JP2022000050A - 核酸の解析のための方法及び組成物 - Google Patents
核酸の解析のための方法及び組成物 Download PDFInfo
- Publication number
- JP2022000050A JP2022000050A JP2021161303A JP2021161303A JP2022000050A JP 2022000050 A JP2022000050 A JP 2022000050A JP 2021161303 A JP2021161303 A JP 2021161303A JP 2021161303 A JP2021161303 A JP 2021161303A JP 2022000050 A JP2022000050 A JP 2022000050A
- Authority
- JP
- Japan
- Prior art keywords
- sample
- nucleic acid
- sequence
- compartment
- nucleic acids
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6809—Methods for determination or identification of nucleic acids involving differential detection
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
- C12Q2525/10—Modifications characterised by
- C12Q2525/155—Modifications characterised by incorporating/generating a new priming site
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
- C12Q2525/10—Modifications characterised by
- C12Q2525/191—Modifications characterised by incorporating an adaptor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2543/00—Reactions characterised by the reaction site, e.g. cell or chromosome
- C12Q2543/10—Reactions characterised by the reaction site, e.g. cell or chromosome the purpose being "in situ" analysis
- C12Q2543/101—Reactions characterised by the reaction site, e.g. cell or chromosome the purpose being "in situ" analysis in situ amplification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2563/00—Nucleic acid detection characterized by the use of physical, structural and functional properties
- C12Q2563/149—Particles, e.g. beads
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2563/00—Nucleic acid detection characterized by the use of physical, structural and functional properties
- C12Q2563/159—Microreactors, e.g. emulsion PCR or sequencing, droplet PCR, microcapsules, i.e. non-liquid containers with a range of different permeability's for different reaction components
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2563/00—Nucleic acid detection characterized by the use of physical, structural and functional properties
- C12Q2563/179—Nucleic acid detection characterized by the use of physical, structural and functional properties the label being a nucleic acid
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2565/00—Nucleic acid analysis characterised by mode or means of detection
- C12Q2565/60—Detection means characterised by use of a special device
- C12Q2565/631—Detection means characterised by use of a special device being a biochannel or pore
Abstract
Description
本出願は、2015年12月4日に出願された米国仮特許出願第62/263,532号の利益を主張し、あらゆる目的のためにその全体が参照によって本明細書に組み入れられる。
本開示は遺伝物質の特徴付けのための方法、組成物及びシステムを提供する。一般に、本明細書に記載されている方法、組成物及びシステムは、それらが元々試料に存在したときのそれらの成分の構造コンテクストと同様に分子コンテクストに関する情報を保持しながら試料の成分を解析する方法を提供する。本明細書の議論の多くは核酸の解析という点であるが、本明細書で議論されている方法及びシステムは、タンパク質及び他の分子を含む試料の他の成分に適用するように適応させることができることが理解されるであろう。
1つの例示的な態様では、本開示に記載されている方法及びシステムは試料を個別区画に入れることまたは区画化することを提供し、その際、各区画は他の区画における内容物からのそれ自体の内容物の分離を維持する。本明細書でさらに詳細に議論されるように、試料は、たとえば、細胞または組織の試料のような患者に由来する試料を含んでもよく、それは核酸を含有することができ、特定の状況では、関連するタンパク質を同様に含有することができる。具体的な態様では、本明細書に記載されている方法で使用される試料には、ホルマリンで固定し、パラフィンで包埋した(FFPE)細胞及び組織の試料等、と同様に試料の分解のリスクが高い他の試料の種類が含まれる。
本開示は遺伝物質の特徴付けのための方法、組成物及びシステムを提供する。一般に、本明細書に記載されている方法、組成物及びシステムは、成分が元々試料に存在したときのそれら成分の構造コンテクストと同様に分子コンテクストに関する情報を保持しながら、試料の成分を解析する方法を提供する。言い換えれば、本明細書の記載は一般に、たとえば、ホルマリンで固定されパラフィンに包埋された試料のような、当該技術分野で既知の方法を用いて固定されているまたは固定される組織試料を含む試料における核酸の空間的な検出に関する。理解されるように、このセクションで記載されている方法のいずれかは、「概説」及び「作業の流れの概説」と題するセクションで上述された方法のいずれかと同様に本明細書の後に続くセクションに記載されている核酸の配列決定法と組み合わせることができる。
本明細書に記載されている方法、組成物及びシステムは核酸の配列決定法で特に使用し易い。短い読み取り及び長い読み取りの配列決定法を含むそのような配列決定法には当該技術分野で既知の技法を挙げることができる。特定の態様では、本明細書に記載されている方法、組成物及びシステムは短い読み取りで精度の高い配列決定法にて使用される。
理解されるように、本明細書で議論されている方法及びシステムを用いて任意の種類のゲノム物質から配列情報を得ることができる。そのようなゲノム物質は患者から採取された試料から得られてもよい。本明細書で議論されている方法及びシステムで使用される例示的な試料及びゲノム物質の種類には限定しないで、ポリヌクレオチド、核酸、オリゴヌクレオチド、循環している無細胞核酸、循環している腫瘍細胞(CTC)、核酸断片、ヌクレオチド、DNA、RNA、ペプチドポリヌクレオチド、相補性のDNA(cDNA)、二本鎖DNA(dsDNA)、一本鎖DNA(ssDNA)、プラスミドDNA、コスミドDNA、染色体DNA、ゲノムDNA(gDNA)、ウイルスDNA、細菌DNA、mtDNA(ミトコンドリアDNA)、リボソームRNA、無細胞DNA、無細胞胎児性DNA(cffDNA)、mRNA、rRNA、tRNA、nRNA、siRNA、snRNA、snoRNA、scaRNA、マイクロRNA、dsRNA、ウイルスRNA、等が挙げられる。要約すれば、使用される試料は特定の処理の必要性に応じて変化してもよい。
一部の態様では、本開示は構造コンテクストを維持しながら核酸を解析する方法を提供する。そのような方法には、(a)核酸が三次元構造を含む核酸を含有する試料を提供するステップと、(b)核酸の三次元構造の一部も個別区画に分離されるように試料の一部を個別区画に分離するステップと、(c)核酸から配列情報を入手し、それによって構造コンテクストを維持しながら核酸を解析するステップとが含まれる。
試料の調製方法を改変してFFPE試料から長いDNA分子を提供した。図7は例示的な作業の流れを説明しており、ゲノム全体の配列決定(WGS)及びエキソーム全体の配列決定(WES)双方のためのFFPE試料を調製するための改変が示されている。たとえば、DNA抽出の後、標準の熱サイクルプロトコールは701で改変されて98度の変性ステップを各サイクルの終了から開始に移した。加えて、70度の保持を各サイクルの終了時に2分間加えた。
FFPE試料(スライド上のFFPE試料を含むことができる)は、たとえば、DNAのマイクロアレイプリンティングで使用されるもののような空間的に十分に定義されたパターンで適用されるDNAバーコードでタグ付けすることができる。DNAバーコード(以後バーコード1と呼ぶ)は、それがその後のステップで拡散してしまわないように、またはFFPE試料に共有結合で適用されるように長い。バーコード付けDNAがFFPEスライドに埋め込まれるのを可能にするために、試料を加熱し、次いでバーコードを加える。異なるバーコードがスライドの異なる部分で提供されるように、バーコードは一般にバーコードのライブラリである。バーコードを異なる集団でスライドの異なる部分に加えて地理的コード化に役立ててもよく―その状況では、バーコードのライブラリは同一のバーコードまたは異なるバーコードを含んでもよい。バーコードを加えた後、次いでスライドを冷却し、一般にたとえば、レーザー微細切断、機械的/音響的手段等を用いた方法での切断を介して小分けする。バーコードの代わりに蛍光色素分子またはQdotsを使用してもよいが、バーコード付けは、局所の空間的情報(たとえば、腫瘍対正常細胞)を保持しながら、試料部分の大規模に平行な無作為封入を可能にする。
Claims (85)
- 構造コンテクストを維持しながら核酸を解析する方法であって、前記方法が
(a)核酸を含む試料を提供し、前記核酸が三次元構造を含むことと、
(b)前記核酸の三次元構造の一部も個別区画に分離されるように前記試料の一部を前記個別区画に分離することと、
(c)前記核酸から配列情報を入手し、それによって構造コンテクストを維持しながら核酸を解析することとを含む、前記方法。 - 入手するステップ(c)に由来する前記配列情報が前記試料にて互いに空間的に近接し合っていた核酸の特定を含む、請求項1に記載の方法。
- 前記入手するステップ(c)がゲノム遺伝子座間での染色体内及び/または染色体間の相互作用に関する情報を提供する、請求項1〜2に記載の方法。
- 前記入手するステップ(c)が染色体の高次構造に関する情報を提供する、請求項1〜2に記載の方法。
- 分離するステップ(b)に先立って、前記三次元構造の少なくとも一部が処理されて前記三次元構造内で互いに近接し合う前記核酸の異なる部分を連結する、請求項1〜4に記載の方法。
- 前記試料がホルマリン固定したパラフィン試料である、請求項1〜5に記載の方法。
- 前記核酸が前記分離するステップ(b)に先立って前記試料から単離されない、請求項1〜6に記載の方法。
