detection and analysis of polynucleotide-binding protein interactions using light harvesting multichromophores
US20070218071A1 (en) * 2003-09-15 2007-09-20 Morris David W Novel therapeutic targets in cancer
US7192703B2 (en) 2003-02-14 2007-03-20 Intel Corporation, Inc. Biomolecule analysis by rolling circle amplification and SERS detection
US20040170982A1 (en) * 2003-02-14 2004-09-02 Morris David W. Novel therapeutic targets in cancer
US7767387B2 (en) * 2003-06-13 2010-08-03 Sagres Discovery, Inc. Therapeutic targets in cancer
US20070149449A1 (en) 2003-02-14 2007-06-28 Morris David W Therapeutic targets in cancer
US20050014249A1 (en) * 2003-02-21 2005-01-20 Norbert Staimer Chromatographic analysis on optical bio-discs and methods relating thereto
US7759513B2 (en) * 2003-02-21 2010-07-20 Nigu Chemie Gmbh Photolabile protective groups for improved processes to prepare oligonucleotide arrays
US20040166495A1 (en) * 2003-02-24 2004-08-26 Greinwald John H. Microarray-based diagnosis of pediatric hearing impairment-construction of a deafness gene chip
CN1791682B (zh) 2003-02-26 2013-05-22 凯利达基因组股份有限公司 通过杂交进行的随机阵列dna分析
US20090124514A1 (en) * 2003-02-26 2009-05-14 Perlegen Sciences, Inc. Selection probe amplification
US20060183132A1 (en) * 2005-02-14 2006-08-17 Perlegen Sciences, Inc. Selection probe amplification
WO2004078923A2 (en) * 2003-02-28 2004-09-16 Plexxikon, Inc. Pyk2 crystal structure and uses
US20040235019A1 (en) * 2003-03-06 2004-11-25 Agouron Pharmaceuticals, Inc. Diagnostics and therapeutics for the gene expression signature of PPAR-gamma receptor ligand
EP3508578A1 (en) 2003-03-06 2019-07-10 BASF Enzymes, LLC Amylases, nucleic acids encoding them and methods for making and using them
DK2853593T3 (en) 2003-03-07 2018-01-08 Dsm Ip Assets Bv Hydrolases, nucleic acids encoding them, and processes for their preparation and use
US6970240B2 (en) * 2003-03-10 2005-11-29 Applera Corporation Combination reader
FR2852317B1 (fr) 2003-03-13 2006-08-04 Biopuces a sondes et leurs methodes d'utilisation
JP2004279196A (ja) * 2003-03-14 2004-10-07 Dainippon Printing Co Ltd バイオマイクロアレイ用基板およびバイオマイクロアレイ
US20040235022A1 (en) * 2003-03-19 2004-11-25 Ralf Mauritz Quality control method for manufacturing biopolymer arrays
WO2004087323A1 (en) * 2003-03-28 2004-10-14 Mergen Ltd. Multi-array systems and methods of use thereof
GB0307428D0 (en) 2003-03-31 2003-05-07 Medical Res Council Compartmentalised combinatorial chemistry
GB0307403D0 (en) 2003-03-31 2003-05-07 Medical Res Council Selection by compartmentalised screening
US20060078893A1 (en) 2004-10-12 2006-04-13 Medical Research Council Compartmentalised combinatorial chemistry by microfluidic control
EP1473085B1 (en) * 2003-03-31 2015-07-22 Canon Kabushiki Kaisha Biochemical reaction cartridge
US20040191782A1 (en) * 2003-03-31 2004-09-30 Yixin Wang Colorectal cancer prognostics
US20040223874A1 (en) * 2003-03-31 2004-11-11 Canon Kabushiki Kaisha Biochemical reaction cartridge
US8043834B2 (en) 2003-03-31 2011-10-25 Qiagen Gmbh Universal reagents for rolling circle amplification and methods of use
DE10315074A1 (de) 2003-04-02 2004-10-14 Clondiag Chip Technologies Gmbh Vorrichtung zur Vervielfältigung und zum Nachweis von Nukleinsäuren
US20040197819A1 (en) 2003-04-03 2004-10-07 Kimberly-Clark Worldwide, Inc. Assay devices that utilize hollow particles
WO2006102264A1 (en) 2005-03-18 2006-09-28 Fluidigm Corporation Thermal reaction device and method for using the same
US7666361B2 (en) 2003-04-03 2010-02-23 Fluidigm Corporation Microfluidic devices and methods of using same
US7851209B2 (en) 2003-04-03 2010-12-14 Kimberly-Clark Worldwide, Inc. Reduction of the hook effect in assay devices
US7604965B2 (en) 2003-04-03 2009-10-20 Fluidigm Corporation Thermal reaction device and method for using the same
WO2004090099A2 (en) 2003-04-04 2004-10-21 Diversa Corporation Pectate lyases, nucleic acids encoding them and methods for making and using them
CA2463719A1 (en) * 2003-04-05 2004-10-05 F. Hoffmann-La Roche Ag Nucleotide analogs with six membered rings
US7833714B1 (en) 2003-04-11 2010-11-16 Affymetrix, Inc. Combinatorial affinity selection
CA2521084A1 (en) 2003-04-14 2004-10-28 Nugen Technologies, Inc. Global amplification using a randomly primed composite primer
WO2004090161A1 (en) 2003-04-14 2004-10-21 Novartis Ag Gene expression associated with osteoblast differentiation
US20040210036A1 (en) * 2003-04-15 2004-10-21 Nanogen, Inc. Peptide substrate libraries
US8652774B2 (en) * 2003-04-16 2014-02-18 Affymetrix, Inc. Automated method of manufacturing polyer arrays
NZ543365A (en) 2003-04-18 2009-02-28 Biogen Idec Inc Polymer-conjugated glycosylated neublastin
US20070042349A1 (en) * 2003-04-24 2007-02-22 Ogle Brenda M Methods for assessing biologic diversity
US7892745B2 (en) 2003-04-24 2011-02-22 Xdx, Inc. Methods and compositions for diagnosing and monitoring transplant rejection
US20050064452A1 (en) * 2003-04-25 2005-03-24 Schmid Matthew J. System and method for the detection of analytes
EP1623010A4 (en) * 2003-04-25 2007-12-26 Janssen Pharmaceutica Nv PRESERVATION OF RNA IN A BIOLOGICAL SAMPLE
CN101675997B (zh) * 2003-05-02 2013-07-17 西安大略省大学 合成放射性药物中连接至甲锡烷基聚合物的辅基
GB0310270D0 (en) * 2003-05-03 2003-06-11 Univ Edinburgh Biomolecular devices
US20050136395A1 (en) * 2003-05-08 2005-06-23 Affymetrix, Inc Methods for genetic analysis of SARS virus
US20050025763A1 (en) 2003-05-08 2005-02-03 Protein Design Laboratories, Inc. Therapeutic use of anti-CS1 antibodies
US7709610B2 (en) 2003-05-08 2010-05-04 Facet Biotech Corporation Therapeutic use of anti-CS1 antibodies
EP1623020A4 (en) * 2003-05-09 2007-05-09 Sigma Aldrich Co GENOMIC AND PROTEOMIC APPROACHES FOR THE DEVELOPMENT OF CELL CULTURE MEDIA
JP2006524988A (ja) * 2003-05-09 2006-11-09 キャピタルバイオ コーポレーション Ｓａｒｓウイルスを検出するための方法および組成物
WO2004101790A1 (en) 2003-05-14 2004-11-25 Domantis Limited A process for recovering polypeptides that unfold reversibly from a polypeptide repertoire
WO2005018534A2 (en) * 2003-05-16 2005-03-03 Rosetta Inpharmatics, Llc Methods and compositions for rna interference
US7651850B2 (en) * 2003-05-16 2010-01-26 Board Of Regents, The University Of Texas System Image and part recognition technology
US9317922B2 (en) 2003-05-16 2016-04-19 Board Of Regents The University Of Texas System Image and part recognition technology
SE527896C2 (sv) * 2003-05-20 2006-07-04 Aamic Ab Optisk testanordning för biologiska prover, samt en microarray till anordningen och metoden för dess användning
JP3898198B2 (ja) * 2003-05-22 2007-03-28 韓国科学技術院 有機超分子の自己集合及び金属の化学吸着を用いたナノアレイの製作方法
WO2005020784A2 (en) * 2003-05-23 2005-03-10 Mount Sinai School Of Medicine Of New York University Surrogate cell gene expression signatures for evaluating the physical state of a subject
CA2526810A1 (en) * 2003-05-23 2005-04-21 Cold Spring Harbor Laboratory Virtual representations of nucleotide sequences
US20040241657A1 (en) * 2003-05-28 2004-12-02 Perlegen Sciences, Inc. Liver related disease compositions and methods
US20040241659A1 (en) * 2003-05-30 2004-12-02 Applera Corporation Apparatus and method for hybridization and SPR detection
US7729864B2 (en) 2003-05-30 2010-06-01 Merck Sharp & Dohme Corp. Computer systems and methods for identifying surrogate markers
FR2855832B1 (fr) * 2003-06-03 2007-09-14 Biomerieux Sa Procede de diagnostic et/ou de pronostic d'un syndrome septique
KR100549103B1 (ko) * 2003-06-05 2006-02-06 한국과학기술원 탄소나노튜브 어레이의 제작방법
US20040248323A1 (en) 2003-06-09 2004-12-09 Protometrix, Inc. Methods for conducting assays for enzyme activity on protein microarrays
WO2005000098A2 (en) 2003-06-10 2005-01-06 The Trustees Of Boston University Detection methods for disorders of the lung
ES2920892T3 (es) 2003-06-12 2022-08-11 Accupath Diagnostic Laboratories Inc Método para formar matrices de células
US8133670B2 (en) 2003-06-13 2012-03-13 Cold Spring Harbor Laboratory Method for making populations of defined nucleic acid molecules
WO2005003301A2 (en) * 2003-06-17 2005-01-13 Signal Pharmaceuticals, Inc. Methods, compositions, and kits for predicting the effect of compounds on hot flash symptoms
US20040259100A1 (en) 2003-06-20 2004-12-23 Illumina, Inc. Methods and compositions for whole genome amplification and genotyping
JP4367901B2 (ja) * 2003-06-20 2009-11-18 キヤノン株式会社 スポット・パターン暗号化機能を具えるスポッター、ならびにスポット・パターン暗号化に対応した検出装置
US7642064B2 (en) * 2003-06-24 2010-01-05 Ventana Medical Systems, Inc. Enzyme-catalyzed metal deposition for the enhanced detection of analytes of interest
ES2330441T3 (es) * 2003-06-24 2009-12-10 Ventana Medical Systems, Inc. Deposito de metal catalizado por una enzima para la deteccion in situ mejorada de epitopos inmunohistoquimicos y secuencias de acido nucleico.
US20070166721A1 (en) * 2003-06-27 2007-07-19 Phan Brigitte C Fluidic circuits, methods and apparatus for use of whole blood samples in colorimetric assays
US7534563B2 (en) * 2003-06-30 2009-05-19 Agilent Technologies, Inc. Methods for producing ligand arrays
US20050158733A1 (en) * 2003-06-30 2005-07-21 Gerber David J. EGR genes as targets for the diagnosis and treatment of schizophrenia
CN100494399C (zh) * 2003-06-30 2009-06-03 清华大学 一种基于dna芯片的基因分型方法及其应用
US7960148B2 (en) 2003-07-02 2011-06-14 Verenium Corporation Glucanases, nucleic acids encoding them and methods for making and using them
US20050079548A1 (en) * 2003-07-07 2005-04-14 Plexxikon, Inc. Ligand development using PDE4B crystal structures
FR2857375B1 (fr) * 2003-07-10 2007-11-09 Biomerieux Sa Procede de detection et/ou d'identification de bacteries de genre staphylococcus
US7341841B2 (en) 2003-07-12 2008-03-11 Accelr8 Technology Corporation Rapid microbial detection and antimicrobial susceptibility testing
US20120077206A1 (en) 2003-07-12 2012-03-29 Accelr8 Technology Corporation Rapid Microbial Detection and Antimicrobial Susceptibility Testing
CA2532414C (en) 2003-07-12 2017-03-14 Accelr8 Technology Corporation Sensitive and rapid biodetection
WO2005007678A2 (en) * 2003-07-14 2005-01-27 Irm Llc Methods for the preparation of rhodamine
WO2005007663A2 (en) * 2003-07-14 2005-01-27 Irm Llc Fluorogenic enzyme substrates and uses thereof
US20050019944A1 (en) * 2003-07-23 2005-01-27 Eastman Kodak Company Colorable microspheres for DNA and protein microarray
US7545494B2 (en) * 2003-07-23 2009-06-09 Bayer Technology Services Gmbh Analytical system and method for analyzing nonlinear optical signals
US20050059054A1 (en) 2003-07-25 2005-03-17 Richard Conrad Methods and compositions for preparing RNA from a fixed sample
US20050059024A1 (en) 2003-07-25 2005-03-17 Ambion, Inc. Methods and compositions for isolating small RNA molecules
US8114978B2 (en) 2003-08-05 2012-02-14 Affymetrix, Inc. Methods for genotyping selected polymorphism
WO2005017652A2 (en) * 2003-08-05 2005-02-24 Rosetta Inpharmatics, Llc Computer systems and methods for inferring causality from cellular constituent abundance data
US20050100911A1 (en) * 2003-08-06 2005-05-12 Perlegen Sciences, Inc. Methods for enriching populations of nucleic acid samples
US7317415B2 (en) 2003-08-08 2008-01-08 Affymetrix, Inc. System, method, and product for scanning of biological materials employing dual analog integrators
CA2535526C (en) 2003-08-11 2015-09-29 Diversa Corporation Laccases, nucleic acids encoding them and methods for making and using them
US20070026406A1 (en) * 2003-08-13 2007-02-01 Iconix Pharmaceuticals, Inc. Apparatus and method for classifying multi-dimensional biological data
CN1580283A (zh) * 2003-08-13 2005-02-16 清华大学 一种检测核酸分子的方法
KR100561842B1 (ko) * 2003-08-25 2006-03-16 삼성전자주식회사 단량체 광산발생제 조성물, 상기 조성물로 코팅된 기판,상기 단량체 광산발생제 조성물을 이용하여 기판상에서화합물을 합성하는 방법 및 상기 방법에 의하여 제조된마이크로어레이
US7723295B2 (en) * 2003-08-28 2010-05-25 Ortho-Mcneil Pharmaceutical, Inc. Peptides and compounds that bind to a receptor
SI1675606T1 (sl) * 2003-08-28 2017-07-31 Janssen Pharmaceuticals, Inc. Peptidi in spojine, ki se vežejo na trombopoietinske receptorje
US7217582B2 (en) 2003-08-29 2007-05-15 Rochester Institute Of Technology Method for non-damaging charge injection and a system thereof
US7287328B2 (en) 2003-08-29 2007-10-30 Rochester Institute Of Technology Methods for distributed electrode injection
JP3824233B2 (ja) * 2003-09-01 2006-09-20 セイコーエプソン株式会社 バイオセンサ及びバイオセンサの製造方法
US8131475B2 (en) 2003-09-03 2012-03-06 The United States Of America As Represented By The Secretary, Department Of Health And Human Services Methods for identifying, diagnosing, and predicting survival of lymphomas
CA2537254A1 (en) 2003-09-03 2005-03-17 Government Of The United States Of America, As Represented By Secretary, Department Of Health And Human Services Methods for identifying, diagnosing, and predicting survival of lymphomas
US20050095627A1 (en) * 2003-09-03 2005-05-05 The Salk Institute For Biological Studies Multiple antigen detection assays and reagents
US7269517B2 (en) * 2003-09-05 2007-09-11 Rosetta Inpharmatics Llc Computer systems and methods for analyzing experiment design
US20050053949A1 (en) * 2003-09-08 2005-03-10 Silin Vitalii Ivanovich Biochip for proteomics applications
WO2005023993A2 (en) 2003-09-09 2005-03-17 Integrigen, Inc. Methods and compositions for generation of germline human antibody genes
WO2005026686A2 (en) * 2003-09-09 2005-03-24 Compass Genetics, Llc Multiplexed analytical platform
CA2536565A1 (en) * 2003-09-10 2005-05-12 Althea Technologies, Inc. Expression profiling using microarrays
GB0321295D0 (en) * 2003-09-11 2003-10-15 Spirogen Ltd Synthesis of protected pyrrolobenzodiazepines
WO2005028624A2 (en) * 2003-09-15 2005-03-31 Plexxikon, Inc. Molecular scaffolds for kinase ligand development
US20050084914A1 (en) * 2003-09-15 2005-04-21 Foulkes J. G. Assays with primary cells
US7488451B2 (en) * 2003-09-15 2009-02-10 Millipore Corporation Systems for particle manipulation
US7317521B2 (en) * 2003-09-18 2008-01-08 Micron Technology, Inc. Particle detection method
WO2005029705A2 (en) 2003-09-18 2005-03-31 Bioarray Solutions, Ltd. Number coding for identification of subtypes of coded types of solid phase carriers
US20050100939A1 (en) * 2003-09-18 2005-05-12 Eugeni Namsaraev System and methods for enhancing signal-to-noise ratios of microarray-based measurements
US20050233472A1 (en) * 2003-09-19 2005-10-20 Kao H P Spotting high density plate using a banded format
US20070111209A1 (en) * 2003-09-19 2007-05-17 Soley Bjornsdottir Inversion on chromosome 8p23 is a risk factor for anxiety disorders, depression and bipolar disorders
US20050226771A1 (en) * 2003-09-19 2005-10-13 Lehto Dennis A High speed microplate transfer
ATE532066T1 (de) 2003-09-22 2011-11-15 Bioarray Solutions Ltd Oberflächenimmobilisierter polyelektrolyt mit mehreren, zur kovalenten bindung an biomoleküle fähigen funktionellen gruppen
WO2005031322A1 (ja) * 2003-09-26 2005-04-07 Nikon Corporation 環境保持装置および環境制御型分析装置
WO2005031335A1 (ja) * 2003-09-26 2005-04-07 Mitsubishi Rayon Co., Ltd. 電気泳動装置および電気泳動法並びにそれを用いた生体関連物質の検出方法
EP2612853A1 (en) * 2003-09-26 2013-07-10 Exelixis Inc. c-Met modulators and methods of use
JP2007507770A (ja) 2003-09-29 2007-03-29 パスワーク インフォーマティクス，インコーポレーテッド 生物学的特徴を検出するためのシステムおよび方法
US20070281896A1 (en) * 2003-09-30 2007-12-06 Morris David W Novel compositions and methods in cancer
FR2860518B1 (fr) * 2003-10-01 2006-02-17 Biomerieux Sa Procede pour le diagnostic/pronostic du neuroblastome
DE10346286B3 (de) 2003-10-06 2005-04-14 J. Eberspächer GmbH & Co. KG Abgasreinigungsanordnung
DK1673475T3 (da) 2003-10-10 2010-07-19 Deutsches Krebsforsch Sammensætninger til diagnose og terapi af sygdomme, som er forbundet med aberrant ekspression af futriner (R-Spondiner) og/eller Wnt
WO2005035569A2 (en) * 2003-10-10 2005-04-21 Five Prime Therapeutics, Inc. Kiaa0779, splice variants thereof, and methods of their use
US20050227251A1 (en) 2003-10-23 2005-10-13 Robert Darnell Method of purifying RNA binding protein-RNA complexes
WO2005040163A1 (en) * 2003-10-28 2005-05-06 Dr. Reddy's Laboratories Ltd Heterocyclic compounds that block the effects of advanced glycation end products (age)
NZ547492A (en) 2003-10-28 2009-12-24 Bioarray Solutions Ltd Optimization of gene expression analysis using immobilized capture probes of different lengths and densities
JP2007509629A (ja) 2003-10-29 2007-04-19 バイオアレイ ソリューションズ リミテッド 二本鎖ｄｎａの切断による複合核酸分析
US20070212689A1 (en) * 2003-10-30 2007-09-13 Bianchi Diana W Prenatal Diagnosis Using Cell-Free Fetal DNA in Amniotic Fluid
US20050239102A1 (en) * 2003-10-31 2005-10-27 Verdine Gregory L Nucleic acid binding oligonucleotides
US20050095600A1 (en) * 2003-10-31 2005-05-05 Xiang Yu Methods of generating gene-specific probes for nucleic acid array detection
US20050095578A1 (en) * 2003-10-31 2005-05-05 Koller Manfred R. Method and apparatus for cell permeabilization
EP1682897A2 (en) * 2003-11-04 2006-07-26 Roche Diagnostics GmbH Method for distinguishing immunologically defined all subtypes
EP1682902A2 (en) * 2003-11-04 2006-07-26 Roche Diagnostics GmbH Method for distinguishing mll-ptd-positive aml from other aml subtypes
US20050287668A1 (en) * 2003-11-04 2005-12-29 Cell Therapeutics, Inc. (Cti) RNA interference compositions and screening methods for the identification of novel genes and biological pathways
EP1682898A2 (en) * 2003-11-04 2006-07-26 Roche Diagnostics GmbH Method for distinguishing aml subtypes with recurring genetic aberrations
WO2005043161A2 (en) * 2003-11-04 2005-05-12 Roche Diagnostics Gmbh Method for distinguishing leukemia subtypes
WO2005043167A2 (en) * 2003-11-04 2005-05-12 Roche Diagnostic Gmbh Method for distinguishing aml subtypes with differents gene dosages
EP1533618A1 (en) * 2003-11-04 2005-05-25 Ludwig-Maximilians-Universität München Method for distinguishing prognostically definable AML
WO2005043168A2 (en) * 2003-11-04 2005-05-12 Roche Diagnostics Gmbh Method for distinguishing aml-specific flt3 length mutations from tkd mutations
EP1682900A2 (en) * 2003-11-04 2006-07-26 Roche Diagnostics GmbH METHOD FOR DISTINGUISHING T(11q23)/MLL-POSITIVE LEUKEMIAS FROM T(11q23)MLL NEGATIVE LEUKEMIAS
WO2005043164A2 (en) * 2003-11-04 2005-05-12 Roche Diagnostics Gmbh Method for distinguishing cbf-positive aml subtypes from cbf-negative aml subtypes
EP1530046A1 (en) * 2003-11-04 2005-05-11 Ludwig-Maximilians-Universität München Method for distinguishing AML subtypes with aberrant and prognostically intermediate karyotypes
EP1685395A2 (en) * 2003-11-05 2006-08-02 EXACT Sciences Corporation Repetitive reversed-field affinity electrophoresis and uses therefor
WO2005047521A2 (en) * 2003-11-10 2005-05-26 Investigen, Inc. Methods of preparing nucleic acid for detection
US7169560B2 (en) * 2003-11-12 2007-01-30 Helicos Biosciences Corporation Short cycle methods for sequencing polynucleotides
EP1689879A4 (en) * 2003-11-12 2008-08-27 Geneohm Sciences Inc METHODS OF HYBRIDIZING NUCLEIC ACID
US8367324B2 (en) * 2003-11-17 2013-02-05 Canon Kabushiki Kaisha Method for judging change in probe-bearing substrate, probe-bearing substrate and detecting apparatus
KR100543705B1 (ko) * 2003-11-20 2006-01-20 삼성전자주식회사 2차원적 격자가 형성되어 있는 기판을 포함하는 마이크로 어레이 및 그를 이용하는 표적 분자의 검출방법
US7943395B2 (en) 2003-11-21 2011-05-17 Kimberly-Clark Worldwide, Inc. Extension of the dynamic detection range of assay devices
US7713748B2 (en) 2003-11-21 2010-05-11 Kimberly-Clark Worldwide, Inc. Method of reducing the sensitivity of assay devices
US20050112703A1 (en) 2003-11-21 2005-05-26 Kimberly-Clark Worldwide, Inc. Membrane-based lateral flow assay devices that utilize phosphorescent detection
KR100580631B1 (ko) * 2003-11-22 2006-05-16 삼성전자주식회사 산화막을 갖는 기판, 그를 이용한 표적 물질 검출 방법 및광학적 센서
US7456968B2 (en) * 2003-11-24 2008-11-25 General Electric Company Sensor system and methods for improved quantitation of environmental parameters
US20050112587A1 (en) * 2003-11-25 2005-05-26 Sherrill James V. Analyzing biological probes
WO2005054494A2 (en) 2003-11-26 2005-06-16 University Of Massachusetts Sequence-specific inhibition of small rna function
EP1709198B1 (en) 2003-11-26 2013-08-14 AdvanDx, Inc. Peptide nucleic acid probes for analysis of certain staphylococcus species
EP1697534B1 (en) 2003-12-01 2010-06-02 Life Technologies Corporation Nucleic acid molecules containing recombination sites and methods of using the same
US7824857B2 (en) * 2003-12-02 2010-11-02 Musc Foundation For Research Development Methods and compositions for diagnosing epithelial cell cancer
KR100695123B1 (ko) * 2003-12-03 2007-03-14 삼성전자주식회사 Ｔｍ에 따라 기판상에 고정화된 프로브 폴리뉴클레오티드군을 2이상 포함하는 폴리뉴클레오티드 어레이 및 그를이용하는 표적 핵산 검출 방법
JP2005173484A (ja) * 2003-12-15 2005-06-30 Canon Inc 画像形成装置及びプロセスカートリッジ
WO2005058471A2 (en) * 2003-12-15 2005-06-30 Applera Corporation Automated oligomer synthesis
US20050136538A1 (en) * 2003-12-17 2005-06-23 Srikant Pathak Lithographic method for attaching biological cells to a solid substrate using a small molecule linker
KR100601936B1 (ko) * 2003-12-17 2006-07-14 삼성전자주식회사 접착부 지지체와 2이상의 접착물질을 갖는 마이크로어레이반응 챔버용 패취
US7943089B2 (en) 2003-12-19 2011-05-17 Kimberly-Clark Worldwide, Inc. Laminated assay devices
EP1696920B8 (en) 2003-12-19 2015-05-06 Plexxikon Inc. Compounds and methods for development of ret modulators
US20070066641A1 (en) * 2003-12-19 2007-03-22 Prabha Ibrahim Compounds and methods for development of RET modulators
CA2490675A1 (en) * 2003-12-22 2005-06-22 Affymetrix, Inc. Process for high-yield synthesis of standard length and long-mer nucleic acid arrays
AU2004303448A1 (en) 2003-12-23 2005-07-07 Mount Sinai Hospital Methods for detecting markers associated with endometrial disease or phase
WO2005065321A2 (en) 2003-12-29 2005-07-21 Nugen Technologies, Inc. Methods for analysis of nucleic acid methylation status and methods for fragmentation, labeling and immobilization of nucleic acids
WO2005067649A2 (en) * 2004-01-08 2005-07-28 The Ohio State University Use of databases to create gene expression microarrays
KR100580642B1 (ko) * 2004-01-12 2006-05-16 삼성전자주식회사 표면에 활성화된 카르복실기를 갖는 기판을 이용하여 생물분자를 고체 기판상에 고밀도로 고정화하는 방법 및 그에 의하여 제조되는 마이크로어레이
US7670771B2 (en) 2004-01-21 2010-03-02 University Of Utah Research Foundation Mutant sodium channel Nav1.7 nucleic acid methods
US20080113874A1 (en) * 2004-01-23 2008-05-15 The Regents Of The University Of Colorado Gefitinib sensitivity-related gene expression and products and methods related thereto
US8017321B2 (en) * 2004-01-23 2011-09-13 The Regents Of The University Of Colorado, A Body Corporate Gefitinib sensitivity-related gene expression and products and methods related thereto
EP1709565B1 (en) * 2004-01-26 2007-08-01 Nimblegen Systems, Inc. Computer software to assist in identifying snps with microarrays
EP1713900A4 (en) * 2004-01-27 2009-06-17 Compugen Ltd METHOD AND SYSTEMS FOR COMMENTING BIOMOLECULAR SEQUENCES
EP1716227A4 (en) * 2004-01-27 2010-01-06 Compugen Ltd METHOD OF IDENTIFYING PUTATIVE GENE PRODUCTS USING THE INTERSPEZIES SEQUENCE COMPARISON AND BIOMOLECULAR SEQUENCES DISCOVERED THEREFOR
US20100216863A1 (en) * 2004-01-30 2010-08-26 Decode Genetics Ehf. Susceptibility Gene for Myocardial Infarction, Stroke, and PAOD; Methods of Treatment
US8158362B2 (en) * 2005-03-30 2012-04-17 Decode Genetics Ehf. Methods of diagnosing susceptibility to myocardial infarction and screening for an LTA4H haplotype
DE602005018166D1 (de) * 2004-02-12 2010-01-21 Population Genetics Technologi Genetische analyse mittels sequenzspezifischem sortieren
US20050272059A1 (en) * 2004-02-12 2005-12-08 Xiaolian Gao Method for providing microarrays
JP4464158B2 (ja) * 2004-02-13 2010-05-19 キヤノン株式会社 生化学反応カートリッジ
KR100580644B1 (ko) 2004-02-16 2006-05-16 삼성전자주식회사 생물분자를 고체 기판상에 비공유적으로 고정화 하는 방법및 그에 의하여 제조되는 마이크로어레이
US20050191682A1 (en) 2004-02-17 2005-09-01 Affymetrix, Inc. Methods for fragmenting DNA
EP1723260A4 (en) * 2004-02-17 2008-05-28 Dana Farber Cancer Inst Inc REPRESENTATION OF NUCLEIC ACID USING COLD PRODUCTS OF TYPE IIB RESTRICTION ENDONUCLEASE
US7433123B2 (en) 2004-02-19 2008-10-07 Illumina, Inc. Optical identification element having non-waveguide photosensitive substrate with diffraction grating therein
US8581308B2 (en) 2004-02-19 2013-11-12 Rochester Institute Of Technology High temperature embedded charge devices and methods thereof
US7981604B2 (en) 2004-02-19 2011-07-19 California Institute Of Technology Methods and kits for analyzing polynucleotide sequences
US20050186577A1 (en) 2004-02-20 2005-08-25 Yixin Wang Breast cancer prognostics
AU2005216949B2 (en) 2004-02-24 2011-09-22 The General Hospital Corporation Catalytic radiofluorination
US20050266432A1 (en) * 2004-02-26 2005-12-01 Illumina, Inc. Haplotype markers for diagnosing susceptibility to immunological conditions
US20060046258A1 (en) * 2004-02-27 2006-03-02 Lapidus Stanley N Applications of single molecule sequencing
US20050209785A1 (en) * 2004-02-27 2005-09-22 Wells Martin D Systems and methods for disease diagnosis
US7981616B2 (en) * 2004-02-27 2011-07-19 Musc Foundation For Research Development Enhanced detection of RNA using a panel of truncated gene-specific primers for reverse transcription
US20100216153A1 (en) 2004-02-27 2010-08-26 Helicos Biosciences Corporation Methods for detecting fetal nucleic acids and diagnosing fetal abnormalities
JP2007534320A (ja) * 2004-02-27 2007-11-29 プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ ポリヌクレオチド合成法
GB0404578D0 (en) * 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
JP4024828B2 (ja) * 2004-03-04 2007-12-19 良一 今中 マイクロアレイ及びスポッティング装置
KR100590550B1 (ko) * 2004-03-12 2006-06-19 삼성전자주식회사 동일한 표적핵산에 결합하는 프로브 폴리뉴클레오티드사이의 거리가 최대가 되도록 배열되어 있는마이크로어레이 및 그를 제조하는 방법
JP2007529015A (ja) 2004-03-12 2007-10-18 バイオトローブ， インコーポレイテッド ナノリットルのアレイローディング
US7425426B2 (en) 2004-03-15 2008-09-16 Cyntellect, Inc. Methods for purification of cells based on product secretion
CN1934447B (zh) * 2004-03-17 2010-11-10 松下电器产业株式会社 生物芯片的制造方法
EP1729130B1 (en) * 2004-03-18 2011-10-05 Nissui Pharmaceutical Co., Ltd. Method of preparing analytical device and kit
KR100882249B1 (ko) 2004-03-24 2009-02-06 트리패스 이미징, 인코포레이티드 자궁경부 질환의 검사 방법 및 조성물
US20050269523A1 (en) * 2004-03-24 2005-12-08 Macaulay Calum E Light modulated microarray reader and methods relating thereto
US7265366B2 (en) * 2004-03-31 2007-09-04 Asml Netherlands B.V. Lithographic apparatus and device manufacturing method
US20050221339A1 (en) 2004-03-31 2005-10-06 Medical Research Council Harvard University Compartmentalised screening by microfluidic control
WO2005100995A2 (en) * 2004-04-06 2005-10-27 Mount Sinai School Of Medicine Methods of determining allergen response using microarray imminoassay techinques
US7745118B2 (en) * 2004-04-08 2010-06-29 Roche Nimblegen, Inc. Comparative genomic resequencing
KR100624420B1 (ko) * 2004-04-10 2006-09-19 삼성전자주식회사 마이크로어레이에 대한 정보가 스팟의 형태로 저장되어있는 마이크로어레이, 그를 제조하는 방법 및 그를이용하는 방법
US20050226535A1 (en) * 2004-04-13 2005-10-13 Srinka Ghosh Method and system for rectilinearizing an image of a microarray having a non-rectilinear feature arrangement
CA2563168A1 (en) * 2004-04-14 2005-11-17 President And Fellows Of Harvard College Nucleic-acid programmable protein arrays
US20050239085A1 (en) * 2004-04-23 2005-10-27 Buzby Philip R Methods for nucleic acid sequence determination
US20080248465A1 (en) * 2004-04-26 2008-10-09 Uab Research Foundation Polymorphisms in the Fcgr2b Promoter and Uses Thereof
WO2006001896A2 (en) * 2004-04-26 2006-01-05 Iconix Pharmaceuticals, Inc. A universal gene chip for high throughput chemogenomic analysis
US20050244984A1 (en) * 2004-04-28 2005-11-03 Parker Russell A Methods and compositions for calibrating chemical array readers
KR100580649B1 (ko) 2004-04-30 2006-05-16 삼성전자주식회사 결합 특이성이 개선된 폴리뉴클레오티드 프로브, 상기프로브가 고정화되어 있는 마이크로어레이 및 상기프로브를 설계하는 방법
US8185367B2 (en) * 2004-04-30 2012-05-22 Merck Sharp & Dohme Corp. Systems and methods for reconstructing gene networks in segregating populations
US20050250108A1 (en) * 2004-05-04 2005-11-10 Jose Remacle Preparation method and use of micro-arrays supports for detection of multiple polynucleotide sequences with high sensitivity
DE102004021904B4 (de) * 2004-05-04 2011-08-18 Carl Zeiss Microlmaging GmbH, 07745 Verfahren und Vorrichtung zur Erzeugung einer Analyseanordnung mit diskreten, separaten Messbereichen zur biologischen, biochemischen oder chemischen Analyse
WO2006078287A2 (en) 2004-05-06 2006-07-27 Plexxikon, Inc. Pde4b inhibitors and uses therefor
DE102005052713A1 (de) 2005-11-04 2007-05-16 Clondiag Chip Tech Gmbh Vorrichtung und Verfahren zum Nachweis von molekularen Wechselwirkungen
DE102004022263A1 (de) 2004-05-06 2005-12-15 Clondiag Chip Technologies Gmbh Vorrichtung und Verfahren zum Nachweis von molekularen Wechselwirkungen
WO2005111242A2 (en) * 2004-05-10 2005-11-24 Parallele Bioscience, Inc. Digital profiling of polynucleotide populations
AU2005280659A1 (en) * 2004-05-11 2006-03-09 Wyeth Novel polynucleotides related to oligonucleotide arrays to monitor gene expression
US8135595B2 (en) 2004-05-14 2012-03-13 H. Lee Moffitt Cancer Center And Research Institute, Inc. Computer systems and methods for providing health care
WO2005113834A2 (en) * 2004-05-20 2005-12-01 Quest Diagnostics Investments Incorporated Single label comparative hybridization
EP2302394A1 (en) 2004-05-21 2011-03-30 The Institute for Systems Biology Compositions and methods for quantification of serum glycoproteins
US20050260609A1 (en) * 2004-05-24 2005-11-24 Lapidus Stanley N Methods and devices for sequencing nucleic acids
JP2008512084A (ja) 2004-05-25 2008-04-24 ヘリコス バイオサイエンシーズ コーポレイション 核酸の配列決定のための方法およびデバイス
US7476734B2 (en) 2005-12-06 2009-01-13 Helicos Biosciences Corporation Nucleotide analogs
WO2005118129A1 (en) * 2004-05-27 2005-12-15 Stratos Biosystems, Llc Solid-phase affinity-based method for preparing and manipulating an analyte-containing solution
ES2537631T3 (es) * 2004-05-27 2015-06-10 The Regents Of The University Of Colorado Métodos para la predicción del resultado clínico para inhibidores del receptor del factor de crecimiento epidérmico para pacientes de cáncer
EP1771563A2 (en) 2004-05-28 2007-04-11 Ambion, Inc. METHODS AND COMPOSITIONS INVOLVING MicroRNA
US7338763B2 (en) * 2004-06-02 2008-03-04 Eppendorf Array Technologies S.A. Method and kit for the detection and/or quantification of homologous nucleotide sequences on arrays
US7302348B2 (en) 2004-06-02 2007-11-27 Agilent Technologies, Inc. Method and system for quantifying and removing spatial-intensity trends in microarray data
EP2527447A1 (en) 2004-06-03 2012-11-28 Athlomics Pty Ltd Agents and methods for diagnosing stress
JP3952042B2 (ja) * 2004-06-07 2007-08-01 ソニー株式会社 凹状部位を有する電極を備えるハイブリダイゼーション検出部と該検出部を備えるｄｎａチップ
US8273579B2 (en) * 2004-06-08 2012-09-25 Bizpac (Australia) Pty. Ltd. Method and apparatus for inspecting biological samples
WO2005124650A2 (en) * 2004-06-10 2005-12-29 Iconix Pharmaceuticals, Inc. Sufficient and necessary reagent sets for chemogenomic analysis
KR100634505B1 (ko) * 2004-06-16 2006-10-16 삼성전자주식회사 패턴화된 박막층을 갖는 마이크로어레이 기판 및마이크로어레이, 상기 마이크로어레이 기판 및마이크로어레이를 제조하는 방법
CN103173282A (zh) 2004-06-16 2013-06-26 帝斯曼知识产权资产管理有限公司 对叶绿素进行酶促脱色的组合物和方法
US7498342B2 (en) * 2004-06-17 2009-03-03 Plexxikon, Inc. Compounds modulating c-kit activity
JP2008503473A (ja) * 2004-06-17 2008-02-07 プレキシコン，インコーポレーテッド Ｃ−ｋｉｔ活性を調節する化合物
JP2008503222A (ja) * 2004-06-18 2008-02-07 ニンブルゲン システムズ インコーポレイテッド 可変長プローブ選択
CA2572176A1 (en) * 2004-06-21 2006-01-05 Nimblegen Systems, Inc. Probe optimization methods
US8034553B2 (en) 2004-06-24 2011-10-11 Kimberly-Clark Worldwide, Inc. Biomarkers for wound healing
US7692219B1 (en) 2004-06-25 2010-04-06 University Of Hawaii Ultrasensitive biosensors
US20060003335A1 (en) * 2004-06-30 2006-01-05 Crispino John D Methods for diagnosing acute megakaryoblastic leukemia
US7521226B2 (en) 2004-06-30 2009-04-21 Kimberly-Clark Worldwide, Inc. One-step enzymatic and amine detection technique
US20060004527A1 (en) * 2004-07-01 2006-01-05 Sampas Nicholas M Methods, systems and computer readable media for identifying dye-normalization probes
AU2005271960B2 (en) 2004-07-09 2011-12-08 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Identification of markers in lung and breast cancer
US20060009038A1 (en) * 2004-07-12 2006-01-12 International Business Machines Corporation Processing for overcoming extreme topography
US20060014680A1 (en) * 2004-07-13 2006-01-19 Caiding Xu Peptides and compounds that bind to the IL-5 receptor
JP4756835B2 (ja) * 2004-07-14 2011-08-24 キヤノン株式会社 生化学反応カートリッジ
US7588892B2 (en) * 2004-07-19 2009-09-15 Entelos, Inc. Reagent sets and gene signatures for renal tubule injury
US20060024677A1 (en) 2004-07-20 2006-02-02 Morris David W Novel therapeutic targets in cancer
WO2006020363A2 (en) 2004-07-21 2006-02-23 Illumina, Inc. Method and apparatus for drug product tracking using encoded optical identification elements
WO2006007664A1 (en) * 2004-07-22 2006-01-26 Genomics Research Partners Pty Ltd Agents and methods for diagnosing osteoarthritis
WO2006022628A1 (en) * 2004-07-22 2006-03-02 Sequenom, Inc. Methods for identifying risk of type ii diabetes and treatments thereof
AU2005269527B2 (en) 2004-07-26 2011-12-01 Pfenex Inc. Process for improved protein expression by strain engineering
US8563328B2 (en) * 2004-07-26 2013-10-22 University Of Louisville Research Foundation, Inc. Fiber-optic biosensor and biosensing methods
CN101087890A (zh) * 2004-07-26 2007-12-12 帕拉列勒生物科学公司 多个基因组的同时分析
FR2873697B1 (fr) * 2004-07-28 2006-10-27 Commissariat Energie Atomique Agents de couplage a groupement protecteur photolabile et leurs utilisations, notamment pour la fonctionnalisation de supports solides
AU2005267756A1 (en) * 2004-07-30 2006-02-09 Rosetta Inpharmatics Llc Prognosis of breast cancer patients
US7848889B2 (en) 2004-08-02 2010-12-07 Bioarray Solutions, Ltd. Automated analysis of multiplexed probe-target interaction patterns: pattern matching and allele identification
US12070731B2 (en) 2004-08-04 2024-08-27 Life Technologies Corporation Methods and systems for aligning dispensing arrays with microfluidic sample arrays
US20060105453A1 (en) * 2004-09-09 2006-05-18 Brenan Colin J Coating process for microfluidic sample arrays