- 前記個別区画がビーズを含む、請求項1〜7に記載の方法。
- 前記ビーズがゲルビーズである、請求項8に記載の方法。
- 前記入手するステップ(c)に先立って、前記個別区画内の前記核酸にバーコードを付け、複数のバーコード付き断片を形成し、所与の個別区画内の断片はそれぞれ共通のバーコードを含むので、前記バーコードによって所与の区画に由来する核酸が特定される、請求項1〜9に記載の方法。
- 前記入手するステップ(c)が、短い読み取り長さの配列決定反応及び長い読み取り長さの配列決定反応から成る群から選択される配列決定反応を含む、請求項1〜10に記載の方法。
- 前記試料が腫瘍試料を含む、請求項1〜11に記載の方法。
- 前記試料が腫瘍細胞と正常細胞の混合物を含む、請求項1〜11に記載の方法。
- 前記試料が核基質を含む、請求項1〜13に記載の方法。
- 前記核酸がRNAを含む、請求項1〜14に記載の方法。
- 試料内で核酸の構造コンテクストを維持しながら前記試料に由来する核酸を解析する方法であって、前記方法が
(a)空間的に隣接する核酸セグメントが連結されるように前記試料内で連結された核酸を形成することと、
(b)前記連結された核酸を処理して複数のライゲーション産物を作り出し、前記ライゲーション産物が前記空間的に隣接する核酸セグメントの一部を含有することと、
(c)前記複数のライゲーション産物を個別区画に入れることと、
(d)前記個別区画内の前記ライゲーション産物にバーコードを付けて複数のバーコード付き断片を形成し、所与の個別区画内の断片はそれぞれ共通のバーコードを含み、それによって、各断片をそれが由来する連結された核酸に関連付けることと、
(e)前記複数のバーコード付き断片から配列情報を入手し、それによって、構造コンテクストを維持しながら前記試料に由来する核酸を解析することとを含む、前記方法。 - 前記処理するステップ(b)が分子内ライゲーションに都合が良い条件下で平滑末端ライゲーションを含むので、前記空間的に隣接する核酸セグメントは同じ分子内でライゲーションされる、請求項16に記載の方法。
- 分子内ライゲーションに都合が良い前記条件が、前記試料を希釈して前記核酸の濃度を10ng/μL未満に減らすことを含む、請求項17に記載の方法。
- 前記試料がホルマリン固定したパラフィン試料である、請求項16〜18に記載の方法。
- 前記試料が核基質を含む、請求項16〜18に記載の方法。
- 前記核酸がRNAを含む、請求項16〜20に記載の方法。
- ステップ(a)に先立って前記核酸が前記試料から単離されない、請求項16〜21に記載の方法。
- ステップ(a)に先立って、関連するDNA結合タンパク質が前記核酸に結合したままであるように前記核酸を免疫沈降させる、請求項16〜21に記載の方法。
- 前記試料における前記核酸の量が50ng/ml未満である、請求項16〜23に記載の方法。
- 前記区画がビーズを含む、請求項16〜24に記載の方法。
- 前記ビーズがゲルビーズである、請求項25に記載の方法。
- 前記試料が腫瘍試料を含む、請求項16〜26に記載の方法。
- 前記試料が腫瘍細胞と正常細胞の混合物を含む、請求項16〜27に記載の方法。
- 前記処理するステップが前記ライゲーション産物を形成することに続く連結することの破棄を含む、請求項16〜28に記載の方法。
- 前記入手するステップ(e)がゲノム遺伝子座間での染色体内及び/または染色体間の相互作用に関する情報を提供する、請求項16〜29に記載の方法。
- 前記入手するステップ(e)が染色体の高次構造に関する情報を提供する、請求項16〜29に記載の方法。
- 前記染色体の高次構造が病状に関連付けられる、請求項31に記載の方法。
- 前記処理するステップが、前記試料にて元々空間的に密に近接し合っていた核酸を含むライゲーション産物を生じる、請求項16〜32に記載の方法。
- 前記入手するステップ(e)が、短い読み取り長さの配列決定反応及び長い読み取り長さの配列決定反応から成る群から選択される配列決定反応を含む、請求項16〜33に記載の方法。
- 前記配列決定反応が短い読み取りで精度の高い配列決定反応である、請求項34に記載の方法。
- 前記形成するステップ(a)が前記試料にて核酸を架橋することを含む、請求項16〜35に記載の方法。
- 前記形成するステップ(a)が空間的に隣接する核酸セグメント間で共有結合を生じる、請求項16〜36に記載の方法。
- 試料内での核酸の構造コンテクストを維持しながら、前記試料に由来する核酸を解析する方法であって、前記方法が、
(a)空間的に隣接する核酸セグメントが連結されるように前記試料内に連結された核酸を形成することと、
(b)前記連結された核酸を個別区画に入れることと、
(c)前記連結された核酸を処理して複数のライゲーション産物を作り出し、前記ライゲーション産物が前記空間的に隣接する核酸セグメントの一部を含有することと、
(d)前記個別区画内の前記ライゲーション産物にバーコードを付けて複数のバーコード付き断片を形成し、所与の個別区画内の断片はそれぞれ共通のバーコードを含み、それによって、各断片をそれが由来する前記連結された核酸に関連付けることと、
(e)前記複数のバーコード付き断片から配列情報を入手し、それによって、構造コンテクストを維持しながら前記試料に由来する核酸を解析することとを含む、前記方法。 - 前記処理するステップ(c)が分子内ライゲーションに都合が良い条件下で平滑末端ライゲーションを含むので、前記空間的に隣接する核酸セグメントは同じ分子内でライゲーションされる、請求項38に記載の方法。
- 前記試料がホルマリン固定したパラフィン試料である、請求項38〜39に記載の方法。
- 前記試料が核基質を含む、請求項38〜39に記載の方法。
- 前記核酸がRNAを含む、請求項38〜41に記載の方法。
- ステップ(a)に先立って前記核酸が前記試料から単離されない、請求項38〜42に記載の方法。
- ステップ(a)に先立って、関連するDNA結合タンパク質が前記核酸に結合したままであるように前記核酸を免疫沈降させる、請求項38〜42に記載の方法。
- 前記区画がビーズを含む、請求項38〜44に記載の方法。
- 前記ビーズがゲルビーズである、請求項45に記載の方法。
- 前記試料が腫瘍試料を含む、請求項38〜46に記載の方法。
- 前記試料が腫瘍細胞と正常細胞の混合物を含む、請求項38〜46に記載の方法。
- 前記処理するステップ(c)が、前記試料にて元々空間的に密に近接し合っていた核酸を含むライゲーション産物を生じる、請求項38〜48に記載の方法。
- 前記入手するステップ(e)がゲノム遺伝子座間での染色体内及び/または染色体間の相互作用に関する情報を提供する、請求項38〜49に記載の方法。
- 前記入手するステップ(e)が、短い読み取り長さの配列決定反応及び長い読み取り長さの配列決定反応から成る群から選択される配列決定反応を含む、請求項38〜50に記載の方法。
- 前記配列決定反応が短い読み取りで精度の高い配列決定反応である、請求項51に記載の方法。
- 試料内での核酸の構造コンテクストを維持しながら、前記試料に由来する核酸を解析する方法であって、前記方法が、
(a)前記試料内の核酸を架橋して架橋した核酸を形成し、前記架橋が空間的に隣接する核酸セグメント間で共有結合を形成することと、
(b)前記架橋した核酸を個別区画に入れることと、
(c)前記架橋した核酸を処理して複数のライゲーション産物を作り出し、前記ライゲーション産物が前記空間的に隣接する核酸セグメントの一部を含有することと、
(d)前記複数のライゲーション産物から配列情報を入手し、それによって、構造コンテクストを維持しながら前記試料に由来する核酸を解析することとを含む、前記方法。 - 前記処理するステップ(b)が分子内ライゲーションに都合が良い条件下で平滑末端ライゲーションを含むので、前記空間的に隣接する核酸セグメントは同じ分子内でライゲーションされる、請求項53に記載の方法。
- 前記試料がホルマリン固定したパラフィン試料である、請求項53〜54に記載の方法。
- 前記試料が核基質を含む、請求項53〜54に記載の方法。
- 前記核酸がRNAを含む、請求項53〜56に記載の方法。
- 前記架橋するステップ(a)に先立って前記核酸が前記試料から単離されない、請求項53〜57に記載の方法。
- 前記架橋するステップ(a)に先立って、関連するDNA結合タンパク質が前記核酸に結合したままであるように前記核酸を免疫沈降させる、請求項53〜57に記載の方法。
- 前記入手するステップ(d)に先立って、前記ライゲーション産物がバーコードに関連付けられる、請求項53〜59に記載の方法。
- 同一区画内のライゲーション産物が共通のバーコードを受け取るので、前記バーコードによって所与の区画に由来するライゲーション産物が特定される、請求項60に記載の方法。
- 前記入手するステップ(d)が、短い読み取り長さの配列決定反応及び長い読み取り長さの配列決定反応から成る群から選択される配列決定反応を含む、請求項53〜61に記載の方法。
- 構造コンテクストを維持しながら核酸を解析する方法であって、前記方法が、
(a)核酸を含む試料を提供することと、
(b)前記試料の異なる地理的領域が異なるタグを受け取るように前記試料にタグのライブラリを適用することと、
(c)前記タグのライブラリの一部と前記核酸の一部も個別区画に分離されるように前記試料の一部を前記個別区画に分離することと、
(d)前記核酸から配列情報を入手することと、
(e)前記個別区画にてタグを特定し、それによって構造コンテクストを維持しながら核酸を解析することとを含む、前記方法。 - 前記タグのライブラリがオリゴヌクレオチドタグを含む、請求項63に記載の方法。
- 前記タグのライブラリがmRNAタグを含む、請求項63〜64に記載の方法。
- 前記適用するステップ(b)が拡散を介して達成される、請求項63〜65に記載の方法。
- 前記適用するステップ(b)が前記試料にて異なる空間的な位置で異なる集団のタグを生じる、請求項66に記載の方法。
- 前記特定するステップ(e)が前記個別区画にてタグの集団を決定することを含む、請求項67に記載の方法。
- 前記適用するステップ(b)が前記試料内での1以上の能動的過程を介して達成される、請求項63〜65に記載の方法。
- 前記試料における異なる空間的位置での同一タグの存在は、それらの異なる空間的位置における前記試料の要素が1以上の能動的過程を介して繋がれることを示す、請求項69に記載の方法。
- 前記1以上の能動的過程には細胞の輸送過程が含まれる、請求項69〜70に記載の方法。
- 前記適用するステップ(b)が前記タグのライブラリの異なる部分を前記試料の異なる空間的位置に無作為に分配することを含む、請求項63〜71に記載の方法。
- 前記適用するステップ(b)が前記タグのライブラリの所定の部分または集団を前記試料の特定された空間的位置に加えることを含む、請求項63〜71に記載の方法。
- 前記入手するステップ(d)及び前記特定するステップ(e)が同時に実施される、請求項63〜73に記載の方法。
- 前記入手するステップ(d)が、短い読み取り長さの配列決定反応及び長い読み取り長さの配列決定反応から成る群から選択される配列決定反応を含む、請求項63〜74に記載の方法。
- 前記配列決定反応が短い読み取りで精度の高い配列決定反応である、請求項75に記載の方法。
- 前記試料が腫瘍試料を含む、請求項63〜76に記載の方法。
- 前記試料が腫瘍細胞と正常細胞の混合物を含む、請求項63〜76に記載の方法。
- 前記試料がホルマリン固定したパラフィン試料である、請求項63〜76に記載の方法。
- 前記試料が核基質を含む、請求項63〜76に記載の方法。
- 前記核酸がRNAを含む、請求項63〜76に記載の方法。
- 前記区画がビーズを含む、請求項63〜82に記載の方法。
- 前記ビーズがゲルビーズである、請求項82に記載の方法。
- 前記個別区画における前記核酸の量が10ng/ml未満である、請求項63〜83に記載の方法。
- 前記個別区画における核酸の前記量が1ng/ml未満である、請求項63〜83に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562263532P | 2015-12-04 | 2015-12-04 | |
US62/263,532 | 2015-12-04 | ||
JP2018524457A JP6954899B2 (ja) | 2015-12-04 | 2016-12-02 | 核酸の解析のための方法及び組成物 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018524457A Division JP6954899B2 (ja) | 2015-12-04 | 2016-12-02 | 核酸の解析のための方法及び組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022000050A true JP2022000050A (ja) | 2022-01-04 |
JP7182679B2 JP7182679B2 (ja) | 2022-12-02 |
Family
ID=57714651
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018524457A Active JP6954899B2 (ja) | 2015-12-04 | 2016-12-02 | 核酸の解析のための方法及び組成物 |
JP2021161303A Active JP7182679B2 (ja) | 2015-12-04 | 2021-09-30 | 核酸の解析のための方法及び組成物 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018524457A Active JP6954899B2 (ja) | 2015-12-04 | 2016-12-02 | 核酸の解析のための方法及び組成物 |
Country Status (12)
Country | Link |
---|---|
US (5) | US10774370B2 (ja) |
EP (3) | EP4144861A1 (ja) |
JP (2) | JP6954899B2 (ja) |
KR (1) | KR20180081164A (ja) |
CN (2) | CN115369161A (ja) |
DE (1) | DE202016009134U1 (ja) |
DK (1) | DK3882357T3 (ja) |
ES (1) | ES2926495T3 (ja) |
IL (1) | IL259736A (ja) |
PT (1) | PT3882357T (ja) |
SG (2) | SG11201804086VA (ja) |
WO (1) | WO2017096158A1 (ja) |
Families Citing this family (93)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10273541B2 (en) | 2012-08-14 | 2019-04-30 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US20150376609A1 (en) | 2014-06-26 | 2015-12-31 | 10X Genomics, Inc. | Methods of Analyzing Nucleic Acids from Individual Cells or Cell Populations |
US10752949B2 (en) | 2012-08-14 | 2020-08-25 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10323279B2 (en) | 2012-08-14 | 2019-06-18 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10400280B2 (en) | 2012-08-14 | 2019-09-03 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US9951386B2 (en) | 2014-06-26 | 2018-04-24 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11591637B2 (en) | 2012-08-14 | 2023-02-28 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US9701998B2 (en) | 2012-12-14 | 2017-07-11 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
MX364957B (es) | 2012-08-14 | 2019-05-15 | 10X Genomics Inc | Composiciones y metodos para microcapsulas. |
CA2894694C (en) | 2012-12-14 | 2023-04-25 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10533221B2 (en) | 2012-12-14 | 2020-01-14 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
CA2900481A1 (en) | 2013-02-08 | 2014-08-14 | 10X Genomics, Inc. | Polynucleotide barcode generation |
WO2014210223A1 (en) | 2013-06-25 | 2014-12-31 | Prognosys Biosciences, Inc. | Spatially encoded biological assays using a microfluidic device |
US9824068B2 (en) | 2013-12-16 | 2017-11-21 | 10X Genomics, Inc. | Methods and apparatus for sorting data |
AU2015243445B2 (en) | 2014-04-10 | 2020-05-28 | 10X Genomics, Inc. | Fluidic devices, systems, and methods for encapsulating and partitioning reagents, and applications of same |
CN114214314A (zh) | 2014-06-24 | 2022-03-22 | 生物辐射实验室股份有限公司 | 数字式pcr条码化 |
SG11201705615UA (en) | 2015-01-12 | 2017-08-30 | 10X Genomics Inc | Processes and systems for preparing nucleic acid sequencing libraries and libraries prepared using same |
EP3262407B1 (en) | 2015-02-24 | 2023-08-30 | 10X Genomics, Inc. | Partition processing methods and systems |
GB2554572B (en) | 2015-03-26 | 2021-06-23 | Dovetail Genomics Llc | Physical linkage preservation in DNA storage |
CN107532207B (zh) | 2015-04-10 | 2021-05-07 | 空间转录公司 | 生物样本的空间区别、多重核酸分析 |
US11371094B2 (en) | 2015-11-19 | 2022-06-28 | 10X Genomics, Inc. | Systems and methods for nucleic acid processing using degenerate nucleotides |
SG11201804086VA (en) | 2015-12-04 | 2018-06-28 | 10X Genomics Inc | Methods and compositions for nucleic acid analysis |
SG11201806757XA (en) | 2016-02-11 | 2018-09-27 | 10X Genomics Inc | Systems, methods, and media for de novo assembly of whole genome sequence data |
IL262946B2 (en) * | 2016-05-13 | 2023-03-01 | Dovetail Genomics Llc | Retrieving long-range grip information from preserved samples |
US10815525B2 (en) | 2016-12-22 | 2020-10-27 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10550429B2 (en) | 2016-12-22 | 2020-02-04 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
EP4029939B1 (en) | 2017-01-30 | 2023-06-28 | 10X Genomics, Inc. | Methods and systems for droplet-based single cell barcoding |
US10995333B2 (en) | 2017-02-06 | 2021-05-04 | 10X Genomics, Inc. | Systems and methods for nucleic acid preparation |
CN117143960A (zh) | 2017-05-18 | 2023-12-01 | 10X基因组学有限公司 | 用于分选液滴和珠的方法和系统 |
US10544413B2 (en) | 2017-05-18 | 2020-01-28 | 10X Genomics, Inc. | Methods and systems for sorting droplets and beads |
CN116064732A (zh) | 2017-05-26 | 2023-05-05 | 10X基因组学有限公司 | 转座酶可接近性染色质的单细胞分析 |
US10400235B2 (en) | 2017-05-26 | 2019-09-03 | 10X Genomics, Inc. | Single cell analysis of transposase accessible chromatin |
US10357771B2 (en) | 2017-08-22 | 2019-07-23 | 10X Genomics, Inc. | Method of producing emulsions |
US10590244B2 (en) | 2017-10-04 | 2020-03-17 | 10X Genomics, Inc. | Compositions, methods, and systems for bead formation using improved polymers |
US10837047B2 (en) | 2017-10-04 | 2020-11-17 | 10X Genomics, Inc. | Compositions, methods, and systems for bead formation using improved polymers |
WO2019083852A1 (en) | 2017-10-26 | 2019-05-02 | 10X Genomics, Inc. | MICROFLUIDIC CHANNEL NETWORKS FOR PARTITIONING |
WO2019084043A1 (en) | 2017-10-26 | 2019-05-02 | 10X Genomics, Inc. | METHODS AND SYSTEMS FOR NUCLEIC ACID PREPARATION AND CHROMATIN ANALYSIS |
WO2019084328A1 (en) * | 2017-10-26 | 2019-05-02 | 10X Genomics, Inc. | METHODS FOR PREPARING NUCLEIC ACID MOLECULES |
EP3700672B1 (en) * | 2017-10-27 | 2022-12-28 | 10X Genomics, Inc. | Methods for sample preparation and analysis |
SG11201913654QA (en) | 2017-11-15 | 2020-01-30 | 10X Genomics Inc | Functionalized gel beads |
US10829815B2 (en) | 2017-11-17 | 2020-11-10 | 10X Genomics, Inc. | Methods and systems for associating physical and genetic properties of biological particles |