US7393903B2 (en) * 2004-08-04 2008-07-01 Guerry Grune Devices and methods for the rapid, reliable detection and determination of acrylamide concentration in food substances and prevention of acrylamide formation in the same
EP1623996A1 (en) * 2004-08-06 2006-02-08 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Improved method of selecting a desired protein from a library
RU2431676C2 (ru) 2004-08-06 2011-10-20 Дженентек, Инк. Анализы и способы с применением биомаркеров
EP2292794A3 (en) 2004-08-06 2011-07-06 Genentech, Inc. Death receptor (DR) antibody for pharmaceutical use and assays employing biomarkers for predicting sensitivity of cells to said antibody
US20060210542A1 (en) * 2004-08-16 2006-09-21 Yurkow Edward J Use of TPO mimetic compounds and pharmaceutical compositions in the treatment of anemia
EP1789786A4 (en) * 2004-08-18 2008-02-13 Abbott Molecular Inc DETERMINING DATA QUALITY AND / OR SEGMENTAL ANEUMS USING A COMPUTER SYSTEM
US20090087848A1 (en) * 2004-08-18 2009-04-02 Abbott Molecular, Inc. Determining segmental aneusomy in large target arrays using a computer system
US8722862B2 (en) * 2004-08-19 2014-05-13 Biogen Idec Ma Inc. Refolding transforming growth factor beta family proteins
EA013565B1 (ru) * 2004-08-19 2010-06-30 Байоджен Айдек Ма Инк. Варианты полипептидов нейбластина, способы их получения и их применение
US7598080B2 (en) 2004-08-20 2009-10-06 Carl Deirmengian Diagnostic assay for source of inflammation
KR100657896B1 (ko) * 2004-08-20 2006-12-14 삼성전자주식회사 Ｕｖ 필름을 이용한 활성기 또는 프로브 분자가고정화되어 있는 기판의 보관 방법, ｕｖ 필름을 이용한마이크로어레이의 제조방법 및 ｕｖ 필름이 부착된 기판
US20060046252A1 (en) * 2004-08-30 2006-03-02 Srinka Ghosh Method and system for developing probes for dye normalization of microarray signal-intensity data
EP1792263A2 (en) * 2004-09-02 2007-06-06 Vialogy Corporation Detecting events of interest using quantum resonance interferometry
WO2006028930A2 (en) * 2004-09-03 2006-03-16 Receptors Llc Combinatorial artificial receptors including tether building blocks on scaffolds
US7323308B2 (en) * 2004-09-03 2008-01-29 Affymetrix, Inc. Methods of genetic analysis of E. coli
US7312035B2 (en) * 2004-09-03 2007-12-25 Affymetrix, Inc. Methods of genetic analysis of yeast
EP1786813A2 (en) * 2004-09-03 2007-05-23 Plexxikon, Inc. Bicyclic heteroaryl pde4b inhibitors
US7645575B2 (en) 2004-09-08 2010-01-12 Xdx, Inc. Genes useful for diagnosing and monitoring inflammation related disorders
US7985715B2 (en) * 2004-09-11 2011-07-26 Receptors Llc Combinatorial artificial receptors including peptide building blocks
KR100682891B1 (ko) * 2004-09-14 2007-02-15 삼성전자주식회사 프로브 세트를 설계하는 방법, 그에 의하여 설계된프로브가 고정화된 기판을 갖는 마이크로어레이 및 상기방법을 컴퓨터가 수행할 수 있도록 하는 프로그램을기록한 컴퓨터 판독가능한 매체
FI20041204A0 (fi) 2004-09-16 2004-09-16 Riikka Lund Menetelmät immuunivälitteisiin sairauksiin liittyvien uusien kohdegeenien hyödyntämiseksi
WO2006030826A1 (ja) * 2004-09-17 2006-03-23 Eisai R & D Management Co., Ltd. 医薬組成物
US20060073506A1 (en) 2004-09-17 2006-04-06 Affymetrix, Inc. Methods for identifying biological samples
US7406391B2 (en) * 2004-09-20 2008-07-29 Affymetrix, Inc. System, method, and computer product for detection instrument calibration
US7828954B2 (en) * 2004-09-21 2010-11-09 Gamida For Life B.V. Electrode based patterning of thin film self-assembled nanoparticles
US7314542B2 (en) * 2004-09-23 2008-01-01 Nanogen, Inc. Methods and materials for optimization of electronic transportation and hybridization reactions
FR2876116B1 (fr) * 2004-10-01 2007-04-06 Biomerieux Sa Methode pour generer des transcrits
US20060073511A1 (en) 2004-10-05 2006-04-06 Affymetrix, Inc. Methods for amplifying and analyzing nucleic acids
CA2582137A1 (en) * 2004-10-05 2007-02-15 Wyeth Probe arrays for detecting multiple strains of different species
CN101080487B (zh) 2004-10-07 2012-11-14 阿戈斯治疗公司 成熟树突细胞组合物及其培养方法
US7968287B2 (en) 2004-10-08 2011-06-28 Medical Research Council Harvard University In vitro evolution in microfluidic systems
US7571055B2 (en) * 2004-10-13 2009-08-04 Regents Of The University Of Minnesota Systemic lupus erythematosus
FR2876705B1 (fr) * 2004-10-19 2008-12-12 Biomerieux Sa Procede pour le diagnostic d'une intolerance a l'aspirine
JP2006126204A (ja) 2004-10-29 2006-05-18 Affymetrix Inc ポリマーアレイを製造するための自動化方法
US7682782B2 (en) 2004-10-29 2010-03-23 Affymetrix, Inc. System, method, and product for multiple wavelength detection using single source excitation
US20060094024A1 (en) * 2004-11-01 2006-05-04 Pirrung Michael C Electrochemical arrays
US20090197249A1 (en) 2004-11-01 2009-08-06 George Mason University Compositions and methods for diagnosing colon disorders
JP3927978B2 (ja) * 2004-11-02 2007-06-13 キヤノン株式会社 生化学反応カートリッジおよび生化学処理装置システム
EP1815021A2 (en) * 2004-11-03 2007-08-08 Almac Diagnostics Limited Transcriptome microarray technology and methods of using the same
US20090118132A1 (en) * 2004-11-04 2009-05-07 Roche Molecular Systems, Inc. Classification of Acute Myeloid Leukemia
DE102004056735A1 (de) 2004-11-09 2006-07-20 Clondiag Chip Technologies Gmbh Vorrichtung für die Durchführung und Analyse von Mikroarray-Experimenten
AU2005310189A1 (en) * 2004-11-11 2006-06-08 Affymax, Inc. Novel peptides that bind to the erythropoietin receptor
US11105808B2 (en) 2004-11-12 2021-08-31 Health Discovery Corporation Methods for screening, predicting and monitoring prostate cancer
ES2534304T3 (es) 2004-11-12 2015-04-21 Asuragen, Inc. Procedimientos y composiciones que implican miARN y moléculas inhibidoras de miARN
US7785785B2 (en) 2004-11-12 2010-08-31 The Board Of Trustees Of The Leland Stanford Junior University Charge perturbation detection system for DNA and other molecules
US20060105348A1 (en) * 2004-11-15 2006-05-18 Lee Jun E Compositions and methods for the detection and discrimination of nucleic acids
US20060275792A1 (en) * 2004-11-15 2006-12-07 Lee Jun E Enhancement of nucleic acid amplification using double-stranded DNA binding proteins
AU2005307746B2 (en) 2004-11-16 2011-05-12 Illumina, Inc. And methods and apparatus for reading coded microbeads
US20060102471A1 (en) 2004-11-18 2006-05-18 Karl Maurer Electrode array device having an adsorbed porous reaction layer
US20060105355A1 (en) * 2004-11-18 2006-05-18 Karl Maurer Electrode array device having an adsorbed porous reaction layer having a linker moiety
ATE482288T1 (de) 2004-11-18 2010-10-15 Eppendorf Array Technologies Echtzeit-pcr von zielen auf einem mikroarray
ATE390562T1 (de) * 2004-11-19 2008-04-15 Ebm Papst St Georgen Gmbh & Co Anordnung mit einem luefter und einer pumpe
DE102004056980A1 (de) * 2004-11-25 2006-06-01 Clondiag Chip Technologies Gmbh Verfahren zur ortsspezifischen Synthese von Biopolymeren auf festen Trägern
KR100695134B1 (ko) * 2004-11-25 2007-03-14 삼성전자주식회사 층류를 이용한 마이크로어레이 및 이의 제조 방법
WO2006060653A2 (en) * 2004-11-30 2006-06-08 Veridex Llc Lung cancer prognostics
US7647186B2 (en) * 2004-12-07 2010-01-12 Illumina, Inc. Oligonucleotide ordering system
JP4455306B2 (ja) 2004-12-13 2010-04-21 キヤノン株式会社 生化学処理方法
US20080119367A1 (en) * 2004-12-17 2008-05-22 Mayo Foundation For Medical Education And Research Prognosis of Renal Cell Carcinoma
WO2006069203A2 (en) 2004-12-22 2006-06-29 California Institute Of Technology Methods for proteomic profiling using non-natural amino acids
KR100763906B1 (ko) * 2004-12-23 2007-10-05 삼성전자주식회사 9 종의 박테리아의 표적 서열을 특이적으로 증폭할 수 있는 프라이머 세트 및 상기 9 종의 박테리아 중 각 표적 서열에 특이적으로 혼성화하는 프로브 올리고뉴클레오티드
US7220549B2 (en) 2004-12-30 2007-05-22 Helicos Biosciences Corporation Stabilizing a nucleic acid for nucleic acid sequencing
EP1838875A4 (en) * 2004-12-30 2010-08-25 Todd M Hauser COMPOSITIONS AND METHODS FOR MODULATING GENE EXPRESSION USING SELF-PROTECTED OLIGONUCLEOTIDES
US20060147943A1 (en) * 2004-12-30 2006-07-06 Lewis Mark A Substrates having pendant epoxide groups for binding biomolecules and methods of making and using thereof
US7547775B2 (en) 2004-12-31 2009-06-16 Affymetrix, Inc. Parallel preparation of high fidelity probes in an array format
US8338093B2 (en) * 2004-12-31 2012-12-25 Affymetrix, Inc. Primer array synthesis and validation
EP1838752B1 (en) 2005-01-10 2017-10-04 The Regents of The University of California Cationic conjugated polymers suitable for strand-specific polynucleotide detection in homogeneous and solid state assays
US20060166224A1 (en) * 2005-01-24 2006-07-27 Norviel Vernon A Associations using genotypes and phenotypes
US20060183893A1 (en) * 2005-01-25 2006-08-17 North Don A Nucleic acids for apoptosis of cancer cells
KR20070095452A (ko) * 2005-01-25 2007-09-28 스카이 제네틱스, 인코포레이티드 암 세포의 세포자멸사를 위한 핵산
ATE491941T1 (de) * 2005-01-27 2011-01-15 Quest Diagnostics Invest Inc Schnelle komparative genomhybridisierung
US7482120B2 (en) 2005-01-28 2009-01-27 Helicos Biosciences Corporation Methods and compositions for improving fidelity in a nucleic acid synthesis reaction
EP1844328A4 (en) * 2005-01-31 2009-09-16 Pacific Biosciences California USE OF REVERSIBLE EXTENSION TERMINATOR IN NUCLEIC ACID SEQUENCING
FR2881437B1 (fr) 2005-01-31 2010-11-19 Biomerieux Sa Procede pour le diagnostic/pronostic d'un syndrome septique
US20070023643A1 (en) * 2005-02-01 2007-02-01 Nolte David D Differentially encoded biological analyzer planar array apparatus and methods
WO2006083917A2 (en) * 2005-02-01 2006-08-10 Purdue Research Foundation Laser scanning interferometric surface metrology
EP2233582A1 (en) 2005-02-01 2010-09-29 AB Advanced Genetic Analysis Corporation Nucleic acid sequencing by performing successive cycles of duplex extension
JP2008528040A (ja) 2005-02-01 2008-07-31 アジェンコート バイオサイエンス コーポレイション ビーズベースの配列決定のための試薬、方法およびライブラリー
US7910356B2 (en) * 2005-02-01 2011-03-22 Purdue Research Foundation Multiplexed biological analyzer planar array apparatus and methods
US7402730B1 (en) 2005-02-03 2008-07-22 Lexicon Pharmaceuticals, Inc. Knockout animals manifesting hyperlipidemia
CA2600199A1 (en) 2005-02-04 2006-08-10 Nimblegen Systems, Inc. Optimized probe selection method
US7407757B2 (en) * 2005-02-10 2008-08-05 Population Genetics Technologies Genetic analysis by sequence-specific sorting
US7393665B2 (en) 2005-02-10 2008-07-01 Population Genetics Technologies Ltd Methods and compositions for tagging and identifying polynucleotides
US20090068650A1 (en) * 2005-02-11 2009-03-12 Southern Illinois University Metabolic Primers for the Detection of (Per) Chlorate-Reducing Bacteria and Methods of Use Thereof
WO2006088950A2 (en) 2005-02-14 2006-08-24 University Of Iowa Research Foundation Methods and reagents for treatment and diagnosis of age-related macular degeneration
EP1859277A4 (en) 2005-02-17 2010-03-17 Biogen Idec Inc TREATMENT OF NEUROLOGICAL DISORDERS
WO2006089268A2 (en) * 2005-02-18 2006-08-24 The University Of North Carolina At Chapel Hill Gene and cognate protein profiles and methods to determine connective tissue markers in normal and pathologic conditions
UA90502C2 (ru) * 2005-02-18 2010-05-11 Сьёрфейс Лоджикс, Инк. Имидазотриазиноновые соединения и фармацевтическая композиция, которая их содержит
JP5053867B2 (ja) 2005-02-18 2012-10-24 ガバメント オブ ザ ユナイテッド ステイツ オブ アメリカ， アズ リプレゼンテッド バイ ザ セクレタリー 低悪性度の子宮頸部形成異常の進行を検出する及び腺癌を検出するための方法
US8178291B2 (en) 2005-02-18 2012-05-15 Monogram Biosciences, Inc. Methods and compositions for determining hypersusceptibility of HIV-1 to non-nucleoside reverse transcriptase inhibitors
US20110172422A1 (en) * 2005-02-18 2011-07-14 Surface Logix, Inc. Methods of Making Pharmacokinetically Improved Compounds Comprising Functional Residues or Groups and Pharmaceutical Compositions Comprising Said Compounds
US20090215028A1 (en) * 2005-02-18 2009-08-27 Ellen Paxinos Methods and Compositions for Determining Anti-HIV Drug Susceptibility and Replication Capacity of HIV
CA2598436A1 (en) * 2005-02-22 2006-08-31 Ceres, Inc. Modulating plant alkaloids
JP2006242926A (ja) 2005-03-07 2006-09-14 Seiko Epson Corp 電極基板、該基板を備える検出装置および該装置を含むキット、並びに該キットを用いた検出方法
JP2006242925A (ja) 2005-03-07 2006-09-14 Seiko Epson Corp 電極基板、該基板を備える検出装置および該装置を含むキット、並びに該キットを用いた検出方法
KR101138864B1 (ko) * 2005-03-08 2012-05-14 삼성전자주식회사 프라이머 및 프로브 세트를 설계하는 방법, 그에 의하여 설계된 프라이머 및 프로브 세트, 상기 세트를 포함하는 키트, 상기 방법을 컴퓨터가 수행할 수 있도록 하는 프로그램을기록한 컴퓨터 판독가능한 매체 및 상기 세트를 이용한 표적 서열의 동정 방법
US20090038023A1 (en) 2005-03-10 2009-02-05 Verenium Corporation Lyase Enzymes, Nucleic Acids Encoding Them and Methods For Making and Using Them
AU2006223086A1 (en) * 2005-03-11 2006-09-21 The Regents Of The University Of Colorado Histone deacetylase inhibitors sensitize cancer cells to epidermal growth factor inhibitors
US20100221186A1 (en) 2005-03-11 2010-09-02 Hueseyin Firat Biomarkers for cardiovascular side-effects induced by cox-2 inhibitory compounds
US7741038B2 (en) 2005-03-14 2010-06-22 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for evaluating graft survival in a solid organ transplant recipient
JP5343212B2 (ja) 2005-03-15 2013-11-13 ヴェレニウム コーポレイション セルラーゼ、それらをコードする核酸、並びにそれらを作製及び使用する方法
EP1856293A2 (en) * 2005-03-16 2007-11-21 Compass Genetics, Llc Methods and compositions for assay readouts on multiple analytical platforms
WO2006101487A1 (en) * 2005-03-18 2006-09-28 The Board Of Trustees Of The Leland Stanford Junior University Production and therapeutic uses of th1-like regulatory t cells
JP2008532559A (ja) 2005-03-19 2008-08-21 メディカル リサーチ カウンシル ウイルス感染の治療及び予防又は治療及び予防の改善
US20070092886A1 (en) * 2005-03-22 2007-04-26 Raymond Tabibiazar Methods and compositions for diagnosis, monitoring and development of therapeutics for treatment of atherosclerotic disease
WO2006102557A2 (en) 2005-03-22 2006-09-28 The President And Fellows Of Harvard College Treatment of protein degradation disorders
CN101495645B (zh) 2005-03-23 2012-08-22 生物-拉德实验室公司 蛋白纯化方法
US20090264635A1 (en) * 2005-03-25 2009-10-22 Applera Corporation Methods and compositions for depleting abundant rna transcripts
US20070034513A1 (en) 2005-03-25 2007-02-15 Combimatrix Corporation Electrochemical deblocking solution for electrochemical oligomer synthesis on an electrode array
KR20130114763A (ko) 2005-03-31 2013-10-18 더 제너럴 하스피탈 코포레이션 Ｈｇｆ／ｈｇｆｒ 활성의 모니터링 및 조정
EP1863908B1 (de) 2005-04-01 2010-11-17 Qiagen GmbH Reverse transkription und amplifikation von rna bei simultaner degradierung von dna
CN101965190A (zh) * 2005-04-04 2011-02-02 维里德克斯有限责任公司 乳腺肿瘤的激光显微解剖和微阵列分析揭示雌激素受体相关的基因和途径
US20060246576A1 (en) * 2005-04-06 2006-11-02 Affymetrix, Inc. Fluidic system and method for processing biological microarrays in personal instrumentation
JP2008535853A (ja) 2005-04-07 2008-09-04 ノバルティス ヴァクシンズ アンド ダイアグノスティクス インコーポレイテッド 癌関連遺伝子
WO2006110599A2 (en) 2005-04-07 2006-10-19 Novartis Vaccines And Diagnostics Inc. Cacna1e in cancer diagnosis, detection and treatment
US20070213293A1 (en) * 2005-04-08 2007-09-13 Nastech Pharmaceutical Company Inc. Rnai therapeutic for respiratory virus infection
WO2006110688A2 (en) 2005-04-08 2006-10-19 Nastech Pharmaceutical Company Inc. Rnai therapeutic for respiratory virus infection
US20100035244A1 (en) 2005-04-14 2010-02-11 The Trustees Of Boston University Diagnostic for lung disorders using class prediction
US9394167B2 (en) 2005-04-15 2016-07-19 Customarray, Inc. Neutralization and containment of redox species produced by circumferential electrodes
US20090042736A1 (en) * 2005-04-18 2009-02-12 Johan Gerrit Bomer Biochip and process for the production of a biochip
US7312376B2 (en) * 2005-04-20 2007-12-25 Ceres, Inc. Regulatory regions from Papaveraceae
US20060240443A1 (en) * 2005-04-20 2006-10-26 Combimatrix Corporation Microarray-based single nucleotide polymorphism, sequencing, and gene expression assay method
US8351026B2 (en) 2005-04-22 2013-01-08 Affymetrix, Inc. Methods and devices for reading microarrays
WO2006114249A1 (de) * 2005-04-26 2006-11-02 Bayer Technology Services Gmbh Neue apparatur und verfahren zur beschichtung von trägersubstraten für einen analytnachweis mittels affinitäts-nachweisverfahren
US20060286571A1 (en) 2005-04-28 2006-12-21 Prometheus Laboratories, Inc. Methods of predicting methotrexate efficacy and toxicity
US7452671B2 (en) * 2005-04-29 2008-11-18 Affymetrix, Inc. Methods for genotyping with selective adaptor ligation
US20060269948A1 (en) * 2005-05-16 2006-11-30 Halloran Philip F Tissue rejection
NZ563444A (en) * 2005-05-17 2011-04-29 Plexxikon Inc Pyrrolo(2,3-b)pyridine derivatives as protein kinase inhibitors
US20090317799A1 (en) 2005-05-18 2009-12-24 Decode Genetics Ehf. Variants at chr8q24.21 confer risk of cancer
DK1889065T3 (da) 2005-05-18 2013-09-02 Xoma Technology Ltd Metoder til diagnostisering og behandling af sygdomme med en autoimmun- og/eller inflammationskomponent
US7666596B2 (en) * 2005-05-23 2010-02-23 University Of Alberta Tissue rejection
US7968697B2 (en) * 2005-05-25 2011-06-28 Chrontech Pharma Ab Hepatitis C virus non-structural NS3/4A fusion gene
CA2609910A1 (en) 2005-05-27 2006-12-07 Monogram Biosciences, Inc. Methods and compositions for determining resistance of hiv-1 to protease inhibitors
US8486629B2 (en) 2005-06-01 2013-07-16 Bioarray Solutions, Ltd. Creation of functionalized microparticle libraries by oligonucleotide ligation or elongation
US7550433B2 (en) 2005-06-03 2009-06-23 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
US7919461B2 (en) * 2005-06-03 2011-04-05 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
US8324159B2 (en) * 2005-06-03 2012-12-04 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
EP1888235A1 (en) * 2005-06-06 2008-02-20 Decision Biomarkers Incorporated Assays based on liquid flow over arrays
US9506121B2 (en) * 2005-06-06 2016-11-29 Monogram Biosciences, Inc. Methods for determining resistance or susceptibility to HIV entry inhibitors
WO2006133267A2 (en) * 2005-06-06 2006-12-14 Monogram Biosciences, Inc. Methods and compositions for determining altered susceptibility of hiv-1 to anti-hiv drugs
US8053774B2 (en) * 2005-06-06 2011-11-08 Intel Corporation Method and apparatus to fabricate polymer arrays on patterned wafers using electrochemical synthesis
US8940143B2 (en) * 2007-06-29 2015-01-27 Intel Corporation Gel-based bio chip for electrochemical synthesis and electrical detection of polymers
EP1731620A1 (en) 2005-06-07 2006-12-13 Institut National De La Sante Et De La Recherche Medicale (Inserm) Method for the diagnosis of immune graft tolerance
WO2006133461A1 (en) * 2005-06-08 2006-12-14 Ceres Inc. Identification of terpenoid-biosynthesis related regulatory protein-regulatory region associations
JP4697944B2 (ja) * 2005-06-10 2011-06-08 キヤノン株式会社 非特異吸着を低減するプローブ固定担体の製造方法
EP2278303A3 (en) * 2005-06-10 2012-02-22 Life Technologies Corporation Method and system for multiplex genetic analysis
US7884260B2 (en) * 2005-06-14 2011-02-08 University Of Chicago Cell-based screen for agents useful for reducing neuronal demyelination or promoting neuronal remyelination
US8053627B2 (en) * 2005-06-14 2011-11-08 University Of Chicago Methods for treating demyelination disorders
US7368242B2 (en) * 2005-06-14 2008-05-06 Affymetrix, Inc. Method and kits for multiplex hybridization assays
US7423194B2 (en) * 2005-06-14 2008-09-09 University Of Chicago Animal models for demyelination disorders
US7709197B2 (en) 2005-06-15 2010-05-04 Callida Genomics, Inc. Nucleic acid analysis by random mixtures of non-overlapping fragments
NZ564285A (en) * 2005-06-20 2010-03-26 Decode Genetics Ehf Genetic variants in the TCF7L2 gene as diagnostic markers for risk of type 2 diabetes mellitus
NZ565255A (en) * 2005-06-22 2010-04-30 Plexxikon Inc Pyrrolo[2,3-b] pyridine derivatives as protein kinase inhibitors
US20060292559A1 (en) * 2005-06-23 2006-12-28 Beckman Coulter, Inc. Cell-based microarrays, and methods for their preparation and use
US20060292576A1 (en) * 2005-06-23 2006-12-28 Quest Diagnostics Investments Incorporated Non-in situ hybridization method for detecting chromosomal abnormalities
EP1736780A1 (en) 2005-06-24 2006-12-27 Eppendorf Array Technologies S.A. Method and means for detecting and/or quantifying hierarchical molecular change of a cell in response to an external stimulus
JP4789518B2 (ja) * 2005-06-30 2011-10-12 キヤノン株式会社 製造条件付きプローブ固定担体を用いた標的物質の検出方法ならびにそのための装置、キット及びシステム
US20080199872A1 (en) 2005-07-06 2008-08-21 Centre For Innovations Pty Ltd Method and Kit for Analyzing a Target Nucleic Acid Sequence
EP1910565A4 (en) 2005-07-07 2009-10-28 Athlomics Pty Ltd POLYNUCLEOTIDE MARKER GENES AND THEIR EXPRESSION IN THE DIAGNOSIS OF ENDOTOXEMIA
EP1925676A4 (en) 2005-08-02 2010-11-10 Eisai R&D Man Co Ltd TEST METHOD FOR THE EFFECT OF A VASCULARIZATION INHIBITOR
CN1908189A (zh) * 2005-08-02 2007-02-07 博奥生物有限公司 体外辅助鉴定肠型胃癌及其分化程度的方法与专用试剂盒
WO2007016502A2 (en) 2005-08-02 2007-02-08 Wisconsin Alumni Research Foundation Synthesis of arrays of oligonucleotides and other chain molecules
WO2007019479A2 (en) * 2005-08-04 2007-02-15 Helicos Biosciences Corporation Multi-channel flow cells
US20080219890A1 (en) * 2005-08-04 2008-09-11 Helicos Biosciences Corporation Sample loading and recovery
ES2383966T3 (es) * 2005-08-05 2012-06-27 Genentech, Inc. Métodos y composiciones para detectar trastornos autoinmunes
US20070037169A1 (en) * 2005-08-09 2007-02-15 Combimatrix Corporation Selective Dehybridization using Electrochemically-Generated Reagent on an Electrode Microarray
EP1924709A1 (en) * 2005-08-10 2008-05-28 Arena Pharmaceuticals, Inc. Methods for determining probability of an adverse or favorable reaction to a niacin receptor agonist
US7807370B2 (en) * 2005-08-16 2010-10-05 Merlogen, Llc Methods for identification of merle gene
EP1915626B1 (en) 2005-08-16 2011-11-09 Genentech, Inc. Apoptosis sensitivity to apo2l/trail by testing for galnac-t14 expression in cells/tissues
US20070047388A1 (en) * 2005-08-25 2007-03-01 Rockwell Scientific Licensing, Llc Fluidic mixing structure, method for fabricating same, and mixing method
US7666593B2 (en) 2005-08-26 2010-02-23 Helicos Biosciences Corporation Single molecule sequencing of captured nucleic acids
WO2007028147A2 (en) * 2005-09-01 2007-03-08 Philadelphia Health & Education Corporation D.B.A. Drexel University College Of Medicin Identification of a prostatic intraepithelial neoplasia (pin)-specific gene and protein (pin-1) useful as a diagnostic treatment for prostate cancer
CN102716490A (zh) * 2005-09-01 2012-10-10 卫材R&D管理有限公司 药物组合物的崩解性的改善方法
WO2007030759A2 (en) 2005-09-07 2007-03-15 Nugen Technologies, Inc. Improved nucleic acid amplification procedure
EP1762627A1 (de) 2005-09-09 2007-03-14 Qiagen GmbH Verfahren zur Aktivierung einer Nukleinsäure für eine Polymerase-Reaktion
JP2007078399A (ja) * 2005-09-12 2007-03-29 Tokyo Institute Of Technology 固体支持体及びｄｎａチップ
US7608395B2 (en) * 2005-09-15 2009-10-27 Baylor Research Institute Systemic lupus erythematosus diagnostic assay
WO2007035527A2 (en) 2005-09-15 2007-03-29 Duke University Non-fouling polymeric surface modification and signal amplification method for biomolecular detection
US7551294B2 (en) * 2005-09-16 2009-06-23 University Of Rochester System and method for brewster angle straddle interferometry
WO2007035690A2 (en) 2005-09-19 2007-03-29 Veridex, Llc Methods for diagnosing pancreatic cancer
US20070065877A1 (en) 2005-09-19 2007-03-22 Combimatrix Corporation Microarray having a base cleavable succinate linker
US20070231794A1 (en) 2005-09-21 2007-10-04 Combimatrix Corporation Process to detect binding events on an electrode microarray using enzymes
WO2007037926A2 (en) * 2005-09-23 2007-04-05 Sharp Laboratories Of America, Inc. Mems pixel sensor
US8855955B2 (en) 2005-09-29 2014-10-07 Custom Array, Inc. Process and apparatus for measuring binding events on a microarray of electrodes
US7763423B2 (en) * 2005-09-30 2010-07-27 Pacific Biosciences Of California, Inc. Substrates having low density reactive groups for monitoring enzyme activity
WO2007041536A2 (en) * 2005-09-30 2007-04-12 Ceres, Inc. Modulating plant tocopherol levels
US7312079B1 (en) 2005-10-06 2007-12-25 Lexicon Pharmaceuticals, Inc. Variants of FAM3C
US7960104B2 (en) * 2005-10-07 2011-06-14 Callida Genomics, Inc. Self-assembled single molecule arrays and uses thereof
WO2007044566A2 (en) * 2005-10-07 2007-04-19 Baylor Research Institute Diagnosis of systemic onset juvenile idiopathic arthritis through blood leukocyte microarray analysis
EP2546360A1 (en) 2005-10-07 2013-01-16 Callida Genomics, Inc. Self-assembled single molecule arrays and uses thereof
WO2007047408A2 (en) * 2005-10-12 2007-04-26 Pathologica, Llc. Promac signature application
US20090178160A1 (en) * 2005-10-25 2009-07-09 Joon-Hyun Park Modulation of Triterpenoid Content in Plants
WO2007120192A2 (en) 2005-10-27 2007-10-25 The President And Fellows Of Harvard College Methods and compositions for labeling nucleic acids
US7842823B2 (en) * 2005-10-27 2010-11-30 The Regents Of The University Of California Fluorogenic probes for reactive oxygen species
AU2005337803B2 (en) 2005-10-29 2013-04-18 Bayer Intellectual Property Gmbh Process for determining one or more analytes in samples of biological origin having complex composition, and use thereof
WO2007053732A2 (en) 2005-11-01 2007-05-10 Mayo Foundation For Medical Education And Research Promoter polymorphisms of the blys gene and use in diagnostic methods
US8075852B2 (en) 2005-11-02 2011-12-13 Affymetrix, Inc. System and method for bubble removal
US8007267B2 (en) * 2005-11-02 2011-08-30 Affymetrix, Inc. System and method for making lab card by embossing
US20080038714A1 (en) * 2005-11-02 2008-02-14 Affymetrix, Inc. Instrument to Pneumatically Control Lab Cards and Method Thereof
US20080311585A1 (en) * 2005-11-02 2008-12-18 Affymetrix, Inc. System and method for multiplex liquid handling
US20070099288A1 (en) * 2005-11-02 2007-05-03 Affymetrix, Inc. Microfluidic Methods, Devices, and Systems for Fluid Handling
US20090291437A1 (en) * 2005-11-02 2009-11-26 O'brien Sean Methods for targeting quadruplex sequences
JPWO2007052849A1 (ja) 2005-11-07 2009-04-30 エーザイ・アール・アンド・ディー・マネジメント株式会社 血管新生阻害物質とｃ−ｋｉｔキナーゼ阻害物質との併用
EP1952147A2 (en) 2005-11-16 2008-08-06 Novartis AG Biomarkers for anti-nogo-a antibody treatment in spinal cord injury
US7576037B2 (en) * 2005-11-18 2009-08-18 Mei Technologies, Inc. Process and apparatus for combinatorial synthesis
WO2007061981A2 (en) * 2005-11-21 2007-05-31 Lumera Corporation Surface plasmon resonance spectrometer with an actuator-driven angle scanning mechanism
US7291471B2 (en) * 2005-11-21 2007-11-06 Agilent Technologies, Inc. Cleavable oligonucleotide arrays
US7329860B2 (en) 2005-11-23 2008-02-12 Illumina, Inc. Confocal imaging methods and apparatus
US8076074B2 (en) 2005-11-29 2011-12-13 Quest Diagnostics Investments Incorporated Balanced translocation in comparative hybridization
US20070122842A1 (en) * 2005-11-30 2007-05-31 Rajasekaran John J Massively parallel synthesis of proteinaceous biomolecules
US7998717B2 (en) 2005-12-02 2011-08-16 Pacific Biosciences Of California, Inc. Mitigation of photodamage in analytical reactions
US7463358B2 (en) * 2005-12-06 2008-12-09 Lumera Corporation Highly stable surface plasmon resonance plates, microarrays, and methods
US7634363B2 (en) 2005-12-07 2009-12-15 Affymetrix, Inc. Methods for high throughput genotyping
KR20080080525A (ko) 2005-12-08 2008-09-04 노파르티스 아게 유전자 전사에 대한 ｆｇｆｒ３의 억제제의 효과
US7994098B2 (en) * 2005-12-09 2011-08-09 Wisconsin Alumni Research Foundation Light directed DNA synthesis using inverse capping for error reduction
JP2009519039A (ja) * 2005-12-13 2009-05-14 ニンブルゲン システムズ インコーポレイテッド 後成的修飾の同定及びモニタリング方法
US20090215055A1 (en) * 2005-12-13 2009-08-27 Erasmus University Medical Center Rotterdam Genetic Brain Tumor Markers
US20090305248A1 (en) * 2005-12-15 2009-12-10 Lander Eric G Methods for increasing accuracy of nucleic acid sequencing
US8014957B2 (en) * 2005-12-15 2011-09-06 Fred Hutchinson Cancer Research Center Genes associated with progression and response in chronic myeloid leukemia and uses thereof
US20070161031A1 (en) * 2005-12-16 2007-07-12 The Board Of Trustees Of The Leland Stanford Junior University Functional arrays for high throughput characterization of gene expression regulatory elements
US20130172274A1 (en) 2005-12-20 2013-07-04 Duke University Methods and compositions for delivering active agents with enhanced pharmacological properties
US8841255B2 (en) 2005-12-20 2014-09-23 Duke University Therapeutic agents comprising fusions of vasoactive intestinal peptide and elastic peptides
CN101384272B (zh) 2005-12-20 2013-05-01 杜克大学 用于递送具有增强的药理性质的活性剂的方法和组合物
KR100738083B1 (ko) * 2005-12-20 2007-07-12 삼성전자주식회사 마이크로어레이용 기판 및 그의 제조방법
US11306351B2 (en) 2005-12-21 2022-04-19 Affymetrix, Inc. Methods for genotyping
WO2007075026A1 (en) * 2005-12-27 2007-07-05 Samsung Electronics Co., Ltd Primers, probes, microarray, and method for specific detection of nine respiratory disease-associated bacterial species
WO2007123579A2 (en) 2005-12-28 2007-11-01 Translational Therapeutics Translational dysfunction based therapeutics
US20070154923A1 (en) * 2005-12-29 2007-07-05 Affymetrix, Inc. Method for Gridding and Quality Control of Polymer Arrays
EP1979088A2 (en) * 2005-12-29 2008-10-15 Affymetrix, Inc. Use of acid scavengers for the synthesis of standard length and long-mer nucleic acid arrays
US20070154946A1 (en) * 2005-12-29 2007-07-05 Rajasekaran John J Massively parallel synthesis of biopolymeric arrays
US20070255054A1 (en) * 2005-12-30 2007-11-01 Affymetrix, Inc. Oligonucleotide synthesis with intermittent and post synthetic oxidation
US20070198653A1 (en) * 2005-12-30 2007-08-23 Kurt Jarnagin Systems and methods for remote computer-based analysis of user-provided chemogenomic data
KR100829574B1 (ko) * 2006-01-03 2008-05-14 삼성전자주식회사 마이크로어레이용 기판, 그 마이크로어레이용 기판을이용하여 생분자를 분석하는 방법, 및 그 마이크로어레이용기판을 포함하는 랩온어칩
US7709227B2 (en) * 2006-01-04 2010-05-04 Phasebio Pharmaceuticals, Inc. Multimeric ELP fusion constructs
EP1984738A2 (en) 2006-01-11 2008-10-29 Raindance Technologies, Inc. Microfluidic devices and methods of use in the formation and control of nanoreactors
HUE025489T2 (en) * 2006-01-17 2016-04-28 Somalogic Inc Multiplexed analysis of test samples
US20070168197A1 (en) * 2006-01-18 2007-07-19 Nokia Corporation Audio coding
CN101426536A (zh) 2006-01-20 2009-05-06 妇女儿童健康研究院公司 治疗、预防和诊断骨病变的方法
WO2007087312A2 (en) * 2006-01-23 2007-08-02 Population Genetics Technologies Ltd. Molecular counting
US20090143238A1 (en) * 2006-01-23 2009-06-04 Junghuei Chen Oligonucleotide matrix and methods of use
US20070172852A1 (en) * 2006-01-24 2007-07-26 Affymetrix, Inc. Non-destructive Quality Control Methods for Microarrays
US20070207487A1 (en) * 2006-01-25 2007-09-06 Emig Christopher J Photoelectrochemical synthesis of high density combinatorial polymer arrays
US8055098B2 (en) 2006-01-27 2011-11-08 Affymetrix, Inc. System, method, and product for imaging probe arrays with small feature sizes
US9445025B2 (en) 2006-01-27 2016-09-13 Affymetrix, Inc. System, method, and product for imaging probe arrays with small feature sizes
JP2009524438A (ja) 2006-01-27 2009-07-02 トライパス イメージング インコーポレイテッド 卵巣癌を有する可能性の高い患者を同定するための方法およびそのための組成物
CA2635343C (en) 2006-01-27 2018-05-15 Athena Diagnostics, Inc. Methods of detecting mutations associated with ataxia-ocular apraxia 2 (aoa2)
WO2007092314A2 (en) 2006-02-02 2007-08-16 Verenium Corporation Esterases and related nucleic acids and methods
PL1986661T3 (pl) 2006-02-08 2019-02-28 Genzyme Corporation Terapia genowa choroby Niemanna-Picka typu A
MY160710A (en) 2006-02-10 2017-03-15 Verenium Corp Cellulolytic enzymes, nucleic acids encoding them and methods for making and using them
CN101400362B (zh) * 2006-02-14 2016-10-12 哈佛大学校长及研究员协会 双官能组蛋白去乙酰化酶抑制剂
CN101528679A (zh) 2006-02-14 2009-09-09 哈佛大学校长及研究员协会 组蛋白去乙酰化酶抑制剂
CA2638801C (en) 2006-02-14 2016-12-13 Verenium Corporation Xylanases, nucleic acids encoding them and methods for making and using them
GB0602992D0 (en) * 2006-02-15 2006-03-29 Morvus Technology Ltd Methods, genes and proteins
DE602007009645D1 (de) * 2006-02-16 2010-11-18 Ventana Med Syst Inc Reagenzien und verfahren für krebsprognose und pathologische einstufung
US8460879B2 (en) * 2006-02-21 2013-06-11 The Trustees Of Tufts College Methods and arrays for target analyte detection and determination of target analyte concentration in solution
US11237171B2 (en) 2006-02-21 2022-02-01 Trustees Of Tufts College Methods and arrays for target analyte detection and determination of target analyte concentration in solution
US20070199090A1 (en) * 2006-02-22 2007-08-23 Nestor Apuya Modulating alkaloid biosynthesis
JP5180845B2 (ja) 2006-02-24 2013-04-10 カリダ・ジェノミックス・インコーポレイテッド Ｄｎａアレイ上でのハイスループットゲノム配列決定
SG10201405158QA (en) 2006-02-24 2014-10-30 Callida Genomics Inc High throughput genome sequencing on dna arrays
TWI501774B (zh) * 2006-02-27 2015-10-01 Biogen Idec Inc 神經性病症之治療
PL2004843T3 (pl) 2006-02-28 2015-12-31 Univ Montana State Zastosowanie pochodnych fenantrydyny dla rozróżniania komórek nienaruszonych i komórek z uszkodzoną błoną za pomocą technik molekularnych opartych o kwas nukleinowy
US7815868B1 (en) 2006-02-28 2010-10-19 Fluidigm Corporation Microfluidic reaction apparatus for high throughput screening
EP1993590B1 (en) * 2006-03-01 2013-12-25 Biogen Idec MA Inc. Compostions and methods for administering gdnf ligand family proteins
CN101437954B (zh) 2006-03-07 2015-09-09 嘉吉公司 醛缩酶和编码醛缩酶的核酸以及它们的制备和使用方法
KR101622894B1 (ko) 2006-03-07 2016-05-19 바스프 엔자임스 엘엘씨 알돌라제, 이것을 코딩하는 핵산과 그 제조 방법 및 사용 방법
US20080309926A1 (en) * 2006-03-08 2008-12-18 Aaron Weber Systems and methods for reducing detected intensity non uniformity in a laser beam
US7397546B2 (en) 2006-03-08 2008-07-08 Helicos Biosciences Corporation Systems and methods for reducing detected intensity non-uniformity in a laser beam
WO2007103541A2 (en) 2006-03-09 2007-09-13 The Trustees Of Boston University Diagnostic and prognostic methods for lung disorders using gene expression profiles from nose epithelial cells
EP2007904A4 (en) * 2006-03-13 2009-06-10 Veridex Llc PROPAGATION OF PRIMARY CELLS
US20100233350A1 (en) * 2006-03-15 2010-09-16 Boston Scientific Scimed, Inc. Drug delivery composition and methods of making same using nanofabrication
US7812206B2 (en) 2006-03-21 2010-10-12 Bp Corporation North America Inc. Apparatus and process for the separation of solids and liquids
MX2008012013A (es) 2006-03-23 2008-10-03 Novartis Ag Tratamiento con anticuerpo antigeno de celulas neoplasicas.