EP3714052A1 (en) * | 2017-11-21 | 2020-09-30 | Arima Genomics, Inc. | Preserving spatial-proximal contiguity and molecular contiguity in nucleic acid templates |
WO2019108851A1 (en) | 2017-11-30 | 2019-06-06 | 10X Genomics, Inc. | Systems and methods for nucleic acid preparation and analysis |
WO2019148042A1 (en) * | 2018-01-26 | 2019-08-01 | 10X Genomics, Inc. | Compositions and methods for sample processing |
WO2019157529A1 (en) | 2018-02-12 | 2019-08-15 | 10X Genomics, Inc. | Methods characterizing multiple analytes from individual cells or cell populations |
US11639928B2 (en) | 2018-02-22 | 2023-05-02 | 10X Genomics, Inc. | Methods and systems for characterizing analytes from individual cells or cell populations |
SG11202009889VA (en) | 2018-04-06 | 2020-11-27 | 10X Genomics Inc | Systems and methods for quality control in single cell processing |
US11932899B2 (en) | 2018-06-07 | 2024-03-19 | 10X Genomics, Inc. | Methods and systems for characterizing nucleic acid molecules |
US11703427B2 (en) | 2018-06-25 | 2023-07-18 | 10X Genomics, Inc. | Methods and systems for cell and bead processing |
US20200032335A1 (en) | 2018-07-27 | 2020-01-30 | 10X Genomics, Inc. | Systems and methods for metabolome analysis |
WO2020047010A2 (en) | 2018-08-28 | 2020-03-05 | 10X Genomics, Inc. | Increasing spatial array resolution |
US11519033B2 (en) | 2018-08-28 | 2022-12-06 | 10X Genomics, Inc. | Method for transposase-mediated spatial tagging and analyzing genomic DNA in a biological sample |
US11459607B1 (en) | 2018-12-10 | 2022-10-04 | 10X Genomics, Inc. | Systems and methods for processing-nucleic acid molecules from a single cell using sequential co-partitioning and composite barcodes |
US11649485B2 (en) | 2019-01-06 | 2023-05-16 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
US11926867B2 (en) | 2019-01-06 | 2024-03-12 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
US11845983B1 (en) | 2019-01-09 | 2023-12-19 | 10X Genomics, Inc. | Methods and systems for multiplexing of droplet based assays |
US11851683B1 (en) | 2019-02-12 | 2023-12-26 | 10X Genomics, Inc. | Methods and systems for selective analysis of cellular samples |
US11467153B2 (en) | 2019-02-12 | 2022-10-11 | 10X Genomics, Inc. | Methods for processing nucleic acid molecules |
EP3924505A1 (en) | 2019-02-12 | 2021-12-22 | 10X Genomics, Inc. | Methods for processing nucleic acid molecules |
US11655499B1 (en) | 2019-02-25 | 2023-05-23 | 10X Genomics, Inc. | Detection of sequence elements in nucleic acid molecules |
SG11202111242PA (en) | 2019-03-11 | 2021-11-29 | 10X Genomics Inc | Systems and methods for processing optically tagged beads |
EP3976820A1 (en) | 2019-05-30 | 2022-04-06 | 10X Genomics, Inc. | Methods of detecting spatial heterogeneity of a biological sample |
WO2021091611A1 (en) | 2019-11-08 | 2021-05-14 | 10X Genomics, Inc. | Spatially-tagged analyte capture agents for analyte multiplexing |
SG11202106899SA (en) | 2019-12-23 | 2021-09-29 | 10X Genomics Inc | Methods for spatial analysis using rna-templated ligation |
US11702693B2 (en) | 2020-01-21 | 2023-07-18 | 10X Genomics, Inc. | Methods for printing cells and generating arrays of barcoded cells |
US11732299B2 (en) | 2020-01-21 | 2023-08-22 | 10X Genomics, Inc. | Spatial assays with perturbed cells |
US11821035B1 (en) | 2020-01-29 | 2023-11-21 | 10X Genomics, Inc. | Compositions and methods of making gene expression libraries |
US11898205B2 (en) | 2020-02-03 | 2024-02-13 | 10X Genomics, Inc. | Increasing capture efficiency of spatial assays |
US11732300B2 (en) | 2020-02-05 | 2023-08-22 | 10X Genomics, Inc. | Increasing efficiency of spatial analysis in a biological sample |
US11835462B2 (en) | 2020-02-11 | 2023-12-05 | 10X Genomics, Inc. | Methods and compositions for partitioning a biological sample |
US11891654B2 (en) | 2020-02-24 | 2024-02-06 | 10X Genomics, Inc. | Methods of making gene expression libraries |
US11926863B1 (en) * | 2020-02-27 | 2024-03-12 | 10X Genomics, Inc. | Solid state single cell method for analyzing fixed biological cells |
US11768175B1 (en) | 2020-03-04 | 2023-09-26 | 10X Genomics, Inc. | Electrophoretic methods for spatial analysis |
EP4242325A3 (en) | 2020-04-22 | 2023-10-04 | 10X Genomics, Inc. | Methods for spatial analysis using targeted rna depletion |
US11851700B1 (en) | 2020-05-13 | 2023-12-26 | 10X Genomics, Inc. | Methods, kits, and compositions for processing extracellular molecules |
WO2021236929A1 (en) | 2020-05-22 | 2021-11-25 | 10X Genomics, Inc. | Simultaneous spatio-temporal measurement of gene expression and cellular activity |
WO2021237087A1 (en) | 2020-05-22 | 2021-11-25 | 10X Genomics, Inc. | Spatial analysis to detect sequence variants |
WO2021242834A1 (en) | 2020-05-26 | 2021-12-02 | 10X Genomics, Inc. | Method for resetting an array |
EP4158054A1 (en) | 2020-06-02 | 2023-04-05 | 10X Genomics, Inc. | Spatial transcriptomics for antigen-receptors |
WO2021247543A2 (en) | 2020-06-02 | 2021-12-09 | 10X Genomics, Inc. | Nucleic acid library methods |
WO2021252499A1 (en) | 2020-06-08 | 2021-12-16 | 10X Genomics, Inc. | Methods of determining a surgical margin and methods of use thereof |
WO2021252591A1 (en) | 2020-06-10 | 2021-12-16 | 10X Genomics, Inc. | Methods for determining a location of an analyte in a biological sample |
CN116034166A (zh) | 2020-06-25 | 2023-04-28 | 10X基因组学有限公司 | Dna甲基化的空间分析 |
US11761038B1 (en) | 2020-07-06 | 2023-09-19 | 10X Genomics, Inc. | Methods for identifying a location of an RNA in a biological sample |
US11926822B1 (en) | 2020-09-23 | 2024-03-12 | 10X Genomics, Inc. | Three-dimensional spatial analysis |
US11827935B1 (en) | 2020-11-19 | 2023-11-28 | 10X Genomics, Inc. | Methods for spatial analysis using rolling circle amplification and detection probes |
AU2021409136A1 (en) | 2020-12-21 | 2023-06-29 | 10X Genomics, Inc. | Methods, compositions, and systems for capturing probes and/or barcodes |
WO2022182682A1 (en) | 2021-02-23 | 2022-09-01 | 10X Genomics, Inc. | Probe-based analysis of nucleic acids and proteins |
EP4301870A1 (en) | 2021-03-18 | 2024-01-10 | 10X Genomics, Inc. | Multiplex capture of gene and protein expression from a biological sample |
WO2023034489A1 (en) | 2021-09-01 | 2023-03-09 | 10X Genomics, Inc. | Methods, compositions, and kits for blocking a capture probe on a spatial array |
US11753677B2 (en) | 2021-11-10 | 2023-09-12 | Encodia, Inc. | Methods for barcoding macromolecules in individual cells |
WO2023204594A1 (ko) * | 2022-04-19 | 2023-10-26 | 서울대학교산학협력단 | 태그멘테이션을 이용한 벡터 삽입위치 검출 및 클론 정량 방법 |
WO2023239733A1 (en) | 2022-06-06 | 2023-12-14 | Genentech, Inc. | Combinatorial indexing for single-cell nucleic acid sequencing |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20120220494A1 (en) * | 2011-02-18 | 2012-08-30 | Raindance Technolgies, Inc. | Compositions and methods for molecular labeling |
WO2013134261A1 (en) * | 2012-03-05 | 2013-09-12 | President And Fellows Of Harvard College | Systems and methods for epigenetic sequencing |
JP2014512826A (ja) * | 2011-04-25 | 2014-05-29 | バイオ−ラド ラボラトリーズ インコーポレイテッド | 核酸分析のための方法および組成物 |
WO2015071748A1 (en) * | 2013-11-18 | 2015-05-21 | Erasmus Universiteit Medisch Centrum Rotterdam | Method for analysing the interaction of nucleotide sequences in a three-dimensional dna structure |
JP2015528283A (ja) * | 2012-08-14 | 2015-09-28 | テンエックス・ジェノミクス・インコーポレイテッド | マイクロカプセル組成物および方法 |
Family Cites Families (562)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2797149A (en) | 1953-01-08 | 1957-06-25 | Technicon International Ltd | Methods of and apparatus for analyzing liquids containing crystalloid and non-crystalloid constituents |
US3047367A (en) | 1959-12-01 | 1962-07-31 | Technicon Instr | Automatic analysis with fluid segmentation |
US3479141A (en) | 1967-05-17 | 1969-11-18 | Technicon Corp | Method and apparatus for analysis |
US4124638A (en) | 1977-09-12 | 1978-11-07 | Hansen John N | Solubilizable polyacrylamide gels containing disulfide cross-linkages |
JPS5949832B2 (ja) | 1978-07-18 | 1984-12-05 | ブラザー工業株式会社 | 電動ミシンにおける主軸定位置停止装置 |
US4253846A (en) | 1979-11-21 | 1981-03-03 | Technicon Instruments Corporation | Method and apparatus for automated analysis of fluid samples |
GB2097692B (en) | 1981-01-10 | 1985-05-22 | Shaw Stewart P D | Combining chemical reagents |
DE3230289A1 (de) | 1982-08-14 | 1984-02-16 | Bayer Ag, 5090 Leverkusen | Herstellung von pharmazeutischen oder kosmetischen dispersionen |
US4582802A (en) | 1983-09-30 | 1986-04-15 | The United States Of America As Represented By The Department Of Health And Human Services | Stimulation of enzymatic ligation of DNA by high concentrations of nonspecific polymers |
JPS60227826A (ja) | 1984-04-27 | 1985-11-13 | Sogo Yatsukou Kk | pHに応答するグラフトカプセル |
US4916070A (en) | 1986-04-14 | 1990-04-10 | The General Hospital Corporation | Fibrin-specific antibodies and method of screening for the antibodies |
US5618711A (en) | 1986-08-22 | 1997-04-08 | Hoffmann-La Roche Inc. | Recombinant expression vectors and purification methods for Thermus thermophilus DNA polymerase |
US4872895A (en) | 1986-12-11 | 1989-10-10 | American Telephone And Telegraph Company, At&T Bell Laboratories | Method for fabricating articles which include high silica glass bodies |
US5202231A (en) | 1987-04-01 | 1993-04-13 | Drmanac Radoje T | Method of sequencing of genomes by hybridization of oligonucleotide probes |
US5525464A (en) | 1987-04-01 | 1996-06-11 | Hyseq, Inc. | Method of sequencing by hybridization of oligonucleotide probes |
US5149625A (en) | 1987-08-11 | 1992-09-22 | President And Fellows Of Harvard College | Multiplex analysis of DNA |
US5137829A (en) | 1987-10-05 | 1992-08-11 | Washington University | DNA transposon TN5SEQ1 |
US5185099A (en) | 1988-04-20 | 1993-02-09 | Institut National De Recherche Chimique Appliquee | Visco-elastic, isotropic materials based on water, fluorinate sufactants and fluorinated oils, process for their preparation, and their use in various fields, such as optics, pharmacology and electrodynamics |
US5237016A (en) | 1989-01-05 | 1993-08-17 | Siska Diagnostics, Inc. | End-attachment of oligonucleotides to polyacrylamide solid supports for capture and detection of nucleic acids |
US5756334A (en) | 1990-04-26 | 1998-05-26 | New England Biolabs, Inc. | Thermostable DNA polymerase from 9°N-7 and methods for producing the same |
ATE176002T1 (de) | 1990-07-24 | 1999-02-15 | Hoffmann La Roche | Verringerung von nicht spezifischer amplifikation während einer (in vitro) nukleinsäure amplifikation unter verwendung von modifizierten nukleinsäure basen |
US5489523A (en) | 1990-12-03 | 1996-02-06 | Stratagene | Exonuclease-deficient thermostable Pyrococcus furiosus DNA polymerase I |
US6582908B2 (en) | 1990-12-06 | 2003-06-24 | Affymetrix, Inc. | Oligonucleotides |
US5270183A (en) | 1991-02-08 | 1993-12-14 | Beckman Research Institute Of The City Of Hope | Device and method for the automated cycling of solutions between two or more temperatures |
US5994056A (en) | 1991-05-02 | 1999-11-30 | Roche Molecular Systems, Inc. | Homogeneous methods for nucleic acid amplification and detection |
DE69213240T2 (de) | 1991-07-04 | 1997-04-24 | Immunodex K S | Wasserlösliche reagenzien und konjugate auf polymerbasis, die vom divinylsulfon abgeleitete reste enthalten |
US5770358A (en) | 1991-09-18 | 1998-06-23 | Affymax Technologies N.V. | Tagged synthetic oligomer libraries |