WO2007111937A1 (en) * 2006-03-23 2007-10-04 Applera Corporation Directed enrichment of genomic dna for high-throughput sequencing
US20080009552A1 (en) * 2006-03-23 2008-01-10 Craig Pennell Markers of pre-term labor
US20070224616A1 (en) * 2006-03-24 2007-09-27 Erdogan Gulari Method for forming molecular sequences on surfaces
US20080045471A1 (en) * 2006-03-27 2008-02-21 North Don A Nucleic Acids For Apoptosis Of Cancer Cells
US8975216B2 (en) * 2006-03-30 2015-03-10 Pacific Biosciences Of California Articles having localized molecules disposed thereon and methods of producing same
US20080050747A1 (en) * 2006-03-30 2008-02-28 Pacific Biosciences Of California, Inc. Articles having localized molecules disposed thereon and methods of producing and using same
US20080026386A1 (en) 2006-03-31 2008-01-31 Behrens Timothy W Irf-5 haplotypes in systemic lupus erythematosus
US7914988B1 (en) 2006-03-31 2011-03-29 Illumina, Inc. Gene expression profiles to predict relapse of prostate cancer
US20070231805A1 (en) * 2006-03-31 2007-10-04 Baynes Brian M Nucleic acid assembly optimization using clamped mismatch binding proteins
US20070232556A1 (en) * 2006-03-31 2007-10-04 Montine Thomas J Methods and compositions for the treatment of neurological diseases and disorders
US7285388B1 (en) * 2006-04-07 2007-10-23 Merlogen, Llc Methods for identification of alport syndrome
US20090222957A1 (en) * 2006-04-07 2009-09-03 Ceres Inc. Regulatory protein-regulatory region associations related to alkaloid biosynthesis
US7830575B2 (en) 2006-04-10 2010-11-09 Illumina, Inc. Optical scanner with improved scan time
JP2009538123A (ja) * 2006-04-19 2009-11-05 アプライド バイオシステムズ， エルエルシー ゲル非含有ビーズベースの配列決定のための試薬、方法およびライブラリー
AR060536A1 (es) * 2006-04-20 2008-06-25 Glaxo Group Ltd Agonista del receptor de glucocorticoides y composiciones farmaceuticas
US20100137239A1 (en) * 2006-04-24 2010-06-03 Gloucester Pharmaceuticals Gemcitabine combination therapy
JP5784272B2 (ja) 2006-04-24 2015-09-24 ジェネンテック， インコーポレイテッド 自己免疫性疾患を検出するための方法及び組成物
AU2007244683A1 (en) 2006-04-27 2007-11-08 Pikamab, Inc. Methods and compositions for antibody therapy
US20070258862A1 (en) * 2006-05-02 2007-11-08 Applera Corporation Variable volume dispenser and method
CA2654540C (en) * 2006-05-03 2017-01-17 President And Fellows Of Harvard College Histone deacetylase and tubulin deacetylase inhibitors
WO2007131103A2 (en) * 2006-05-03 2007-11-15 Quadraspec, Inc. Direct printing of patterned hydrophobic wells
US10522240B2 (en) 2006-05-03 2019-12-31 Population Bio, Inc. Evaluating genetic disorders
US7702468B2 (en) 2006-05-03 2010-04-20 Population Diagnostics, Inc. Evaluating genetic disorders
EP2481815B1 (en) 2006-05-11 2016-01-27 Raindance Technologies, Inc. Microfluidic devices
US9562837B2 (en) 2006-05-11 2017-02-07 Raindance Technologies, Inc. Systems for handling microfludic droplets
WO2007133740A1 (en) * 2006-05-15 2007-11-22 Generation Biotech, Llc Method for identification of novel physical linkage of genomic sequences
JP2007304043A (ja) * 2006-05-15 2007-11-22 Canon Inc プローブ固定担体の製造方法
US20100216657A1 (en) * 2006-05-16 2010-08-26 Arcxis Biotechnologies, Inc. Pcr-free sample preparation and detection systems for high speed biologic analysis and identification
WO2007136103A1 (ja) * 2006-05-18 2007-11-29 Eisai R & D Management Co., Ltd. 甲状腺癌に対する抗腫瘍剤
BRPI0713098A2 (pt) 2006-05-22 2012-10-16 Clinical Genomics Pty Ltd método para determinar a origem anatÈmica de uma célula ou população celular derivada do intestino grosso de um indivìduo, método de detecção para determinar a origem anatÈmica de uma célula ou população celular derivada do intestino grosso de um indivìduo, sistema de detecção, meio de armazenagem legìvel por computador, arranjo de ácido nucleico, uso de um arranjo, método para determinar o inìcio ou predisposição para o inìcio de uma anormalidade celular ou uma condição destinguida por uma anormalidade celular no intestino grosso, kit de diagnóstico para ensaiar amostras biológicas
EP1862538A1 (en) * 2006-05-29 2007-12-05 IMBA-Institut für Molekulare Biotechnologie GmbH siRNA kinase and methods of use
AU2007268369A1 (en) * 2006-05-30 2007-12-06 Synergenz Bioscience Limited Methods and compositions for assessment of pulmonary function and disorders
US8679741B2 (en) 2006-05-31 2014-03-25 Sequenom, Inc. Methods and compositions for the extraction and amplification of nucleic acid from a sample
US7713750B2 (en) * 2006-05-31 2010-05-11 The Johns Hopkins University Ablation based laser machining of biomolecule patterns on substrates
US11001881B2 (en) 2006-08-24 2021-05-11 California Institute Of Technology Methods for detecting analytes
WO2007140599A1 (en) 2006-06-05 2007-12-13 Cancer Care Ontario Assessment of risk for colorectal cancer
EP2489745B1 (en) * 2006-06-05 2017-01-11 California Institute Of Technology Real time micro arrays
WO2007146730A2 (en) 2006-06-08 2007-12-21 Gloucester Pharmaceuticals Deacetylase inhibitor therapy
EP2027253A4 (en) * 2006-06-12 2014-04-30 Pacific Biosciences California SUBSTATES FOR EFFECTING ANALYSIS REACTIONS
US8372584B2 (en) 2006-06-14 2013-02-12 The General Hospital Corporation Rare cell analysis using sample splitting and DNA tags
KR100954322B1 (ko) 2006-06-14 2010-04-21 주식회사 엘지생명과학 췌장암과 관련된 신규한 ｌｂｆｌ313 유전자
EP3424598B1 (en) 2006-06-14 2022-06-08 Verinata Health, Inc. Rare cell analysis using sample splitting and dna tags
EP2024512A4 (en) 2006-06-14 2009-12-09 Artemis Health Inc METHODS FOR THE DIAGNOSIS OF ABNORMAL F CHARACTERS
US20080009007A1 (en) * 2006-06-16 2008-01-10 Pacific Biosciences Of California, Inc. Controlled initiation of primer extension
EP2057435A4 (en) * 2006-06-23 2011-04-20 Life Technologies Corp SYSTEMS AND METHOD FOR COOLING IN DEVICES FOR BIOLOGICAL ANALYSIS
US8009889B2 (en) 2006-06-27 2011-08-30 Affymetrix, Inc. Feature intensity reconstruction of biological probe array
US8178316B2 (en) * 2006-06-29 2012-05-15 President And Fellows Of Harvard College Evaluating proteins
WO2008005459A2 (en) * 2006-06-30 2008-01-10 Nugen Technologies, Inc. Methods for fragmentation and labeling of nucleic acids
US20080004410A1 (en) * 2006-06-30 2008-01-03 Yu-Chin Lai Hydrophilic macromonomers having alpha,beta-conjugated carboxylic terminal group and medical devices incorporating same
EP2083264A1 (en) 2006-07-10 2009-07-29 Toto Ltd. Electrolyte-containing sheet for use in specific detection of analyte using photocurrent, and, employing the sheet, method of detection, sensor unit and measuring apparatus
NZ574046A (en) 2006-07-13 2012-09-28 Univ Iowa Res Found Methods and reagents for treatment and diagnosis of vascular disorders and age-related macular degeneration
WO2008008284A2 (en) 2006-07-14 2008-01-17 The Regents Of The University Of California Cancer biomarkers and methods of use threof
US8213017B2 (en) * 2006-07-17 2012-07-03 Max Wiki Analytical system comprising an arrangement for temporally variable spatial light modulation and detection method executable therewith
US20080241951A1 (en) * 2006-07-20 2008-10-02 Visigen Biotechnologies, Inc. Method and apparatus for moving stage detection of single molecular events
EP2049713A4 (en) * 2006-07-21 2010-06-16 Univ Alberta TISSUE REJECTION
KR100813262B1 (ko) * 2006-07-25 2008-03-13 삼성전자주식회사 광 촉매를 이용한 패터닝된 스팟 마이크로어레이의 제조방법 및 상기 방법에 의해 제조된 마이크로어레이
WO2008013918A2 (en) * 2006-07-26 2008-01-31 Myelin Repair Foundation, Inc. Cell cycle regulation and differentiation
US20080026373A1 (en) * 2006-07-26 2008-01-31 Rodionova Natalia A Assays Based On Light Emission From Analyte Complexes Within A Cassette
US7700756B2 (en) * 2006-07-27 2010-04-20 Southern Illinois University Metabolic primers for the detection of perchlorate-reducing bacteria and methods of use thereof
WO2008014485A2 (en) 2006-07-28 2008-01-31 California Institute Of Technology Multiplex q-pcr arrays
US11525156B2 (en) 2006-07-28 2022-12-13 California Institute Of Technology Multiplex Q-PCR arrays
JP4866462B2 (ja) 2006-08-03 2012-02-01 ナショナル ユニバーシティ オブ シンガポール マイクロアレイシステム、およびマイクロアレイの製造方法
CN101528766A (zh) 2006-08-04 2009-09-09 维莱尼姆公司 葡聚糖酶、编码它们的核酸及制备和使用它们的方法
EP3536396B1 (en) 2006-08-07 2022-03-30 The President and Fellows of Harvard College Fluorocarbon emulsion stabilizing surfactants
CA2660143A1 (en) 2006-08-07 2008-02-14 Nsure Holding B.V. Genomics-based quality diagnostics for fresh agricultural products
TWI316873B (en) * 2006-08-08 2009-11-11 Ind Tech Res Inst Apparatus of manufacturing biochip and manufacture method of biochip tip array
AU2007284651B2 (en) 2006-08-09 2014-03-20 Institute For Systems Biology Organ-specific proteins and methods of their use
US7626185B2 (en) * 2006-08-11 2009-12-01 Battelle Memorial Institute Patterning compositions, masks, and methods
WO2008021431A2 (en) 2006-08-14 2008-02-21 Xdx, Inc. Methods and compositions for diagnosing and monitoring the status of transplant rejection and immune disorders
KR100755672B1 (ko) * 2006-08-24 2007-09-05 삼성전자주식회사 기판 내에 형성된 프로브 셀 액티브를 포함하는 올리고머프로브 어레이 및 그 제조 방법
CA2661483A1 (en) 2006-08-24 2008-02-28 Surface Logix, Inc. Pharmacokinetically improved 2-phenyl-substituted imidazotriazinone derivatives and their use
US11560588B2 (en) 2006-08-24 2023-01-24 California Institute Of Technology Multiplex Q-PCR arrays
WO2008026748A1 (fr) * 2006-08-28 2008-03-06 Eisai R & D Management Co., Ltd. Agent antitumoral pour cancer gastrique non différencié
US7687103B2 (en) * 2006-08-31 2010-03-30 Gamida For Life B.V. Compositions and methods for preserving permeation layers for use on active electronic matrix devices
WO2008027558A2 (en) 2006-08-31 2008-03-06 Codon Devices, Inc. Iterative nucleic acid assembly using activation of vector-encoded traits
US20080131893A1 (en) * 2006-08-31 2008-06-05 Mayo Foundation For Medical Education And Research Predicting Parkinson's Disease
AU2007289057C1 (en) 2006-09-01 2014-01-16 Pacific Biosciences Of California, Inc. Substrates, systems and methods for analyzing materials
US7985542B2 (en) * 2006-09-07 2011-07-26 Institut Pasteur Genomic morse code
EP1900824A1 (en) * 2006-09-14 2008-03-19 Deutsches Krebsforschungszentrum Stiftung Des Öffentlichen Rechts Gene expression signature for the prognosis, diagnosis and therapy of prostate cancer and uses thereof
US20100021885A1 (en) * 2006-09-18 2010-01-28 Mark Fielden Reagent sets and gene signatures for non-genotoxic hepatocarcinogenicity
CA2663962A1 (en) 2006-09-19 2008-03-27 Asuragen, Inc. Mir-15, mir-26, mir-31,mir-145, mir-147, mir-188, mir-215, mir-216, mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention
EP2487240B1 (en) 2006-09-19 2016-11-16 Interpace Diagnostics, LLC Micrornas differentially expressed in pancreatic diseases and uses thereof
GB0618514D0 (en) * 2006-09-20 2006-11-01 Univ Nottingham Trent Method of detecting interactions on a microarray using nuclear magnetic resonance
EP2617818B1 (en) 2006-09-21 2016-03-23 BASF Enzymes LLC Phytases, nucleic acids encoding them and methods for making and using them
MX2009003034A (es) 2006-09-21 2009-11-18 Verenium Corp Fosfolipasas, acidos nucleicos que las codifican, y metodos de hacerlas y usarlas.
US8273539B2 (en) 2006-09-25 2012-09-25 Mayo Foundation For Medical Education And Research Extracellular and membrane-associated prostate cancer markers
KR100818275B1 (ko) * 2006-09-26 2008-03-31 삼성전자주식회사 노로바이러스의 표적 서열을 증폭하기 위한 프라이머 세트,노로바이러스의 표적 서열에 특이적으로 혼성화하는프로브 세트, 상기 프로브 세트가 고정화되어 있는마이크로어레이 및 상기 프로브 세트를 이용하여노로바이러스의 존재를 검출하는 방법
US20090318534A1 (en) 2006-09-27 2009-12-24 The Regents Of The University Of California Methods and compositions for the treatment of skin diseases and disorders
KR100868760B1 (ko) * 2006-09-28 2008-11-17 삼성전자주식회사 그람 음성 및 양성 박테리아를 구별하기 위한 프라이머세트, 프로브 세트, 방법 및 키트
FR2906537A1 (fr) * 2006-09-28 2008-04-04 Biomerieux Sa Procede de diagnostic in vitro du cancer broncho-pulmonaire par detection des transcrits majoritaires alternatifs du gene klk8 codant la kallicreine 8 et son utilisation pour le pronostic de survie
KR100868765B1 (ko) * 2006-09-29 2008-11-17 삼성전자주식회사 항생제 내성 박테리아의 표적 서열을 증폭시킬 수 있는프라이머 세트, 박테리아의 표적 서열에 특이적으로혼성화하는 프로브 세트, 상기 프로브 세트가 고정화되어있는 마이크로어레이 및 상기 프로브 세트를 이용하여박테리아의 존재를 검출하는 방법
AU2007320026B2 (en) 2006-09-29 2014-04-03 Translational Therapeutics, Inc. eIF4E regulon-based diagnostics
US20100240544A1 (en) * 2006-09-29 2010-09-23 Liu David J Aptamer biochip for multiplexed detection of biomolecules
US9096953B2 (en) * 2006-09-29 2015-08-04 Intel Corporation Method for high throughput, high volume manufacturing of biomolecule micro arrays
US20080079663A1 (en) * 2006-10-03 2008-04-03 Sharp Laboratories Of America, Inc. Micro-pixelated fluid-assay precursor structure
US8231831B2 (en) * 2006-10-06 2012-07-31 Sharp Laboratories Of America, Inc. Micro-pixelated fluid-assay structure
US8236571B2 (en) * 2006-10-06 2012-08-07 Sharp Laboratories Of America, Inc. Method of making micro-pixelated fluid-assay precursor structure
ES2567143T3 (es) * 2006-10-06 2016-04-20 Sirigen Inc. Métodos y materiales fluorescentes para amplificación dirigida de señales de biomarcadores
US8232109B2 (en) * 2006-10-06 2012-07-31 Sharp Laboratories Of America, Inc. Micro-pixelated active-matrix fluid-assay performance
US8232108B2 (en) * 2006-10-06 2012-07-31 Sharp Laboratories Of America, Inc. Method of making micro-pixelated fluid-assay structure
US8236245B2 (en) 2006-10-06 2012-08-07 Sharp Laboratories Of America, Inc. Micro-pixelated fluid-assay precursor structure
US8236244B2 (en) * 2006-10-06 2012-08-07 Sharp Laboratories Of America, Inc. Micro-pixelated fluid-assay structure with on-board addressable, pixel-specific functionalization
DK2084519T3 (da) 2006-10-10 2012-08-20 Los Alamos Nat Security Llc Røntgenfluorescens-analysefremgangsmåde
US20080090236A1 (en) * 2006-10-13 2008-04-17 Yakhini Zohar H Methods and systems for identifying tumor progression in comparative genomic hybridization data
US20080167532A1 (en) * 2006-10-13 2008-07-10 Mayo Foundation For Medical Education And Research Assessing cancer treatment responsiveness
JP2010506588A (ja) * 2006-10-17 2010-03-04 シナージェンズ バイオサイエンス リミティド 肺の機能と障害の評価のための方法と組成物
US9845494B2 (en) 2006-10-18 2017-12-19 Affymetrix, Inc. Enzymatic methods for genotyping on arrays
US20080108149A1 (en) * 2006-10-23 2008-05-08 Narayan Sundararajan Solid-phase mediated synthesis of molecular microarrays
US7910302B2 (en) 2006-10-27 2011-03-22 Complete Genomics, Inc. Efficient arrays of amplified polynucleotides
US8618248B2 (en) 2006-10-31 2013-12-31 President And Fellows Of Harvard College Phosphopeptide compositions and anti-phosphopeptide antibody compositions and methods of detecting phosphorylated peptides
EP2444807B1 (en) 2006-11-01 2014-06-11 Ventana Medical Systems, Inc. Mono- and dinitropyrazole hapten conjugates
DE102006035393A1 (de) 2006-11-02 2008-05-15 Signature Diagnostics Ag Prognostische Marker für die Klassifizierung des dreijährigen progessionsfreien Überlebens von Patienten mit Kolonkarzinomen basierend auf Expressionsprofilen von biologischen Proben
CA2668235A1 (en) 2006-11-02 2008-06-05 Yale University Assessment of oocyte competence
US8338109B2 (en) 2006-11-02 2012-12-25 Mayo Foundation For Medical Education And Research Predicting cancer outcome
DE102006035392A1 (de) 2006-11-02 2008-10-16 Signature Diagnostics Ag Prognostische Marker für die Vorhersage des fünfjährigen progressionsfreien Überlebens von Patienten mit Kolonkarzinomen basierend auf Expressionsprofilen von biologischen Proben
DE102006035388A1 (de) * 2006-11-02 2008-05-15 Signature Diagnostics Ag Prognostische Marker für die Klassifizierung von Kolonkarzinomen basierend auf Expressionsprofilen von biologischen Proben
NZ598954A (en) 2006-11-03 2012-10-26 Baylor Res Inst Diagnosis of metastatic melanoma and monitoring indicators of immunosuppression through blood leukocyte microarray analysis
NZ551157A (en) * 2006-11-08 2008-06-30 Rebecca Lee Roberts Method of identifying individuals at risk of thiopurine drug resistance and intolerance - GMPS
US20090111705A1 (en) 2006-11-09 2009-04-30 Complete Genomics, Inc. Selection of dna adaptor orientation by hybrid capture
US8148067B2 (en) 2006-11-09 2012-04-03 Xdx, Inc. Methods for diagnosing and monitoring the status of systemic lupus erythematosus
US20080113915A1 (en) * 2006-11-09 2008-05-15 Duke University SAPAP3 knockout mouse and clinical modeling associated with the SAPAP3 gene
US20090105961A1 (en) * 2006-11-09 2009-04-23 Complete Genomics, Inc. Methods of nucleic acid identification in large-scale sequencing
US8293481B2 (en) * 2006-11-10 2012-10-23 Mayo Foundation For Medical Education And Research Biomarkers for chronic vascular dysfunction
US20110294782A1 (en) 2006-11-10 2011-12-01 Massachusetts Institute Of Technology Small molecule pak inhibitors
CA2669135A1 (en) * 2006-11-15 2008-05-22 The University Of British Columbia Polymorphisms predictive of platinum-coordinating complex-induced ototoxicity
WO2008058394A1 (en) 2006-11-15 2008-05-22 The University Of British Columbia Polymorphisms predictive of anthracycline-induced cardiotoxicity
US7791013B2 (en) * 2006-11-21 2010-09-07 Illumina, Inc. Biological microarray line scanning method and system
US20080242560A1 (en) * 2006-11-21 2008-10-02 Gunderson Kevin L Methods for generating amplified nucleic acid arrays
US7813013B2 (en) * 2006-11-21 2010-10-12 Illumina, Inc. Hexagonal site line scanning method and system
WO2008063888A2 (en) 2006-11-22 2008-05-29 Plexxikon, Inc. Compounds modulating c-fms and/or c-kit activity and uses therefor
US8293684B2 (en) * 2006-11-29 2012-10-23 Exiqon Locked nucleic acid reagents for labelling nucleic acids
US9114398B2 (en) 2006-11-29 2015-08-25 Canon U.S. Life Sciences, Inc. Device and method for digital multiplex PCR assays
US20100291569A1 (en) * 2006-11-30 2010-11-18 Abbott Laboratories Assay for prediction of response to met antagonists
US20100086921A1 (en) * 2006-11-30 2010-04-08 Valgerdur Steinthorsdottir Genetic susceptibility variants of type 2 diabetes mellitus
WO2008130394A2 (en) * 2006-11-30 2008-10-30 The Regents Of The University Of California Array for detecting microbes
US7522282B2 (en) * 2006-11-30 2009-04-21 Purdue Research Foundation Molecular interferometric imaging process and apparatus
US7807359B2 (en) * 2006-12-01 2010-10-05 Quest Diagnostics Investments Incorporated Methods of detecting TPMT mutations
US8637244B2 (en) * 2006-12-05 2014-01-28 Decode Genetics Ehf. Genetic markers for risk management of atrial fibrillation, atrial flutter, and stroke
US7989396B2 (en) * 2006-12-05 2011-08-02 The Board Of Trustees Of The Leland Stanford Junior University Biomolecule immobilization on biosensors
US7902345B2 (en) 2006-12-05 2011-03-08 Sequenom, Inc. Detection and quantification of biomolecules using mass spectrometry
KR20090088932A (ko) 2006-12-06 2009-08-20 메디뮨 엘엘씨 전신 홍반성 낭창의 치료 방법
CA2671299A1 (en) 2006-12-08 2008-06-19 Asuragen, Inc. Functions and targets of let-7 micro rnas
US11339430B2 (en) 2007-07-10 2022-05-24 Life Technologies Corporation Methods and apparatus for measuring analytes using large scale FET arrays
US8349167B2 (en) 2006-12-14 2013-01-08 Life Technologies Corporation Methods and apparatus for detecting molecular interactions using FET arrays
EP2639578B1 (en) 2006-12-14 2016-09-14 Life Technologies Corporation Apparatus for measuring analytes using large scale fet arrays
US8262900B2 (en) 2006-12-14 2012-09-11 Life Technologies Corporation Methods and apparatus for measuring analytes using large scale FET arrays
US20080182328A1 (en) * 2006-12-19 2008-07-31 The Burnham Institute Mammalian extraembryonic endoderm cells and methods of isolation
EP2129795A4 (en) * 2006-12-19 2010-10-20 Synergenz Bioscience Ltd METHODS AND COMPOSITIONS FOR ASSESSING FUNCTION AND CARDIOVASCULAR DISORDERS
US7622295B2 (en) * 2006-12-19 2009-11-24 Edelmira Cabezas Molecular microarrays and helical peptides
WO2008079972A2 (en) 2006-12-20 2008-07-03 Bayer Healthcare Llc 4-{4- [ ({3-tert-butyl-1- [3- (hydroxymethyl) phenyl] - 1h- pyrazol- 5 -yl } carbamoyl) -amin o] -3-chlorophenoxy} -n-methylpyridine-2-carboxamide as an inhibitor of the vegfr kinase for the treatment of cancer
US7932034B2 (en) 2006-12-20 2011-04-26 The Board Of Trustees Of The Leland Stanford Junior University Heat and pH measurement for sequencing of DNA
KR100834745B1 (ko) * 2006-12-20 2008-06-09 삼성전자주식회사 분석 친화적 레이아웃에 기반한 올리고머 프로브 어레이칩, 이의 제조에 사용되는 마스크 및 이의 혼성화 분석방법
US20080153135A1 (en) * 2006-12-20 2008-06-26 Liu Timothy Z Methods and apparatus for conducting amplification reactions on high density hydrophilic patterned microplates
PE20121126A1 (es) * 2006-12-21 2012-08-24 Plexxikon Inc Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa
DK2479266T3 (en) 2006-12-21 2016-06-20 Basf Enzymes Llc Amylases and glucoamylases, nucleic acids encoding them, and methods of making and using the same
WO2008079909A1 (en) * 2006-12-21 2008-07-03 Plexxikon, Inc. Pyrrolo [2,3-b] pyridines as kinase modulators
US7872018B2 (en) 2006-12-21 2011-01-18 Plexxikon, Inc. Compounds and methods for kinase modulation, and indications therefor
US20080153134A1 (en) * 2006-12-22 2008-06-26 Willy Wiyatno Methods and apparatus for generating hydrophilic patterning of high density microplates using an amphiphilic polymer
US8614086B2 (en) * 2006-12-28 2013-12-24 Intel Corporation Quality control methods for the manufacture of polymer arrays
US7923237B2 (en) * 2006-12-28 2011-04-12 Intel Corporation Method and apparatus for combined electrochemical synthesis and detection of analytes
US20100248975A1 (en) * 2006-12-29 2010-09-30 Gunjan Tiwari Fluorogenic peptide substrate arrays for highly multiplexed, real-time monitoring of kinase activities
US20080161202A1 (en) * 2006-12-29 2008-07-03 Edelmira Cabezas Novel strategy for selective regulation of background surface property in microarray fabrication and method to eliminated self quenching in micro arrays
US8930178B2 (en) 2007-01-04 2015-01-06 Children's Hospital Medical Center Processing text with domain-specific spreading activation methods
WO2008086322A2 (en) * 2007-01-05 2008-07-17 Integrated Dna Technologies, Inc. Method for estimating melting temperature of a nucleic acid in buffers containing divalent ions
KR101443214B1 (ko) * 2007-01-09 2014-09-24 삼성전자주식회사 폐암 환자 또는 폐암 치료를 받은 폐암 환자의 폐암 재발 위험을 진단하기 위한 조성물, 키트 및 마이크로어레이
DK2121977T3 (en) * 2007-01-11 2017-09-18 Erasmus Univ Medical Center Capture (4C) OF CHROMOSOMES WITH CIRCULAR CONFORMATION
US20110136099A1 (en) * 2007-01-16 2011-06-09 Somalogic, Inc. Multiplexed Analyses of Test Samples
US7855054B2 (en) * 2007-01-16 2010-12-21 Somalogic, Inc. Multiplexed analyses of test samples
WO2008089495A2 (en) 2007-01-19 2008-07-24 Purdue Research Foundation System with extended range of molecular sensing through integrated multi-modal data acquisition
US20080175757A1 (en) * 2007-01-19 2008-07-24 Andrew Powell Microarray device with elastomeric well structure
US20080176958A1 (en) 2007-01-24 2008-07-24 Insert Therapeutics, Inc. Cyclodextrin-based polymers for therapeutics delivery
WO2008092041A2 (en) 2007-01-24 2008-07-31 Carnegie Mellon University Optical biosensors
US9164037B2 (en) * 2007-01-26 2015-10-20 Palo Alto Research Center Incorporated Method and system for evaluation of signals received from spatially modulated excitation and emission to accurately determine particle positions and distances
US8821799B2 (en) 2007-01-26 2014-09-02 Palo Alto Research Center Incorporated Method and system implementing spatially modulated excitation or emission for particle characterization with enhanced sensitivity
CN101600694A (zh) * 2007-01-29 2009-12-09 卫材R&D管理有限公司 未分化型胃癌治疗用组合物
NZ598285A (en) 2007-01-30 2013-10-25 Syngenta Participations Ag Enzymes for the treatment of lignocellulosics, nucleic acids encoding them and methods for making and using them
EA201201640A1 (ru) 2007-01-30 2013-09-30 Фармасайкликс, Инк. Способы определения устойчивости рака к ингибиторам гистондеацетилазы
US11940413B2 (en) 2007-02-05 2024-03-26 IsoPlexis Corporation Methods and devices for sequencing nucleic acids in smaller batches
US8481259B2 (en) 2007-02-05 2013-07-09 Intelligent Bio-Systems, Inc. Methods and devices for sequencing nucleic acids in smaller batches
US8612161B2 (en) 2008-03-19 2013-12-17 Intelligent Biosystems Inc. Methods and compositions for base calling nucleic acids
US11035823B2 (en) 2009-03-17 2021-06-15 Qiagen Sciences, Llc Methods and devices for sequencing nucleic acids in smaller batches
US8772046B2 (en) 2007-02-06 2014-07-08 Brandeis University Manipulation of fluids and reactions in microfluidic systems
US8865400B2 (en) 2007-02-07 2014-10-21 Decode Genetics Ehf. Genetic variants contributing to risk of prostate cancer
KR100827449B1 (ko) * 2007-02-07 2008-05-07 삼성전자주식회사 광분해성 화합물과 상기 화합물이 커플링된 올리고머프로브 어레이용 기판, 올리고머 프로브 어레이 및 이의제조 방법
WO2008098142A2 (en) 2007-02-08 2008-08-14 Sequenom, Inc. Nucleic acid-based tests for rhd typing, gender determination and nucleic acid quantification
KR101571523B1 (ko) * 2007-02-21 2015-11-24 디코드 제네틱스 이에이치에프 심혈관 질환과 연관된 유전적 감수성 변이
EP1961825A1 (en) 2007-02-26 2008-08-27 INSERM (Institut National de la Santé et de la Recherche Medicale) Method for predicting the occurrence of metastasis in breast cancer patients
US9581595B2 (en) 2007-02-26 2017-02-28 Laboratory Corporation Of America Holdings Compositions and methods for determining whether a subject would benefit from co-receptor inhibitor therapy
US20110189663A1 (en) 2007-03-05 2011-08-04 Cancer Care Ontario Assessment of risk for colorectal cancer
US20080220537A1 (en) * 2007-03-07 2008-09-11 Pacific Biosciences Of California, Inc. Substrates and methods for selective immobilization of active molecules
WO2008112127A2 (en) * 2007-03-08 2008-09-18 Switchgear Genomics Functional arrays for high throughput characterization of regulatory elements in untranslated regions of genes
US7844609B2 (en) 2007-03-16 2010-11-30 Expanse Networks, Inc. Attribute combination discovery
US20080234143A1 (en) * 2007-03-23 2008-09-25 Pacific Biosciences Of California, Inc. Mechanical methods for producing substrates having selectively immobilized molecules
US8652780B2 (en) 2007-03-26 2014-02-18 Sequenom, Inc. Restriction endonuclease enhanced polymorphic sequence detection
AU2008231425B2 (en) * 2007-03-26 2014-03-20 Decode Genetics Ehf Genetic variants on Chr2 and Chr16 as markers for use in breast cancer risk assessment, diagnosis, prognosis and treatment
US7787126B2 (en) * 2007-03-26 2010-08-31 Purdue Research Foundation Method and apparatus for conjugate quadrature interferometric detection of an immunoassay
US20080243865A1 (en) * 2007-03-28 2008-10-02 Oracle International Corporation Maintaining global state of distributed transaction managed by an external transaction manager for clustered database systems
US20080241831A1 (en) * 2007-03-28 2008-10-02 Jian-Bing Fan Methods for detecting small RNA species
US7572990B2 (en) * 2007-03-30 2009-08-11 Intermec Ip Corp. Keypad overlay membrane
US20100255004A1 (en) * 2007-04-13 2010-10-07 Dana Farber Cancer Institute Receptor tyrosine kinase profiling
US8715665B2 (en) 2007-04-13 2014-05-06 The General Hospital Corporation Methods for treating cancer resistant to ErbB therapeutics
WO2008128333A1 (en) * 2007-04-19 2008-10-30 The Governors Of The University Of Alberta A method to distinguish antibody-mediated tissue rejection from t cell-mediated tissue rejection
US8592221B2 (en) 2007-04-19 2013-11-26 Brandeis University Manipulation of fluids, fluid components and reactions in microfluidic systems
US20080268440A1 (en) * 2007-04-26 2008-10-30 Liu Timothy Z Biomolecule immobilization on surface via hydrophobic interactions
US9580719B2 (en) 2007-04-27 2017-02-28 Pfenex, Inc. Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins
CA2685326A1 (en) 2007-04-27 2008-11-06 Dow Global Technologies Inc. Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins
EP3196310B1 (en) 2007-04-27 2020-07-08 The Regents of The University of California Plant co2 sensors, nucleic acids encoding them, and methods for making and using them
EP2481805A3 (en) 2007-04-30 2012-10-24 The Ohio State University Research Foundation Methods for differentiating pancreatic cancer from normal pancreatic function and/or chronic pancreatitis
DK2155907T3 (da) 2007-04-30 2015-08-31 Decode Genetics Ehf Genetiske varianter nyttige til risikovurdering af koronararteriesygdom og myokardieinfarkt
US20100197518A1 (en) 2007-05-01 2010-08-05 Huichun Xu Methods for Diagnosing Ischemia
US20080274458A1 (en) * 2007-05-01 2008-11-06 Latham Gary J Nucleic acid quantitation methods
EP2162459B1 (en) * 2007-05-01 2017-10-04 University of Miami Transcriptomic biomarkers for individual risk assessment in new onset heart failure
TWI445544B (zh) 2007-05-01 2014-07-21 Biogen Idec Inc 增進血管形成之組合物及方法
WO2008137835A2 (en) 2007-05-03 2008-11-13 Medimmune, Llc Auto-antibody markers of autoimmune disease
US20080286881A1 (en) * 2007-05-14 2008-11-20 Apel William A Compositions and methods for combining report antibodies
US8200440B2 (en) 2007-05-18 2012-06-12 Affymetrix, Inc. System, method, and computer software product for genotype determination using probe array data
CA2687787A1 (en) * 2007-05-21 2008-12-18 Dana Farber Cancer Institute, Inc. Compositions and methods for cancer gene discovery
US20080293589A1 (en) * 2007-05-24 2008-11-27 Affymetrix, Inc. Multiplex locus specific amplification
EP2164984A2 (en) 2007-05-25 2010-03-24 Decode Genetics EHF. Genetic variants on chr 5pl2 and 10q26 as markers for use in breast cancer risk assessment, diagnosis, prognosis and treatment
US20080300796A1 (en) * 2007-05-31 2008-12-04 Lassahn Gordon D Biological analysis methods, biological analysis devices, and articles of manufacture
US20100203051A1 (en) 2007-05-31 2010-08-12 The University Of Queensland Diagnostic markers for ankylosing spondylitis and uses thereof
US20090176664A1 (en) * 2007-06-01 2009-07-09 Keting Chu High density peptide arrays containing kinase or phosphatase substrates
PE20090321A1 (es) 2007-06-04 2009-04-20 Genentech Inc Anticuerpos anti-notch1 nrr, metodo de preparacion y composicion farmaceutica
KR20100018040A (ko) 2007-06-06 2010-02-16 도만티스 리미티드 프로테아제 내성 폴리펩티드를 선택하는 방법
NZ581742A (en) 2007-06-08 2012-09-28 Biogen Idec Inc Biomarkers for predicting anti-tnf responsiveness or non-responsiveness
US8097422B2 (en) 2007-06-20 2012-01-17 Salk Institute For Biological Studies Kir channel modulators
GB0713183D0 (en) * 2007-07-06 2007-08-15 King S College London Method
DE102007031526B4 (de) 2007-07-06 2010-07-08 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Verwendung einer Anode in einer Brennstoffzelle zur Oxidation von Ethanol und/oder zumindest eines C3 bis C10-haltigen Alkohols
WO2009009662A1 (en) * 2007-07-10 2009-01-15 University Of South Florida Method of predicting non-response to first line chemotherapy
ES2567094T3 (es) 2007-07-12 2016-04-19 The Brigham And Women's Hospital, Inc. Composiciones y métodos para diagnosticar y evaluar las miopatías inflamatorias
EP2676678A1 (en) 2007-07-17 2013-12-25 The General Hospital Corporation Methods to identify and enrich populations of ovarian cancer stem cells and somatic stem cells and uses thereof
US20100190777A1 (en) 2007-07-17 2010-07-29 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
KR20090012582A (ko) * 2007-07-30 2009-02-04 삼성전자주식회사 기판 상에 폴리머를 합성하는 장치 및 그 방법
US7507539B2 (en) * 2007-07-30 2009-03-24 Quest Diagnostics Investments Incorporated Substractive single label comparative hybridization
SI2185198T1 (sl) 2007-08-02 2015-04-30 Gilead Biologics, Inc. Inhibitorji LOX in LOXL2 ter njihova uporaba
US20110135648A1 (en) * 2007-08-08 2011-06-09 Biogen Idec Ma Inc. Anti-neublastin antibodies and uses thereof
WO2009023676A1 (en) * 2007-08-12 2009-02-19 Integrated Dna Technologies, Inc. Microarray system with improved sequence specificity
EP2201142A1 (en) * 2007-08-13 2010-06-30 Almac Diagnostics Limited A 3' -based sequencing approach for microarray manufacture
US20090136916A1 (en) * 2007-08-13 2009-05-28 Trustees Of Tufts College Methods and microarrays for detecting enteric viruses
CN101778954A (zh) 2007-08-14 2010-07-14 霍夫曼-拉罗奇有限公司 Egfr抑制剂治疗的预测性标记物
JP5276103B2 (ja) 2007-08-14 2013-08-28 エフ．ホフマン−ラ ロシュ アーゲー Ｅｇｆｒ阻害因子治療マーカー
KR101169246B1 (ko) 2007-08-14 2012-08-03 에프. 호프만-라 로슈 아게 Ｅｇｆｒ 저해제 치료에 대한 예측 마커
EP2188390A1 (en) 2007-08-14 2010-05-26 F. Hoffmann-Roche AG Predictive markers for egfr inhibitors treatment
US20090214593A1 (en) * 2007-08-16 2009-08-27 Tripep Ab Immunogen platform
EP2185195A2 (en) * 2007-08-16 2010-05-19 Tripep Ab Immunogen platform
CA2697106A1 (en) * 2007-08-28 2009-03-12 Donald Bergstrom Expression profiles of biomarker genes in notch mediated cancers
US9404150B2 (en) 2007-08-29 2016-08-02 Sequenom, Inc. Methods and compositions for universal size-specific PCR
US20090060786A1 (en) * 2007-08-29 2009-03-05 Gibum Kim Microfluidic apparatus for wide area microarrays
WO2009029073A1 (en) 2007-08-30 2009-03-05 The Trustees Of Tufts College Methods for determining the concentration of an analyte in solution.
US9388457B2 (en) 2007-09-14 2016-07-12 Affymetrix, Inc. Locus specific amplification using array probes
US20090180931A1 (en) 2007-09-17 2009-07-16 Sequenom, Inc. Integrated robotic sample transfer device
EP2548962B1 (en) 2007-09-19 2016-01-13 Applied Biosystems, LLC Sirna sequence-independent modification formats for reducing off-target phenotypic effects in rnai, and stabilized forms thereof
EP2212434A1 (en) * 2007-10-01 2010-08-04 Applied Biosystems Inc. Chase ligation sequencing
NZ601191A (en) 2007-10-03 2014-01-31 Verenium Corp Xylanases, nucleic acids encoding them and methods for making and using them
US20090139311A1 (en) * 2007-10-05 2009-06-04 Applied Biosystems Inc. Biological Analysis Systems, Devices, and Methods
CA2702169A1 (en) * 2007-10-12 2009-04-16 Decode Genetics Ehf Sequence variants for inferring human pigmentation patterns
WO2009050444A1 (en) * 2007-10-15 2009-04-23 King's College London Diagnostic methods for hiv infection
WO2009052214A2 (en) * 2007-10-15 2009-04-23 Complete Genomics, Inc. Sequence analysis using decorated nucleic acids
DK2644711T3 (en) 2007-10-23 2018-08-20 Clinical Genomics Pty Ltd A method for diagnosing neoplasms
AU2008316319A1 (en) 2007-10-23 2009-04-30 Clinical Genomics Pty. Ltd. A method of diagnosing neoplasms
EP2053132A1 (en) * 2007-10-23 2009-04-29 Roche Diagnostics GmbH Enrichment and sequence analysis of geomic regions
US7897344B2 (en) * 2007-11-06 2011-03-01 Complete Genomics, Inc. Methods and oligonucleotide designs for insertion of multiple adaptors into library constructs
US20090263872A1 (en) * 2008-01-23 2009-10-22 Complete Genomics Inc. Methods and compositions for preventing bias in amplification and sequencing reactions
US8415099B2 (en) 2007-11-05 2013-04-09 Complete Genomics, Inc. Efficient base determination in sequencing reactions
US8518640B2 (en) * 2007-10-29 2013-08-27 Complete Genomics, Inc. Nucleic acid sequencing and process
US20110038924A1 (en) * 2007-10-29 2011-02-17 Goomer Randal S Osteoarthritis gene therapy
US8298768B2 (en) 2007-11-29 2012-10-30 Complete Genomics, Inc. Efficient shotgun sequencing methods
CN101910399B (zh) 2007-10-30 2015-11-25 考利达基因组股份有限公司 用于核酸高通量测序的装置
JP4400668B2 (ja) 2007-11-01 2010-01-20 株式会社豊田中央研究所 微小物体が固定化された固相体の製造方法及びその利用
WO2009061840A1 (en) * 2007-11-05 2009-05-14 Complete Genomics, Inc. Methods and oligonucleotide designs for insertion of multiple adaptors employing selective methylation
US8906700B2 (en) 2007-11-06 2014-12-09 Ambergen, Inc. Methods and compositions for phototransfer
MX2010005080A (es) 2007-11-07 2010-07-28 Genentech Inc Metodos y composiciones para determinar la sensibilidad de linfoma de celula b al tratamiento con anticuerpos anti-cd40.
CA2704000C (en) * 2007-11-09 2016-12-13 Eisai R&D Management Co., Ltd. Combination of anti-angiogenic substance and anti-tumor platinum complex
WO2009067657A2 (en) * 2007-11-21 2009-05-28 Arizona Board Of Regents, Acting For And On Behalf Of Arizona State University Methods of identifying molecular function
US8093063B2 (en) * 2007-11-29 2012-01-10 Quest Diagnostics Investments Incorporated Assay for detecting genetic abnormalities in genomic nucleic acids
US20090142759A1 (en) * 2007-11-29 2009-06-04 Erik Larsson qPCR array with IN SITU primer synthesis
WO2009073511A2 (en) * 2007-11-30 2009-06-11 Mayo Foundation For Medical Education And Research Polymorphisms of the blys gene and use in diagnostic methods
US8697360B2 (en) 2007-11-30 2014-04-15 Decode Genetics Ehf. Genetic variants on CHR 11Q and 6Q as markers for prostate and colorectal cancer predisposition
US8592150B2 (en) 2007-12-05 2013-11-26 Complete Genomics, Inc. Methods and compositions for long fragment read sequencing
EP2610351B1 (en) 2007-12-05 2015-07-08 Complete Genomics, Inc. Efficient base determination in sequencing reactions
WO2009075773A2 (en) * 2007-12-07 2009-06-18 Goldstein Steven A Identification of toxin ligands
US8004669B1 (en) 2007-12-18 2011-08-23 Plexera Llc SPR apparatus with a high performance fluid delivery system
AU2008352940B2 (en) 2007-12-19 2014-06-05 Singulex, Inc. Scanning analyzer for single molecule detection and methods of use
US20110003708A1 (en) * 2007-12-27 2011-01-06 Compugen Ltd. Biomarkers for the prediction of renal injury
EP2570499A3 (en) 2008-01-02 2013-04-03 Suregene Llc Genetic markers of mental illness
CN104651381A (zh) 2008-01-03 2015-05-27 巴斯夫酶有限责任公司 转移酶和氧化还原酶、编码它们的核酸以及其制备和应用方法
CA2712075A1 (en) 2008-01-17 2009-07-23 Suregene Llc Genetic markers of mental illness
EP2240609A4 (en) * 2008-01-22 2011-08-03 Veridex Llc MOLECULAR CLASSIFICATION OF COLONCARCINOMA STADIAS II AND III AND FORECAST
EP2514841A1 (en) 2008-01-25 2012-10-24 Theranostics Laboratory Methods and compositions for the assessment of drug response
WO2009097368A2 (en) 2008-01-28 2009-08-06 Complete Genomics, Inc. Methods and compositions for efficient base calling in sequencing reactions
WO2009097424A1 (en) * 2008-01-29 2009-08-06 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Fstl-1 as a biomarker of inflammation
US8658379B2 (en) 2008-01-29 2014-02-25 University of Pittsburgh—of the Commonwealth System of Higher Education Follistatin-like protein-1 as a biomarker for sepsis
US7701580B2 (en) * 2008-02-01 2010-04-20 Palo Alto Research Center Incorporated Transmitting/reflecting emanating light with time variation
US8153950B2 (en) * 2008-12-18 2012-04-10 Palo Alto Research Center Incorporated Obtaining sensing results and/or data in response to object detection
US7763856B2 (en) * 2008-01-31 2010-07-27 Palo Alto Research Center Incorporated Producing time variation in emanating light
US7894068B2 (en) * 2008-02-04 2011-02-22 Palo Alto Research Center Incorporated Producing filters with combined transmission and/or reflection functions
US8263955B2 (en) * 2008-12-18 2012-09-11 Palo Alto Research Center Incorporated Causing relative motion
EP2245055A2 (en) * 2008-01-31 2010-11-03 Compugen Ltd. Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics
US8629981B2 (en) 2008-02-01 2014-01-14 Palo Alto Research Center Incorporated Analyzers with time variation based on color-coded spatial modulation
US8373860B2 (en) * 2008-02-01 2013-02-12 Palo Alto Research Center Incorporated Transmitting/reflecting emanating light with time variation
US20090203022A1 (en) * 2008-02-07 2009-08-13 Arizona Board Of Regents For And On Behalf Of Arizona State University Analysis
CA2618163A1 (en) 2008-02-07 2009-08-07 K. W. Michael Siu Head and neck cancer biomarkers
US8034568B2 (en) * 2008-02-12 2011-10-11 Nugen Technologies, Inc. Isothermal nucleic acid amplification methods and compositions
US8105777B1 (en) 2008-02-13 2012-01-31 Nederlands Kanker Instituut Methods for diagnosis and/or prognosis of colon cancer
NZ587903A (en) 2008-02-14 2013-05-31 Decode Genetics Ehf Susceptibility for lung cancer using the polymorphic marker rs1051730
US20090233809A1 (en) * 2008-03-04 2009-09-17 Affymetrix, Inc. Resequencing methods for identification of sequence variants
KR101030476B1 (ko) 2008-03-11 2011-04-25 국립암센터 Ｓｎｐ 어레이를 이용한 염색체, 유전자, 또는 특정 뉴클레오티드 서열의 카피 수 측정방법
AU2009223671B2 (en) 2008-03-11 2014-11-27 Sequenom, Inc. Nucleic acid-based tests for prenatal gender determination
US9074244B2 (en) 2008-03-11 2015-07-07 Affymetrix, Inc. Array-based translocation and rearrangement assays
US7932036B1 (en) 2008-03-12 2011-04-26 Veridex, Llc Methods of determining acute myeloid leukemia response to treatment with farnesyltransferase
JP5670755B2 (ja) 2008-03-12 2015-02-18 ザ ロックフェラー ユニバーシティ 翻訳プロファイリング及び分子表現型解析のための方法及び組成物
US10745740B2 (en) 2008-03-19 2020-08-18 Qiagen Sciences, Llc Sample preparation
US9017973B2 (en) 2008-03-19 2015-04-28 Intelligent Biosystems, Inc. Methods and compositions for incorporating nucleotides
WO2009117698A2 (en) 2008-03-21 2009-09-24 Nugen Technologies, Inc. Methods of rna amplification in the presence of dna
CA2718137A1 (en) 2008-03-26 2009-10-01 Sequenom, Inc. Restriction endonuclease enhanced polymorphic sequence detection
US8796184B2 (en) 2008-03-28 2014-08-05 Sentilus, Inc. Detection assay devices and methods of making and using the same
EP2107125A1 (en) 2008-03-31 2009-10-07 Eppendorf Array Technologies SA (EAT) Real-time PCR of targets on a micro-array
CA2724666A1 (en) 2008-04-01 2009-10-08 Decode Genetics Ehf Susceptibility variants for peripheral arterial disease and abdominal aortic aneurysm
US20090246788A1 (en) 2008-04-01 2009-10-01 Roche Nimblegen, Inc. Methods and Assays for Capture of Nucleic Acids
WO2009132028A1 (en) * 2008-04-21 2009-10-29 Complete Genomics, Inc. Array structures for nucleic acid detection
US20090269746A1 (en) * 2008-04-25 2009-10-29 Gil Atzmon Microsequencer-whole genome sequencer
US20110118125A1 (en) * 2008-05-03 2011-05-19 Tufts Medical Center, Inc. Neonatal salivary genomics
US8039817B2 (en) 2008-05-05 2011-10-18 Illumina, Inc. Compensator for multiple surface imaging
EP2294214A2 (en) * 2008-05-07 2011-03-16 Illumina, Inc. Compositions and methods for providing substances to and from an array
JP2009268665A (ja) * 2008-05-07 2009-11-19 Canon Inc 吸入装置
EP2990487A1 (en) 2008-05-08 2016-03-02 Asuragen, INC. Compositions and methods related to mirna modulation of neovascularization or angiogenesis
SG176464A1 (en) 2008-05-09 2011-12-29 Agency Science Tech & Res Diagnosis and treatment of kawasaki disease
EP2297347B1 (en) 2008-05-14 2017-03-08 Millennium Pharmaceuticals, Inc. Methods and kits for monitoring the effects of immunomodulators on adaptive immunity
KR100956447B1 (ko) * 2008-05-16 2010-05-06 한국전자통신연구원 바이오센서의 기판의 패턴의 제조 방법 및 이를 이용한바이오센서
EP2806054A1 (en) 2008-05-28 2014-11-26 Genomedx Biosciences Inc. Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer
US20090298082A1 (en) * 2008-05-30 2009-12-03 Klee George G Biomarker panels for predicting prostate cancer outcomes
KR20110020853A (ko) 2008-05-30 2011-03-03 더 유니버시티 오브 브리티시 콜롬비아 유전자 또는 단백질 발현 프로파일을 이용한 신장 동종이식 거부반응 진단방법
US10407731B2 (en) 2008-05-30 2019-09-10 Mayo Foundation For Medical Education And Research Biomarker panels for predicting prostate cancer outcomes
US20110159492A1 (en) * 2008-06-04 2011-06-30 Rimsza Lisa M Diffuse Large B-Cell Lymphoma Markers and Uses Therefore
CA2726811C (en) 2008-06-06 2019-11-26 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services Survival predictor for diffuse large b cell lymphoma
US8791258B2 (en) * 2008-06-10 2014-07-29 The Regents Of The University Of California Pro-fluorescent probes
JP5667049B2 (ja) 2008-06-25 2015-02-12 ライフ テクノロジーズ コーポレーション 大規模なｆｅｔアレイを用いて分析物を測定するための方法および装置
CN105727261A (zh) 2008-06-27 2016-07-06 杜克大学 包含弹性蛋白样肽的治疗剂
NZ590832A (en) * 2008-07-04 2013-01-25 Decode Genetics Ehf Genetic variants for schizophrenia risk assessment
AU2009269542A1 (en) 2008-07-07 2010-01-14 Decode Genetics Ehf Genetic variants for breast cancer risk assessment
WO2010004695A1 (ja) 2008-07-09 2010-01-14 パナソニック株式会社 シークエンサー
US12038438B2 (en) 2008-07-18 2024-07-16 Bio-Rad Laboratories, Inc. Enzyme quantification
EP4047367A1 (en) 2008-07-18 2022-08-24 Bio-Rad Laboratories, Inc. Method for detecting target analytes with droplet libraries
CA2731730C (en) 2008-07-23 2017-06-13 President And Fellows Of Harvard College Deacetylase inhibitors and uses thereof
US9182406B2 (en) 2008-08-04 2015-11-10 Biodesy, Inc. Nonlinear optical detection of molecules comprising an unnatural amino acid possessing a hyperpolarizability
CA2733910A1 (en) * 2008-08-12 2010-02-18 Decode Genetics Ehf. Genetic variants useful for risk assessment of thyroid cancer
US8530716B2 (en) * 2008-08-14 2013-09-10 Bp Corporation North America Inc. Melt-crystallization separation and purification process
WO2010018601A2 (en) * 2008-08-15 2010-02-18 Decode Genetics Ehf Genetic variants predictive of cancer risk
US20110201519A1 (en) 2008-08-18 2011-08-18 Sarwal Minnie M Methods and Compositions for Determining a Graft Tolerant Phenotype in a Subject
US8808986B2 (en) 2008-08-27 2014-08-19 Gen9, Inc. Methods and devices for high fidelity polynucleotide synthesis
KR20100025328A (ko) * 2008-08-27 2010-03-09 삼성전자주식회사 이중가닥 영역과 말단 단일가닥 영역을 포함하는 이중가닥 핵산 프로브가 고정된 마이크로어레이를 제조하는 방법
US8153391B2 (en) 2008-08-29 2012-04-10 Bunge Oils, Inc. Hydrolases, nucleic acids encoding them and methods for making and using them
US8357503B2 (en) 2008-08-29 2013-01-22 Bunge Oils, Inc. Hydrolases, nucleic acids encoding them and methods for making and using them
US8198062B2 (en) 2008-08-29 2012-06-12 Dsm Ip Assets B.V. Hydrolases, nucleic acids encoding them and methods for making and using them
DK2329259T3 (en) 2008-08-29 2016-05-09 Janssen Biotech Inc MARKERS AND PROCEDURES FOR ASSESSING AND TREATING ULCERATIVE COLITIS AND RELATED DISEASES USING A 20-GEN PANEL
US8962247B2 (en) * 2008-09-16 2015-02-24 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses
US8476013B2 (en) 2008-09-16 2013-07-02 Sequenom, Inc. Processes and compositions for methylation-based acid enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
AU2009292629B2 (en) 2008-09-16 2014-03-20 Pacific Biosciences Of California, Inc. Substrates and optical systems and methods of use thereof
US20100075439A1 (en) * 2008-09-23 2010-03-25 Quanterix Corporation Ultra-sensitive detection of molecules by capture-and-release using reducing agents followed by quantification
US20100075862A1 (en) * 2008-09-23 2010-03-25 Quanterix Corporation High sensitivity determination of the concentration of analyte molecules or particles in a fluid sample
US8222047B2 (en) 2008-09-23 2012-07-17 Quanterix Corporation Ultra-sensitive detection of molecules on single molecule arrays
EP2344672B8 (en) 2008-09-25 2014-12-24 SureGene LLC Genetic markers for optimizing treatment for schizophrenia
US20100087325A1 (en) * 2008-10-07 2010-04-08 Illumina, Inc. Biological sample temperature control system and method
US20100137143A1 (en) 2008-10-22 2010-06-03 Ion Torrent Systems Incorporated Methods and apparatus for measuring analytes
US20100301398A1 (en) 2009-05-29 2010-12-02 Ion Torrent Systems Incorporated Methods and apparatus for measuring analytes
US8541207B2 (en) 2008-10-22 2013-09-24 Illumina, Inc. Preservation of information related to genomic DNA methylation
JP5502413B2 (ja) * 2008-10-31 2014-05-28 シスメックス株式会社 検査チップ、被検物質検出装置および被検物質の特異的検出方法
EP2358912B1 (en) 2008-10-30 2016-10-12 Caris Life Sciences Switzerland Holdings GmbH Methods for assessing rna patterns
CA2739461A1 (en) * 2008-10-31 2010-05-06 Abbott Laboratories Genomic classification of malignant melanoma based on patterns of gene copy number alterations
CA2739459A1 (en) * 2008-10-31 2010-05-06 Abbott Laboratories Genomic classification of colorectal cancer based on patterns of gene copy number alterations
JP5391279B2 (ja) * 2008-10-31 2014-01-15 アッヴィ・インコーポレイテッド １種以上の医薬組成物の有効性を試験することに使用する癌細胞系のパネルを構築するための方法
EP2362958A2 (en) * 2008-10-31 2011-09-07 Abbott Laboratories Genomic classification of non-small cell lung carcinoma based on patterns of gene copy number alterations
US9506119B2 (en) 2008-11-07 2016-11-29 Adaptive Biotechnologies Corp. Method of sequence determination using sequence tags
EP2352998A4 (en) 2008-11-07 2011-09-21 Centocor Ortho Biotech Inc MARKERS AND METHOD FOR THE STUDY AND TREATMENT OF LIGHT-SENSITIVELY LUPUS PATIENTS
GB2463401B (en) 2008-11-12 2014-01-29 Caris Life Sciences Luxembourg Holdings S A R L Characterizing prostate disorders by analysis of microvesicles
GB0820822D0 (en) 2008-11-13 2008-12-24 Inst Catala D Oncologia Novel product and processes
ES2796111T3 (es) 2008-11-14 2020-11-25 Brigham & Womens Hospital Inc Métodos terapéuticos relacionados con células madre cancerosas
US9495515B1 (en) 2009-12-09 2016-11-15 Veracyte, Inc. Algorithms for disease diagnostics
US10236078B2 (en) 2008-11-17 2019-03-19 Veracyte, Inc. Methods for processing or analyzing a sample of thyroid tissue
ES2688621T3 (es) 2008-12-05 2018-11-05 Glaxo Group Limited Métodos para seleccionar polipéptidos resistentes a proteasa
WO2010068702A2 (en) * 2008-12-10 2010-06-17 Illumina, Inc. Methods and compositions for hybridizing nucleic acids
US8039794B2 (en) 2008-12-16 2011-10-18 Quest Diagnostics Investments Incorporated Mass spectrometry assay for thiopurine-S-methyl transferase activity and products generated thereby
US8374818B2 (en) * 2008-12-19 2013-02-12 Affymetrix, Inc. System, method and apparatus for calibrating inspection tools
US20100161607A1 (en) 2008-12-22 2010-06-24 Jasjit Singh System and method for analyzing genome data
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
KR20160021308A (ko) 2008-12-23 2016-02-24 제넨테크, 인크. 암 환자에서의 진단 목적용 방법 및 조성물
US8108406B2 (en) 2008-12-30 2012-01-31 Expanse Networks, Inc. Pangenetic web user behavior prediction system
EP3276526A1 (en) 2008-12-31 2018-01-31 23Andme, Inc. Finding relatives in a database
US8715732B2 (en) * 2009-01-05 2014-05-06 Cornell University Nucleic acid hydrogel via rolling circle amplification
KR20110106436A (ko) * 2009-01-09 2011-09-28 신텔렉트 인코포레이티드 세포의 유전적 분석
WO2010081171A2 (en) 2009-01-12 2010-07-15 Cyntellect, Inc. Laser mediated sectioning and transfer of cell colonies
US8685898B2 (en) 2009-01-15 2014-04-01 Imdaptive, Inc. Adaptive immunity profiling and methods for generation of monoclonal antibodies
TWI447108B (zh) 2009-01-16 2014-08-01 Exelixis Inc Ｎ－（４－｛〔６，７雙（甲氧基）喹啉－４－基〕氧基｝苯基）－ｎ’－（４－氟苯基）環丙烷－１，１－二甲醯胺之蘋果酸鹽及其結晶型
AU2009338190C1 (en) * 2009-01-22 2014-07-17 Momenta Pharmaceuticals, Inc. Galactose-alpha-1, 3-galactose-containing N-glycans in glycoprotein products derived from CHO cells
KR20100086827A (ko) * 2009-01-23 2010-08-02 삼성전자주식회사 프로브 핵산의 서열을 분석하는 방법, 그를 위한 마이크로어레이 및 키트 및 프로브 핵산의 합성 효율을 결정하는 방법
EP2391714B2 (en) 2009-01-30 2019-07-24 Whitehead Institute for Biomedical Research Methods for ligation and uses thereof
EP2393941A2 (en) * 2009-02-09 2011-12-14 Frederic Zenhausern Improvements in and relating to microfluidic devices for processing a sample
WO2010093465A1 (en) 2009-02-11 2010-08-19 Caris Mpi, Inc. Molecular profiling of tumors
US20100331204A1 (en) 2009-02-13 2010-12-30 Jeff Jeddeloh Methods and systems for enrichment of target genomic sequences
US20110306069A1 (en) 2009-02-19 2011-12-15 Qingyu Wu Corin As A Marker For Heart Failure
US9074258B2 (en) 2009-03-04 2015-07-07 Genomedx Biosciences Inc. Compositions and methods for classifying thyroid nodule disease
CN105132395A (zh) 2009-03-09 2015-12-09 生物蛋白有限公司 Mirac蛋白
JP5342421B2 (ja) * 2009-03-11 2013-11-13 信越化学工業株式会社 分子固定用基板の製造方法
DK2408905T3 (en) 2009-03-16 2017-08-28 Pangu Biopharma Ltd Compositions and Methods comprising Histidyl-tRNA Synthetase Splicing Variants with Non-Canonical Biological Activities
JP4826860B2 (ja) 2009-03-18 2011-11-30 Ｔｏｔｏ株式会社 光電流を用いた被検物質の特異的検出に用いられる測定装置、それに用いられるセンサユニット、および光電流を用いた被検物質の特異的検出方法
WO2010107946A2 (en) * 2009-03-18 2010-09-23 Sequenom, Inc. Use of thermostable endonucleases for generating reporter molecules
US8528589B2 (en) 2009-03-23 2013-09-10 Raindance Technologies, Inc. Manipulation of microfluidic droplets
US8603792B2 (en) 2009-03-27 2013-12-10 Life Technologies Corporation Conjugates of biomolecules to nanoparticles
WO2010113088A1 (en) * 2009-03-31 2010-10-07 Centre Hospitalier Universitaire Vaudois Methylation ligation-dependent macroarray (mlm)
WO2010120509A2 (en) 2009-03-31 2010-10-21 Atyr Pharma, Inc. Compositions and methods comprising aspartyl-trna synthetases having non-canonical biological activities
EP2414543B1 (en) 2009-04-03 2016-10-12 Decode Genetics EHF Genetic markers for risk management of atrial fibrillation and stroke
EP3514244B1 (en) 2009-04-03 2021-07-07 Sequenom, Inc. Nucleic acid preparation methods
CN105237530A (zh) * 2009-04-03 2016-01-13 豪夫迈罗氏公司 丙烷-1-磺酸{3-[5-(4-氯-苯基)-1H-吡咯并[2,3-b]吡啶-3-羰基]-2,4-二氟-苯基}-酰胺组合物及其用途
US20100297127A1 (en) 2009-04-08 2010-11-25 Ghilardi Nico P Use of il-27 antagonists to treat lupus
CN102448977A (zh) * 2009-04-09 2012-05-09 加州理工学院 用于聚合物合成的多路复用位点
US9617600B2 (en) 2009-04-18 2017-04-11 Genentech, Inc. Methods for assessing responsiveness of B-cell lymphoma to treatment with anti-CD40 antibodies
US20100330569A1 (en) * 2009-04-23 2010-12-30 Intelligent Bio-Systems, Inc. Hydroxymethyl Linkers For Labeling Nucleotides
WO2010125566A2 (en) 2009-04-27 2010-11-04 Technion Research And Development Foundation Ltd. Markers for cancer detection
WO2010124372A1 (en) 2009-04-29 2010-11-04 Genomedx Biosciences, Inc. Systems and methods for expression-based classification of thyroid tissue
WO2010129934A2 (en) 2009-05-07 2010-11-11 Veracyte, Inc. Methods and compositions for diagnosis of thyroid conditions
CA2759851A1 (en) * 2009-05-08 2010-11-11 Decode Genetics Ehf. Genetic variants contributing to risk of prostate cancer
WO2010129937A2 (en) * 2009-05-08 2010-11-11 Life Technologies Corporation Methods for detecting genetic variations in dna samples
EP2253715A1 (en) 2009-05-14 2010-11-24 RWTH Aachen New targets for cancer therapy and/or diagnosis
WO2010135588A2 (en) 2009-05-21 2010-11-25 Verenium Corporation Phytases, nucleic acids encoding them and methods for making and using them
US9767342B2 (en) 2009-05-22 2017-09-19 Affymetrix, Inc. Methods and devices for reading microarrays
US20100298171A1 (en) * 2009-05-22 2010-11-25 Affymetrix, Inc. Apparatus for polymer synthesis
US8776573B2 (en) 2009-05-29 2014-07-15 Life Technologies Corporation Methods and apparatus for measuring analytes
US20120261274A1 (en) 2009-05-29 2012-10-18 Life Technologies Corporation Methods and apparatus for measuring analytes
AU2010254259A1 (en) 2009-05-29 2012-01-12 Emory University B cell signature associated with tolerance in transplant recipients
US8673627B2 (en) 2009-05-29 2014-03-18 Life Technologies Corporation Apparatus and methods for performing electrochemical reactions
CA2764158A1 (en) 2009-06-01 2010-12-09 Halo-Bio Rnai Therapeutics, Inc. Polynucleotides for multivalent rna interference, compositions and methods of use thereof
US20120142544A1 (en) 2009-06-02 2012-06-07 University Of Miami Diagnostic transcriptomic biomarkers in inflammatory cardiomyopathies
WO2010141390A2 (en) 2009-06-05 2010-12-09 Life Technologies Corporation Nucleotide transient binding for sequencing methods
US9524369B2 (en) 2009-06-15 2016-12-20 Complete Genomics, Inc. Processing and analysis of complex nucleic acid sequence data
CA2765427A1 (en) 2009-06-15 2010-12-23 Complete Genomics, Inc. Methods and compositions for long fragment read sequencing
US20120190574A1 (en) 2009-06-19 2012-07-26 The Arizona Board of Regents, A body Corporate of the State of Arizona for and on behalf of Arizona Compound Arrays for Sample Profiling
JP5359600B2 (ja) * 2009-06-24 2013-12-04 Ｊｓｒ株式会社 酸転写樹脂組成物及びバイオチップの製造方法
US8969509B2 (en) 2009-06-26 2015-03-03 Sirigen, Inc. Signal amplified biological detection with conjugated polymers
WO2011006169A1 (en) 2009-07-10 2011-01-13 Portola Pharmaceuticals, Inc. Methods for diagnosis and treatment of thrombotic disorders mediated by cyp2c19*2
AU2010269841A1 (en) 2009-07-10 2012-02-23 Decode Genetics Ehf Genetic markers associated with risk of diabetes mellitus
SG10201510152RA (en) 2009-07-13 2016-01-28 Genentech Inc Diagnostic methods and compositions for treatment of cancer
US8501406B1 (en) 2009-07-14 2013-08-06 Pacific Biosciences Of California, Inc. Selectively functionalized arrays
US8329724B2 (en) 2009-08-03 2012-12-11 Hoffmann-La Roche Inc. Process for the manufacture of pharmaceutically active compounds
UA108618C2 (uk) 2009-08-07 2015-05-25 Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку
WO2011019393A2 (en) 2009-08-11 2011-02-17 President And Fellows Of Harvard College Class- and isoform-specific hdac inhibitors and uses thereof
PT2464370T (pt) 2009-08-14 2017-05-17 Phasebio Pharmaceuticals Inc Péptidos vasoativos intestinais modificados
MX2012001716A (es) 2009-08-14 2012-04-02 Genentech Inc Marcadores biologicos para monitorizar la respuesta del paciente a los antagonistas vegf.
US9771618B2 (en) * 2009-08-19 2017-09-26 Bioarray Genetics, Inc. Methods for treating breast cancer
SG178536A1 (en) 2009-08-22 2012-03-29 Univ Leland Stanford Junior Imaging and evaluating embryos, oocytes, and stem cells
US20110059453A1 (en) * 2009-08-23 2011-03-10 Affymetrix, Inc. Poly(A) Tail Length Measurement by PCR
WO2011026128A2 (en) 2009-08-31 2011-03-03 Life Technologies Corporation Flowcells and methods of filling and using same
US10174368B2 (en) 2009-09-10 2019-01-08 Centrillion Technology Holdings Corporation Methods and systems for sequencing long nucleic acids
WO2011032040A1 (en) 2009-09-10 2011-03-17 Centrillion Technology Holding Corporation Methods of targeted sequencing
US8815779B2 (en) 2009-09-16 2014-08-26 SwitchGear Genomics, Inc. Transcription biomarkers of biological responses and methods
CA2772670A1 (en) 2009-09-17 2011-03-24 F. Hoffmann-La Roche Ag Methods and compositions for diagnostics use in cancer patients
US8969009B2 (en) * 2009-09-17 2015-03-03 Vicki S. Thompson Identification of discriminant proteins through antibody profiling, methods and apparatus for identifying an individual
US9410965B2 (en) * 2009-09-17 2016-08-09 Battelle Energy Alliance, Llc Identification of discriminant proteins through antibody profiling, methods and apparatus for identifying an individual
CN102630250A (zh) 2009-09-25 2012-08-08 基因诊断测试公司 用于检测与癌症和其他疾病相关的染色体异常的多重(+/-)链阵列和测试
TWI384554B (zh) * 2009-10-02 2013-02-01 Univ Southern Taiwan Tech 具三層式電極的微圓洞陣列之生物微粒控制晶片及其製造方法
WO2011042564A1 (en) 2009-10-09 2011-04-14 Universite De Strasbourg Labelled silica-based nanomaterial with enhanced properties and uses thereof
PL2488873T3 (pl) 2009-10-16 2016-01-29 Novartis Ag Biomarkery odpowiedzi farmakodynamicznej wobec guza
UA111708C2 (uk) 2009-10-16 2016-06-10 Бандж Ойлз, Інк. Спосіб рафінування олії
UA109884C2 (uk) 2009-10-16 2015-10-26 Поліпептид, що має активність ферменту фосфатидилінозитол-специфічної фосфоліпази с, нуклеїнова кислота, що його кодує, та спосіб його виробництва і застосування
EP2491141A2 (en) 2009-10-19 2012-08-29 Stichting Het Nederlands Kanker Instituut Differentiation between brca2-associated tumours and sporadic tumours via array comparative genomic hybridization
EP2491139A1 (en) 2009-10-19 2012-08-29 Stichting Het Nederlands Kanker Instituut Predicting benefit of anti-cancer therapy via array comparative genomic hybridization
EP2491140A1 (en) 2009-10-19 2012-08-29 Stichting Het Nederlands Kanker Instituut Predicting response to anti-cancer therapy via array comparative genomic hybridization
EP2314714A1 (en) 2009-10-22 2011-04-27 Universiteit Leiden Disease susceptibility
US9644240B2 (en) 2009-10-22 2017-05-09 Leiden University Disease susceptibility
WO2011056505A1 (en) 2009-10-26 2011-05-12 Abbott Laboratories Detection of chromosomal abnormalities associated with prognosis of non small cell lung cancer
CA2779223A1 (en) 2009-10-27 2011-05-12 Caris Mpi, Inc. Molecular profiling for personalized medicine
WO2011050981A2 (en) 2009-10-30 2011-05-05 Roche Diagnostics Gmbh Method for detecting balanced chromosomal aberrations in a genome
WO2011056872A2 (en) 2009-11-03 2011-05-12 Gen9, Inc. Methods and microfluidic devices for the manipulation of droplets in high fidelity polynucleotide assembly
US7972793B2 (en) 2009-11-04 2011-07-05 Suregene, Llc Methods and compositions for the treatment of psychotic disorders through the identification of the SULT4A1-1 haplotype
EP2496944A2 (en) 2009-11-05 2012-09-12 Novartis AG Biomarkers predictive of progression of fibrosis
WO2011057022A1 (en) 2009-11-06 2011-05-12 Plexxikon, Inc. Compounds and methods for kinase modulation, and indications therefor
JP2013510574A (ja) 2009-11-11 2013-03-28 モメンタ ファーマシューティカルズ インコーポレイテッド チャイニーズハムスターからのグリコシルトランスフェラーゼおよび関連方法
WO2011060332A2 (en) * 2009-11-12 2011-05-19 Texas Tech University Compositions and methods for treating hyperproliferative disorders
WO2011062962A2 (en) 2009-11-17 2011-05-26 The Trustees Of The University Of Pennsylvania Smndelta7 degron: novel compositions and methods of use
WO2011063283A2 (en) 2009-11-20 2011-05-26 Oregon Health & Science University Methods for detecting a mycobacterium tuberculosis infection
EA201200617A1 (ru) * 2009-11-23 2012-11-30 Серулин Фарма Инк. Полимеры на основе циклодекстрина для доставки лекарственных средств
US9216414B2 (en) 2009-11-25 2015-12-22 Gen9, Inc. Microfluidic devices and methods for gene synthesis
EP3597771A1 (en) 2009-11-25 2020-01-22 Gen9, Inc. Methods and apparatuses for chip-based dna error reduction
US20130203061A1 (en) 2009-11-30 2013-08-08 Michael KLASS Methods and systems for isolating, storing, and analyzing vesicles
EP2507630B1 (en) 2009-12-02 2017-01-25 The Board of Trustees of The Leland Stanford Junior University Biomarkers for determining an allograft tolerant phenotype
US8501122B2 (en) 2009-12-08 2013-08-06 Affymetrix, Inc. Manufacturing and processing polymer arrays
US10446272B2 (en) 2009-12-09 2019-10-15 Veracyte, Inc. Methods and compositions for classification of samples
US20110143966A1 (en) * 2009-12-15 2011-06-16 Affymetrix, Inc. Surface Modifications and Methods for their Synthesis and Use
US8835358B2 (en) 2009-12-15 2014-09-16 Cellular Research, Inc. Digital counting of individual molecules by stochastic attachment of diverse labels
US9315857B2 (en) 2009-12-15 2016-04-19 Cellular Research, Inc. Digital counting of individual molecules by stochastic attachment of diverse label-tags
GB0922085D0 (en) 2009-12-17 2010-02-03 Cambridge Entpr Ltd Cancer diagnosis and treatment
DE102009059112A1 (de) 2009-12-18 2011-06-22 Biotype Diagnostic GmbH, 01109 Eine Vorrichtung zur Bestimmung molekularer Wechselwirkungen, sowie eine Folie zur Herstellung einer solchen
WO2011087760A2 (en) 2009-12-22 2011-07-21 Sequenom, Inc. Processes and kits for identifying aneuploidy
GB0922377D0 (en) 2009-12-22 2010-02-03 Arab Gulf University The Mutant LDL receptor
FR2954349A1 (fr) 2009-12-22 2011-06-24 Agronomique Inst Nat Rech Sulfatase modifiant selectivement les glycosaminoglycanes
HUE027713T2 (en) 2009-12-23 2016-10-28 Hoffmann La Roche Anti-BV8 antibodies and their use
WO2011079176A2 (en) 2009-12-23 2011-06-30 Raindance Technologies, Inc. Microfluidic systems and methods for reducing the exchange of molecules between droplets
US9476868B2 (en) 2009-12-23 2016-10-25 Hill's Pet Nutrition, Inc. Compositions and methods for diagnosing and treating kidney disorders in a canine
DK2493491T3 (da) 2009-12-29 2014-06-30 Hills Pet Nutrition Inc Sammensætninger, indeholdende ingefær til lindringen eller forebyggelsen af inflammatoriske tilstande hos katte og hunde
KR101590220B1 (ko) 2009-12-31 2016-01-29 벤타나 메디컬 시스템즈, 인코포레이티드 유일 특이적 핵산 프로브 제조 방법
WO2011085075A2 (en) 2010-01-07 2011-07-14 Gen9, Inc. Assembly of high fidelity polynucleotides
AU2011205230A1 (en) 2010-01-13 2012-08-02 Caris Life Sciences Switzerland Holdings Gmbh Detection of gastrointestinal disorders
EP4322238A3 (en) 2010-01-19 2024-05-15 Sirigen II Limited Novel reagents for directed biomarker signal amplification
US9927434B2 (en) 2010-01-20 2018-03-27 Customarray, Inc. Multiplex microarray of serially deposited biomolecules on a microarray
CA3101636A1 (en) 2010-01-26 2011-08-04 National Jewish Health Diagnosis and prognosis of idiopathic interstitial pneumonia by rs35705950 snp in muc5b gene promoter
WO2011093939A1 (en) 2010-02-01 2011-08-04 Illumina, Inc. Focusing methods and optical systems and assemblies using the same
US20130071408A1 (en) 2010-02-01 2013-03-21 Atul J. Butte Methods for Diagnosis and Treatment of Non-Insulin Dependent Diabetes Mellitus
IN2012DN06588A (fi) 2010-02-10 2015-10-23 Novartis Ag
US9366632B2 (en) 2010-02-12 2016-06-14 Raindance Technologies, Inc. Digital analyte analysis
WO2011100604A2 (en) 2010-02-12 2011-08-18 Raindance Technologies, Inc. Digital analyte analysis
US9399797B2 (en) 2010-02-12 2016-07-26 Raindance Technologies, Inc. Digital analyte analysis
US10351905B2 (en) 2010-02-12 2019-07-16 Bio-Rad Laboratories, Inc. Digital analyte analysis
US8415171B2 (en) * 2010-03-01 2013-04-09 Quanterix Corporation Methods and systems for extending dynamic range in assays for the detection of molecules or particles
US9678068B2 (en) 2010-03-01 2017-06-13 Quanterix Corporation Ultra-sensitive detection of molecules using dual detection methods
ES2544635T3 (es) 2010-03-01 2015-09-02 Quanterix Corporation Métodos para extender el rango dinámico en ensayos para la detección de moléculas o partículas
US8236574B2 (en) 2010-03-01 2012-08-07 Quanterix Corporation Ultra-sensitive detection of molecules or particles using beads or other capture objects
KR20130056855A (ko) 2010-03-01 2013-05-30 카리스 라이프 사이언스 룩셈부르크 홀딩스 치료진단용 생물학적 지표들
US8716467B2 (en) 2010-03-03 2014-05-06 Gen9, Inc. Methods and devices for nucleic acid synthesis
EP2542678B1 (en) 2010-03-04 2017-04-12 InteRNA Technologies B.V. A MiRNA MOLECULE DEFINED BY ITS SOURCE AND ITS THERAPEUTIC USES IN CANCER ASSOCIATED WITH EMT
DE202011003570U1 (de) 2010-03-06 2012-01-30 Illumina, Inc. Systeme und Vorrichtungen zum Detektieren optischer Signale aus einer Probe
EP2369325A1 (en) 2010-03-12 2011-09-28 Eppendorf Ag Array analysis for online detection
WO2011119980A1 (en) 2010-03-25 2011-09-29 The Board Of Trustees Of The Leland Stanford Junior University Protein and gene biomarkers for rejection of organ transplants
WO2011127194A1 (en) 2010-04-06 2011-10-13 The George Washington University Compositions and methods for identifying autism spectrum disorders
AU2011237669B2 (en) 2010-04-06 2016-09-08 Caris Life Sciences Switzerland Holdings Gmbh Circulating biomarkers for disease
WO2011128096A1 (en) 2010-04-16 2011-10-20 Roche Diagnostics Gmbh Polymorphism markers for predicting response to interleukin-6 receptor-inhibiting monoclonal antibody drug treatment
SG10201502900PA (en) 2010-04-16 2015-06-29 Zeus Scientific Inc Methods for measuring enzyme activity useful in determining cell viability in non-purified samples
CA2796744A1 (en) 2010-04-17 2011-10-20 Bayer Healthcare Llc Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions
CA2795671A1 (en) 2010-04-19 2011-10-27 The Procter & Gamble Company Genetic signatures and gene chips associated with administration of electrically conducted radio frequency current to skin and methods and treatments relating thereto
WO2011133539A2 (en) 2010-04-19 2011-10-27 The Procter & Gamble Company Combined energy and topical composition application for regulating the condition of mammalian skin
EP2563380B1 (en) 2010-04-26 2018-05-30 aTyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-trna synthetase
US20120003639A1 (en) 2010-04-27 2012-01-05 Prelude, Inc. Cancer biomarkers and methods of use thereof
JP6294074B2 (ja) 2010-04-27 2018-03-14 エータイアー ファーマ， インコーポレイテッド イソロイシルｔＲＮＡ合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
US8993723B2 (en) 2010-04-28 2015-03-31 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of alanyl-tRNA synthetases
AU2011248490B2 (en) 2010-04-29 2016-11-10 Pangu Biopharma Limited Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Asparaginyl tRNA synthetases
CA2800557A1 (en) 2010-04-29 2011-11-03 Medical Prognosis Institute A/S Methods and devices for predicting treatment efficacy
US9068177B2 (en) 2010-04-29 2015-06-30 Atyr Pharma, Inc Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-tRNA synthetases
CA2797393C (en) 2010-04-29 2020-03-10 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of valyl trna synthetases
WO2011139986A2 (en) 2010-05-03 2011-11-10 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of arginyl-trna synthetases
WO2011140132A2 (en) 2010-05-03 2011-11-10 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-alpha-trna synthetases
CN103140233B (zh) 2010-05-03 2017-04-05 Atyr 医药公司 与甲硫氨酰‑tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的发现
JP6008844B2 (ja) 2010-05-04 2016-10-19 エータイアー ファーマ， インコーポレイテッド ｐ３８ＭＵＬＴＩ−ｔＲＮＡ合成酵素複合体のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
EP2569624B1 (en) 2010-05-10 2017-03-15 Mayo Foundation for Medical Education and Research Detection of chromosomal abnormalities associated with endometrial cancer
WO2011143556A1 (en) 2010-05-13 2011-11-17 Gen9, Inc. Methods for nucleotide sequencing and high fidelity polynucleotide synthesis
JP6396656B2 (ja) 2010-05-14 2018-09-26 エータイアー ファーマ， インコーポレイテッド フェニルアラニルβｔＲＮＡ合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
US9482664B2 (en) 2010-05-17 2016-11-01 Sentilus Holdco LLC Detection devices and related methods of use
JP6027965B2 (ja) 2010-05-17 2016-11-16 エータイアー ファーマ， インコーポレイテッド ロイシルｔＲＮＡ合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
EP2388336A1 (en) 2010-05-19 2011-11-23 Signature Diagnostics AG Method and kits for diagnosing colorectal cancer
WO2011146725A1 (en) 2010-05-19 2011-11-24 Bayer Healthcare Llc Biomarkers for a multikinase inhibitor
WO2011150168A1 (en) 2010-05-28 2011-12-01 Gen9, Inc. Methods and devices for in situ nucleic acid synthesis
JP5906237B2 (ja) 2010-06-01 2016-04-20 エータイアー ファーマ， インコーポレイテッド リジルｔＲＮＡ合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
WO2011153224A2 (en) 2010-06-02 2011-12-08 Genentech, Inc. Diagnostic methods and compositions for treatment of cancer
US9228240B2 (en) 2010-06-03 2016-01-05 California Institute Of Technology Methods for detecting and quantifying viable bacterial endo-spores
CA3113343A1 (en) 2010-06-03 2011-12-08 Pharmacyclics Llc Use of inhibitors of bruton's tyrosine kinase (btk) in the treatment of follicular lymphoma
PL2576837T3 (pl) 2010-06-04 2018-04-30 Chronix Biomedical Krążeniowe biomarkery typu kwasu nukleinowego związane z rakiem prostaty
EP2576815B1 (en) 2010-06-04 2018-02-14 Biomérieux Method for the prognosis of colorectal cancer
JP2013529089A (ja) 2010-06-07 2013-07-18 エフ．ホフマン−ラ ロシュ アーゲー インターロイキン−６受容体を阻害するモノクローナル抗体による薬剤治療に対する応答を予測するための遺伝子発現マーカー
US8940310B2 (en) 2010-06-16 2015-01-27 Dynavax Technologies Corporation Methods of treatment using TLR7 and/or TLR9 inhibitors
WO2011159942A1 (en) 2010-06-18 2011-12-22 Illumina, Inc. Conformational probes and methods for sequencing nucleic acids
MX2012014776A (es) 2010-06-25 2013-01-29 Eisai R&D Man Co Ltd Agente antitumoral que emplea compuestos con efecto inhibidor de cinasas combinados.