US5413924A (en) | 1992-02-13 | 1995-05-09 | Kosak; Kenneth M. | Preparation of wax beads containing a reagent for release by heating |
WO1993019205A1 (en) | 1992-03-19 | 1993-09-30 | The Regents Of The University Of California | Multiple tag labeling method for dna sequencing |
WO1993022058A1 (en) | 1992-05-01 | 1993-11-11 | Trustees Of The University Of Pennsylvania | Polynucleotide amplification analysis using a microfabricated device |
US5587128A (en) | 1992-05-01 | 1996-12-24 | The Trustees Of The University Of Pennsylvania | Mesoscale polynucleotide amplification devices |
US5840865A (en) | 1992-09-14 | 1998-11-24 | Institute Of Molecular Biology And Biotechnology/Forth | Eukaryotic transposable element |
US5897783A (en) | 1992-09-24 | 1999-04-27 | Amersham International Plc | Magnetic separation method |
US5569364A (en) | 1992-11-05 | 1996-10-29 | Soane Biosciences, Inc. | Separation media for electrophoresis |
IL108497A0 (en) | 1993-02-01 | 1994-05-30 | Seq Ltd | Methods and apparatus for dna sequencing |
WO1994019101A1 (en) | 1993-02-16 | 1994-09-01 | Alliance Pharmaceutical Corp. | Method of microemulsifying fluorinated oils |
NZ265555A (en) | 1993-04-19 | 1997-09-22 | Medisorb Technologies Internat | Biodegradable microparticle compositions of antisense oligodeoxyribonucleotides |
DE69429038T2 (de) | 1993-07-28 | 2002-03-21 | Pe Corp Ny Norwalk | Vorrichtung und Verfahren zur Nukleinsäurevervielfältigung |
WO1995004069A1 (en) | 1993-07-30 | 1995-02-09 | Affymax Technologies N.V. | Biotinylation of proteins |
US5512131A (en) | 1993-10-04 | 1996-04-30 | President And Fellows Of Harvard College | Formation of microstamped patterns on surfaces and derivative articles |
US20030044777A1 (en) | 1993-10-28 | 2003-03-06 | Kenneth L. Beattie | Flowthrough devices for multiple discrete binding reactions |
US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
US5558071A (en) | 1994-03-07 | 1996-09-24 | Combustion Electromagnetics, Inc. | Ignition system power converter and controller |
US5648211A (en) | 1994-04-18 | 1997-07-15 | Becton, Dickinson And Company | Strand displacement amplification using thermophilic enzymes |
DE69515675T2 (de) | 1994-05-11 | 2000-07-20 | Genera Technologies Ltd | Verfahren zum Einfangen von einem Ligand aus einer Flüssigkeit und Vorrichtung zur dessen Ausführung |
US5705628A (en) | 1994-09-20 | 1998-01-06 | Whitehead Institute For Biomedical Research | DNA purification and isolation using magnetic particles |
US5846719A (en) | 1994-10-13 | 1998-12-08 | Lynx Therapeutics, Inc. | Oligonucleotide tags for sorting and identification |
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 |
EP0812434B1 (en) | 1995-03-01 | 2013-09-18 | President and Fellows of Harvard College | Microcontact printing on surfaces and derivative articles |
US5700642A (en) | 1995-05-22 | 1997-12-23 | Sri International | Oligonucleotide sizing using immobilized cleavable primers |
DE69637285T2 (de) | 1995-06-07 | 2008-07-10 | Solexa, Inc., Hayward | Oligonukleotid-tags zur sortierung und identifizierung |
EP0832287B1 (en) | 1995-06-07 | 2007-10-10 | Solexa, Inc | Oligonucleotide tags for sorting and identification |
US5856174A (en) | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US6866760B2 (en) | 1998-08-27 | 2005-03-15 | E Ink Corporation | Electrophoretic medium and process for the production thereof |
US5872010A (en) | 1995-07-21 | 1999-02-16 | Northeastern University | Microscale fluid handling system |
US6057149A (en) | 1995-09-15 | 2000-05-02 | The University Of Michigan | Microscale devices and reactions in microscale devices |
US5851769A (en) | 1995-09-27 | 1998-12-22 | The Regents Of The University Of California | Quantitative DNA fiber mapping |
US5736330A (en) | 1995-10-11 | 1998-04-07 | Luminex Corporation | Method and compositions for flow cytometric determination of DNA sequences |
US5736332A (en) | 1995-11-30 | 1998-04-07 | Mandecki; Wlodek | Method of determining the sequence of nucleic acids employing solid-phase particles carrying transponders |
US6051377A (en) | 1995-11-30 | 2000-04-18 | Pharmaseq, Inc. | Multiplex assay for nucleic acids employing transponders |
US6001571A (en) | 1995-11-30 | 1999-12-14 | Mandecki; Wlodek | Multiplex assay for nucleic acids employing transponders |
US5709153A (en) | 1995-12-29 | 1998-01-20 | Motion Controls, Inc. | High dog indexer |
US6355198B1 (en) | 1996-03-15 | 2002-03-12 | President And Fellows Of Harvard College | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
EP0832436A1 (en) | 1996-04-15 | 1998-04-01 | Dade Behring Inc. | Apparatus and method for analysis |
WO1997045559A1 (en) | 1996-05-29 | 1997-12-04 | Cornell Research Foundation, Inc. | Detection of nucleic acid sequence differences using coupled ligase detection and polymerase chain reactions |
US5846727A (en) | 1996-06-06 | 1998-12-08 | Board Of Supervisors Of Louisiana State University And Agricultural & Mechanical College | Microsystem for rapid DNA sequencing |
DE69707288T2 (de) | 1996-07-15 | 2002-07-18 | Calcitech Ltd | Herstellung von pulvern |
US5965443A (en) | 1996-09-09 | 1999-10-12 | Wisconsin Alumni Research Foundation | System for in vitro transposition |
US5900481A (en) | 1996-11-06 | 1999-05-04 | Sequenom, Inc. | Bead linkers for immobilizing nucleic acids to solid supports |
US6133436A (en) | 1996-11-06 | 2000-10-17 | Sequenom, Inc. | Beads bound to a solid support and to nucleic acids |
AU746549B2 (en) | 1996-11-20 | 2002-05-02 | Becton Dickinson & Company | Microfabricated isothermal nucleic acid amplification devices and methods |
US5958703A (en) | 1996-12-03 | 1999-09-28 | Glaxo Group Limited | Use of modified tethers in screening compound libraries |