US20120001646A1 (en) 2010-06-30 2012-01-05 Life Technologies Corporation Methods and apparatus for testing isfet arrays
EP2589084B1 (en) 2010-06-30 2016-11-16 Life Technologies Corporation Transistor circuits for detection and measurement of chemical reactions and compounds
US8858782B2 (en) 2010-06-30 2014-10-14 Life Technologies Corporation Ion-sensing charge-accumulation circuits and methods
US11307166B2 (en) 2010-07-01 2022-04-19 Life Technologies Corporation Column ADC
EP2589065B1 (en) 2010-07-03 2015-08-19 Life Technologies Corporation Chemically sensitive sensor with lightly doped drains
CA2804599C (en) 2010-07-06 2023-01-31 Interna Technologies Bv Mirna and its diagnostic and therapeutic uses in diseases or conditions associated with melanoma, or in diseases or conditions associated with activated braf pathway
RU2607634C2 (ru) 2010-07-12 2017-01-10 Селджин Корпорейшн Твердые формы ромидепсина и их применение
JP6116479B2 (ja) 2010-07-12 2017-04-19 エータイアー ファーマ， インコーポレイテッド グリシルｔＲＮＡ合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見
ES2655500T3 (es) 2010-07-16 2018-02-20 Tocagen Inc. Detección de retrovirus
DK2601609T3 (en) 2010-08-02 2017-06-06 Population Bio Inc COMPOSITIONS AND METHODS FOR DISCOVERING MUTATIONS CAUSING GENETIC DISORDERS
WO2012019099A2 (en) 2010-08-05 2012-02-09 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Follistatin-like-protein-1 as a biomarker for inflammatory disorders
US20120034603A1 (en) 2010-08-06 2012-02-09 Tandem Diagnostics, Inc. Ligation-based detection of genetic variants
US20130261003A1 (en) 2010-08-06 2013-10-03 Ariosa Diagnostics, In. Ligation-based detection of genetic variants
US11203786B2 (en) 2010-08-06 2021-12-21 Ariosa Diagnostics, Inc. Detection of target nucleic acids using hybridization
US8700338B2 (en) 2011-01-25 2014-04-15 Ariosa Diagnosis, Inc. Risk calculation for evaluation of fetal aneuploidy
US10167508B2 (en) 2010-08-06 2019-01-01 Ariosa Diagnostics, Inc. Detection of genetic abnormalities
US20140342940A1 (en) 2011-01-25 2014-11-20 Ariosa Diagnostics, Inc. Detection of Target Nucleic Acids using Hybridization
US11031095B2 (en) 2010-08-06 2021-06-08 Ariosa Diagnostics, Inc. Assay systems for determination of fetal copy number variation
US10533223B2 (en) 2010-08-06 2020-01-14 Ariosa Diagnostics, Inc. Detection of target nucleic acids using hybridization
US20130040375A1 (en) 2011-08-08 2013-02-14 Tandem Diagnotics, Inc. Assay systems for genetic analysis
US8834847B2 (en) 2010-08-12 2014-09-16 Pacific Biosciences Of California, Inc. Photodamage mitigation compounds and systems
US9040464B2 (en) 2010-08-16 2015-05-26 Mount Sinai Hosptial Markers of the male urogenital tract
DK3109325T3 (en) 2010-08-24 2019-01-28 Dana Farber Cancer Inst Inc Methods for predicting anticancer response
CA2808539C (en) 2010-08-25 2021-05-25 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of tyrosyl-trna synthetases
US8859502B2 (en) 2010-09-13 2014-10-14 Celgene Corporation Therapy for MLL-rearranged leukemia
DK3508589T3 (da) 2010-09-13 2023-06-06 Clinical Genomics Pty Ltd Epigenetiske markører af kolorektale kræftformer og diagnostiske fremgangsmåder under anvendelse af det samme
EP2975399B1 (en) 2010-09-15 2022-05-11 Almac Diagnostic Services Limited Molecular diagnostic test for cancer
EP2617061B1 (en) 2010-09-15 2021-06-30 Life Technologies Corporation Methods and apparatus for measuring analytes
CN103459611B (zh) 2010-09-17 2016-11-02 哈佛大学校长及研究员协会 对多能干细胞的效用和安全性进行表征的功能基因组学研究
US20140018251A1 (en) 2010-09-20 2014-01-16 Stichting Het Nederlands Kanker Instituut Methods for Predicting Response to Anti-Cancer Therapy in Cancer Patients
ES2595433T3 (es) 2010-09-21 2016-12-30 Population Genetics Technologies Ltd. Aumento de la confianza en las identificaciones de alelos con el recuento molecular
CN103299182A (zh) 2010-09-24 2013-09-11 生命科技公司 匹配的晶体管对电路
US9110079B2 (en) 2010-09-29 2015-08-18 Biomerieux Method and kit for establishing an in vitro prognosis on a patient exhibiting SIRS
WO2012050920A1 (en) 2010-09-29 2012-04-19 Illumina, Inc. Compositions and methods for sequencing nucleic acids
WO2012045012A2 (en) 2010-09-30 2012-04-05 Raindance Technologies, Inc. Sandwich assays in droplets
EP2625268B1 (en) 2010-10-06 2015-12-30 BP Corporation North America Inc. Variant cbh i polypeptides
WO2012051476A1 (en) 2010-10-15 2012-04-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Mid-infrared imaging of microarrays
US20120095029A1 (en) 2010-10-15 2012-04-19 Hoffmann-La Roche Inc. Ipp complex as marker for erlotinib treatment
US8753816B2 (en) 2010-10-26 2014-06-17 Illumina, Inc. Sequencing methods
WO2012058532A2 (en) 2010-10-28 2012-05-03 Yale University Methods and compositions for assessing and treating cancer
GB201018312D0 (en) 2010-10-29 2010-12-15 Vib Vzw Metagene expression signature for prognosis of breast cancer patients
EP2638157B1 (en) 2010-11-12 2015-07-22 Gen9, Inc. Methods and devices for nucleic acids synthesis
EP4039363A1 (en) 2010-11-12 2022-08-10 Gen9, Inc. Protein arrays and methods of using and making the same
JP6163104B2 (ja) 2010-11-15 2017-07-12 アクセラレイテッド・バイオサイエンシズ・コーポレーション ヒト・トロホブラスト幹細胞からの神経幹細胞の生成
EP2640851A2 (en) 2010-11-17 2013-09-25 Asuragen, Inc. Mirnas as biomarkers for distinguishing benign from malignant thyroid neoplasms
JP2014506117A (ja) 2010-11-24 2014-03-13 エフ．ホフマン−ラ ロシュ アーゲー 軽度の炎症を検出するための方法
US9308255B2 (en) 2010-11-24 2016-04-12 Yale University Methods of administering D-dopachrome tautomerase (D-DT) to treat ischemia-reperfusion injury
JP5754685B2 (ja) * 2010-12-02 2015-07-29 国立研究開発法人農業・食品産業技術総合研究機構 基板上でビルドアップ型コンビナトリアルライブラリーを合成する方法
US20140017797A1 (en) 2010-12-13 2014-01-16 De Staadt der Nederlanden, vert doorde minister van VWS Protein affinity tag and uses thereof
KR20120066924A (ko) 2010-12-15 2012-06-25 제일모직주식회사 오르토-니트로벤질 에스테르 화합물 및 이를 포함하는 포지티브형 감광성 수지 조성물
US8969254B2 (en) 2010-12-16 2015-03-03 Dana-Farber Cancer Institute, Inc. Oligonucleotide array for tissue typing
JP2012131718A (ja) 2010-12-20 2012-07-12 Samsung Electronics Co Ltd 化合物合成方法、マイクロアレイ、酸転写用組成物及びバイオチップ製造用組成物
WO2012090073A2 (en) 2010-12-30 2012-07-05 The Netherlands Cancer Institute Methods and compositions for predicting chemotherapy sensitivity
US8951781B2 (en) 2011-01-10 2015-02-10 Illumina, Inc. Systems, methods, and apparatuses to image a sample for biological or chemical analysis
EP2474617A1 (en) 2011-01-11 2012-07-11 InteRNA Technologies BV Mir for treating neo-angiogenesis
EP2663656B1 (en) 2011-01-13 2016-08-24 Decode Genetics EHF Genetic variants as markers for use in urinary bladder cancer risk assessment
US8756020B2 (en) 2011-01-25 2014-06-17 Ariosa Diagnostics, Inc. Enhanced risk probabilities using biomolecule estimations
WO2012103031A2 (en) 2011-01-25 2012-08-02 Ariosa Diagnostics, Inc. Detection of genetic abnormalities
US9994897B2 (en) 2013-03-08 2018-06-12 Ariosa Diagnostics, Inc. Non-invasive fetal sex determination
US11270781B2 (en) 2011-01-25 2022-03-08 Ariosa Diagnostics, Inc. Statistical analysis for non-invasive sex chromosome aneuploidy determination
US10131947B2 (en) 2011-01-25 2018-11-20 Ariosa Diagnostics, Inc. Noninvasive detection of fetal aneuploidy in egg donor pregnancies
US9952237B2 (en) 2011-01-28 2018-04-24 Quanterix Corporation Systems, devices, and methods for ultra-sensitive detection of molecules or particles
PT2672967T (pt) 2011-02-07 2018-12-07 Plexxikon Inc Compostos e métodos de modulação da quinase e suas indicações
EP3369828B1 (en) 2011-02-07 2020-07-15 The Governing Council Of The University Of Toronto Bioprobes and methods of use thereof
JP6020164B2 (ja) 2011-02-10 2016-11-02 三菱レイヨン株式会社 核酸の検出方法
WO2012109600A2 (en) 2011-02-11 2012-08-16 Raindance Technologies, Inc. Methods for forming mixed droplets
WO2012112804A1 (en) 2011-02-18 2012-08-23 Raindance Technoligies, Inc. Compositions and methods for molecular labeling
TWI558702B (zh) 2011-02-21 2016-11-21 普雷辛肯公司 醫藥活性物質的固態形式
JP2014507664A (ja) 2011-02-23 2014-03-27 ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー ヒト胚における異数性の検出方法
AU2011360257B2 (en) 2011-02-24 2015-08-06 Hill's Pet Nutrition, Inc. Compositions and methods for diagnosing and treating kidney disorders in a feline
WO2012118745A1 (en) 2011-02-28 2012-09-07 Arnold Oliphant Assay systems for detection of aneuploidy and sex determination
EP2681566A2 (en) 2011-02-28 2014-01-08 University of Iowa Research Foundation Anti-müllerian hormone changes in pregnancy and prediction ofadverse pregnancy outcomes and gender
WO2012119129A1 (en) 2011-03-02 2012-09-07 Berg Biosystems, Llc Interrogatory cell-based assays and uses thereof
EP2683831B1 (en) 2011-03-07 2015-09-23 Accelerate Diagnostics, Inc. Rapid cell purification systems
US10254204B2 (en) 2011-03-07 2019-04-09 Accelerate Diagnostics, Inc. Membrane-assisted purification
SG10201602147YA (en) 2011-03-18 2016-05-30 Eisai R&D Man Co Ltd Methods And Compositions For Predicting Response To Eribulin
WO2012129347A1 (en) 2011-03-21 2012-09-27 Biodesy, Llc Classification of kinase inhibitors using nonlinear optical techniques
EP2689028B1 (en) 2011-03-23 2017-08-30 Pacific Biosciences Of California, Inc. Isolation of polymerase-nucleic acid complexes and loading onto substrates
WO2012129758A1 (en) 2011-03-25 2012-10-04 Biomerieux Method and kit for determining in vitro probability for individual to suffer from colorectal cancer
US20140005070A1 (en) 2011-03-28 2014-01-02 Novartis Ag Markers associated with cyclin-dependent kinase inhibitors
US9777332B2 (en) 2011-03-31 2017-10-03 St. Jude Children's Research Hospital Methods and compositions for identifying minimal residual disease in acute lymphoblastic leukemia
US20120252682A1 (en) 2011-04-01 2012-10-04 Maples Corporate Services Limited Methods and systems for sequencing nucleic acids
EP2694677A2 (en) 2011-04-04 2014-02-12 Netherland Cancer Institute Methods and compositions for predicting resistance to anticancer treatment with protein kinase inhibitors
EP2694678A2 (en) 2011-04-04 2014-02-12 Netherland Cancer Institute Methods and compositions for predicting resistance to anticancer treatment
US20140186340A1 (en) 2011-04-08 2014-07-03 Gilead Biologics, Inc. Methods and Compositions for Normalization of Tumor Vasculature by Inhibition of LOXL2
EP2694709B1 (en) 2011-04-08 2016-09-14 Prognosys Biosciences, Inc. Peptide constructs and assay systems
WO2012142301A2 (en) 2011-04-12 2012-10-18 Quanterix Corporation Methods of determining a treatment protocol for and/or a prognosis of a patients recovery from a brain injury
AU2012246490B2 (en) 2011-04-18 2016-08-04 Eisai R&D Management Co., Ltd. Therapeutic agent for tumor
EP2699699A4 (en) 2011-04-18 2014-12-31 Garvan Inst Med Res METHOD FOR THE DIAGNOSIS OF CANCER
CA2834218C (en) 2011-04-29 2021-02-16 Sequenom, Inc. Quantification of a minority nucleic acid species using inhibitory oligonucleotides
EP2520661A1 (en) 2011-05-02 2012-11-07 Rheinische Friedrich-Wilhelms-Universität Bonn Blood-based gene expression signatures in lung cancer
EP2527459A1 (en) 2011-05-02 2012-11-28 Rheinische Friedrich-Wilhelms-Universität Bonn Blood-based gene detection of non-small cell lung cancer
CN103649335B (zh) 2011-05-04 2015-11-25 Htg分子诊断有限公司 定量核酸酶保护测定（qnpa）和测序（qnps）的改进
WO2012158957A2 (en) 2011-05-17 2012-11-22 Plexxikon Inc. Kinase modulation and indications therefor
WO2012156515A1 (en) 2011-05-18 2012-11-22 Rheinische Friedrich-Wilhelms-Universität Bonn Molecular analysis of acute myeloid leukemia
EP2524967A1 (en) 2011-05-19 2012-11-21 Signature Diagnostics AG Methods and kits for diagnosing colorectal cancer
EA027558B1 (ru) 2011-05-19 2017-08-31 Эйджена Байосайенс, Инк. Способ обнаружения мультиплексных нуклеиновых кислот
EP2524968A1 (en) 2011-05-19 2012-11-21 Signature Diagnostics AG Methods and kits for diagnosing colorectal cancer
US20140106986A1 (en) 2011-06-01 2014-04-17 Medical Prognosis Institute A/S Methods and devices for prognosis of cancer relapse
EP3709018A1 (en) 2011-06-02 2020-09-16 Bio-Rad Laboratories, Inc. Microfluidic apparatus for identifying components of a chemical reaction
US8841071B2 (en) 2011-06-02 2014-09-23 Raindance Technologies, Inc. Sample multiplexing
CN103733065B (zh) 2011-06-02 2017-12-15 阿尔玛克诊断有限公司 用于癌症的分子诊断试验
MX349011B (es) 2011-06-02 2017-07-05 Novartis Ag Biomarcadores para terapia de inhibidor de hedgehog.
EP2714937B1 (en) 2011-06-03 2018-11-14 Eisai R&D Management Co., Ltd. Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds
US9561262B2 (en) 2011-06-06 2017-02-07 Phasebio Pharmaceuticals, Inc. Use of modified vasoactive intestinal peptides in the treatment of hypertension
US8778848B2 (en) 2011-06-09 2014-07-15 Illumina, Inc. Patterned flow-cells useful for nucleic acid analysis
CN103732744A (zh) 2011-06-15 2014-04-16 Gen9股份有限公司 制备性体外克隆的方法
RU2593952C2 (ru) 2011-06-15 2016-08-10 Хилл'С Пет Ньютришн, Инк. Композиции и способы для диагностики и мониторинга гипертиреоза у животных семейства кошачьих
US9752176B2 (en) 2011-06-15 2017-09-05 Ginkgo Bioworks, Inc. Methods for preparative in vitro cloning
WO2012174378A2 (en) 2011-06-17 2012-12-20 Myriad Genetics, Inc. Methods and materials for assessing allelic imbalance
EP2721176A2 (en) 2011-06-17 2014-04-23 Dana-Farber Cancer Institute, Inc. Signatures for predicting the survivability of myelodysplastic syndrome subjects
WO2012178007A1 (en) 2011-06-22 2012-12-27 Yale University COMPOSITIONS AND METHODS OF DIAGNOSING DISEASES AND DISORDERS ASSOCIATED WITH β CELL DEATH
US20140235474A1 (en) 2011-06-24 2014-08-21 Sequenom, Inc. Methods and processes for non invasive assessment of a genetic variation
WO2013009705A2 (en) 2011-07-09 2013-01-17 The Trustees Of Columbia University In The City Of New York Biomarkers, methods, and compositions for inhibiting a multi-cancer mesenchymal transition mechanism
US8658430B2 (en) 2011-07-20 2014-02-25 Raindance Technologies, Inc. Manipulating droplet size
US9034797B2 (en) 2011-07-25 2015-05-19 Csir Array printing
US9029800B2 (en) 2011-08-09 2015-05-12 Palo Alto Research Center Incorporated Compact analyzer with spatial modulation and multiple intensity modulated excitation sources
US8723140B2 (en) 2011-08-09 2014-05-13 Palo Alto Research Center Incorporated Particle analyzer with spatial modulation and long lifetime bioprobes
LT2944693T (lt) 2011-08-26 2019-08-26 Gen9, Inc. Kompozicijos ir būdai, skirti nukleorūgščių didelio tikslumo sąrankai
US9435812B2 (en) 2011-08-31 2016-09-06 Ventana Medical Systems, Inc. Expression of ETS related gene (ERG) and phosphatase and tensin homolog (PTEN) correlates with prostate cancer capsular penetration
US8712697B2 (en) 2011-09-07 2014-04-29 Ariosa Diagnostics, Inc. Determination of copy number variations using binomial probability calculations
WO2013036290A1 (en) 2011-09-09 2013-03-14 Yale University Compositions and methods for assessing and treating inflammatory diseases and disorders
WO2013040251A2 (en) 2011-09-13 2013-03-21 Asurgen, Inc. Methods and compositions involving mir-135b for distinguishing pancreatic cancer from benign pancreatic disease
AU2012313353B2 (en) 2011-09-22 2018-03-08 Precision Medicine Holdings Pty Ltd Screening method
WO2013047624A1 (ja) 2011-09-26 2013-04-04 Toto株式会社 被検物質の特異的検出方法
WO2013052505A2 (en) 2011-10-03 2013-04-11 Celmatix, Inc. Methods and devices for assessing risk to a putative offspring of developing a condition
US9984198B2 (en) 2011-10-06 2018-05-29 Sequenom, Inc. Reducing sequence read count error in assessment of complex genetic variations
US9367663B2 (en) 2011-10-06 2016-06-14 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US10424394B2 (en) 2011-10-06 2019-09-24 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US20140242588A1 (en) 2011-10-06 2014-08-28 Sequenom, Inc Methods and processes for non-invasive assessment of genetic variations
US10196681B2 (en) 2011-10-06 2019-02-05 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US9566560B2 (en) 2011-10-06 2017-02-14 Illumina, Inc. Array domains having rotated patterns
US20130090329A1 (en) 2011-10-07 2013-04-11 Suregene, Llc Methods and Compositions for the Treatment of Psychotic Disorders Through the Identification of the Olanzapine Poor Response Predictor Genetic Signature
CA2851388C (en) 2011-10-10 2023-11-21 The Hospital For Sick Children Methods and compositions for screening and treating developmental disorders
US9347900B2 (en) 2011-10-14 2016-05-24 Pacific Biosciences Of California, Inc. Real-time redox sequencing
EP2766498B1 (en) 2011-10-14 2019-06-19 President and Fellows of Harvard College Sequencing by structure assembly
GB2497838A (en) 2011-10-19 2013-06-26 Nugen Technologies Inc Compositions and methods for directional nucleic acid amplification and sequencing
US20140303008A1 (en) 2011-10-21 2014-10-09 Chronix Biomedical Colorectal cancer associated circulating nucleic acid biomarkers
US20130157884A1 (en) 2011-10-26 2013-06-20 Asuragen, Inc. Methods and compositions involving mirna expression levels for distinguishing pancreatic cysts
EP2771487A1 (en) 2011-10-27 2014-09-03 Asuragen, INC. Mirnas as diagnostic biomarkers to distinguish benign from malignant thyroid tumors
CN104302180B (zh) 2011-10-28 2017-05-17 米伦纽姆医药公司 对nedd8活化酶(nae)抑制剂的反应的生物标记
AU2012328662B2 (en) 2011-10-28 2015-12-17 Illumina, Inc. Microarray fabrication system and method
US10837879B2 (en) 2011-11-02 2020-11-17 Complete Genomics, Inc. Treatment for stabilizing nucleic acid arrays
US10100092B2 (en) 2011-11-03 2018-10-16 Vca, Inc. Compositions and methods to detect various infectious organisms
DK2773779T3 (da) 2011-11-04 2020-11-23 Population Bio Inc Fremgangsmåder og sammensætninger til diagnosticering, prognose og forebyggelse af neurologiske tilstande
US9212381B2 (en) 2011-11-10 2015-12-15 President And Fellows Of Harvard College Methods and compositions for labeling polypeptides
EP2776043B1 (en) 2011-11-11 2018-02-21 Millennium Pharmaceuticals, Inc. Biomarkers of response to proteasome inhibitors
WO2013071163A2 (en) 2011-11-11 2013-05-16 Millennium Pharamaceuticals, Inc. Biomarkers of response to proteasome inhibitors
US11262362B2 (en) 2011-11-18 2022-03-01 Memorial Sloan-Kettering Cancer Center 2-hydroxyglutarate as a biomarker for chronic hypoxia
PE20142362A1 (es) 2011-11-18 2015-01-30 Alnylam Pharmaceuticals Inc Agentes de iarn, composiciones y metodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (ttr)
US10437858B2 (en) 2011-11-23 2019-10-08 23Andme, Inc. Database and data processing system for use with a network-based personal genetics services platform
AU2012346861A1 (en) 2011-11-30 2014-06-19 AbbVie Deutschland GmbH & Co. KG Methods and compositions for determining responsiveness to treatment with a tnf-alpha inhibitor
WO2013080473A1 (ja) * 2011-11-30 2013-06-06 ソニー株式会社 ケミカルセンサ、ケミカルセンサモジュール、化学物質検出装置及び化学物質検出方法
US9944985B2 (en) 2011-11-30 2018-04-17 Children's Hospital Medical Center Personalized pain management and anesthesia: preemptive risk identification and therapeutic decision support
US9970984B2 (en) 2011-12-01 2018-05-15 Life Technologies Corporation Method and apparatus for identifying defects in a chemical sensor array
US8748097B1 (en) 2011-12-02 2014-06-10 President And Fellows Of Harvard College Identification of agents for treating calcium disorders and uses thereof
US10513737B2 (en) 2011-12-13 2019-12-24 Decipher Biosciences, Inc. Cancer diagnostics using non-coding transcripts
WO2013087789A1 (en) 2011-12-13 2013-06-20 Glykos Finland Ltd. Antibody isoform arrays and methods thereof
WO2013095935A1 (en) 2011-12-19 2013-06-27 Hill's Pet Nutrition, Inc. Compositions and methods for diagnosing and treating hyperthyroidism in companion animals
EP2795500B1 (en) 2011-12-20 2020-04-15 Siemens Healthcare Diagnostics Inc. Coated substrates for high energy capture phase binding and methods of production and use thereof
DK2794907T4 (da) 2011-12-21 2023-02-27 Myriad Genetics Inc Fremgangsmåder og materialer til vurdering af tab af heterozygositet
WO2013096819A2 (en) 2011-12-22 2013-06-27 Ibis Biosciences, Inc. Macromolecule positioning by electrical potential
US9823246B2 (en) 2011-12-28 2017-11-21 The Board Of Trustees Of The Leland Stanford Junior University Fluorescence enhancing plasmonic nanoscopic gold films and assays based thereon
WO2013102081A2 (en) 2011-12-29 2013-07-04 Ibis Biosciences, Inc. Macromolecule delivery to nanowells
WO2013102101A1 (en) 2011-12-30 2013-07-04 Somalogic, Inc. Aptamers and diagnostic methods for detecting the egf receptor
WO2013101771A2 (en) 2011-12-30 2013-07-04 Genentech, Inc. Compositions and method for treating autoimmune diseases
RU2659173C2 (ru) 2012-01-13 2018-06-28 Дженентек, Инк. Биологические маркеры для идентификации пациентов для лечения антагонистами vegf
US8821798B2 (en) 2012-01-19 2014-09-02 Life Technologies Corporation Titanium nitride as sensing layer for microwell structure
US8747748B2 (en) 2012-01-19 2014-06-10 Life Technologies Corporation Chemical sensor with conductive cup-shaped sensor surface
EP2805280B1 (en) 2012-01-20 2022-10-05 Sequenom, Inc. Diagnostic processes that factor experimental conditions
EP2807271B1 (en) 2012-01-24 2018-08-22 CD Diagnostics, Inc. System for detecting infection in synovial fluid
EP4372084A3 (en) 2012-01-26 2024-08-14 Tecan Genomics, Inc. Compositions and methods for targeted nucleic acid sequence enrichment and high efficiency library generation
US9135497B2 (en) 2012-01-27 2015-09-15 National Instruments Corporation Identifying randomly distributed microparticles in images to sequence a polynucleotide
EP2812344A4 (en) 2012-02-07 2015-10-28 Vibrant Holdings Llc SUBSTRATE, PEPTIDARRAYS AND METHOD
DK2812452T3 (da) 2012-02-09 2020-06-29 Population Bio Inc Fremgangsmåder og sammensætninger til screening og behandling af udviklingsforstyrrelser
EP2814514B1 (en) 2012-02-16 2017-09-13 Atyr Pharma, Inc. Histidyl-trna synthetases for treating autoimmune and inflammatory diseases
WO2013123125A1 (en) 2012-02-17 2013-08-22 President And Fellows Of Harvard College Assembly of nucleic acid sequences in emulsions
CA2865170C (en) 2012-02-21 2020-12-22 Cytonics Corporation Systems, compositions, and methods for transplantation
MX2014010183A (es) 2012-02-22 2015-03-20 Univ Pennsylvania Composiciones y metodos para generar una poblacion persistente de celulas t utiles para el tratamiento de cancer.
NZ628813A (en) 2012-02-23 2015-10-30 Univ Denmark Tech Dtu Methods for predicting anti-cancer response
WO2013124740A2 (en) 2012-02-23 2013-08-29 Stichting Vu-Vumc BRCA DEFICIENCY PROTEIN AND mRNA SIGNATURES USEFUL IN IDENTIFICATION OF PATIENTS WITH BRCA-DEFICIENT TUMORS AND PREDICTING BENEFIT OF ANTI-CANCER THERAPY IN CANCER PATIENTS
WO2013130512A2 (en) 2012-02-27 2013-09-06 The University Of North Carolina At Chapel Hill Methods and uses for molecular tags
CN104364392B (zh) 2012-02-27 2018-05-25 赛卢拉研究公司 用于分子计数的组合物和试剂盒
WO2013128281A1 (en) 2012-02-28 2013-09-06 Population Genetics Technologies Ltd Method for attaching a counter sequence to a nucleic acid sample
ES2930180T3 (es) 2012-03-02 2022-12-07 Sequenom Inc Métodos para enriquecer ácido nucleico canceroso a partir de una muestra biológica
WO2013134162A2 (en) 2012-03-05 2013-09-12 Sequenta, Inc. Determining paired immune receptor chains from frequency matched subunits
US9150853B2 (en) 2012-03-21 2015-10-06 Gen9, Inc. Methods for screening proteins using DNA encoded chemical libraries as templates for enzyme catalysis
WO2013144202A1 (en) 2012-03-29 2013-10-03 Roche Diagnostics Gmbh Biomarkers for discriminating healthy and/or non-malignant neoplastic colorectal cells from colorectal cancer cells
CA2867588A1 (en) 2012-03-30 2013-10-03 Genentech, Inc. Diagnostic methods and compositions for treatment of cancer
SG10201608234UA (en) 2012-04-02 2016-11-29 Berg Llc Interrogatory cell-based assays and uses thereof
AU2013243300B2 (en) 2012-04-05 2018-12-06 Oregon Health & Science University Gene expression panel for breast cancer prognosis
EP4001427A1 (en) 2012-04-24 2022-05-25 Gen9, Inc. Methods for sorting nucleic acids and multiplexed preparative in vitro cloning
KR20150011822A (ko) 2012-05-04 2015-02-02 노파르티스 아게 Iap 억제제 요법을 위한 바이오마커
SG10201507700VA (en) 2012-05-08 2015-10-29 Adaptive Biotechnologies Corp Compositions and method for measuring and calibrating amplification bias in multiplexed pcr reactions
WO2013167387A1 (en) 2012-05-10 2013-11-14 Ventana Medical Systems, Inc. Uniquely specific probes for pten, pik3ca, met, top2a, and mdm2
NZ701527A (en) 2012-05-11 2016-07-29 Clinical Genomics Pty Ltd Diagnostic gene marker panel for colorectal cancer
DK3608421T3 (da) 2012-05-18 2022-09-05 Clinical Genomics Pty Ltd Fremgangsmåde til screening for colorektal cancer
EP2850086B1 (en) 2012-05-18 2023-07-05 Pacific Biosciences Of California, Inc. Heteroarylcyanine dyes
CA2873964A1 (en) 2012-05-21 2013-11-28 Steven F. Dowdy Generation of human ips cells by a synthetic self-replicative rna
US10504613B2 (en) 2012-12-20 2019-12-10 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US10289800B2 (en) 2012-05-21 2019-05-14 Ariosa Diagnostics, Inc. Processes for calculating phased fetal genomic sequences
US9920361B2 (en) 2012-05-21 2018-03-20 Sequenom, Inc. Methods and compositions for analyzing nucleic acid
US8786331B2 (en) 2012-05-29 2014-07-22 Life Technologies Corporation System for reducing noise in a chemical sensor array
US9150570B2 (en) 2012-05-31 2015-10-06 Plexxikon Inc. Synthesis of heterocyclic compounds
WO2013184754A2 (en) 2012-06-05 2013-12-12 President And Fellows Of Harvard College Spatial sequencing of nucleic acids using dna origami probes
AU2013273466B2 (en) 2012-06-07 2018-11-01 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods for detecting inactivation of the homologous recombination pathway (BRCA1/2) in human tumors
EP3339861B8 (en) 2012-06-15 2023-11-01 Genesis Theranostix Korlatolt Felelossegu Tarsasag Biomarker test for prediction or early detection of preeclampsia
CN104704364B (zh) 2012-06-15 2018-12-04 韦恩州立大学 用于先兆子痫和/或hellp综合征的预测或早期检测的生物标记物测试
CN104619894B (zh) 2012-06-18 2017-06-06 纽亘技术公司 用于非期望核酸序列的阴性选择的组合物和方法
US10497461B2 (en) 2012-06-22 2019-12-03 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
CN104685116A (zh) 2012-06-25 2015-06-03 Gen9股份有限公司 用于核酸组装和高通量测序的方法
US20150152499A1 (en) 2012-07-03 2015-06-04 Interna Technologies B.V. Diagnostic portfolio and its uses
US20150011396A1 (en) 2012-07-09 2015-01-08 Benjamin G. Schroeder Methods for creating directional bisulfite-converted nucleic acid libraries for next generation sequencing
WO2014009245A2 (en) 2012-07-09 2014-01-16 Qithera Gmbh Novel drug target indentification methods
WO2014011398A1 (en) 2012-07-09 2014-01-16 Novartis Ag Biomarkers associated with cdk inhibitors
CA2878979C (en) 2012-07-13 2021-09-14 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
WO2014015217A1 (en) 2012-07-19 2014-01-23 Vertex Pharmaceuticals Incorporated Biomarkers for hcv infected patients
CN104583421A (zh) 2012-07-19 2015-04-29 阿瑞奥萨诊断公司 遗传变体的基于多重的顺序连接的检测
CN108875312A (zh) 2012-07-19 2018-11-23 哈佛大学校长及研究员协会 利用核酸存储信息的方法
JP2015524397A (ja) 2012-07-20 2015-08-24 ラトローブ ユニヴァーシティ 診断及び処置の方法
EP2877494B1 (en) 2012-07-23 2020-07-15 La Jolla Institute for Allergy and Immunology Ptprs and proteoglycans in autoimmune disease
EP3550031A1 (en) 2012-07-24 2019-10-09 Pharmacyclics, LLC Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (btk)
AU2013295855A1 (en) 2012-07-27 2015-02-12 Novartis Ag Prediction of treatment response to JAK/STAT inhibitor
PL2880447T3 (pl) 2012-07-31 2019-10-31 Novartis Ag Markery związane z wrażliwością na inhibitory ludzkiego białka „double minute " 2 (mdm2)
DK3435084T3 (da) 2012-08-16 2023-05-30 Mayo Found Medical Education & Res Prostatakræftprognose under anvendelse af biomarkører
AU2013306373B2 (en) 2012-08-20 2017-09-07 Illumina, Inc. Method and system for fluorescence lifetime based sequencing
WO2014039556A1 (en) 2012-09-04 2014-03-13 Guardant Health, Inc. Systems and methods to detect rare mutations and copy number variation
US11913065B2 (en) 2012-09-04 2024-02-27 Guardent Health, Inc. Systems and methods to detect rare mutations and copy number variation
US20160040229A1 (en) 2013-08-16 2016-02-11 Guardant Health, Inc. Systems and methods to detect rare mutations and copy number variation
US10876152B2 (en) 2012-09-04 2020-12-29 Guardant Health, Inc. Systems and methods to detect rare mutations and copy number variation
AU2013202506B2 (en) 2012-09-07 2015-06-18 Celgene Corporation Resistance biomarkers for hdac inhibitors
WO2014043519A1 (en) 2012-09-14 2014-03-20 Population Diagnostics Inc. Methods and compositions for diagnosing, prognosing, and treating neurological conditions
WO2014048942A1 (en) 2012-09-25 2014-04-03 Ventana Medical Systems, Inc. Probes for pten, pik3ca, met, and top2a, and method for using the probes
EP2900835A4 (en) 2012-09-27 2016-05-11 Population Diagnotics Inc METHODS AND COMPOSITIONS FOR DETECTING AND TREATING DEVELOPMENTAL DISORDERS
EP3974564A1 (en) 2012-09-28 2022-03-30 Vibrant Holdings, LLC Methods, systems, and arrays for biomolecular analysis
US10006909B2 (en) 2012-09-28 2018-06-26 Vibrant Holdings, Llc Methods, systems, and arrays for biomolecular analysis
CN104822844B (zh) 2012-10-01 2019-05-07 米伦纽姆医药公司 预测对抑制剂的反应的生物标记物和方法以及其用途
WO2014055493A1 (en) 2012-10-02 2014-04-10 Cerulean Pharma Inc. Methods and systems for polymer precipitation and generation of particles
US20140100124A1 (en) 2012-10-04 2014-04-10 Asuragen, Inc. Diagnostic mirnas for differential diagnosis of incidental pancreatic cystic lesions
US10482994B2 (en) 2012-10-04 2019-11-19 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US10162800B2 (en) 2012-10-17 2018-12-25 Celmatix Inc. Systems and methods for determining the probability of a pregnancy at a selected point in time
US9177098B2 (en) 2012-10-17 2015-11-03 Celmatix Inc. Systems and methods for determining the probability of a pregnancy at a selected point in time
US9476089B2 (en) 2012-10-18 2016-10-25 President And Fellows Of Harvard College Methods of making oligonucleotide probes
US20150354006A1 (en) 2012-10-19 2015-12-10 Novartis Ag Markers for acute lymphoblastic leukemia
EP2722105A1 (en) 2012-10-22 2014-04-23 Universität Wien Method of in situ synthesizing microarrays
US11181448B2 (en) 2012-11-06 2021-11-23 Biodot, Inc. Controlled printing of a cell sample for karyotyping
WO2014074942A1 (en) 2012-11-08 2014-05-15 Illumina, Inc. Risk variants of alzheimer's disease
EP3617219A1 (en) 2012-11-14 2020-03-04 Vibrant Holdings, LLC Methods for array synthesis
AU2013202507B9 (en) 2012-11-14 2015-08-13 Celgene Corporation Inhibition of drug resistant cancer cells
US10286376B2 (en) 2012-11-14 2019-05-14 Vibrant Holdings, Llc Substrates, systems, and methods for array synthesis and biomolecular analysis
WO2014078652A1 (en) 2012-11-16 2014-05-22 Zs Genetics, Inc. Heavy atom labeled nucleosides, nucleotides, and nucleic acid polymers, and uses thereof
GB201220924D0 (en) 2012-11-21 2013-01-02 Cancer Res Inst Royal Materials and methods for determining susceptibility or predisposition to cancer
WO2014085434A1 (en) 2012-11-27 2014-06-05 Pontificia Universidad Catolica De Chile Compositions and methods for diagnosing thyroid tumors
PL2925888T3 (pl) 2012-11-28 2018-03-30 Merck Sharp & Dohme Corp. Kompozycje i sposoby do stosowania w leczeniu nowotworów
CN113604423A (zh) 2012-11-30 2021-11-05 艾克塞利瑞提德生物技术公司 通过调节mir-124分化干细胞的方法
KR20150090246A (ko) 2012-12-03 2015-08-05 알막 다이아그노스틱스 리미티드 암을 위한 분자 진단 테스트
RS56783B9 (sr) 2012-12-05 2021-12-31 Alnylam Pharmaceuticals Inc Sastavi pcsk9 irnk i postupci njihovih primena
WO2014093655A2 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains
EP3031921A1 (en) 2012-12-12 2016-06-15 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
EP2931899A1 (en) 2012-12-12 2015-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
WO2014093709A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
DK3064585T3 (da) 2012-12-12 2020-04-27 Broad Inst Inc Konstruering og optimering af forbedrede systemer, fremgangsmåder og enzymsammensætninger til sekvensmanipulation
SG11201504523UA (en) 2012-12-12 2015-07-30 Broad Inst Inc Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
US9836577B2 (en) 2012-12-14 2017-12-05 Celmatix, Inc. Methods and devices for assessing risk of female infertility
WO2014100626A1 (en) 2012-12-21 2014-06-26 Hutman Diagnostics AG Microarrays
KR20150098605A (ko) 2012-12-21 2015-08-28 에자이 알앤드디 매니지먼트 가부시키가이샤 퀴놀린 유도체의 비정질 형태 및 그의 제조방법
US9080968B2 (en) 2013-01-04 2015-07-14 Life Technologies Corporation Methods and systems for point of use removal of sacrificial material
US9841398B2 (en) 2013-01-08 2017-12-12 Life Technologies Corporation Methods for manufacturing well structures for low-noise chemical sensors
US9932626B2 (en) 2013-01-15 2018-04-03 Quanterix Corporation Detection of DNA or RNA using single molecule arrays and other techniques
US9128861B2 (en) 2013-01-17 2015-09-08 Personalis, Inc. Methods and systems for genetic analysis
US20140206841A1 (en) * 2013-01-18 2014-07-24 Protein Technologies, Inc. Peptide Synthesis Apparatus and Methods Using Infrared Energy
JP2016506720A (ja) 2013-01-21 2016-03-07 アッヴィ・インコーポレイテッド 炎症性疾患のための抗ｔｎｆ及び抗ｉｌ１７併用治療薬バイオマーカー
US20130309666A1 (en) 2013-01-25 2013-11-21 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US8962366B2 (en) 2013-01-28 2015-02-24 Life Technologies Corporation Self-aligned well structures for low-noise chemical sensors
US9896728B2 (en) 2013-01-29 2018-02-20 Arcticrx Ltd. Method for determining a therapeutic approach for the treatment of age-related macular degeneration (AMD)
US9411930B2 (en) 2013-02-01 2016-08-09 The Regents Of The University Of California Methods for genome assembly and haplotype phasing
CN108624668B (zh) 2013-02-01 2022-12-02 加利福尼亚大学董事会 用于基因组组装及单体型定相的方法
US10568975B2 (en) 2013-02-05 2020-02-25 The Johns Hopkins University Nanoparticles for magnetic resonance imaging tracking and methods of making and using thereof
WO2014124334A2 (en) 2013-02-08 2014-08-14 Misfolding Diagnostics, Inc. Transthyretin antibodies and uses thereof
EP3252169B1 (en) 2013-02-14 2022-04-06 The Regents Of The University Of Colorado Methods for predicting risk of interstitial pneumonia
EP2956771B1 (en) 2013-02-15 2020-04-08 Vibrant Holdings, LLC Methods and compositions for amplified electrochemiluminescence detection
EP2959014B1 (en) 2013-02-25 2019-11-13 Genentech, Inc. Methods and compositions for detecting and treating drug resistant akt mutant
US9512422B2 (en) 2013-02-26 2016-12-06 Illumina, Inc. Gel patterned surfaces
US9267171B2 (en) 2013-02-28 2016-02-23 New York University DNA photolithography with cinnamate crosslinkers
EP2962100B1 (en) 2013-02-28 2021-07-28 Caprion Proteomics Inc. Tuberculosis biomarkers and uses thereof
ES2942031T3 (es) 2013-03-11 2023-05-29 Meso Scale Technologies Llc Métodos mejorados para realizar ensayos multiplexados
TWI582239B (zh) 2013-03-11 2017-05-11 諾華公司 與ｗｎｔ抑制劑相關之標記
US8841217B1 (en) 2013-03-13 2014-09-23 Life Technologies Corporation Chemical sensor with protruded sensor surface
WO2014168711A1 (en) 2013-03-13 2014-10-16 Sequenom, Inc. Primers for dna methylation analysis
US8963216B2 (en) 2013-03-13 2015-02-24 Life Technologies Corporation Chemical sensor with sidewall spacer sensor surface
US10308986B2 (en) 2013-03-14 2019-06-04 Children's Medical Center Corporation Cancer diagnosis, treatment selection and treatment
WO2014159242A1 (en) 2013-03-14 2014-10-02 Novartis Ag Notch 3 mutants and uses thereof
CA2904654C (en) 2013-03-14 2023-12-05 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions and methods of use thereof
US9146248B2 (en) 2013-03-14 2015-09-29 Intelligent Bio-Systems, Inc. Apparatus and methods for purging flow cells in nucleic acid sequencing instruments
WO2014159239A2 (en) 2013-03-14 2014-10-02 Novartis Ag Antibodies against notch 3
EP2971132B1 (en) 2013-03-15 2020-05-06 Baylor Research Institute Tissue and blood-based mirna biomarkers for the diagnosis, prognosis and metastasis-predictive potential in colorectal cancer
EP3404116B1 (en) 2013-03-15 2022-10-19 The University of Chicago Methods and compositions related to t-cell activity
US9591268B2 (en) 2013-03-15 2017-03-07 Qiagen Waltham, Inc. Flow cell alignment methods and systems
WO2014145123A2 (en) 2013-03-15 2014-09-18 Arizona Board Of Regents, A Body Corporate Of The State Of Arizona, Acting For And On Behalf Of Arizona State Unversity Peptide array quality control
GB2525568B (en) 2013-03-15 2020-10-14 Abvitro Llc Single cell barcoding for antibody discovery
US20140274749A1 (en) 2013-03-15 2014-09-18 Affymetrix, Inc. Systems and Methods for SNP Characterization and Identifying off Target Variants
EP2972279B1 (en) 2013-03-15 2021-10-06 Life Technologies Corporation Chemical sensors with consistent sensor surface areas
JP2016510895A (ja) 2013-03-15 2016-04-11 ライフ テクノロジーズ コーポレーション 一貫性のあるセンサ表面積を有する化学センサ
WO2014149779A1 (en) 2013-03-15 2014-09-25 Life Technologies Corporation Chemical device with thin conductive element
US9970932B2 (en) 2013-03-15 2018-05-15 Arizona Board Of Regents On Behalf Of Arizona State University Non-covalent patterned chemical features and use thereof in MALDI-based quality control
US9835585B2 (en) 2013-03-15 2017-12-05 Life Technologies Corporation Chemical sensor with protruded sensor surface
US11976329B2 (en) 2013-03-15 2024-05-07 Veracyte, Inc. Methods and systems for detecting usual interstitial pneumonia
US9677109B2 (en) 2013-03-15 2017-06-13 Accelerate Diagnostics, Inc. Rapid determination of microbial growth and antimicrobial susceptibility
US10535420B2 (en) 2013-03-15 2020-01-14 Affymetrix, Inc. Systems and methods for probe design to detect the presence of simple and complex indels
US9116117B2 (en) 2013-03-15 2015-08-25 Life Technologies Corporation Chemical sensor with sidewall sensor surface
EP2971149B1 (en) 2013-03-15 2018-05-09 Baylor Research Institute Ulcerative colitis (uc)-associated colorectal neoplasia markers
US20140274738A1 (en) 2013-03-15 2014-09-18 Nugen Technologies, Inc. Sequential sequencing
EP2978860B8 (en) 2013-03-27 2019-12-11 BlueGnome Ltd Assessment of risk of aneuploidy
HUE061261T2 (hu) 2013-04-03 2023-05-28 Sequenom Inc Eljárások és folyamatok genetikai variánsok nem invazív értékelésére
WO2014169928A1 (de) * 2013-04-17 2014-10-23 Karlsruher Institut für Technologie Verfahren zur kombinatorischen partikelmanipulation zur herstellung von hochdichten molekülarrays, insbesondere von peptidarrays, und damit erhältliche molekülarrays
US20160091485A1 (en) 2013-04-25 2016-03-31 The Broad Institute, Inc. Markers for ezh2 inhibitors
CA2908391A1 (en) 2013-05-01 2014-11-06 Five Prime Therapeutics, Inc. Methods of treating cancer
CN111187811B (zh) 2013-05-06 2024-03-08 加利福尼亚太平洋生物科学股份有限公司 实时电子测序
US20140336063A1 (en) 2013-05-09 2014-11-13 Life Technologies Corporation Windowed Sequencing
JP6411379B2 (ja) 2013-05-14 2018-10-24 エーザイ・アール・アンド・ディー・マネジメント株式会社 レンバチニブ化合物に対する子宮内膜がん対象の応答性を予測及び評価するためのバイオマーカー
WO2014187308A2 (zh) 2013-05-21 2014-11-27 生物梅里埃股份公司 一种大肠癌预后试剂盒
BR112015029276B1 (pt) 2013-05-22 2022-07-12 Alnylam Pharmaceuticals, Inc Agente de irna fita dupla capaz de inibir a expressão de tmprss6, composição farmacêutica e uso dos mesmos
HUE038146T2 (hu) 2013-05-22 2018-09-28 Alnylam Pharmaceuticals Inc Serpina1 IRNS készítmények és eljárások alkalmazásukra
JP2016524611A (ja) 2013-05-23 2016-08-18 ファイヴ プライム セラピューティクス インク がんを治療する方法
JP6561046B2 (ja) 2013-05-24 2019-08-14 セクエノム， インコーポレイテッド 遺伝子の変動の非侵襲性評価のための方法および処理
US10392667B2 (en) 2013-06-07 2019-08-27 Medical Prognosis Institute A/S Methods and devices for predicting treatment efficacy of fulvestrant in cancer patients
US10458942B2 (en) 2013-06-10 2019-10-29 Life Technologies Corporation Chemical sensor array having multiple sensors per well
EP3008229B1 (en) 2013-06-10 2020-05-27 President and Fellows of Harvard College Early developmental genomic assay for characterizing pluripotent stem cell utility and safety
WO2014200579A1 (en) 2013-06-13 2014-12-18 Ariosa Diagnostics, Inc. Statistical analysis for non-invasive sex chromosome aneuploidy determination
EP3008094B1 (en) 2013-06-14 2018-12-26 Pacific Biosciences Of California, Inc. Bis-biotinylation tags
US10544449B2 (en) 2013-06-14 2020-01-28 Pacific Biosciences Of California, Inc. Bis-biotinylation tags
CN106062197A (zh) 2013-06-17 2016-10-26 布罗德研究所有限公司 用于序列操纵的串联指导系统、方法和组合物的递送、工程化和优化
CA2915845A1 (en) 2013-06-17 2014-12-24 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for targeting and modeling diseases and disorders of post mitotic cells
CA2915842C (en) 2013-06-17 2022-11-29 The Broad Institute, Inc. Delivery and use of the crispr-cas systems, vectors and compositions for hepatic targeting and therapy
EP4245853A3 (en) 2013-06-17 2023-10-18 The Broad Institute, Inc. Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
KR20160056869A (ko) 2013-06-17 2016-05-20 더 브로드 인스티튜트, 인코퍼레이티드 바이러스 구성성분을 사용하여 장애 및 질환을 표적화하기 위한 crispr-cas 시스템 및 조성물의 전달, 용도 및 치료 적용
SI3011051T1 (sl) 2013-06-21 2019-05-31 Sequenom, Inc. Postopek za neinvazivno oceno genetskih variacij
US9069358B2 (en) 2013-06-24 2015-06-30 Biolytic Lab Performance, Inc. System for controlling and optimizing reactions in solid phase synthesis of small molecules
US9708657B2 (en) 2013-07-01 2017-07-18 Adaptive Biotechnologies Corp. Method for generating clonotype profiles using sequence tags
US9404922B2 (en) 2013-07-15 2016-08-02 The Rockefeller University Recombinant phages and proteins
KR102160389B1 (ko) 2013-08-05 2020-09-28 트위스트 바이오사이언스 코포레이션 드 노보 합성된 유전자 라이브러리
KR20160042438A (ko) 2013-08-12 2016-04-19 제넨테크, 인크. 보체-연관 상태의 치료를 위한 조성물 및 방법
GB201314721D0 (en) * 2013-08-16 2013-10-02 Almagen Ltd A method of selectively masking one or more sites on a surface and a method of synthesising an array of molecules
US9683937B2 (en) * 2013-08-23 2017-06-20 Semiconductor Components Industries, Llc Imaging devices for molecule detection
PT3039424T (pt) 2013-08-28 2020-09-03 Crown Bioscience Inc Taicang Assinaturas de expressão genética que permitem prever a resposta de um sujeito a um inibidor multiquinase e métodos de utilização do mesmo
GB2546833B (en) 2013-08-28 2018-04-18 Cellular Res Inc Microwell for single cell analysis comprising single cell and single bead oligonucleotide capture labels
AU2014312249A1 (en) 2013-08-28 2016-03-24 Cytonics Corporation Systems, compositions, and methods for transplantation and treating conditions
EP3965111A1 (en) 2013-08-30 2022-03-09 Personalis, Inc. Methods and systems for genomic analysis
US10456470B2 (en) 2013-08-30 2019-10-29 Genentech, Inc. Diagnostic methods and compositions for treatment of glioblastoma
DK3046628T3 (da) 2013-09-19 2020-02-10 Univ Leland Stanford Junior Fremgangsmåder og sammensætninger til fremstilling af hepatocyt-lignende celler
AR097738A1 (es) 2013-09-23 2016-04-13 Alnylam Pharmaceuticals Inc Métodos para tratar o prevenir enfermedades asociadas con la transtiretina (ttr)
CN112592975A (zh) 2013-09-23 2021-04-02 芝加哥大学 关于dna损伤制剂用于癌症治疗的方法和组合物
US9352315B2 (en) 2013-09-27 2016-05-31 Taiwan Semiconductor Manufacturing Company, Ltd. Method to produce chemical pattern in micro-fluidic structure
EP3052121B1 (en) 2013-10-02 2023-02-22 The Board of Trustees of the Leland Stanford Junior University Wnt compositions and methods for purification
GB2535066A (en) 2013-10-03 2016-08-10 Personalis Inc Methods for analyzing genotypes
US20150098940A1 (en) 2013-10-03 2015-04-09 Oklahoma Medical Research Foundation Biomarkers for Systemic Lupus Erythematosus Disease Activity, and Intensity and Flare
IL289974B (en) 2013-10-04 2022-09-01 Sequenom Inc Methods and processes for non-invasive evaluation of genetic variations
US11901041B2 (en) 2013-10-04 2024-02-13 Bio-Rad Laboratories, Inc. Digital analysis of nucleic acid modification
JP6680680B2 (ja) 2013-10-07 2020-04-15 セクエノム， インコーポレイテッド 染色体変化の非侵襲性評価のための方法およびプロセス
EP3055676A1 (en) 2013-10-07 2016-08-17 Cellular Research, Inc. Methods and systems for digitally counting features on arrays
WO2015058052A1 (en) 2013-10-18 2015-04-23 The Broad Institute Inc. Spatial and cellular mapping of biomolecules in situ by high-throughput sequencing
KR20160068802A (ko) 2013-10-23 2016-06-15 제넨테크, 인크. 호산구성 장애를 진단 및 치료하는 방법
US20160265036A1 (en) 2013-11-05 2016-09-15 Htg Molecular Diagnostics, Inc. Methods for detecting nucleic acids
JP6657105B2 (ja) 2013-11-06 2020-03-04 アメリカ合衆国 発現プロファイリングによりリンパ腫のタイプをサブタイピングするための方法
DK3511422T3 (da) 2013-11-12 2023-02-06 Population Bio Inc Fremgangsmåder og sammensætninger til diagnosticering, prognose og behandling af endometriose
CA2929596C (en) 2013-11-13 2022-07-05 Nugen Technologies, Inc. Compositions and methods for identification of a duplicate sequencing read
CA2931181C (en) 2013-12-09 2023-01-24 Institut Curie Methods for detecting inactivation of the homologous recombination pathway (brca1/2) in human tumors
CN106536729A (zh) 2013-12-12 2017-03-22 布罗德研究所有限公司 使用粒子递送组分靶向障碍和疾病的crispr‑cas系统和组合物的递送、用途和治疗应用
US9944977B2 (en) 2013-12-12 2018-04-17 Raindance Technologies, Inc. Distinguishing rare variations in a nucleic acid sequence from a sample
SG11201604692UA (en) 2013-12-12 2016-07-28 Alnylam Pharmaceuticals Inc Complement component irna compositions and methods of use thereof
US20160304969A1 (en) 2013-12-17 2016-10-20 Merck Sharp & Dohme Corp. Ifn-gamma gene signature biomarkers of tumor response to pd-1 antagonists
IL285107B2 (en) 2013-12-20 2024-02-01 Univ Lausanne Diagnostic, prognostic and therapeutic uses of long non-coding RNA molecules for heart diseases and rehabilitation medicine
NZ630311A (en) 2013-12-27 2016-03-31 Celgene Corp Romidepsin formulations and uses thereof
EP3087204B1 (en) 2013-12-28 2018-02-14 Guardant Health, Inc. Methods and systems for detecting genetic variants
EP3090063B1 (en) 2013-12-31 2019-11-06 Bio-Rad Laboratories, Inc. Method for detection of latent retrovirus
US20150259743A1 (en) 2013-12-31 2015-09-17 Roche Nimblegen, Inc. Methods of assessing epigenetic regulation of genome function via dna methylation status and systems and kits therefor
CA2935720A1 (en) 2014-01-16 2015-07-23 Illumina, Inc. Gene expression panel for prognosis of prostate cancer recurrence
US10850278B2 (en) 2014-01-29 2020-12-01 Arizona Board Of Regents On Behalf Of Arizona State University Microreactor array platform
GB201409479D0 (en) 2014-05-28 2014-07-09 Almac Diagnostics Ltd Molecular diagnostic test for cancer
US20170073754A1 (en) 2014-02-07 2017-03-16 Novartis Ag Impact of genetic factors on disease progression and response to anti-c5 antibody in geographic atrophy
SG10201901076WA (en) 2014-02-08 2019-03-28 Genentech Inc Methods of treating alzheimer's disease
AU2015218635B2 (en) 2014-02-21 2017-08-31 Vibrant Holdings, Llc Selective photo activation of amino acids for single step peptide coupling
CN106232827A (zh) 2014-02-21 2016-12-14 哈佛学院董事及会员团体 变构蛋白的从头设计
CN106460042A (zh) 2014-02-24 2017-02-22 儿童医院医学中心 用于个性化疼痛管理的方法与组合物
WO2015131107A1 (en) 2014-02-28 2015-09-03 Nugen Technologies, Inc. Reduced representation bisulfite sequencing with diversity adaptors
WO2015134787A2 (en) 2014-03-05 2015-09-11 Adaptive Biotechnologies Corporation Methods using randomer-containing synthetic molecules
EP3736344A1 (en) 2014-03-13 2020-11-11 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
WO2015143400A1 (en) 2014-03-20 2015-09-24 Pharmacyclics, Inc. Phospholipase c gamma 2 and resistance associated mutations
EP3800267A1 (en) 2014-03-27 2021-04-07 Yale University Circulating micrornas as biomarkers for endometriosis
US10066265B2 (en) 2014-04-01 2018-09-04 Adaptive Biotechnologies Corp. Determining antigen-specific t-cells
ES2777529T3 (es) 2014-04-17 2020-08-05 Adaptive Biotechnologies Corp Cuantificación de genomas de células inmunitarias adaptativas en una mezcla compleja de células
AU2015255752B2 (en) 2014-05-08 2020-07-23 Immunoforge Co., Ltd. Methods and compositions for treating Cystic Fibrosis
KR102246800B1 (ko) 2014-05-13 2021-04-30 바이오아트라, 인코퍼레이티드 조건부 활성 생체 단백질
CA2950623A1 (en) 2014-05-30 2015-12-03 Myla LAI-GOLDMAN Methods for typing of lung cancer
US20160000936A1 (en) 2014-06-10 2016-01-07 Abbvie Inc. Biomarkers for inflammatory disease and methods of using same
AU2015273443B2 (en) 2014-06-13 2021-03-04 Q-Linea Ab Method for detecting and characterising a microorganism
WO2016011052A1 (en) 2014-07-14 2016-01-21 Genentech, Inc. Diagnostic methods and compositions for treatment of glioblastoma
US11214836B2 (en) 2014-07-15 2022-01-04 Ontario Institute For Cancer Research Methods and devices for predicting anthracycline treatment efficacy
US10208350B2 (en) 2014-07-17 2019-02-19 Celmatix Inc. Methods and systems for assessing infertility and related pathologies
EP3175000B1 (en) 2014-07-30 2020-07-29 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
WO2016019360A1 (en) 2014-08-01 2016-02-04 Dovetail Genomics Llc Tagging nucleic acids for sequence assembly
US10422004B2 (en) 2014-08-08 2019-09-24 Children's Hospital Medical Center Diagnostic method for distinguishing forms of esophageal eosinophilia
US10093967B2 (en) 2014-08-12 2018-10-09 The Regents Of The University Of Michigan Detection of nucleic acids
US20180363070A9 (en) 2014-08-12 2018-12-20 Univ Wayne State Systems and methods to detect stem cell stress and uses thereof
JP6877334B2 (ja) 2014-08-15 2021-05-26 ミリアド・ジェネティックス・インコーポレイテッド 相同組換え欠損を評価するための方法および材料
EP3180426B1 (en) 2014-08-17 2019-12-25 The Broad Institute, Inc. Genome editing using cas9 nickases
WO2016033439A2 (en) 2014-08-28 2016-03-03 Yale University Compositions and methods for the treating an inflammatory disease or disorder
US11111288B2 (en) 2014-08-28 2021-09-07 Bioatla, Inc. Conditionally active chimeric antigen receptors for modified t-cells
CA2959141A1 (en) 2014-08-28 2016-03-03 Bioatla, Llc Conditionally active chimeric antigen receptors for modified t-cells
ES2926687T3 (es) 2014-08-28 2022-10-27 Eisai R&D Man Co Ltd Derivado de quinolina muy puro y método para su producción
AU2015311911B2 (en) 2014-09-03 2019-01-24 Bioatla, Llc Discovering and producing conditionally active biologic proteins in the same eukaryotic cell production hosts
US10724096B2 (en) 2014-09-05 2020-07-28 Population Bio, Inc. Methods and compositions for inhibiting and treating neurological conditions
WO2016038550A1 (en) 2014-09-11 2016-03-17 Novartis Ag Inhibition of prmt5 to treat mtap-deficiency-related diseases
WO2016040589A1 (en) 2014-09-12 2016-03-17 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting complement component c5 and methods of use thereof
US10590483B2 (en) 2014-09-15 2020-03-17 Abvitro Llc High-throughput nucleotide library sequencing
AU2015318823A1 (en) 2014-09-15 2016-03-24 Garvan Institute Of Medical Research Methods for diagnosis, prognosis and monitoring of breast cancer and reagents therefor
DK3198035T3 (da) 2014-09-26 2023-01-30 Allarity Therapeutics Europe ApS Fremgangsmåder til forudsigelse af medicinrespons
JP6585167B2 (ja) 2014-10-03 2019-10-02 ノバルティス アーゲー Ｆｇｆｒ４阻害剤としての縮環二環式ピリジル誘導体の使用
JOP20200115A1 (ar) 2014-10-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات))
EP3207138B1 (en) 2014-10-17 2020-07-15 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof
EP3715455A1 (en) 2014-10-29 2020-09-30 Adaptive Biotechnologies Corp. Highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune receptor heterodimers from many samples
EP4026913A1 (en) 2014-10-30 2022-07-13 Personalis, Inc. Methods for using mosaicism in nucleic acids sampled distal to their origin
EP3212794B1 (en) 2014-10-30 2021-04-07 Genzyme Corporation Polynucleotide agents targeting serpinc1 (at3) and methods of use thereof
EP3770274A1 (en) 2014-11-05 2021-01-27 Veracyte, Inc. Systems and methods of diagnosing idiopathic pulmonary fibrosis on transbronchial biopsies using machine learning and high dimensional transcriptional data
EP3215846B1 (en) 2014-11-05 2020-03-11 Nirmidas Biotech, Inc. Metal composites for enhanced imaging
JP7231326B2 (ja) 2014-11-10 2023-03-01 ジェネンテック， インコーポレイテッド Ｉｌ－３３媒介性障害のための治療及び診断方法
US10030268B2 (en) 2014-11-11 2018-07-24 Abbott Molecular Inc. Hybridization probes and methods
US10246701B2 (en) 2014-11-14 2019-04-02 Adaptive Biotechnologies Corp. Multiplexed digital quantitation of rearranged lymphoid receptors in a complex mixture
JP6836990B2 (ja) 2014-11-26 2021-03-03 アクセラレイテッド・バイオサイエンシズ・コーポレーション 誘導肝細胞およびそれらの使用
WO2016089883A1 (en) 2014-12-01 2016-06-09 Novartis Ag Compositions and methods for diagnosis and treatment of prostate cancer
JP6769962B2 (ja) 2014-12-03 2020-10-14 オークランド ユニサービシーズ リミティド 癌治療のためのキナーゼ阻害剤プロドラッグ
WO2016090323A1 (en) 2014-12-05 2016-06-09 Prelude, Inc. Dcis recurrence and invasive breast cancer
KR102657306B1 (ko) 2014-12-08 2024-04-12 버그 엘엘씨 전립선암의 진단 및 치료에서 필라민을 포함하는 마커의 용도
BR112017012222A2 (pt) 2014-12-09 2018-01-30 Merck Sharp & Dohme métodos para derivar um biomarcador de assinatura gênica e para tratar um paciente que tem um tumor, método e sistema para testar uma amostra de tumor removida de um paciente, e, kit.
WO2016094867A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Protected guide rnas (pgrnas)
EP3230452A1 (en) 2014-12-12 2017-10-18 The Broad Institute Inc. Dead guides for crispr transcription factors
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
EP4354131A3 (en) 2014-12-18 2024-06-26 Life Technologies Corporation High data rate integrated circuit with transmitter configuration
US10077472B2 (en) 2014-12-18 2018-09-18 Life Technologies Corporation High data rate integrated circuit with power management
CN107407656B (zh) 2014-12-18 2020-04-07 生命科技公司 使用大规模 fet 阵列测量分析物的方法和装置
WO2016106286A1 (en) 2014-12-23 2016-06-30 Biodesy, Inc. Attachment of proteins to interfaces for use in nonlinear optical detection
CA2969830A1 (en) 2014-12-24 2016-06-30 Genentech, Inc. Therapeutic, diagnostic and prognostic methods for cancer of the bladder
CA2970370A1 (en) 2014-12-24 2016-06-30 Massachusetts Institute Of Technology Crispr having or associated with destabilization domains
US10302972B2 (en) 2015-01-23 2019-05-28 Pacific Biosciences Of California, Inc. Waveguide transmission
EP3250184A1 (en) 2015-01-27 2017-12-06 The Johns Hopkins University Hypotonic hydrogel formulations for enhanced transport of active agents at mucosal surfaces
CN107428818A (zh) 2015-01-29 2017-12-01 密西根州立大学校董会 隐藏多肽及其用途
WO2016126987A1 (en) 2015-02-04 2016-08-11 Twist Bioscience Corporation Compositions and methods for synthetic gene assembly
WO2016126882A1 (en) 2015-02-04 2016-08-11 Twist Bioscience Corporation Methods and devices for de novo oligonucleic acid assembly
CA2976038A1 (en) 2015-02-09 2016-08-18 Phasebio Pharmaceuticals, Inc. Methods and compositions for treating muscle disease and disorders
US10801065B2 (en) 2015-02-10 2020-10-13 Dana-Farber Cancer Institute, Inc. Methods of determining levels of exposure to radiation and uses thereof
EP3256855B1 (en) 2015-02-13 2020-10-07 Quanterix Corporation Immunoassays for diffrential detection of clostridium difficile
CA2976445A1 (en) 2015-02-13 2016-08-18 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
EP3259696A1 (en) 2015-02-17 2017-12-27 Dovetail Genomics LLC Nucleic acid sequence assembly
ES2975332T3 (es) 2015-02-19 2024-07-04 Becton Dickinson Co Análisis unicelular de alto rendimiento que combina información proteómica y genómica
HUE058813T2 (hu) 2015-02-24 2022-09-28 Hope City Kémiailag kódolt térbeli címzésû könyvtárszûrõ platformok
CN107580603A (zh) 2015-02-24 2018-01-12 生物蛋白有限公司 条件活性生物蛋白
EP3591074B1 (en) 2015-02-24 2024-10-23 Adaptive Biotechnologies Corp. Methods for diagnosing infectious disease and determining hla status using immune repertoire sequencing
US20180028662A1 (en) 2015-02-25 2018-02-01 Eisai R&D Management Co., Ltd. Method for Suppressing Bitterness of Quinoline Derivative
EP3262192B1 (en) 2015-02-27 2020-09-16 Becton, Dickinson and Company Spatially addressable molecular barcoding
CA2978226A1 (en) 2015-03-04 2016-09-09 Merck Sharpe & Dohme Corp. Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer
CA3208979A1 (en) 2015-03-12 2016-09-15 Vibrant Holdings, Llc Polypeptide arrays and methods of attaching polypeptides to an array
US9708647B2 (en) 2015-03-23 2017-07-18 Insilixa, Inc. Multiplexed analysis of nucleic acid hybridization thermodynamics using integrated arrays
CA3225867A1 (en) 2015-03-24 2016-09-29 Illumina, Inc. Methods, carrier assemblies, and systems for imaging samples for biological or chemical analysis
US11807896B2 (en) 2015-03-26 2023-11-07 Dovetail Genomics, Llc Physical linkage preservation in DNA storage
US10253355B2 (en) 2015-03-30 2019-04-09 Accelerate Diagnostics, Inc. Instrument and system for rapid microorganism identification and antimicrobial agent susceptibility testing
JP7508191B2 (ja) 2015-03-30 2024-07-01 ベクトン・ディキンソン・アンド・カンパニー コンビナトリアルバーコーディングのための方法および組成物
EP3278115A2 (en) 2015-03-30 2018-02-07 Accelerate Diagnostics, Inc. Instrument and system for rapid microorganism identification and antimicrobial agent susceptibility testing
EP3277294B1 (en) 2015-04-01 2024-05-15 Adaptive Biotechnologies Corp. Method of identifying human compatible t cell receptors specific for an antigenic target
WO2016164641A1 (en) 2015-04-08 2016-10-13 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
EP3839510A3 (en) 2015-04-17 2021-08-25 Merck Sharp & Dohme Corp. Blood-based biomarkers of tumor sensitivity to pd-1 antagonists
CA2983351C (en) 2015-04-20 2024-06-04 F. Hoffmann-La Roche Ag Specific peptide binders to proteins identified via systemic discovery, maturation and extension process
US9981239B2 (en) 2015-04-21 2018-05-29 Twist Bioscience Corporation Devices and methods for oligonucleic acid library synthesis
US11390914B2 (en) 2015-04-23 2022-07-19 Becton, Dickinson And Company Methods and compositions for whole transcriptome amplification
CN114540470A (zh) 2015-04-24 2022-05-27 基纳生物技术有限公司 用于次要等位基因和多态性的鉴定和定量的多重化方法
GB201507026D0 (en) 2015-04-24 2015-06-10 Linea Ab Q Medical sample transportation container
WO2016172579A1 (en) 2015-04-24 2016-10-27 Agena Bioscience, Inc, Multiplex methods for detection and quantification of minor variants
WO2016176726A1 (en) 2015-05-01 2016-11-10 Griffith University Diagnostic methods
EP3289107A4 (en) 2015-05-01 2018-09-12 The University of British Columbia Biomarkers for the detection of acute rejection in heart transplantation
US10900975B2 (en) 2015-05-12 2021-01-26 Arizona Board Of Regents On Behalf Of Arizona State University Systems and methods of epitope binning and antibody profiling
CA2987397C (en) 2015-05-29 2022-03-01 Illumina, Inc. Sample carrier and assay system for conducting designated reactions
WO2016196065A1 (en) 2015-05-29 2016-12-08 Genentech, Inc. Methods and compositions for assessing responsiveness of cancers to bet inhibitors
WO2016196229A1 (en) 2015-06-01 2016-12-08 Cellular Research, Inc. Methods for rna quantification
EP3307316A1 (en) 2015-06-12 2018-04-18 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions and methods of use thereof
CA2988707C (en) 2015-06-16 2023-10-10 Eisai R&D Management Co., Ltd. Combination of cbp/catenin inhibitor and immune checkpoint inhibitor for treating cancer
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems
WO2016205323A1 (en) 2015-06-18 2016-12-22 Alnylam Pharmaceuticals, Inc. Polynucleotde agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof
CA3012631A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Novel crispr enzymes and systems
WO2016205749A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Novel crispr enzymes and systems
US10494632B2 (en) 2015-07-10 2019-12-03 Alnylam Pharmaceuticals, Inc. Insulin-like growth factor binding protein, acid labile subunit (IGFALS) compositions and methods of use thereof
EP3325966B1 (en) 2015-07-20 2021-01-20 Sentilus Holdco, LLC Chips, detectors, and methods of making and using the same
GB201512869D0 (en) 2015-07-21 2015-09-02 Almac Diagnostics Ltd Gene signature for minute therapies
KR101844048B1 (ko) 2015-07-22 2018-03-30 주식회사 스몰머신즈 분자 고정화 패턴 및 그를 형성하는 방법
US10829484B2 (en) 2015-07-28 2020-11-10 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
JP6923509B2 (ja) 2015-07-28 2021-08-18 オトノミ—，インク． 切断型のｔｒｋｂおよびｔｒｋｃのアンタゴニストを使用する処置
EP3124619B1 (en) 2015-07-31 2019-03-06 Menicon Co., Ltd Reagents, method and kit for across and within dog breed glaucoma diagnosis
CN108136051A (zh) 2015-08-04 2018-06-08 Cd诊断股份有限公司 检测不良局部组织反应(altr)坏死的方法
EP3332032B1 (en) 2015-08-06 2023-12-27 Pacific Biosciences Of California, Inc. Integrated circuits for selectively addressing sparsely arranged electronic measurement devices
EP3130681B1 (en) 2015-08-13 2019-11-13 Centrillion Technology Holdings Corporation Methods for synchronizing nucleic acid molecules
EP3130682B1 (en) * 2015-08-13 2020-03-18 Centrillion Technology Holdings Corporation Methods for generating polymer arrays
CN108366966A (zh) 2015-08-24 2018-08-03 光环生物干扰疗法公司 用于调节基因表达的多核苷酸纳米颗粒及其用途
US10976334B2 (en) 2015-08-24 2021-04-13 Illumina, Inc. In-line pressure accumulator and flow-control system for biological or chemical assays
AU2016315584B2 (en) 2015-09-02 2022-07-14 Alnylam Pharmaceuticals, Inc. Programmed cell death 1 ligand 1 (PD-L1) iRNA compositions and methods of use thereof
US10647981B1 (en) 2015-09-08 2020-05-12 Bio-Rad Laboratories, Inc. Nucleic acid library generation methods and compositions
US9499861B1 (en) 2015-09-10 2016-11-22 Insilixa, Inc. Methods and systems for multiplex quantitative nucleic acid amplification
ES2745694T3 (es) 2015-09-11 2020-03-03 Cellular Res Inc Métodos y composiciones para normalización de biblioteca de ácido nucleico
EP3141613A1 (en) 2015-09-11 2017-03-15 Nederlandse Organisatie voor toegepast- natuurwetenschappelijk onderzoek TNO Detection of quality of surface water
US10758886B2 (en) 2015-09-14 2020-09-01 Arizona Board Of Regents On Behalf Of Arizona State University Conditioned surfaces for in situ molecular array synthesis
EP3350314A4 (en) 2015-09-18 2019-02-06 Twist Bioscience Corporation BANKS OF OLIGONUCLEIC ACID VARIANTS AND SYNTHESIS THEREOF
KR20180058772A (ko) 2015-09-22 2018-06-01 트위스트 바이오사이언스 코포레이션 핵산 합성을 위한 가요성 기판
WO2018057051A1 (en) 2016-09-24 2018-03-29 Abvitro Llc Affinity-oligonucleotide conjugates and uses thereof
AU2016326737B2 (en) 2015-09-24 2023-01-12 Abvitro Llc Affinity-oligonucleotide conjugates and uses thereof
EP3353314A1 (en) 2015-09-25 2018-08-01 H. Hoffnabb-La Roche Ag Transamidation employing sortase a in deep eutectic solvents
JP6895953B2 (ja) 2015-09-25 2021-06-30 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ ソルターゼａを利用してチオエステルを作製するための方法
WO2017050866A1 (en) 2015-09-25 2017-03-30 F. Hoffmann-La Roche Ag Novel soluble sortase a
AU2016326734B2 (en) 2015-09-25 2022-07-07 Abvitro Llc High throughput process for T cell receptor target identification of natively-paired T cell receptor sequences
WO2017059108A1 (en) 2015-09-29 2017-04-06 Htg Molecular Diagnostics, Inc. Methods for subtyping diffuse b-cell lymphoma (dlbcl)
WO2017054058A1 (en) 2015-09-30 2017-04-06 Immunexpress Pty Ltd Pathogen biomarkers and uses therefor
ES2941968T3 (es) 2015-10-01 2023-05-29 The Whitehead Institute For Biomedical Res Marcaje de anticuerpos
CN108367081A (zh) 2015-10-14 2018-08-03 生命技术公司 核糖核蛋白转染剂
JP6858783B2 (ja) 2015-10-18 2021-04-14 アフィメトリックス インコーポレイテッド 一塩基多型及びインデルの複対立遺伝子遺伝子型決定
KR20180096586A (ko) 2015-10-19 2018-08-29 더브테일 제노믹스 엘엘씨 게놈 어셈블리, 하플로타입 페이징 및 표적 독립적 핵산 검출을 위한 방법
AU2016342269A1 (en) 2015-10-22 2018-03-29 Jounce Therapeutics, Inc. Gene signatures for determining icos expression
WO2017070605A1 (en) 2015-10-22 2017-04-27 The Broad Institute Inc. Type vi-b crispr enzymes and systems
US11996168B2 (en) 2015-10-28 2024-05-28 The Broad Institute, Inc. Systems and methods for determining relative abundances of biomolecules
US10427126B2 (en) 2015-10-28 2019-10-01 Roche Sequencing Solutions, Inc. System and method for longitudinal analysis of peptide synthesis
WO2017075294A1 (en) 2015-10-28 2017-05-04 The Board Institute Inc. Assays for massively combinatorial perturbation profiling and cellular circuit reconstruction
EP3377654B1 (en) 2015-11-16 2024-01-31 Revere Biosensors, LLC Systems and methods for identifying and distinguishing genetic samples
WO2017087696A1 (en) 2015-11-18 2017-05-26 Pacific Biosciences Of California, Inc. Methods and compositions for loading of polymerase complexes
WO2017093246A1 (en) 2015-11-30 2017-06-08 F. Hoffmann-La Roche Ag System and method for identification of protease substrates
CN115920796A (zh) 2015-12-01 2023-04-07 特韦斯特生物科学公司 功能化表面及其制备
US9938273B2 (en) 2015-12-07 2018-04-10 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
EP3978619A1 (en) 2015-12-09 2022-04-06 Intuitive Biosciences, Inc. Automated silver enhancement system
EP3390668A4 (en) 2015-12-17 2020-04-01 Guardant Health, Inc. METHODS OF DETERMINING THE NUMBER OF TUMOR GENE COPIES BY ACELLULAR DNA ANALYSIS
US12110490B2 (en) 2015-12-18 2024-10-08 The Broad Institute, Inc. CRISPR enzymes and systems
AU2016377391B2 (en) 2015-12-24 2022-09-01 Immunexpress Pty Ltd Triage biomarkers and uses therefor
WO2017123401A1 (en) 2016-01-13 2017-07-20 Children's Hospital Medical Center Compositions and methods for treating allergic inflammatory conditions
US10519442B2 (en) 2016-02-11 2019-12-31 City Of Hope Twist signaling inhibitor compositions and methods of using the same
US10184939B2 (en) 2016-02-12 2019-01-22 Roche Sequencing Solutions, Inc. Detection of neoantigens using peptide arrays
CA3014911A1 (en) 2016-02-23 2017-08-31 Dovetail Genomics, Llc Generation of phased read-sets for genome assembly and haplotype phasing
WO2017155858A1 (en) 2016-03-07 2017-09-14 Insilixa, Inc. Nucleic acid sequence identification using solid-phase cyclic single base extension
CN109641935A (zh) 2016-03-25 2019-04-16 莫拉利达尔·瑞迪·穆拉 组合合成和生物标志物开发
WO2017167712A1 (en) 2016-03-30 2017-10-05 F. Hoffmann-La Roche Ag Improved sortase
WO2017173247A1 (en) 2016-03-31 2017-10-05 City Of Hope Aptamer compositions and the use thereof
AU2017240164A1 (en) * 2016-04-01 2018-11-15 HealthTell, Inc. Array-based peptide libraries for therapeutic antibody characterization
WO2017176652A2 (en) 2016-04-04 2017-10-12 Sinopia Biosciences, Inc. Treating extrapyramidal syndrome using trapidil
WO2017184768A1 (en) 2016-04-19 2017-10-26 The Broad Institute Inc. Novel crispr enzymes and systems
MA45295A (fr) 2016-04-19 2019-02-27 Alnylam Pharmaceuticals Inc Composition d'arni de protéine de liaison de lipoprotéines haute densité (hdlbp/vigiline) et procédés pour les utiliser
CA3026110A1 (en) 2016-04-19 2017-11-02 The Broad Institute, Inc. Novel crispr enzymes and systems
WO2017184786A1 (en) 2016-04-19 2017-10-26 The Broad Institute Inc. Cpf1 complexes with reduced indel activity
US20190128895A1 (en) 2016-04-20 2019-05-02 Ldx Prognostics Limited Co. Methods and compositions for prognosing preterm birth
JP7075896B2 (ja) 2016-04-20 2022-05-26 アメリカ合衆国 マントル細胞リンパ腫の評価及びそれに関連する方法
GB2554767A (en) 2016-04-21 2018-04-11 Q Linea Ab Detecting and characterising a microorganism
ES2956757T3 (es) 2016-05-02 2023-12-27 Becton Dickinson Co Codificación con códigos de barras moleculares precisa
IL262946B2 (en) 2016-05-13 2023-03-01 Dovetail Genomics Llc Retrieving long-range grip information from preserved samples
US11254742B2 (en) 2016-05-13 2022-02-22 Bioatla, Inc. Anti-Ror2 antibodies, antibody fragments, their immunoconjugates and uses thereof
JP7241352B2 (ja) 2016-05-17 2023-03-17 ジーンセントリック セラピューティクス， インコーポレイテッド 肺扁平上皮癌のサブタイピングのための方法
CA3024747A1 (en) 2016-05-17 2017-11-23 Genecentric Therapeutics, Inc. Methods for subtyping of lung adenocarcinoma
JP6691617B2 (ja) 2016-05-17 2020-04-28 エルディエックス・プログノスティクス・リミテッド・カンパニーＬｄｘ Ｐｒｏｇｎｏｓｔｉｃｓ Ｌｉｍｉｔｅｄ Ｃｏ． 子癇前症の評価を提供するための方法及び組成物
US10301677B2 (en) 2016-05-25 2019-05-28 Cellular Research, Inc. Normalization of nucleic acid libraries
EP3465502B1 (en) 2016-05-26 2024-04-10 Becton, Dickinson and Company Molecular label counting adjustment methods
US11299783B2 (en) 2016-05-27 2022-04-12 Personalis, Inc. Methods and systems for genetic analysis
WO2017205823A1 (en) 2016-05-27 2017-11-30 Personalis, Inc. Personalized genetic testing
US10202641B2 (en) 2016-05-31 2019-02-12 Cellular Research, Inc. Error correction in amplification of samples
US10640763B2 (en) 2016-05-31 2020-05-05 Cellular Research, Inc. Molecular indexing of internal sequences
WO2017214068A1 (en) 2016-06-05 2017-12-14 Berg Llc Systems and methods for patient stratification and identification of potential biomarkers
WO2017222834A1 (en) 2016-06-10 2017-12-28 City Of Hope Compositions and methods for mitochondrial genome editing
JP2019518028A (ja) 2016-06-10 2019-06-27 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 補体成分Ｃ５ｉＲＮＡ組成物及び発作性夜間血色素尿症（ＰＮＨ）を処置するためのその使用方法
WO2017219027A1 (en) 2016-06-17 2017-12-21 The Broad Institute Inc. Type vi crispr orthologs and systems
CN109642252A (zh) 2016-06-17 2019-04-16 加州理工学院 核酸反应及相关方法和组合物
WO2017223117A1 (en) 2016-06-20 2017-12-28 Healthtell Inc. Methods for diagnosis and treatment of autoimmune diseases
JP2019528428A (ja) 2016-06-20 2019-10-10 ヘルステル・インコーポレイテッドＨｅａｌｔｈｔｅｌｌ Ｉｎｃ． 自己免疫疾患の鑑別診断方法
WO2018005873A1 (en) 2016-06-29 2018-01-04 The Broad Institute Inc. Crispr-cas systems having destabilization domain
CN109563502A (zh) 2016-06-29 2019-04-02 三菱化学株式会社 凝胶防干燥用组合物、凝胶复合物和含有其的dna芯片以及它们的制造方法
EP3875603A1 (en) 2016-07-12 2021-09-08 Life Technologies Corporation Compositions and methods for detecting nucleic acid regions
WO2018013883A1 (en) 2016-07-14 2018-01-18 Caprion Proteomics Inc. Biomarkers of latent tuberculosis infection
US11200963B2 (en) 2016-07-27 2021-12-14 Sequenom, Inc. Genetic copy number alteration classifications
JP2019529351A (ja) 2016-08-04 2019-10-17 ベイラー リサーチ インスティテュートＢａｙｌｏｒ Ｒｅｓｅａｒｃｈ Ｉｎｓｔｉｔｕｔｅ 食道癌を診断するおよび治療するための方法
WO2018033478A1 (en) 2016-08-15 2018-02-22 F. Hoffmann-La Roche Ag Method and composition for detection of peptide cyclization using protein tags
CA3034769A1 (en) 2016-08-22 2018-03-01 Twist Bioscience Corporation De novo synthesized nucleic acid libraries
EP3504348B1 (en) 2016-08-24 2022-12-14 Decipher Biosciences, Inc. Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy
WO2018053228A1 (en) 2016-09-15 2018-03-22 The Regents Of The University Of California Biomarkers for bipolar disorder and schizophrenia
US10428325B1 (en) 2016-09-21 2019-10-01 Adaptive Biotechnologies Corporation Identification of antigen-specific B cell receptors
US10417457B2 (en) 2016-09-21 2019-09-17 Twist Bioscience Corporation Nucleic acid based data storage
TW201815766A (zh) 2016-09-22 2018-05-01 美商普雷辛肯公司 用於ｉｄｏ及ｔｄｏ調節之化合物及方法以及其適應症
KR102363716B1 (ko) 2016-09-26 2022-02-18 셀룰러 리서치, 인크. 바코딩된 올리고뉴클레오티드 서열을 갖는 시약을 이용한 단백질 발현의 측정
WO2018064116A1 (en) 2016-09-28 2018-04-05 Illumina, Inc. Methods and systems for data compression
US11278629B2 (en) 2016-11-02 2022-03-22 Debiopharm International, S.A. Methods for improving anti-CD37 immunoconjugate therapy
ES2980967T3 (es) 2016-11-08 2024-10-03 Becton Dickinson And Company Métodos para la clasificación de perfiles de expresión
KR20190077061A (ko) 2016-11-08 2019-07-02 셀룰러 리서치, 인크. 세포 표지 분류 방법
EP3538536A4 (en) 2016-11-09 2020-05-13 Healthtell Inc. PRE-ASSEMBLED, PROTECTED, CHEMICALLY STABLE, CHEMOSELECTIVE LEFT
EP3538591A4 (en) 2016-11-09 2020-07-29 Healthtell Inc. ADJUSTABLE AMINE DENSITY COATINGS
CA3043264A1 (en) 2016-11-11 2018-05-17 Healthtell Inc. Methods for identifying candidate biomarkers
US10646540B2 (en) 2016-11-18 2020-05-12 City Of Hope Peptide inhibitors of twist
WO2018098241A1 (en) 2016-11-22 2018-05-31 University Of Rochester Methods of assessing risk of recurrent prostate cancer
TWI788312B (zh) 2016-11-23 2023-01-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法
CN110249082B (zh) 2016-12-01 2023-07-07 诺迪勒思附属公司 测定蛋白质的方法
US20210072255A1 (en) 2016-12-16 2021-03-11 The Brigham And Women's Hospital, Inc. System and method for protein corona sensor array for early detection of diseases
GB2573069A (en) 2016-12-16 2019-10-23 Twist Bioscience Corp Variant libraries of the immunological synapse and synthesis thereof
SG10201913552UA (en) 2016-12-16 2020-03-30 Alnylam Pharmaceuticals Inc Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions
DE202017007364U1 (de) 2016-12-16 2021-02-11 The Brigham And Women's Hospital Inc. Anordnung markierter Sensorelemente zum Erfassen unterschiedlicher Proteine, die unterschiedliche Sensorelemente binden
EP3558991A2 (en) 2016-12-23 2019-10-30 Plexxikon Inc. Compounds and methods for cdk8 modulation and indications therefor
JP7104048B2 (ja) 2017-01-13 2022-07-20 セルラー リサーチ， インコーポレイテッド 流体チャネルの親水性コーティング
US11208697B2 (en) 2017-01-20 2021-12-28 Decipher Biosciences, Inc. Molecular subtyping, prognosis, and treatment of bladder cancer
US11618924B2 (en) 2017-01-20 2023-04-04 Children's Hospital Medical Center Methods and compositions relating to OPRM1 DNA methylation for personalized pain management
JP7237003B2 (ja) 2017-01-24 2023-03-10 セクエノム， インコーポレイテッド 遺伝子片の評価のための方法およびプロセス
AU2018213315A1 (en) 2017-01-26 2019-07-25 Oklahoma Medical Research Foundation Biomarkers for systemic lupus erythematosus disease activity, and intensity and flare
US11267885B2 (en) 2017-01-26 2022-03-08 Zlip Holding Limited CD47 antigen binding unit and uses thereof
WO2018144240A1 (en) 2017-02-01 2018-08-09 Cellular Research, Inc. Selective amplification using blocking oligonucleotides
US10240205B2 (en) 2017-02-03 2019-03-26 Population Bio, Inc. Methods for assessing risk of developing a viral disease using a genetic test
CA3054303A1 (en) 2017-02-22 2018-08-30 Twist Bioscience Corporation Nucleic acid based data storage
WO2018163051A1 (en) 2017-03-06 2018-09-13 Novartis Ag Methods of treatment of cancer with reduced ubb expression
US11873532B2 (en) 2017-03-09 2024-01-16 Decipher Biosciences, Inc. Subtyping prostate cancer to predict response to hormone therapy
WO2018165532A1 (en) 2017-03-10 2018-09-13 Baylor Research Institute Methods for diagnosing and treating gastric cancer using mirna expression
US10894959B2 (en) 2017-03-15 2021-01-19 Twist Bioscience Corporation Variant libraries of the immunological synapse and synthesis thereof
WO2018177325A1 (en) 2017-03-29 2018-10-04 Crown Bioscience Inc. (Taicang) System and method for determining cetuximab sensitivity on gastric cancer
US20200024351A1 (en) 2017-04-03 2020-01-23 Jounce Therapeutics, Inc. Compositions and Methods for the Treatment of Cancer
CN110913898B (zh) 2017-04-18 2024-04-05 阿尔尼拉姆医药品有限公司 具有乙肝病毒(hbv)感染的受试者的治疗方法
TW201900193A (zh) 2017-04-28 2019-01-01 美商默沙東藥廠 用於癌症治療之生物標記物
EP3622085A4 (en) * 2017-05-09 2020-12-16 Revere Biosensors, LLC SYSTEMS AND METHODS FOR IDENTIFYING AND DIFFERENTIATING GENETIC SAMPLES
WO2018205035A1 (en) 2017-05-12 2018-11-15 Genomedx Biosciences, Inc Genetic signatures to predict prostate cancer metastasis and identify tumor agressiveness
CA3063283A1 (en) 2017-05-17 2018-11-22 Microbio Pty Ltd Methods and agents for identifying or classifying microbes based on polymorphisms within ribosomal rna genes
EP3625248A4 (en) 2017-05-18 2021-01-20 The Rockefeller University COMPOSITIONS AND METHODS OF DIAGNOSIS AND TREATMENT OF DISEASES AND DISEASES ASSOCIATED WITH KCNJ5 MUTATIONS
WO2018213803A1 (en) 2017-05-19 2018-11-22 Neon Therapeutics, Inc. Immunogenic neoantigen identification
EP3635402B1 (en) 2017-05-22 2024-01-24 Edith Cowan University Biomarker of disease
WO2018218250A2 (en) 2017-05-26 2018-11-29 Vibrant Holdings, Llc Photoactive compounds and methods for biomolecule detection and sequencing
US11441174B2 (en) 2017-06-02 2022-09-13 Affymetrix, Inc. Array-based methods for analysing mixed samples using differently labelled allele-specific probes
WO2018223055A1 (en) 2017-06-02 2018-12-06 Affymetrix, Inc. Array-based methods for analysing mixed samples using differently labelled allele-specific probes
WO2018223057A1 (en) 2017-06-02 2018-12-06 Affymetrix, Inc. Array-based methods for analysing mixed samples using different allele-specific labels, in particular for detection of fetal aneuploidies
EP3635135A1 (en) 2017-06-05 2020-04-15 Becton, Dickinson and Company Sample indexing for single cells
WO2018226846A1 (en) 2017-06-07 2018-12-13 Plexxikon Inc. Compounds and methods for kinase modulation
WO2018231864A1 (en) 2017-06-12 2018-12-20 Twist Bioscience Corporation Methods for seamless nucleic acid assembly
AU2018284227B2 (en) 2017-06-12 2024-05-02 Twist Bioscience Corporation Methods for seamless nucleic acid assembly
EP3638814B8 (en) 2017-06-14 2023-06-21 The United States of America, as Represented by The Secretary, Department of Health and Human Services Method for determining lymphoma type
US11851651B2 (en) 2017-06-19 2023-12-26 Massachusetts Institute Of Technology Automated methods for scalable, parallelized enzymatic biopolymer synthesis and modification using microfluidic devices
EP3655418A4 (en) 2017-06-22 2021-05-19 Triact Therapeutics, Inc. METHOD OF TREATMENT OF GLIOBLASTOMA
EP3642334B1 (en) 2017-06-23 2023-12-27 Inscripta, Inc. Nucleic acid-guided nucleases
US11217329B1 (en) 2017-06-23 2022-01-04 Veracyte, Inc. Methods and systems for determining biological sample integrity
EP3645547A4 (en) 2017-06-26 2021-04-21 Phase Genomics Inc. PROCESS FOR GROUPING DNA SEQUENCES
US11420941B2 (en) * 2017-06-29 2022-08-23 Cowper Sciences Inc. Methods and systems for mask alignment in manufacturing process of arrays
US11739386B2 (en) 2017-07-21 2023-08-29 Genecentric Therapeutics, Inc. Methods for determining response to PARP inhibitors
US11530413B2 (en) 2017-07-21 2022-12-20 Novartis Ag Compositions and methods to treat cancer
WO2019032525A1 (en) 2017-08-07 2019-02-14 Genecentric Therapeutics, Inc. PROCESS FOR SUBTYPING EPIDERMOID CARCINOMA OF HEAD AND NECK
CA3072575A1 (en) 2017-08-11 2019-02-14 City Of Hope Rna aptamers against transferrin receptor (tfr)
WO2019036055A2 (en) 2017-08-18 2019-02-21 Ignite Biosciences, Inc. METHODS OF SELECTING BINDING REAGENTS
CN111433375B (zh) 2017-08-31 2024-07-30 诺华股份有限公司 选择针对癌症患者的治疗的方法
EP3676598B1 (en) * 2017-09-01 2024-10-02 Bio-Rad Laboratories, Inc. High powered lasers for western blotting
EP3679143A1 (en) 2017-09-08 2020-07-15 Life Technologies Corporation Methods for improved homologous recombination and compositions thereof
JP2020534813A (ja) 2017-09-08 2020-12-03 ライフ テクノロジーズ コーポレイション 改良された相同組換えおよびその組成物のための方法
CN111566125A (zh) 2017-09-11 2020-08-21 特韦斯特生物科学公司 Gpcr结合蛋白及其合成
US12025615B2 (en) 2017-09-15 2024-07-02 Arizona Board Of Regents On Behalf Of Arizona State University Methods of classifying response to immunotherapy for cancer
WO2019060607A1 (en) 2017-09-20 2019-03-28 Quanterix Corporation METHODS AND SYSTEMS FOR DETECTING MOLECULES OF ANALYTES
EP3687501A4 (en) 2017-09-29 2021-06-23 Triact Therapeutics, Inc. INIPARIB FORMS AND USES THEREOF
EP3696275A4 (en) 2017-10-11 2021-05-26 MGI Tech Co., Ltd. PROCESS FOR IMPROVING THE LOAD AND STABILITY OF NUCLEIC ACIDS ON A SOLID SUPPORT
GB2583590A (en) 2017-10-20 2020-11-04 Twist Bioscience Corp Heated nanowells for polynucleotide synthesis
US11099202B2 (en) 2017-10-20 2021-08-24 Tecan Genomics, Inc. Reagent delivery system
US11721412B2 (en) 2017-10-23 2023-08-08 Nautilus Subsidiary, Inc. Methods for identifying a protein in a sample of unknown proteins
WO2019084434A1 (en) 2017-10-26 2019-05-02 National University Of Singapore NEW APPROACH FOR UNIVERSAL MONITORING OF MINIMUM RESIDUAL DISEASE IN ACUTE MYELOID LEUKEMIA
US11124833B2 (en) 2017-10-27 2021-09-21 Colgate-Palmolive Company Salivary extracellular RNA biomarkers for gingivitis
EP3704252A1 (en) 2017-11-01 2020-09-09 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof
AU2018358016A1 (en) 2017-11-03 2020-05-07 Interna Technologies B.V. MiRNA molecule, equivalent, antagomir, or source thereof for treating and/or diagnosing a condition and/or a disease associated with neuronal deficiency or for neuronal (re)generation
WO2019099610A1 (en) 2017-11-16 2019-05-23 Alnylam Pharmaceuticals, Inc. Kisspeptin 1 (kiss1) irna compositions and methods of use thereof
WO2019100039A1 (en) 2017-11-20 2019-05-23 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
US11254980B1 (en) 2017-11-29 2022-02-22 Adaptive Biotechnologies Corporation Methods of profiling targeted polynucleotides while mitigating sequencing depth requirements
WO2019109016A1 (en) 2017-12-01 2019-06-06 Millennium Pharmaceuticals, Inc. Biomarkers and methods for treatment with nae inhibitors
WO2019113506A1 (en) 2017-12-07 2019-06-13 The Broad Institute, Inc. Methods and compositions for multiplexing single cell and single nuclei sequencing
UY38003A (es) 2017-12-12 2019-06-28 Amgen Inc Construcciones de arni para inhibir la expresión de pnpla3 y métodos de uso de las mismas
KR20200110655A (ko) 2017-12-18 2020-09-24 알닐람 파마슈티칼스 인코포레이티드 고이동성 그룹 박스-1 (hmgb1) irna 조성물 및 이의 사용 방법
WO2019126037A1 (en) 2017-12-19 2019-06-27 City Of Hope Modified tracrrnas grnas, and uses thereof
WO2019126209A1 (en) 2017-12-19 2019-06-27 Cellular Research, Inc. Particles associated with oligonucleotides
WO2019126472A1 (en) 2017-12-22 2019-06-27 Genentech, Inc. Use of pilra binding agents for treatment of a disease
MX2020006803A (es) 2017-12-29 2020-10-28 Nautilus Biotechnology Inc Estrategias de descodificacion para identificacion de proteinas.