US20020172965A1 (en) | 1996-12-13 | 2002-11-21 | Arcaris, Inc. | Methods for measuring relative amounts of nucleic acids in a complex mixture and retrieval of specific sequences therefrom |
US20050042625A1 (en) | 1997-01-15 | 2005-02-24 | Xzillion Gmbh & Co. | Mass label linked hybridisation probes |
US6297006B1 (en) | 1997-01-16 | 2001-10-02 | Hyseq, Inc. | Methods for sequencing repetitive sequences and for determining the order of sequence subfragments |
US20020034737A1 (en) | 1997-03-04 | 2002-03-21 | Hyseq, Inc. | Methods and compositions for detection or quantification of nucleic acid species |
WO1998035012A2 (en) | 1997-02-12 | 1998-08-13 | Chan Eugene Y | Methods and products for analyzing polymers |
US6327410B1 (en) | 1997-03-14 | 2001-12-04 | The Trustees Of Tufts College | Target analyte sensors utilizing Microspheres |
US7622294B2 (en) | 1997-03-14 | 2009-11-24 | Trustees Of Tufts College | Methods for detecting target analytes and enzymatic reactions |
US6391622B1 (en) | 1997-04-04 | 2002-05-21 | Caliper Technologies Corp. | Closed-loop biochemical analyzers |
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 |
DE69823347T2 (de) | 1997-05-16 | 2005-05-12 | Alberta Research Council, Edmonton | Mikrofluidisches system und verfahren zu dessen betrieb |
EP0985142A4 (en) | 1997-05-23 | 2006-09-13 | Lynx Therapeutics Inc | SYSTEM AND APPARATUS FOR THE SEQUENTIAL TREATMENT OF ANALYTES |
US6969488B2 (en) | 1998-05-22 | 2005-11-29 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
US20040241759A1 (en) | 1997-06-16 | 2004-12-02 | Eileen Tozer | High throughput screening of libraries |
EP1019496B1 (en) | 1997-07-07 | 2004-09-29 | Medical Research Council | In vitro sorting method |
GB9714716D0 (en) | 1997-07-11 | 1997-09-17 | Brax Genomics Ltd | Characterising nucleic acids |
FI103809B (fi) | 1997-07-14 | 1999-09-30 | Finnzymes Oy | In vitro -menetelmä templaattien tuottamiseksi DNA-sekventointia varten |
US6974669B2 (en) | 2000-03-28 | 2005-12-13 | Nanosphere, Inc. | Bio-barcodes based on oligonucleotide-modified nanoparticles |
US6368871B1 (en) | 1997-08-13 | 2002-04-09 | Cepheid | Non-planar microstructures for manipulation of fluid samples |
CA2300940A1 (en) | 1997-08-15 | 1999-02-25 | Hyseq, Inc. | Methods and compositions for detection or quantification of nucleic acid species |
US6207031B1 (en) | 1997-09-15 | 2001-03-27 | Whitehead Institute For Biomedical Research | Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device |
US20020092767A1 (en) | 1997-09-19 | 2002-07-18 | Aclara Biosciences, Inc. | Multiple array microfluidic device units |
US7214298B2 (en) | 1997-09-23 | 2007-05-08 | California Institute Of Technology | Microfabricated cell sorter |
WO1999018438A1 (en) | 1997-10-02 | 1999-04-15 | Aclara Biosciences, Inc. | Capillary assays involving separation of free and bound species |
US5842787A (en) | 1997-10-09 | 1998-12-01 | Caliper Technologies Corporation | Microfluidic systems incorporating varied channel dimensions |
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 |
US6511803B1 (en) | 1997-10-10 | 2003-01-28 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
US6485944B1 (en) | 1997-10-10 | 2002-11-26 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
AU1080999A (en) | 1997-10-14 | 1999-05-03 | Luminex Corporation | Precision fluorescently dyed particles and methods of making and using same |
JP4318859B2 (ja) | 1997-12-04 | 2009-08-26 | ジーイー・ヘルスケア・ユーケイ・リミテッド | 複合アッセイ方法 |
WO1999033963A1 (en) | 1997-12-31 | 1999-07-08 | Chiron Corporation | Metastatic cancer regulated gene |
BR9908082A (pt) | 1998-02-19 | 2000-10-31 | Harvard College | Proteìna de fusão do complexo de histocompatibilidade principal classe ii, conjugado dos domìnios de ligação do complexo de histocompatibilidade principal multimérico, processos para detectar células t tendo uma especificidade do complexo definido de mhc / peptìdeo, para conferir a um indivìduo imunidade adotiva a um complexo definido de mhc / peptìdeo, para estimular ou ativar as células t reativas a um complexo definido de mhc / peptìdeo, para seletivamente matar células t reativas a um complexo definido de mhc / peptìdeo, para tolerizar um indivìduo humano a um complexo definido de mhc / peptìdeo, e, ácido nucleico isolado |
AU3196099A (en) | 1998-03-27 | 1999-10-18 | President And Fellows Of Harvard College | Systematic identification of essential genes by (in vitro) transposon mutagenesis |
US6022716A (en) | 1998-04-10 | 2000-02-08 | Genset Sa | High throughput DNA sequencing vector |
EP1079967A4 (en) | 1998-04-13 | 2003-07-23 | Luminex Corp | LIQUID MARKING USING FLUORESCENT MICROPARTICLES |
US6780591B2 (en) | 1998-05-01 | 2004-08-24 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and DNA molecules |
US5997636A (en) | 1998-05-01 | 1999-12-07 | Instrumentation Technology Associates, Inc. | Method and apparatus for growing crystals |
US6306590B1 (en) | 1998-06-08 | 2001-10-23 | Caliper Technologies Corp. | Microfluidic matrix localization apparatus and methods |
US6586176B1 (en) | 1998-08-07 | 2003-07-01 | Cellay, Llc | Gel microdrops in genetic analysis |
US6159736A (en) | 1998-09-23 | 2000-12-12 | Wisconsin Alumni Research Foundation | Method for making insertional mutations using a Tn5 synaptic complex |
AR021833A1 (es) | 1998-09-30 | 2002-08-07 | Applied Research Systems | Metodos de amplificacion y secuenciacion de acido nucleico |
KR20010089295A (ko) | 1998-10-13 | 2001-09-29 | 마이클 알. 맥닐리 | 수동 유체 동역학에 의한 유체회로 및 유체회로내에서의방법 |
US6489096B1 (en) | 1998-10-15 | 2002-12-03 | Princeton University | Quantitative analysis of hybridization patterns and intensities in oligonucleotide arrays |