AU2019205269A1 (en) 2018-01-04 2020-07-30 Twist Bioscience Corporation DNA-based digital information storage
CN112567246A (zh) 2018-01-25 2021-03-26 比奥根Ma公司 治疗脊髓性肌萎缩症的方法
JP7418337B2 (ja) 2018-02-09 2024-01-19 ジェネンテック， インコーポレイテッド マスト細胞媒介性炎症性疾患の治療法及び診断法
US11859250B1 (en) 2018-02-23 2024-01-02 Children's Hospital Medical Center Methods for treating eosinophilic esophagitis
WO2019195633A1 (en) 2018-04-04 2019-10-10 Ignite Biosciences, Inc. Methods of generating nanoarrays and microarrays
IT201800004253A1 (it) 2018-04-05 2019-10-05 Composizioni e metodi per il trattamento della tachicardia ventricolare polimorfa catecolaminergica dominante ereditaria.
US11957695B2 (en) 2018-04-26 2024-04-16 The Broad Institute, Inc. Methods and compositions targeting glucocorticoid signaling for modulating immune responses
EP3788138A1 (en) 2018-05-02 2021-03-10 Novartis AG Regulators of human pluripotent stem cells and uses thereof
US11365409B2 (en) 2018-05-03 2022-06-21 Becton, Dickinson And Company Molecular barcoding on opposite transcript ends
CA3097976A1 (en) 2018-05-03 2019-11-07 Becton, Dickinson And Company High throughput multiomics sample analysis
WO2019213660A2 (en) 2018-05-04 2019-11-07 The Broad Institute, Inc. Compositions and methods for modulating cgrp signaling to regulate innate lymphoid cell inflammatory responses
AU2019266303A1 (en) 2018-05-09 2021-01-07 Vibrant Holdings, Llc Methods of synthesizing a polynucleotide array using photactivated agents
CN118685406A (zh) 2018-05-14 2024-09-24 阿尔尼拉姆医药品有限公司 血管紧张素原(AGT)iRNA组合物及其使用方法
CN112639130B (zh) 2018-05-18 2024-08-09 特韦斯特生物科学公司 用于核酸杂交的多核苷酸、试剂和方法
US20190366292A1 (en) * 2018-05-29 2019-12-05 Centrillion Technologies, Inc. Increasing Efficiency Of Photochemical Reactions On Substrates
US10801064B2 (en) 2018-05-31 2020-10-13 Personalis, Inc. Compositions, methods and systems for processing or analyzing multi-species nucleic acid samples
US11814750B2 (en) 2018-05-31 2023-11-14 Personalis, Inc. Compositions, methods and systems for processing or analyzing multi-species nucleic acid samples
NL2021377B1 (en) 2018-07-03 2020-01-08 Illumina Inc Interposer with first and second adhesive layers
WO2020023509A1 (en) 2018-07-24 2020-01-30 Affymetrix, Inc. Array based method and kit for determining copy number and genotype in pseudogenes
AU2019316556C1 (en) 2018-08-08 2024-09-12 Pml Screening, Llc Methods for assessing the risk of developing progressive multifocal leukoencephalopathy caused by john cunningham virus by genetic testing
MX2021001056A (es) 2018-08-13 2021-04-12 Alnylam Pharmaceuticals Inc Composiciones de agente de acido ribonucleico bicatenario (arnbc) de virus de la hepatitis b (vhb) y metodos de uso de las mismas.
EP3837380A4 (en) 2018-08-17 2022-05-11 Cellecta, Inc. MULTIPLEX PREPARATION OF BARCODE GENE-SPECIFIC DNA FRAGMENTS
US20210317429A1 (en) 2018-08-20 2021-10-14 The Broad Institute, Inc. Methods and compositions for optochemical control of crispr-cas9
JP2022500504A (ja) 2018-09-14 2022-01-04 プレリュード コーポレーションPrelude Corporation 浸潤性乳癌のリスクを有する対象の治療の選択方法
US20210332367A1 (en) 2018-09-18 2021-10-28 Alnylam Pharmaceuticals, Inc. KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
US20210393740A1 (en) 2018-09-19 2021-12-23 La Jolla Institute For Immunology Ptprs and proteoglycans in rheumatoid arthritis
TW202028465A (zh) 2018-09-28 2020-08-01 美商阿尼拉製藥公司 甲狀腺素運載蛋白（ＴＴＲ）ｉＲＮＡ組成物及其治療或預防ＴＴＲ相關眼部疾病之使用方法
JP2022511398A (ja) 2018-10-01 2022-01-31 ベクトン・ディキンソン・アンド・カンパニー ５’転写物配列の決定
US20210349097A1 (en) 2018-10-05 2021-11-11 Eisai R&D Management Co., Ltd. Biomarkers for a combination therapy comprising lenvatinib and everolimus
US20210333281A1 (en) 2018-10-05 2021-10-28 Eisai R&D Management Co., Ltd. Biomarkers for a therapy comprising a sorafenib compound
CA3115922A1 (en) 2018-10-09 2020-04-16 Genecentric Therapeutics, Inc. Detecting cancer cell of origin
US20220401460A1 (en) 2018-10-10 2022-12-22 Dana-Farber Cancer Institute, Inc. Modulating resistance to bcl-2 inhibitors
EP3867645B1 (en) 2018-10-18 2024-06-05 Oklahoma Medical Research Foundation Biomarkers for a systemic lupus erythematosus (sle) disease activity immune index that characterizes disease activity
KR102594366B1 (ko) 2018-11-07 2023-10-27 시어 인코퍼레이티드 단백질 코로나 분석을 위한 조성물, 방법 및 시스템 및 그것들의 용도
JP2022506546A (ja) 2018-11-08 2022-01-17 ベクトン・ディキンソン・アンド・カンパニー ランダムプライミングを使用した単一細胞の全トランスクリプトーム解析
EP3884048A4 (en) 2018-11-20 2022-08-17 Nautilus Biotechnology, Inc. DESIGN AND SELECTION OF AFFINITY REAGENTS
US11884980B2 (en) 2018-11-28 2024-01-30 Bioscreening & Diagnostics Llc Method for detection of traumatic brain injury
EP3888021B1 (en) 2018-11-30 2024-02-21 Caris MPI, Inc. Next-generation molecular profiling
GB2588716B (en) 2018-12-07 2023-11-01 Element Biosciences Inc Flow cell device and use thereof
AR117297A1 (es) 2018-12-10 2021-07-28 Amgen Inc Constructos de arni para inhibir la expresión de pnpla3 y métodos de uso de estos
CN113195717A (zh) 2018-12-13 2021-07-30 贝克顿迪金森公司 单细胞全转录组分析中的选择性延伸
CA3124110A1 (en) 2018-12-17 2020-06-25 The Broad Institute, Inc. Crispr-associated transposase systems and methods of use thereof
WO2020132521A1 (en) 2018-12-20 2020-06-25 Praxis Precision Medicines, Inc. Compositions and methods for the treatment of kcnt1 related disorders
EP3677693A1 (en) 2019-01-03 2020-07-08 Ecole Polytechnique Federale De Lausanne (EPFL) EPFL-TTO Transpochimeric gene trancripts (tcgts) as cancer biomarkers
US11371076B2 (en) 2019-01-16 2022-06-28 Becton, Dickinson And Company Polymerase chain reaction normalization through primer titration
CN113574178A (zh) 2019-01-23 2021-10-29 贝克顿迪金森公司 与抗体关联的寡核苷酸
WO2020160156A2 (en) 2019-01-30 2020-08-06 Immutics, Inc. Anti-gal3 antibodies and uses thereof
CN113365661A (zh) 2019-01-31 2021-09-07 新加坡科技研究局 用于治疗或预防癌症的cnx/erp57抑制剂
WO2020160450A1 (en) 2019-02-01 2020-08-06 Health Research, Inc. Methods and compositions for treating resistant and recurrent forms of cancer
EP3924739A1 (en) 2019-02-12 2021-12-22 Biogen MA Inc. Biomarkers of progressive multifocal leukoencephalopathy
EP3924506A1 (en) 2019-02-14 2021-12-22 Becton Dickinson and Company Hybrid targeted and whole transcriptome amplification
WO2020176678A1 (en) 2019-02-26 2020-09-03 Twist Bioscience Corporation Variant nucleic acid libraries for glp1 receptor
JP2022522668A (ja) 2019-02-26 2022-04-20 ツイスト バイオサイエンス コーポレーション 抗体を最適化するための変異体核酸ライブラリ
CA3131740A1 (en) 2019-02-27 2020-09-03 Madera Therapeutics, LLC Use of caseinolytic protease p function as a biomarker of drug response to imipridone-like agents
US20220154282A1 (en) 2019-03-12 2022-05-19 The Broad Institute, Inc. Detection means, compositions and methods for modulating synovial sarcoma cells
US20220143148A1 (en) 2019-03-14 2022-05-12 The Broad Institute, Inc. Compositions and methods for modulating cgrp signaling to regulate intestinal innate lymphoid cells
EP3937780A4 (en) 2019-03-14 2022-12-07 InSilixa, Inc. METHODS AND SYSTEMS FOR TIMED FLUORESCENCE-BASED DETECTION
WO2020191069A1 (en) 2019-03-18 2020-09-24 The Broad Institute, Inc. Modulation of type 2 immunity by targeting clec-2 signaling
US20220177863A1 (en) 2019-03-18 2022-06-09 The Broad Institute, Inc. Type vii crispr proteins and systems
US20220142948A1 (en) 2019-03-18 2022-05-12 The Broad Institute, Inc. Compositions and methods for modulating metabolic regulators of t cell pathogenicity
WO2020201267A1 (en) 2019-04-01 2020-10-08 Københavns Universitet Identification of pan-gamma secretase inhibitor (pan-gsi) theranostic response signatures for cancers
WO2020206046A1 (en) 2019-04-01 2020-10-08 The Broad Institute, Inc. Methods and compositions for cell therapy
JP7566775B2 (ja) 2019-04-12 2024-10-15 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 筋肉量及び酸化的代謝を増加させるための組成物及び方法
BR112021020779A8 (pt) 2019-04-17 2022-01-25 Igenomix S L Métodos aperfeiçoados para diagnóstico precoce de leiomiomas e leiomiossarcomas uterinos
WO2020214642A1 (en) 2019-04-19 2020-10-22 Becton, Dickinson And Company Methods of associating phenotypical data and single cell sequencing data
CA3138566A1 (en) 2019-04-30 2020-11-05 Larimar Therapeutics, Inc. Frataxin-sensitive markers for determining effectiveness of frataxin replacement therapy
EP3965932B1 (en) 2019-05-08 2024-08-14 Scienion GmbH Assay plate with nano-vessels and sample recovery assembly
EP3969591A1 (en) 2019-05-15 2022-03-23 Squadra Lifesciences, Inc Aptamers against glioblastoma
WO2020236967A1 (en) 2019-05-20 2020-11-26 The Broad Institute, Inc. Random crispr-cas deletion mutant
UY38733A (es) 2019-05-30 2020-11-30 Amgen Inc Construcciones de arni para inhibir la expresión de scap y métodos de uso de las mismas
US20220396794A1 (en) 2019-06-04 2022-12-15 Apterna Limited APTAMERS AGAINST TRANSFERRIN RECEPTOR (TfR)
MX2021015058A (es) 2019-06-07 2022-04-06 Scribe Therapeutics Inc Sistemas de casx artificiales.
CA3144644A1 (en) 2019-06-21 2020-12-24 Twist Bioscience Corporation Barcode-based nucleic acid sequence assembly
EP3990470A1 (en) 2019-06-27 2022-05-04 Roche Sequencing Solutions, Inc. Peptide libraries having enhanced subsequence diversity and methods for use thereof
CA3145212A1 (en) 2019-06-27 2020-12-30 Dovetail Genomics, Llc Methods and compositions for proximity ligation
US11939622B2 (en) 2019-07-22 2024-03-26 Becton, Dickinson And Company Single cell chromatin immunoprecipitation sequencing assay
WO2021022109A1 (en) 2019-08-01 2021-02-04 Alnylam Pharmaceuticals, Inc. SERPIN FAMILY F MEMBER 2 (SERPINF2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4007811A2 (en) 2019-08-01 2022-06-08 Alnylam Pharmaceuticals, Inc. Carboxypeptidase b2 (cpb2) irna compositions and methods of use thereof
EP4010456A4 (en) 2019-08-05 2023-09-13 Seer, Inc. SYSTEMS AND METHODS FOR SAMPLE PREPARATION, DATA GENERATION AND ANALYSIS OF CORONA PROTEIN
JP2022544238A (ja) 2019-08-13 2022-10-17 アムジエン・インコーポレーテツド ＳＬＣ３０Ａ８発現を阻害するためのＲＮＡｉコンストラクト及びその使用方法
WO2021030522A1 (en) 2019-08-13 2021-02-18 Alnylam Pharmaceuticals, Inc. SMALL RIBOSOMAL PROTEIN SUBUNIT 25 (RPS25) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
US20220282333A1 (en) 2019-08-13 2022-09-08 The General Hospital Corporation Methods for predicting outcomes of checkpoint inhibition and treatment thereof
US20220298501A1 (en) 2019-08-30 2022-09-22 The Broad Institute, Inc. Crispr-associated mu transposase systems
US20230081117A1 (en) 2019-09-09 2023-03-16 Scribe Therapeutics Inc. Compositions and methods for use in immunotherapy
EP4028522A1 (en) 2019-09-09 2022-07-20 Scribe Therapeutics Inc. Compositions and methods for the targeting of sod1
WO2021053556A1 (en) 2019-09-18 2021-03-25 Novartis Ag Nkg2d fusion proteins and uses thereof
AU2020356471A1 (en) 2019-09-23 2022-04-21 Twist Bioscience Corporation Variant nucleic acid libraries for CRTH2
EP4038222A4 (en) 2019-10-02 2023-10-18 Arizona Board of Regents on behalf of Arizona State University METHODS AND COMPOSITIONS FOR IDENTIFYING NEOANTIGENS FOR USE IN THE TREATMENT AND PREVENTION OF CANCER
US11981922B2 (en) 2019-10-03 2024-05-14 Dana-Farber Cancer Institute, Inc. Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment
US11793787B2 (en) 2019-10-07 2023-10-24 The Broad Institute, Inc. Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis
WO2021076828A1 (en) 2019-10-18 2021-04-22 Alnylam Pharmaceuticals, Inc. Solute carrier family member irna compositions and methods of use thereof
MX2022004726A (es) 2019-10-22 2022-05-13 Alnylam Pharmaceuticals Inc Composiciones de acido ribonucleico de interferencia (arni) de componente c3 de complemento y metodos de uso de las mismas.
WO2021086982A2 (en) 2019-10-28 2021-05-06 Beckman Coulter, Inc. Compounds for the identification of microbial classes and uses thereof
US11844800B2 (en) 2019-10-30 2023-12-19 Massachusetts Institute Of Technology Methods and compositions for predicting and preventing relapse of acute lymphoblastic leukemia
TW202132567A (zh) 2019-11-01 2021-09-01 美商阿尼拉製藥公司 亨汀頓蛋白（ＨＴＴ）ｉＲＮＡ劑組成物及其使用方法
WO2021092145A1 (en) 2019-11-06 2021-05-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna composition and methods of use thereof for treating or preventing ttr-associated ocular diseases
WO2021092386A1 (en) 2019-11-08 2021-05-14 Becton Dickinson And Company Using random priming to obtain full-length v(d)j information for immune repertoire sequencing
EP4061945A1 (en) 2019-11-22 2022-09-28 Alnylam Pharmaceuticals, Inc. Ataxin3 (atxn3) rnai agent compositions and methods of use thereof
CA3163319A1 (en) 2019-12-02 2021-06-10 Caris Mpi, Inc. Pan-cancer platinum response predictor
WO2021113763A1 (en) 2019-12-06 2021-06-10 Scribe Therapeutics Inc. Compositions and methods for the targeting of rhodopsin
WO2021113769A1 (en) 2019-12-07 2021-06-10 Scribe Therapeutics Inc. Compositions and methods for the targeting of htt
KR20220115995A (ko) 2019-12-13 2022-08-19 알닐람 파마슈티칼스 인코포레이티드 인간 염색체 ９ 개방 판독 프레임 72 (C9orf72) iRNA 제제 조성물 및 이의 사용 방법
WO2021126734A1 (en) 2019-12-16 2021-06-24 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
WO2021127610A1 (en) 2019-12-20 2021-06-24 EDWARD Via COLLEGE OF OSTEOPATHIC MEDICINE Cancer signatures, methods of generating cancer signatures, and uses thereof
KR20220125332A (ko) 2020-01-10 2022-09-14 스크라이브 테라퓨틱스 인크. Pcsk9의 표적화를 위한 조성물 및 방법
US20230089426A1 (en) 2020-01-13 2023-03-23 Jounce Therapeutics, Inc. Methods for the treatment of cancer
EP4090763A1 (en) 2020-01-13 2022-11-23 Becton Dickinson and Company Methods and compositions for quantitation of proteins and rna
WO2021154941A1 (en) 2020-01-31 2021-08-05 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als)
US12059674B2 (en) 2020-02-03 2024-08-13 Tecan Genomics, Inc. Reagent storage system
US20230102503A1 (en) 2020-02-10 2023-03-30 ObsEva S.A. Biomarkers for oxytocin receptor antagonist therapy
IL295496A (en) 2020-02-18 2022-10-01 Alnylam Pharmaceuticals Inc Apolipoprotein c3 (apoc3) irna preparations and methods of using them
WO2021178607A1 (en) 2020-03-05 2021-09-10 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases
CN115485383A (zh) 2020-03-06 2022-12-16 阿尔尼拉姆医药品有限公司 己酮糖激酶(KHK)iRNA组合物及其使用方法
EP4121534A1 (en) 2020-03-18 2023-01-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant
WO2021188729A1 (en) 2020-03-18 2021-09-23 Scribe Therapeutics Inc. Compositions and methods for the targeting of c9orf72
EP4127168A1 (en) 2020-03-26 2023-02-08 Alnylam Pharmaceuticals, Inc. Coronavirus irna compositions and methods of use thereof
WO2021206917A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4133077A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof
CA3172579A1 (en) 2020-04-15 2021-10-21 David C. Duffy Methods and systems related to highly sensitive assays and by deliveringcapture objects
MX2022013525A (es) 2020-04-27 2023-01-24 Alnylam Pharmaceuticals Inc Composiciones de agentes de ácido ribonucleico de interferencia (arni) de apolipoproteína e (apoe) y métodos de uso de las mismas.
EP4142738A1 (en) 2020-04-30 2023-03-08 Alnylam Pharmaceuticals, Inc. Complement factor b (cfb) irna compositions and methods of use thereof
US20230193212A1 (en) 2020-05-06 2023-06-22 Orchard Therapeutics (Europe) Limited Treatment for neurodegenerative diseases
EP4146395A2 (en) 2020-05-08 2023-03-15 Scienion GmbH Assay plate with nano-vessels and sample recovery assembly
WO2021231779A1 (en) 2020-05-14 2021-11-18 Becton, Dickinson And Company Primers for immune repertoire profiling
EP4150087A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2)
CA3162416C (en) 2020-05-15 2023-07-04 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1)
EP4150086A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2)
EP4150077A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1)
WO2021231691A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of retinoschisin 1 (rsi)
EP4150076A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2)
EP4150078A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl)
WO2021231692A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of otoferlin (otof)
AU2021284377A1 (en) 2020-06-01 2022-12-22 Amgen Inc. RNAi constructs for inhibiting HSD17B13 expression and methods of use thereof
AR122534A1 (es) 2020-06-03 2022-09-21 Triplet Therapeutics Inc Métodos para el tratamiento de los trastornos de expansión por repetición de nucleótidos asociados con la actividad de msh3
EP4162050A1 (en) 2020-06-09 2023-04-12 Alnylam Pharmaceuticals, Inc. Rnai compositions and methods of use thereof for delivery by inhalation
AU2021292296A1 (en) 2020-06-18 2023-01-19 Alnylam Pharmaceuticals, Inc. Xanthine dehydrogenase (XDH) iRNA compositions and methods of use thereof
KR20230050336A (ko) 2020-07-10 2023-04-14 인스티튜트 내셔널 드 라 싼테 에 드 라 리셰르셰 메디칼르 (인 썸) 뇌전증을 치료하기 위한 방법과 조성물
US11932901B2 (en) 2020-07-13 2024-03-19 Becton, Dickinson And Company Target enrichment using nucleic acid probes for scRNAseq
WO2022047359A1 (en) 2020-08-31 2022-03-03 Berg Llc Protein biomarkers for pancreatic cancer
US20230340611A1 (en) 2020-09-16 2023-10-26 Novigenix Sa Biomarkers For Immune Checkpoint Inhibitors Treatment
EP4217489A1 (en) 2020-09-24 2023-08-02 Alnylam Pharmaceuticals, Inc. Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof
EP4225917A1 (en) 2020-10-05 2023-08-16 Alnylam Pharmaceuticals, Inc. G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof
EP4232582A1 (en) 2020-10-23 2023-08-30 Alnylam Pharmaceuticals, Inc. Mucin 5b (muc5b) irna compositions and methods of use thereof
EP4244382A1 (en) 2020-11-11 2023-09-20 Nautilus Subsidiary, Inc. Affinity reagents having enhanced binding and detection characteristics
WO2022103999A1 (en) 2020-11-13 2022-05-19 Alnylam Pharmaceuticals, Inc. COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4247423A2 (en) 2020-11-18 2023-09-27 Astrazeneca AB Steroid sparing
WO2022109343A1 (en) 2020-11-20 2022-05-27 Becton, Dickinson And Company Profiling of highly expressed and lowly expressed proteins
WO2022119873A1 (en) 2020-12-01 2022-06-09 Alnylam Pharmaceuticals, Inc. Methods and compositions for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
WO2022120089A1 (en) 2020-12-03 2022-06-09 Scribe Therapeutics Inc. Compositions and methods for the targeting of ptbp1
TW202237836A (zh) 2020-12-03 2022-10-01 美商斯奎柏治療公司 工程化之第2類第v型crispr系統
WO2022125490A1 (en) 2020-12-08 2022-06-16 Alnylam Pharmaceuticals, Inc. Coagulation factor x (f10) irna compositions and methods of use thereof
US20240055076A1 (en) 2020-12-09 2024-02-15 Cambridge Enterprise Limited Treatment of diseases associated with variant novel open reading frames
GB202019692D0 (en) 2020-12-14 2021-01-27 Apterna Ltd Aptamer-sirna fusions
US20240060070A1 (en) 2020-12-16 2024-02-22 Cambridge Enterprise Limited Treatment of cancer associated with variant novel open reading frames
WO2022130259A2 (en) 2020-12-16 2022-06-23 Cambridge Enterprise Limited Treatment of cancer associated with dysregulated novel open reading frame products
EP4274896A1 (en) 2021-01-05 2023-11-15 Alnylam Pharmaceuticals, Inc. Complement component 9 (c9) irna compositions and methods of use thereof
WO2022162588A1 (en) 2021-01-28 2022-08-04 Cambridge Enterprise Limited Method of treatment of malaria by targetting open reading frames
AU2022220704A1 (en) 2021-02-12 2022-08-18 Alnylam Pharmaceuticals, Inc. Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases
US20240122865A1 (en) 2021-02-19 2024-04-18 Pfizer Inc. Methods of Protecting RNA
CN117222739A (zh) 2021-02-25 2023-12-12 阿尔尼拉姆医药品有限公司 朊病毒蛋白(prnp)irna组合物和其使用方法
CA3211059A1 (en) 2021-02-26 2022-09-01 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
IL305442A (en) 2021-03-04 2023-10-01 Alnylam Pharmaceuticals Inc Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them
US20240150453A1 (en) 2021-03-09 2024-05-09 Massachusetts Institute Of Technology Methods of predicting response to anti-tnf blockade in inflammatory bowel disease
WO2022192519A1 (en) 2021-03-12 2022-09-15 Alnylam Pharmaceuticals, Inc. Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof
BR112023019981A2 (pt) 2021-03-29 2023-12-12 Alnylam Pharmaceuticals Inc Composições do agente irna de huntingtina (htt) e métodos de uso das mesmas
WO2022212153A1 (en) 2021-04-01 2022-10-06 Alnylam Pharmaceuticals, Inc. Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof
IL307528A (en) 2021-04-06 2023-12-01 Bpgbio Inc Protein markers for the prognosis of breast cancer progression
IL307531A (en) 2021-04-06 2023-12-01 Bpgbio Inc Protein markers for estrogen receptor (ER)-like and estrogen receptor (ER)-negative breast cancer
EP4320440A1 (en) 2021-04-06 2024-02-14 BPGbio, Inc. Protein markers for estrogen receptor (er)-positive luminal a(la)-like and luminal b1 (lb1)-like breast cancer
BR112023022284A2 (pt) 2021-04-26 2023-12-26 Alnylam Pharmaceuticals Inc Composições de irna de protease transmembrana, serina 6 (tmprss6) e métodos de uso da mesma
WO2022232343A1 (en) 2021-04-29 2022-11-03 Alnylam Pharmaceuticals, Inc. Signal transducer and activator of transcription factor 6 (stat6) irna compositions and methods of use thereof
WO2022237974A1 (en) 2021-05-12 2022-11-17 Ecole Polytechnique Federale De Lausanne (Epfl) Krab-containing zinc finger protein and cancer
JP2024522068A (ja) 2021-05-18 2024-06-11 アルナイラム ファーマシューティカルズ， インコーポレイテッド ナトリウム－グルコース共輸送体２（ｓｇｌｔ２）ｉｒｎａ組成物およびその使用方法
WO2022246023A1 (en) 2021-05-20 2022-11-24 Korro Bio, Inc. Methods and compositions for adar-mediated editing
WO2022248574A1 (en) 2021-05-28 2022-12-01 Centre Hospitalier Universitaire Vaudois (C.H.U.V.) Novel incrna controlling cardiac fibrosis
WO2022256283A2 (en) 2021-06-01 2022-12-08 Korro Bio, Inc. Methods for restoring protein function using adar
EP4347823A1 (en) 2021-06-02 2024-04-10 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
AU2022283796A1 (en) 2021-06-04 2023-11-09 Alnylam Pharmaceuticals, Inc. HUMAN CHROMOSOME 9 OPEN READING FRAME 72 (C9ORF72) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
WO2022260939A2 (en) 2021-06-08 2022-12-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
US11756285B2 (en) 2021-06-10 2023-09-12 Bank Of America Corporation Image processing system and method for image noise removal
EP4363574A1 (en) 2021-06-29 2024-05-08 Korro Bio, Inc. Methods and compositions for adar-mediated editing
US20230194709A9 (en) 2021-06-29 2023-06-22 Seagate Technology Llc Range information detection using coherent pulse sets with selected waveform characteristics
JP2024526764A (ja) 2021-07-13 2024-07-19 トゥルーバインディング，インコーポレイテッド タンパク質凝集を防止する方法
WO2023285616A1 (en) 2021-07-14 2023-01-19 Cambridge Enterprise Limited Treatment of schizophrenia and bipolar disorder
WO2023003922A1 (en) 2021-07-21 2023-01-26 Alnylam Pharmaceuticals, Inc. Metabolic disorder-associated target gene irna compositions and methods of use thereof
EP4373933A1 (en) 2021-07-23 2024-05-29 Alnylam Pharmaceuticals, Inc. Beta-catenin (ctnnb1) irna compositions and methods of use thereof
JP2024529437A (ja) 2021-07-29 2024-08-06 アルナイラム ファーマシューティカルズ， インコーポレイテッド ３－ヒドロキシ－３－メチルグリタル－ＣＯＡレダクターゼ（ＨＭＧＣＲ）ｉＲＮＡ組成物およびその使用方法
MX2024001194A (es) 2021-08-03 2024-02-27 Alnylam Pharmaceuticals Inc Composiciones de acido ribonucleico de interferencia (arni) de transtiretina (ttr) y sus metodos de uso.
WO2023014765A1 (en) 2021-08-04 2023-02-09 Alnylam Pharmaceuticals, Inc. iRNA COMPOSITIONS AND METHODS FOR SILENCING ANGIOTENSINOGEN (AGT)
WO2023019246A1 (en) 2021-08-13 2023-02-16 Alnylam Pharmaceuticals, Inc. Factor xii (f12) irna compositions and methods of use thereof
EP4401742A2 (en) 2021-09-17 2024-07-24 Alnylam Pharmaceuticals, Inc. Irna compositions and methods for silencing complement component 3 (c3)
CA3232420A1 (en) 2021-09-20 2023-03-23 Alnylam Pharmaceuticals, Inc. Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof
WO2023064530A1 (en) 2021-10-15 2023-04-20 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
IL311839A (en) 2021-10-22 2024-05-01 Amgen Inc RNA interference constructs to inhibit gpam expression and methods for using them
CA3234835A1 (en) 2021-10-22 2023-04-27 Korro Bio, Inc. Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing
TW202334418A (zh) 2021-10-29 2023-09-01 美商艾拉倫製藥股份有限公司 杭丁頓（ＨＴＴ）ｉＲＮＡ劑組成物及其使用方法
IL312399A (en) 2021-10-29 2024-06-01 Alnylam Pharmaceuticals Inc Complement factor B (CFB) iRNA compositions and methods of using them
CA3242118A1 (en) 2021-12-22 2023-06-29 Alfica Sehgal Modulation of gene transcription using antisense oligonucleotides targeting regulatory rnas
US20230215515A1 (en) 2021-12-23 2023-07-06 Illumina Software, Inc. Facilitating secure execution of external workflows for genomic sequencing diagnostics
WO2023122363A1 (en) 2021-12-23 2023-06-29 Illumina Software, Inc. Dynamic graphical status summaries for nucelotide sequencing
CA3242624A1 (en) 2021-12-29 2023-07-06 Shannon Whitmore Automatically switching variant analysis model versions for genomic analysis applications
WO2023141314A2 (en) 2022-01-24 2023-07-27 Alnylam Pharmaceuticals, Inc. Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof
US20230264294A1 (en) * 2022-02-23 2023-08-24 Corning Incorporated Methods of preparing a workpiece for laser bonding
WO2023196937A1 (en) 2022-04-06 2023-10-12 Larimar Therapeutics, Inc. Frataxin-sensitive markers for monitoring frataxin replacement therapy
KR20230147016A (ko) * 2022-04-13 2023-10-20 고려대학교 산학협력단 정밀 dna 광학 합성을 위한 시스템 및 방법
TW202411426A (zh) 2022-06-02 2024-03-16 美商斯奎柏治療公司 經工程化的２類ｖ型ｃｒｉｓｐｒ系統
WO2023240074A1 (en) 2022-06-07 2023-12-14 Scribe Therapeutics Inc. Compositions and methods for the targeting of pcsk9
WO2023240076A1 (en) 2022-06-07 2023-12-14 Scribe Therapeutics Inc. Compositions and methods for the targeting of pcsk9
WO2023240201A1 (en) 2022-06-08 2023-12-14 Larimar Therapeutics, Inc. Frataxin-sensitive markers for monitoring progression and treatment of leigh syndrome
WO2023240277A2 (en) 2022-06-10 2023-12-14 Camp4 Therapeutics Corporation Methods of modulating progranulin expression using antisense oligonucleotides targeting regulatory rnas
WO2024020572A1 (en) 2022-07-22 2024-01-25 New York Stem Cell Foundation, Inc. Methods and compositions for the treatment of ptsd
WO2024028794A1 (en) 2022-08-02 2024-02-08 Temple Therapeutics BV Methods for treating endometrial and ovarian hyperproliferative disorders
WO2024039776A2 (en) 2022-08-18 2024-02-22 Alnylam Pharmaceuticals, Inc. Universal non-targeting sirna compositions and methods of use thereof
WO2024056902A2 (en) 2022-09-16 2024-03-21 Christopher Shaw Compositions and methods for treating neurological diseases
WO2024119145A1 (en) 2022-12-01 2024-06-06 Camp4 Therapeutics Corporation Modulation of syngap1 gene transcription using antisense oligonucleotides targeting regulatory rnas
WO2024124044A1 (en) 2022-12-07 2024-06-13 The Brigham And Women’S Hospital, Inc. Compositions and methods targeting sat1 for enhancing anti¬ tumor immunity during tumor progression
WO2024126696A1 (en) 2022-12-14 2024-06-20 King's College London Compositions and methods for treating neurological diseases
WO2024130142A2 (en) 2022-12-16 2024-06-20 Amgen Inc. Rnai constructs for inhibiting ttr expression and methods of use thereof
WO2024160683A1 (en) 2023-01-30 2024-08-08 Ecole Polytechnique Federale De Lausanne (Epfl) Pou5f1b inhibitors
WO2024161022A2 (en) 2023-02-03 2024-08-08 King's College London Compositions and methods for treating neurological diseases
WO2024168010A2 (en) 2023-02-09 2024-08-15 Alnylam Pharmaceuticals, Inc. Reversir molecules and methods of use thereof
WO2024192141A1 (en) 2023-03-13 2024-09-19 Dana-Farber Cancer Institute, Inc. Treatment of cancers having a drug-resistant mesenchymal cell state
WO2024199256A1 (en) 2023-03-28 2024-10-03 Chengdu Anticancer Bioscience , Ltd. Methods and compositions for the diagnosis and treatment of cancer
WO2024206555A1 (en) 2023-03-29 2024-10-03 Scribe Therapeutics Inc. Compositions and methods for the targeting of pcsk9
WO2024206676A1 (en) 2023-03-29 2024-10-03 Scribe Therapeutics Inc. Compositions and methods for the targeting of lpa
WO2024206565A1 (en) 2023-03-29 2024-10-03 Scribe Therapeutics Inc. Repressor fusion protein systems

Family Cites Families (306)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR333561A (fr) 1903-07-03 1903-11-28 Georges Rollet Procédé et appareil pour le nettoyage des vetements
US3862056A (en) * 1967-12-15 1975-01-21 Allied Chem Semiconductor polymer compositions comprising a grafted block copolymer of synthetic rubber and polyolefin and carbon black
IL33640A (en) * 1969-01-16 1973-05-31 Kabi Ab Test strip packaged-unit
US3730844A (en) 1971-08-27 1973-05-01 Purdue Research Foundation Polynucleotide analysis
DE2150691C2 (de) * 1971-10-12 1982-09-09 Basf Ag, 6700 Ludwigshafen Lichtempfindliches Gemisch und Verwendung eines lichtempfindlichen Gemisches zur Herstellung einer Flachdruckplatte
DE2242394A1 (de) * 1972-08-29 1974-03-14 Basf Ag Unter lichteinwirkung haertbare stoffgemische
JPS5183B2 (fi) * 1973-03-07 1976-01-05
US3939350A (en) * 1974-04-29 1976-02-17 Board Of Trustees Of The Leland Stanford Junior University Fluorescent immunoassay employing total reflection for activation
JPS6112373B2 (fi) * 1974-09-04 1986-04-08 Hitachi Ltd
SE407115B (sv) * 1975-10-06 1979-03-12 Kabi Ab Forfarande och metelektroder for studium av enzymatiska och andra biokemiska reaktioner
US4238757A (en) * 1976-03-19 1980-12-09 General Electric Company Field effect transistor for detection of biological reactions
DE2612359C3 (de) 1976-03-24 1978-10-26 Konishiroku Photo Ind. Co., Ltd., Tokio Elektrophotographisches Aufzeichnungsmaterial
US4259223A (en) * 1976-03-29 1981-03-31 California Institute Of Technology Cross-linked polyvinyl pyridine coated glass particle catalyst support and aqueous composition or polyvinyl pyridine adducted microspheres
US4145406A (en) * 1977-04-11 1979-03-20 Miles Laboratories, Inc. Specific binding - adsorbent assay method and test means
US4086254A (en) * 1977-04-13 1978-04-25 The Upjohn Company Photocleavable steroids
US4121222A (en) 1977-09-06 1978-10-17 A. B. Dick Company Drop counter ink replenishing system
US4180739A (en) 1977-12-23 1979-12-25 Varian Associates, Inc. Thermostatable flow cell for fluorescence measurements
US4448534A (en) * 1978-03-30 1984-05-15 American Hospital Corporation Antibiotic susceptibility testing
US4269933A (en) 1978-06-08 1981-05-26 E. I. Du Pont De Nemours And Company Methods of developing photopolymerizable compositions containing an 0-nitroaromatic compound as photoinhibitor
US4216245A (en) 1978-07-25 1980-08-05 Miles Laboratories, Inc. Method of making printed reagent test devices
US4258001A (en) * 1978-12-27 1981-03-24 Eastman Kodak Company Element, structure and method for the analysis or transport of liquids
US4427415A (en) * 1979-01-05 1984-01-24 Cleveland Patrick H Manifold vacuum biochemical test method and device
US4314821A (en) * 1979-04-09 1982-02-09 Minnesota Mining And Manufacturing Company Sandwich immunoassay using piezoelectric oscillator
US4342905A (en) 1979-08-31 1982-08-03 Nippon Kogaku K.K. Automatic focusing device of a microscope
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4327073A (en) 1980-04-07 1982-04-27 Huang Henry V Automated method for quantitative analysis of biological fluids
US4478967A (en) 1980-08-11 1984-10-23 Minnesota Mining And Manufacturing Company Photolabile blocked surfactants and compositions containing the same
US4444892A (en) * 1980-10-20 1984-04-24 Malmros Mark K Analytical device having semiconductive organic polymeric element associated with analyte-binding substance
IL61351A (en) * 1980-10-27 1983-12-30 Yeda Res & Dev Organometallic polymers,their preparation and compositions of co-ordination compounds containing them
US4711955A (en) 1981-04-17 1987-12-08 Yale University Modified nucleotides and methods of preparing and using same
AR231590A1 (es) 1981-04-29 1984-12-28 Ciba Geigy Ag Dispositivo de analisis inmunologico y procedimiento para obtenerlo
US4373071A (en) 1981-04-30 1983-02-08 City Of Hope Research Institute Solid-phase synthesis of polynucleotides
US4339528A (en) * 1981-05-19 1982-07-13 Rca Corporation Etching method using a hardened PVA stencil
US4430299A (en) * 1981-06-18 1984-02-07 Coulter Electronics, Inc. Apparatus for monitoring chemical reactions
US4498774A (en) 1981-07-22 1985-02-12 Iowa State University Research Foundation, Inc. Micro-polarimeter for high performance liquid chromatography
US4395486A (en) 1981-08-19 1983-07-26 Medical College Of Ga. Research Inst., Inc. Method for the direct analysis of sickle cell anemia
USRE33064E (en) * 1981-09-18 1989-09-19 Prutec Limited Method for the determination of species in solution with an optical wave-guide
FI63596C (fi) 1981-10-16 1983-07-11 Orion Yhtymae Oy Mikrobdiagnostiskt foerfarande som grundar sig pao skiktshybridisering av nukleinsyror och vid foerfarandet anvaenda kombinationer av reagenser
US4444878A (en) * 1981-12-21 1984-04-24 Boston Biomedical Research Institute, Inc. Bispecific antibody determinants
US5073484A (en) * 1982-03-09 1991-12-17 Bio-Metric Systems, Inc. Quantitative analysis apparatus and method
US4500919A (en) 1982-05-04 1985-02-19 Massachusetts Institute Of Technology Color reproduction system
US4483920A (en) 1982-05-17 1984-11-20 Hahnemann University Immobilization of message RNA directly from cells onto filter material
US4556643A (en) 1982-07-26 1985-12-03 Agracetus Assay method and probe for polynucleotide sequences
US4624915A (en) * 1982-07-29 1986-11-25 Board Of Trustees Of Michigan State University Positive selection sorting of cells
US4477556A (en) 1982-08-18 1984-10-16 E. I. Du Pont De Nemours And Company Acidic o-nitroaromatics as photoinhibitors of polymerization in positive working films
US4455089A (en) 1982-08-25 1984-06-19 Iowa State University Research Foundation, Inc. Refractive index and absorption detector for liquid chromatography based on Fabry-Perot interferometry
US5599720A (en) 1982-08-27 1997-02-04 Multilyte Limited Measurement of analyte concentration
US4973493A (en) * 1982-09-29 1990-11-27 Bio-Metric Systems, Inc. Method of improving the biocompatibility of solid surfaces
US4722906A (en) * 1982-09-29 1988-02-02 Bio-Metric Systems, Inc. Binding reagents and methods
US4588682A (en) 1982-12-13 1986-05-13 Integrated Genetics, Inc. Binding nucleic acid to a support
JPH0627742B2 (ja) 1982-12-21 1994-04-13 コムテツク リサ−チ ユニツト リミテツド 検定方法及びそのための装置
US4516833A (en) 1982-12-27 1985-05-14 University Of Dayton Production of high performance optical spatial filters
DE3301833A1 (de) * 1983-01-20 1984-07-26 Gesellschaft für Biotechnologische Forschung mbH (GBF), 3300 Braunschweig Verfahren zur simultanen synthese mehrerer oligonocleotide an fester phase
US4994373A (en) 1983-01-27 1991-02-19 Enzo Biochem, Inc. Method and structures employing chemically-labelled polynucleotide probes
US4634574A (en) 1983-01-31 1987-01-06 Iowa State Research Foundation, Inc. Apparatus for use in sulfide chemiluminescence detection
US4575433A (en) 1983-01-31 1986-03-11 Iowa State University Research Foundation, Inc. Method of generating chemiluminescent light
US4555491A (en) 1983-01-31 1985-11-26 Iowa State University Research Foundation, Inc. Sulfide chemiluminescence detection
US4591570A (en) 1983-02-02 1986-05-27 Centocor, Inc. Matrix of antibody-coated spots for determination of antigens
US4537861A (en) 1983-02-03 1985-08-27 Elings Virgil B Apparatus and method for homogeneous immunoassay
NZ207394A (en) * 1983-03-08 1987-03-06 Commw Serum Lab Commission Detecting or determining sequence of amino acids
US4584277A (en) 1983-04-05 1986-04-22 Syntex (U.S.A.) Inc. Fluorescent multiparameter particle analysis
GB8311018D0 (en) 1983-04-22 1983-05-25 Amersham Int Plc Detecting mutations in dna
US4533682A (en) 1983-04-29 1985-08-06 Desoto, Inc. Imidazolidine-blocked amine polymers
GB8314523D0 (en) * 1983-05-25 1983-06-29 Lowe C R Diagnostic device
US4517338A (en) * 1983-06-20 1985-05-14 Chiron Corporation Multiple reactor system and method for polynucleotide synthesis
US4987065A (en) 1983-07-05 1991-01-22 Enzo Biochem, Inc. In vivo labelling of polynucleotide sequences
US4713326A (en) * 1983-07-05 1987-12-15 Molecular Diagnostics, Inc. Coupling of nucleic acids to solid support by photochemical methods
US4542102A (en) * 1983-07-05 1985-09-17 Molecular Diagnostics, Inc. Coupling of nucleic acids to solid support by photochemical methods
US4626684A (en) * 1983-07-13 1986-12-02 Landa Isaac J Rapid and automatic fluorescence immunoassay analyzer for multiple micro-samples
US4677054A (en) 1983-08-08 1987-06-30 Sloan-Kettering Institute For Cancer Research Method for simple analysis of relative nucleic acid levels in multiple small samples by cytoplasmic dot hybridization
US4719615A (en) * 1983-08-22 1988-01-12 Optical Data, Inc. Erasable optical data storage medium
US4598049A (en) 1983-08-31 1986-07-01 Systec Inc. General purpose gene synthesizer
JP2548112B2 (ja) 1983-09-02 1996-10-30 シンジェン，インコーポレイテッド 担体およびオリゴヌクレオチドの合成
US4569967A (en) * 1983-10-24 1986-02-11 The Salk Institute For Biological Studies Synthesis of N-substituted peptide amides
US4580895A (en) * 1983-10-28 1986-04-08 Dynatech Laboratories, Incorporated Sample-scanning photometer
US4849513A (en) 1983-12-20 1989-07-18 California Institute Of Technology Deoxyribonucleoside phosphoramidites in which an aliphatic amino group is attached to the sugar ring and their use for the preparation of oligonucleotides containing aliphatic amino groups
US5171534A (en) 1984-01-16 1992-12-15 California Institute Of Technology Automated DNA sequencing technique
US5821058A (en) 1984-01-16 1998-10-13 California Institute Of Technology Automated DNA sequencing technique
US4613566A (en) 1984-01-23 1986-09-23 President And Fellows Of Harvard College Hybridization assay and kit therefor
JPS60155942A (ja) 1984-01-25 1985-08-16 Fuji Photo Film Co Ltd 液体試料点着装置
FI71768C (fi) 1984-02-17 1987-02-09 Orion Yhtymae Oy Foerbaettrade nykleinsyrareagenser och foerfarande foer deras framstaellning.
GB8405437D0 (en) 1984-03-01 1984-04-04 Amersham Int Plc Detecting polynucleotide sequences
US4704353A (en) * 1984-04-27 1987-11-03 Molecular Devices Corporation Photoresponsive redox detection and discrimination
EP0164206B1 (en) 1984-05-02 1988-11-02 Brendan James Hamill An apparatus for the chemical synthesis of oligonucleotides
US4766062A (en) 1984-05-07 1988-08-23 Allied Corporation Displacement polynucleotide assay method and polynucleotide complex reagent therefor
JPS60248699A (ja) * 1984-05-23 1985-12-09 Fujisawa Pharmaceut Co Ltd ウロガストロンの製造法
US4670380A (en) 1984-05-23 1987-06-02 Molecular Diagnostics, Inc. Assays utilizing labeled nucleic acid probes
US4555490A (en) * 1984-06-08 1985-11-26 The United States Of America As Represented By The Department Of Health And Human Services Rapid visualization system for gel electrophoresis
IL75464A (en) 1984-06-12 1990-08-31 Orgenics Ltd Method and apparatus for multi-analyte assay
CA1255586A (en) * 1984-07-24 1989-06-13 Hendrik M. Geysen Method of determining mimotopes
US4767927A (en) 1984-08-16 1988-08-30 Kabushiki Kaisha Toshiba Apparatus for reading radiation image information stored in imaging plate
US4755458A (en) 1984-08-30 1988-07-05 Enzo Biochem, Inc. Composition and method for the detection of the presence of a polynucleotide sequence of interest
US4563417A (en) * 1984-08-31 1986-01-07 Miles Laboratories, Inc. Nucleic acid hybridization assay employing antibodies to intercalation complexes
US4681859A (en) * 1984-09-21 1987-07-21 Ortho Diagnostic Systems Inc. Fluorescence polarization immunoassay for heavy antigens
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
DE3440141A1 (de) * 1984-11-02 1986-05-07 Heiner Dipl.-Chem. Dr. 8000 München Eckert Verwendung von kohlensaeure-bis-trichlormethylester als proreagens fuer phosgen
US4820630A (en) 1984-11-23 1989-04-11 Digene Diagnostics, Incorporated Assay for nucleic acid sequences, particularly genetic lesions, using interactive labels
US4719179A (en) 1984-11-30 1988-01-12 Pharmacia P-L Biochemicals, Inc. Six base oligonucleotide linkers and methods for their use
US5242794A (en) 1984-12-13 1993-09-07 Applied Biosystems, Inc. Detection of specific sequences in nucleic acids
US5064754A (en) 1984-12-14 1991-11-12 Mills Randell L Genomic sequencing method
US4670379A (en) 1984-12-19 1987-06-02 E. I. Du Pont De Nemours And Company Polynucleotide hydridization assays employing catalyzed luminescence
US5026840A (en) * 1985-01-10 1991-06-25 Molecular Diagnostics, Inc. Photochemical nucleic acid-labeling reagent having a polyalklamine spacer
US4713347A (en) * 1985-01-14 1987-12-15 Sensor Diagnostics, Inc. Measurement of ligand/anti-ligand interactions using bulk conductance
US4767700A (en) 1985-02-15 1988-08-30 Beckman Research Institute Of The City Of Hope Detection of particular nucleotide sequences
EP0194132A3 (en) * 1985-03-06 1988-08-03 Murex Corporation Imaging immunoassay detection system and method
US5096807A (en) 1985-03-06 1992-03-17 Murex Corporation Imaging immunoassay detection system with background compensation and its use
US4631211A (en) * 1985-03-25 1986-12-23 Scripps Clinic & Research Foundation Means for sequential solid phase organic synthesis and methods using the same
US4965188A (en) 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US6040166A (en) 1985-03-28 2000-03-21 Roche Molecular Systems, Inc. Kits for amplifying and detecting nucleic acid sequences, including a probe
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
DE3513168A1 (de) * 1985-04-12 1986-10-16 Thomas 8000 München Dandekar Biosensor bestehend aus einem halbleiter auf silizium oder kohlenstoffbasis (elektronischer teil) und nukleinbasen (od. anderen biol. monomeren)
US4720786A (en) * 1985-04-19 1988-01-19 Fuji Photo Film Co., Ltd. Method of compensating for offset distortion in rows of electrophoretic patterns
NZ215865A (en) * 1985-04-22 1988-10-28 Commw Serum Lab Commission Method of determining the active site of a receptor-binding analogue
WO1986006487A1 (en) * 1985-04-22 1986-11-06 Commonwealth Serum Laboratories Commission Method for determining mimotopes
US4797355A (en) * 1985-06-13 1989-01-10 Amgen Inc. Methods for attaching polynucleotides to supports
JPS61290311A (ja) 1985-06-19 1986-12-20 Hitachi Ltd はんだ付部の検査装置及びその方法
FR2583772B1 (fr) 1985-06-20 1987-08-28 Roussel Uclaf Nouveaux supports, la preparation de ces supports, les intermediaires nouveaux obtenus, leur application a la synthese d'oligonucleotides et les nouveaux nucleosides et oligonucleotides relies aux supports ainsi obtenus
FR2584090B1 (fr) 1985-06-27 1987-08-28 Roussel Uclaf Nouveaux supports, leur preparation et les intermediaires obtenus, leur application a la synthese d'oligonucleotides et les nouveaux nucleosides et oligonucleotides relies aux supports ainsi obtenus
US4719087A (en) * 1985-07-01 1988-01-12 Baxter Travenol Laboratories, Inc. Tray for analyzing system
EP0212807A3 (en) * 1985-07-15 1988-01-07 Imperial Chemical Industries Plc Coloured compound containing a cationic group and a reactive group
JPS6221151A (ja) 1985-07-19 1987-01-29 Matsushita Electric Ind Co Ltd パタ−ン形成方法
DD254998A1 (de) 1985-07-26 1988-03-16 Zeiss Jena Veb Carl Anordnung zur bildlichen darstellung und analyse von fluoreszenzsignalen
DE3677364D1 (de) 1985-08-05 1991-03-07 Univ Leiden Markierte makromolekuele; verfahren zu ihrer herstellung und ihre verwendung in immunologischen oder immunocytochemischen testen.
JPS6242057A (ja) * 1985-08-19 1987-02-24 Fuji Photo Film Co Ltd 核酸の塩基配列決定のための信号処理方法
EP0213825A3 (en) 1985-08-22 1989-04-26 Molecular Devices Corporation Multiple chemically modulated capacitance
US4731335A (en) * 1985-09-13 1988-03-15 Fisher Scientific Company Method for treating thin samples on a surface employing capillary flow
SE450171B (sv) 1985-10-18 1987-06-09 Carl Urban Ungerstedt Anordning for automatisk uppsamling av sma vetskevolymer
US4888278A (en) * 1985-10-22 1989-12-19 University Of Massachusetts Medical Center In-situ hybridization to detect nucleic acid sequences in morphologically intact cells
US4822566A (en) * 1985-11-19 1989-04-18 The Johns Hopkins University Optimized capacitive sensor for chemical analysis and measurement
US4868105A (en) 1985-12-11 1989-09-19 Chiron Corporation Solution phase nucleic acid sandwich assay
US4882269A (en) 1985-12-13 1989-11-21 Princeton University Amplified hybridization assay
US4637861A (en) * 1985-12-16 1987-01-20 Allied Corporation Stabilized, lipid membrane-based device and method of analysis
EP0232967B1 (en) 1986-01-10 1993-04-28 Amoco Corporation Competitive homogeneous assay
US5447841A (en) 1986-01-16 1995-09-05 The Regents Of The Univ. Of California Methods for chromosome-specific staining
US4855225A (en) 1986-02-07 1989-08-08 Applied Biosystems, Inc. Method of detecting electrophoretically separated oligonucleotides
US4758727A (en) 1986-02-12 1988-07-19 Ohio State University Research Foundation Method and apparatus for the measurement of low-level laser-induced fluorescence
JPH0685387B2 (ja) 1986-02-14 1994-10-26 株式会社東芝 位置合わせ方法
US4868103A (en) 1986-02-19 1989-09-19 Enzo Biochem, Inc. Analyte detection by means of energy transfer
NO870613L (no) 1986-03-05 1987-09-07 Molecular Diagnostics Inc Deteksjon av mikroorganismer i en prŸve inneholdende nukleinsyre.
EP0240729A3 (en) * 1986-03-05 1988-08-24 Fuji Photo Film Co., Ltd. Method of analyzing autoradiograph for determining base sequence of nucleic acid
US5348855A (en) 1986-03-05 1994-09-20 Miles Inc. Assay for nucleic acid sequences in an unpurified sample
US4925785A (en) 1986-03-07 1990-05-15 Biotechnica Diagnostics, Inc. Nucleic acid hybridization assays
US4728591A (en) * 1986-03-07 1988-03-01 Trustees Of Boston University Self-assembled nanometer lithographic masks and templates and method for parallel fabrication of nanometer scale multi-device structures
US5310893A (en) 1986-03-31 1994-05-10 Hoffmann-La Roche Inc. Method for HLA DP typing
US5604099A (en) 1986-03-13 1997-02-18 Hoffmann-La Roche Inc. Process for detecting specific nucleotide variations and genetic polymorphisms present in nucleic acids
CA1284931C (en) 1986-03-13 1991-06-18 Henry A. Erlich Process for detecting specific nucleotide variations and genetic polymorphisms present in nucleic acids
US4894796A (en) * 1986-03-17 1990-01-16 Westinghouse Electric Corp. Automatic transfer switch with programmable display
US5256549A (en) 1986-03-28 1993-10-26 Chiron Corporation Purification of synthetic oligomers
US5153319A (en) 1986-03-31 1992-10-06 University Patents, Inc. Process for preparing polynucleotides
US4875169A (en) 1986-04-11 1989-10-17 Iowa State University Research Foundation, Inc. Method for improving the limit of detection in a data signal
US4981783A (en) 1986-04-16 1991-01-01 Montefiore Medical Center Method for detecting pathological conditions
US4846552A (en) 1986-04-16 1989-07-11 The United States Of America As Represented By The Secretary Of The Air Force Method of fabricating high efficiency binary planar optical elements
US4857656A (en) * 1986-05-08 1989-08-15 Sanshin Kagaku Kogyo Co., Ltd. Active esters used for production of esters or amides and process for producing esters or amides
GB8612221D0 (en) * 1986-05-20 1986-06-25 Amersham Int Plc Assaying species in sample
US4811218A (en) 1986-06-02 1989-03-07 Applied Biosystems, Inc. Real time scanning electrophoresis apparatus for DNA sequencing
US4808508A (en) * 1986-07-01 1989-02-28 Hoechst Celanese Corporation Negative working color proofing process comprising diazo compound and polyvinyl acetal/polyvinyl alcohol/polyvinyl acetate resin
AU614935B2 (en) 1986-08-06 1991-09-19 Multilyte Limited Determination of analyte concentration using two labelling markers
US4786684A (en) * 1986-08-21 1988-11-22 The Mount Sinai School Of Medicine Of The City University Of New York Benzylthioether-linked solid support-bound thiol compounds and method for peptide synthesis
GB8621337D0 (en) * 1986-09-04 1986-10-15 Agricultural Genetics Co Non-radioactive nucleic acid hybridization probes
DE3631662A1 (de) * 1986-09-17 1988-03-24 Biotechnolog Forschung Gmbh Verfahren zur simultanen synthese mehrerer peptide an fester phase
JPS6384499A (ja) * 1986-09-26 1988-04-15 Toho Yakuhin Kogyo Kk 酵素によるデルタ睡眠誘発ペプチドの製造法
US5021550A (en) 1986-10-07 1991-06-04 Thomas Jefferson University Method for preventing deletion sequences in solid phase synthesis
GB8624637D0 (en) 1986-10-14 1986-11-19 Emi Plc Thorn Electrical device
US4979959A (en) * 1986-10-17 1990-12-25 Bio-Metric Systems, Inc. Biocompatible coating for solid surfaces
US4877745A (en) 1986-11-17 1989-10-31 Abbott Laboratories Apparatus and process for reagent fluid dispensing and printing
US5028525A (en) 1986-11-24 1991-07-02 Regents Of The University Of California Method of preparing and applying single stranded DNA probes to double stranded target DNAs in situ
AU636562B2 (en) * 1986-12-15 1993-05-06 British Technology Group Usa, Inc. Monomeric phthalocyanine reagents
JPS63167313A (ja) 1986-12-27 1988-07-11 Hitachi Ltd 自動焦点制御方法
JPH0664057B2 (ja) * 1987-01-06 1994-08-22 富士写真フイルム株式会社 オ−トラジオグラフ解析のための信号処理方法
US4762881A (en) * 1987-01-09 1988-08-09 E. I. Du Pont De Nemours And Company Photoreactive benzoylphenylalanines and related peptides
US5077085A (en) 1987-03-06 1991-12-31 Schnur Joel M High resolution metal patterning of ultra-thin films on solid substrates
US5079600A (en) * 1987-03-06 1992-01-07 Schnur Joel M High resolution patterning on solid substrates
US5037882A (en) 1987-03-11 1991-08-06 Steel Samuel L Synthesis of oligonucleotide analogs
US5026773A (en) 1987-03-11 1991-06-25 Samuel Steel Apparatus for a solid phase synthesis of peptide analogs
AU601021B2 (en) 1987-03-11 1990-08-30 Molecular Diagnostics, Inc. Assay for necleic acid sequences in a sample
US4794150A (en) * 1987-03-11 1988-12-27 Samuel Steel Synthesis of peptide analogs
JPS63223557A (ja) 1987-03-13 1988-09-19 Nec Corp 半導体バイオセンサの製造方法
US5525464A (en) 1987-04-01 1996-06-11 Hyseq, Inc. Method of sequencing by hybridization of oligonucleotide probes
US6270961B1 (en) 1987-04-01 2001-08-07 Hyseq, Inc. Methods and apparatus for DNA sequencing and DNA identification
US5202231A (en) 1987-04-01 1993-04-13 Drmanac Radoje T Method of sequencing of genomes by hybridization of oligonucleotide probes
NZ224284A (en) * 1987-04-24 1990-11-27 Unilever Plc Porous substrate containing gel for use in chemical synthesis, separation etc
US5100777A (en) 1987-04-27 1992-03-31 Tanox Biosystems, Inc. Antibody matrix device and method for evaluating immune status
US4833332A (en) * 1987-06-12 1989-05-23 E. I. Du Pont De Nemours And Company Scanning fluorescent detection system
SE458968B (sv) 1987-06-16 1989-05-22 Wallac Oy Biospecifikt analysfoerfarande foer flera analyter i vilket ingaar partikelraekning och maerkning med fluorescerande maerksubstanser
US4874500A (en) 1987-07-15 1989-10-17 Sri International Microelectrochemical sensor and sensor array
US4921805A (en) 1987-07-29 1990-05-01 Life Technologies, Inc. Nucleic acid capture method
GB8803000D0 (en) 1988-02-10 1988-03-09 Ekins Roger Philip Determination of ambient concentrations of several analytes
US5149625A (en) 1987-08-11 1992-09-22 President And Fellows Of Harvard College Multiplex analysis of DNA
CA1321488C (en) * 1987-08-22 1993-08-24 Martin Francis Finlan Biological sensors
US5011770A (en) 1987-09-04 1991-04-30 Molecular Devices, Inc. DNA detection method
US4923901A (en) * 1987-09-04 1990-05-08 Millipore Corporation Membranes with bound oligonucleotides and peptides
US5006464A (en) 1987-10-01 1991-04-09 E-Y Laboratories, Inc. Directed flow diagnostic device and method
US4981985A (en) 1987-10-20 1991-01-01 Trustees Of The University Of Pennsylvania Synthesis of photolabile chelators for multivalent cations
AU2635088A (en) * 1987-12-04 1989-06-08 Du Pont Merck Pharmaceutical Company, The Immobilized interleukin 2 and interleukin 2 containing a carboxyl-terminal extension
US4886741A (en) * 1987-12-09 1989-12-12 Microprobe Corporation Use of volume exclusion agents for the enhancement of in situ hybridization
CA1335721C (en) * 1987-12-24 1995-05-30 Patrick E. Guire Biomolecule attached to a solid surface by means of a spacer and methods of attaching biomolecules to surfaces
US4844617A (en) 1988-01-20 1989-07-04 Tencor Instruments Confocal measuring microscope with automatic focusing
EP0328256A1 (en) * 1988-01-21 1989-08-16 Owens-Corning Fiberglas Corporation Glass fibers coated with agarose for use as column packing or chromatographic media for bioseparations
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
GB8810400D0 (en) 1988-05-03 1988-06-08 Southern E Analysing polynucleotide sequences
FR2628530B1 (fr) 1988-03-08 1994-01-28 Chemunex Sa Appareil et procede de detection et de numeration de particules fluorescentes, portees par un support solide
US4946942A (en) * 1988-03-11 1990-08-07 Bioresearch, Inc. Urethane-protected amino acid-N-carboxyanhydrides
US4988617A (en) 1988-03-25 1991-01-29 California Institute Of Technology Method of detecting a nucleotide change in nucleic acids
IL89964A0 (en) 1988-04-15 1989-12-15 Montefiore Med Center Method for determining malignant progression,cdna,polypeptides encoded thereby and pharmaceutical compositions containing the same
US5002867A (en) 1988-04-25 1991-03-26 Macevicz Stephen C Nucleic acid sequence determination by multiple mixed oligonucleotide probes
US5700637A (en) 1988-05-03 1997-12-23 Isis Innovation Limited Apparatus and method for analyzing polynucleotide sequences and method of generating oligonucleotide arrays
US6054270A (en) 1988-05-03 2000-04-25 Oxford Gene Technology Limited Analying polynucleotide sequences
ATE173508T1 (de) * 1988-05-20 1998-12-15 Hoffmann La Roche Befestigung von sequenzspezifischen proben
US5013669A (en) 1988-06-01 1991-05-07 Smithkline Diagnostics, Inc. Mass producible biologically active solid phase devices
US5108576A (en) * 1988-06-13 1992-04-28 Ohmicron Corporation Pyroelectric thermometric device
DE3923165A1 (de) 1988-07-15 1990-01-18 Hitachi Ltd Magnetplattenvorrichtung
DE3856430T2 (de) * 1988-07-22 2001-05-03 Surmodics, Inc. Herstellung von polymeren oberflächen
US5188963A (en) 1989-11-17 1993-02-23 Gene Tec Corporation Device for processing biological specimens for analysis of nucleic acids
US5281540A (en) * 1988-08-02 1994-01-25 Abbott Laboratories Test array for performing assays
US4992383A (en) 1988-08-05 1991-02-12 Porton Instruments, Inc. Method for protein and peptide sequencing using derivatized glass supports
US5225326A (en) 1988-08-31 1993-07-06 Research Development Foundation One step in situ hybridization assay
US5206137A (en) 1988-09-08 1993-04-27 Lifecodes Corporation Compositions and methods useful for genetic analysis
DE3880679D1 (de) 1988-09-14 1993-06-03 Siemens Ag Roentgendiagnostikeinrichtung mit einem speicherleucht- schirm.
GB8822228D0 (en) * 1988-09-21 1988-10-26 Southern E M Support-bound oligonucleotides
JP2897027B2 (ja) 1988-10-27 1999-05-31 スズキ株式会社 免疫学的凝集反応検出装置
SE8804074D0 (sv) * 1988-11-10 1988-11-10 Pharmacia Ab Sensorenhet och dess anvaendning i biosensorsystem
US5200051A (en) * 1988-11-14 1993-04-06 I-Stat Corporation Wholly microfabricated biosensors and process for the manufacture and use thereof
US5869237A (en) 1988-11-15 1999-02-09 Yale University Amplification karyotyping
US5215889A (en) 1988-11-18 1993-06-01 The Regents Of The University Of California Catalytic and reactive polypeptides and methods for their preparation and use
US5489507A (en) 1988-11-30 1996-02-06 Perkin-Elmer Corporation DNA detection by color complementation
US5047524A (en) 1988-12-21 1991-09-10 Applied Biosystems, Inc. Automated system for polynucleotide synthesis and purification
US4992583A (en) 1989-01-06 1991-02-12 The Goodyear Tire & Rubber Company Process for synthesizing N-chlorothio-sulfonamides
US5077210A (en) 1989-01-13 1991-12-31 Eigler Frances S Immobilization of active agents on substrates with a silane and heterobifunctional crosslinking agent
US4984857A (en) 1989-01-17 1991-01-15 Iowa State University Research Foundation, Inc. Linearization of scan velocity of resonant vibrating-mirror beam deflectors
US4921348A (en) 1989-01-26 1990-05-01 Iowa State University Research Foundation, Inc. Method and means for a spatial and temporal probe for laser-generated plumes based on density gradients
IT1232252B (it) 1989-02-22 1992-01-28 Rotta Research Lab Derivati della n fenil benzamide ad attivita' antiulcera ed antiallerica e procedimento per la loro preparazione
US5081584A (en) 1989-03-13 1992-01-14 United States Of America Computer-assisted design of anti-peptides based on the amino acid sequence of a target peptide
EP0392546A3 (en) 1989-04-14 1991-09-11 Ro Institut Za Molekularnu Genetiku I Geneticko Inzenjerstvo Process for determination of a complete or a partial contents of very short sequences in the samples of nucleic acids connected to the discrete particles of microscopic size by hybridization with oligonucleotide probes
US5112962A (en) 1989-04-19 1992-05-12 Northwestern University Labile anchors for solid phase polynucleotide synthesis
US5219726A (en) 1989-06-02 1993-06-15 The Salk Institute For Biological Studies Physical mapping of complex genomes
US5744101A (en) 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US6379895B1 (en) * 1989-06-07 2002-04-30 Affymetrix, Inc. Photolithographic and other means for manufacturing arrays
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5424186A (en) 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
US5547839A (en) * 1989-06-07 1996-08-20 Affymax Technologies N.V. Sequencing of surface immobilized polymers utilizing microflourescence detection
US5800992A (en) * 1989-06-07 1998-09-01 Fodor; Stephen P.A. Method of detecting nucleic acids
US6346413B1 (en) 1989-06-07 2002-02-12 Affymetrix, Inc. Polymer arrays
US5527681A (en) 1989-06-07 1996-06-18 Affymax Technologies N.V. Immobilized molecular synthesis of systematically substituted compounds
US5242974A (en) 1991-11-22 1993-09-07 Affymax Technologies N.V. Polymer reversal on solid surfaces
US6406844B1 (en) 1989-06-07 2002-06-18 Affymetrix, Inc. Very large scale immobilized polymer synthesis
GB2233654A (en) 1989-07-07 1991-01-16 Nat Res Dev Immobilised polynucleotides
DE3924454A1 (de) 1989-07-24 1991-02-07 Cornelis P Prof Dr Hollenberg Die anwendung von dna und dna-technologie fuer die konstruktion von netzwerken zur verwendung in der chip-konstruktion und chip-produktion (dna chips)
US5061075A (en) 1989-08-07 1991-10-29 Alfano Robert R Optical method and apparatus for diagnosing human spermatozoa
US5141813A (en) 1989-08-28 1992-08-25 Clontech Laboratories, Inc. Multifunctional controlled pore glass reagent for solid phase oligonucleotide synthesis
US5196305A (en) * 1989-09-12 1993-03-23 Eastman Kodak Company Diagnostic and amplification methods using primers having thymine at 3' end to overcome primer-target mismatch at the 3' end
EP0498801B1 (en) * 1989-09-15 1998-11-04 Chiron Mimotopes Pty. Ltd. Solid surface for peptide synthesis
US5232829A (en) 1989-09-29 1993-08-03 Hoffmann-La Roche Inc. Detection of chlamydia trachomatis by polymerase chain reaction using biotin labelled lina primers and capture probes
US5252743A (en) 1989-11-13 1993-10-12 Affymax Technologies N.V. Spatially-addressable immobilization of anti-ligands on surfaces
US5297288A (en) * 1989-11-28 1994-03-22 United States Biochemical Corporation System for use with a high resolution scanner for scheduling a sequence of software tools for determining the presence of bands in DNA sequencing samples
US5215882A (en) 1989-11-30 1993-06-01 Ortho Diagnostic Systems, Inc. Method of immobilizing nucleic acid on a solid surface for use in nucleic acid hybridization assays
FI896202A (fi) * 1989-12-22 1991-06-23 Ahlstroem Valmet Metod och anordning vid inloppslaodan av en pappers-, kartong- eller torkmaskin.
US5091652A (en) 1990-01-12 1992-02-25 The Regents Of The University Of California Laser excited confocal microscope fluorescence scanner and method
US5192407A (en) 1990-01-30 1993-03-09 Iowa State University Research Foundation, Inc. Means and method of detection in chemical separation procedures
US6506558B1 (en) * 1990-03-07 2003-01-14 Affymetrix Inc. Very large scale immobilized polymer synthesis
US5494810A (en) 1990-05-03 1996-02-27 Cornell Research Foundation, Inc. Thermostable ligase-mediated DNA amplifications system for the detection of genetic disease
US5100626A (en) 1990-05-24 1992-03-31 Levin Andrew E Binding assay device with removable cassette and manifold
GB9014263D0 (en) 1990-06-27 1990-08-15 Dixon Arthur E Apparatus and method for spatially- and spectrally- resolvedmeasurements
GB9015793D0 (en) 1990-07-18 1990-09-05 Medical Res Council Confocal scanning optical microscope
US5306641A (en) 1990-07-27 1994-04-26 Saccocio Edward J Apparatus and method for determining gel rate of polymerizable compositions
US5235028A (en) 1990-08-31 1993-08-10 University Of Minnesota Polyethylene glycol derivatives for solid-phase applications
US5491224A (en) * 1990-09-20 1996-02-13 Bittner; Michael L. Direct label transaminated DNA probe compositions for chromosome identification and methods for their manufacture
EP0562025B1 (en) 1990-12-06 2001-02-07 Affymetrix, Inc. (a Delaware Corporation) Compounds and their use in a binary synthesis strategy
DK0834575T3 (da) * 1990-12-06 2002-04-02 Affymetrix Inc A Delaware Corp Identifikation af nucleinsyrer i prøver
RU1794088C (ru) 1991-03-18 1993-02-07 Институт Молекулярной Биологии Ан@ Ссср Способ определени нуклеотидной последовательности ДНК и устройство дл его осуществлени
US5380489A (en) * 1992-02-18 1995-01-10 Eastman Kodak Company Element and method for nucleic acid amplification and detection using adhered probes
US5198871A (en) 1991-06-18 1993-03-30 Southwest Research Institute Laser-induced-fluorescence inspection of jet fuels
US5491570A (en) * 1991-07-26 1996-02-13 Accuwave Corporation Methods and devices for using photorefractive materials at infrared wavelengths
WO1993002992A1 (en) 1991-08-07 1993-02-18 H & N Instruments, Inc. Synthesis of chain chemical compounds
US5474796A (en) 1991-09-04 1995-12-12 Protogene Laboratories, Inc. Method and apparatus for conducting an array of chemical reactions on a support surface
US5291763A (en) * 1991-09-18 1994-03-08 Cuisinot Charles P Universal lock for quick release mechanism
US5556961A (en) 1991-11-15 1996-09-17 Foote; Robert S. Nucleosides with 5'-O-photolabile protecting groups
US5846708A (en) 1991-11-19 1998-12-08 Massachusetts Institiute Of Technology Optical and electrical methods and apparatus for molecule detection
US5384261A (en) 1991-11-22 1995-01-24 Affymax Technologies N.V. Very large scale immobilized polymer synthesis using mechanically directed flow paths
ATE241426T1 (de) * 1991-11-22 2003-06-15 Affymetrix Inc A Delaware Corp Verfahren zur herstellung von polymerarrays
US5324633A (en) 1991-11-22 1994-06-28 Affymax Technologies N.V. Method and apparatus for measuring binding affinity
US5667667A (en) 1992-04-24 1997-09-16 Isis Innovation Limited Electrochemical treatment of surfaces
GB9218131D0 (en) 1992-08-26 1992-10-14 Slater James H A method of marking a liquid
US5288514A (en) * 1992-09-14 1994-02-22 The Regents Of The University Of California Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support
US5386221A (en) * 1992-11-02 1995-01-31 Etec Systems, Inc. Laser pattern generation apparatus
US5837832A (en) 1993-06-25 1998-11-17 Affymetrix, Inc. Arrays of nucleic acid probes on biological chips
US5382512A (en) * 1993-08-23 1995-01-17 Chiron Corporation Assay device with captured particle reagent
US5381224A (en) 1993-08-30 1995-01-10 A. E. Dixon Scanning laser imaging system
JPH0772378A (ja) 1993-09-02 1995-03-17 Nikon Corp 合焦装置
ES2176308T3 (es) 1993-10-28 2002-12-01 Houston Advanced Res Ct Dispositivo de microestructura porosa que permite un flujo.
US5578832A (en) 1994-09-02 1996-11-26 Affymetrix, Inc. Method and apparatus for imaging a sample on a device
US5571639A (en) 1994-05-24 1996-11-05 Affymax Technologies N.V. Computer-aided engineering system for design of sequence arrays and lithographic masks
US5807522A (en) 1994-06-17 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods for fabricating microarrays of biological samples
US5727098A (en) * 1994-09-07 1998-03-10 Jacobson; Joseph M. Oscillating fiber optic display and imager
US5830645A (en) 1994-12-09 1998-11-03 The Regents Of The University Of California Comparative fluorescence hybridization to nucleic acid arrays
US5776737A (en) 1994-12-22 1998-07-07 Visible Genetics Inc. Method and composition for internal identification of samples
US6673533B1 (en) * 1995-03-10 2004-01-06 Meso Scale Technologies, Llc. Multi-array multi-specific electrochemiluminescence testing
US5707806A (en) 1995-06-07 1998-01-13 Genzyme Corporation Direct sequence identification of mutations by cleavage- and ligation-associated mutation-specific sequencing
US5777888A (en) 1995-08-09 1998-07-07 Regents Of The University Of California Systems for generating and analyzing stimulus-response output signal matrices
US5698393A (en) 1995-08-18 1997-12-16 Abbott Laboratories Method for elimination of rheumatoid factor interference in diagnostic assays
US5871697A (en) 1995-10-24 1999-02-16 Curagen Corporation Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing
WO1999042813A1 (en) * 1998-02-23 1999-08-26 Wisconsin Alumni Research Foundation Method and apparatus for synthesis of arrays of dna probes
US6306643B1 (en) * 1998-08-24 2001-10-23 Affymetrix, Inc. Methods of using an array of pooled probes in genetic analysis
US6346423B1 (en) * 1999-07-16 2002-02-12 Agilent Technologies, Inc. Methods and compositions for producing biopolymeric arrays
US6171797B1 (en) * 1999-10-20 2001-01-09 Agilent Technologies Inc. Methods of making polymeric arrays

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