SE9803614L (sv) | 1998-10-19 | 2000-04-20 | Muhammed Mamoun | Förfarande och anordning för framställning av nanopartiklar |
WO2000026412A1 (en) | 1998-11-02 | 2000-05-11 | Kenneth Loren Beattie | Nucleic acid analysis using sequence-targeted tandem hybridization |
US6569631B1 (en) | 1998-11-12 | 2003-05-27 | 3-Dimensional Pharmaceuticals, Inc. | Microplate thermal shift assay for ligand development using 5-(4″dimethylaminophenyl)-2-(4′-phenyl)oxazole derivative fluorescent dyes |
US5942609A (en) | 1998-11-12 | 1999-08-24 | The Porkin-Elmer Corporation | Ligation assembly and detection of polynucleotides on solid-support |
NO986133D0 (no) | 1998-12-23 | 1998-12-23 | Preben Lexow | FremgangsmÕte for DNA-sekvensering |
GB9900298D0 (en) | 1999-01-07 | 1999-02-24 | Medical Res Council | Optical sorting method |
US6416642B1 (en) | 1999-01-21 | 2002-07-09 | Caliper Technologies Corp. | Method and apparatus for continuous liquid flow in microscale channels using pressure injection, wicking, and electrokinetic injection |
US6635419B1 (en) | 1999-02-16 | 2003-10-21 | Applera Corporation | Polynucleotide sequencing method |
US20030027214A1 (en) | 1999-02-17 | 2003-02-06 | Kamb Carl Alexander | Methods for substrate-ligand interaction screening |
ATE469699T1 (de) | 1999-02-23 | 2010-06-15 | Caliper Life Sciences Inc | Manipulation von mikroteilchen in mikrofluiden systemen |
US6171850B1 (en) | 1999-03-08 | 2001-01-09 | Caliper Technologies Corp. | Integrated devices and systems for performing temperature controlled reactions and analyses |
US6303343B1 (en) | 1999-04-06 | 2001-10-16 | Caliper Technologies Corp. | Inefficient fast PCR |
US6908737B2 (en) | 1999-04-15 | 2005-06-21 | Vitra Bioscience, Inc. | Systems and methods of conducting multiplexed experiments |
US20060275782A1 (en) | 1999-04-20 | 2006-12-07 | Illumina, Inc. | Detection of nucleic acid reactions on bead arrays |
AU4806100A (en) | 1999-04-28 | 2000-11-10 | Board Of Trustees Of The Leland Stanford Junior University | P element derived vector and methods for its use |
CA2373537A1 (en) | 1999-05-12 | 2000-11-16 | Aclara Biosciences, Inc. | Multiplexed fluorescent detection in microfluidic devices |
WO2000070095A2 (en) | 1999-05-17 | 2000-11-23 | Dade Behring Inc. | Homogeneous isothermal amplification and detection of nucleic acids using a template switch oligonucleotide |
US20020051971A1 (en) | 1999-05-21 | 2002-05-02 | John R. Stuelpnagel | Use of microfluidic systems in the detection of target analytes using microsphere arrays |
US6846622B1 (en) | 1999-05-26 | 2005-01-25 | Oregon Health & Science University | Tagged epitope protein transposable element |
US20030124509A1 (en) | 1999-06-03 | 2003-07-03 | Kenis Paul J.A. | Laminar flow patterning and articles made thereby |
US6372813B1 (en) | 1999-06-25 | 2002-04-16 | Motorola | Methods and compositions for attachment of biomolecules to solid supports, hydrogels, and hydrogel arrays |
AU6068300A (en) | 1999-07-06 | 2001-01-22 | Caliper Technologies Corporation | Microfluidic systems and methods for determining modulator kinetics |
US6977145B2 (en) | 1999-07-28 | 2005-12-20 | Serono Genetics Institute S.A. | Method for carrying out a biochemical protocol in continuous flow in a microreactor |
US6524456B1 (en) | 1999-08-12 | 2003-02-25 | Ut-Battelle, Llc | Microfluidic devices for the controlled manipulation of small volumes |
WO2001013086A2 (en) | 1999-08-13 | 2001-02-22 | Brandeis University | Detection of nucleic acids |
WO2001014589A2 (en) | 1999-08-20 | 2001-03-01 | Luminex Corporation | Liquid array technology |
WO2001016372A1 (en) | 1999-08-27 | 2001-03-08 | Matrix Technologies Corporation | Methods of immobilizing ligands on solid supports and apparatus and methods of use therefor |
US6982146B1 (en) | 1999-08-30 | 2006-01-03 | The United States Of America As Represented By The Department Of Health And Human Services | High speed parallel molecular nucleic acid sequencing |
AU8023500A (en) | 1999-10-13 | 2001-04-23 | Mds Sciex | System and method for detecting and identifying molecular events in a test sample |
US6958225B2 (en) | 1999-10-27 | 2005-10-25 | Affymetrix, Inc. | Complexity management of genomic DNA |
AU1100201A (en) | 1999-10-28 | 2001-05-08 | Board Of Trustees Of The Leland Stanford Junior University | Methods of in vivo gene transfer using a sleeping beauty transposon system |
JP4721603B2 (ja) | 1999-11-08 | 2011-07-13 | 栄研化学株式会社 | 変異および/または多型の検出方法 |
US6432290B1 (en) | 1999-11-26 | 2002-08-13 | The Governors Of The University Of Alberta | Apparatus and method for trapping bead based reagents within microfluidic analysis systems |
WO2001062887A1 (en) | 2000-02-23 | 2001-08-30 | Zyomyx, Inc. | Chips having elevated sample surfaces |
IL134830A0 (en) | 2000-03-01 | 2001-05-20 | Chay 13 Medical Res Group N V | Peptides and immunostimulatory and anti-bacterial pharmaceutical compositions containing them |
KR20030009389A (ko) | 2000-03-14 | 2003-01-29 | 브루카드 괴케 | 유문동-유문-십이지장 운동성에 대한 글루카곤 유사펩티드-1 (7-36)의 효과 |
US6409832B2 (en) | 2000-03-31 | 2002-06-25 | Micronics, Inc. | Protein crystallization in microfluidic structures |
AU2001250058A1 (en) | 2000-04-06 | 2001-10-23 | Caliper Technologies Corp. | Methods and devices for achieving long incubation times in high-throughput systems |
DK2206791T3 (en) | 2000-04-10 | 2016-10-24 | Taxon Biosciences Inc | Methods of study and genetic analysis of populations |
US6481453B1 (en) | 2000-04-14 | 2002-11-19 | Nanostream, Inc. | Microfluidic branch metering systems and methods |
US6800298B1 (en) | 2000-05-11 | 2004-10-05 | Clemson University | Biological lubricant composition and method of applying lubricant composition |
US20060008799A1 (en) | 2000-05-22 | 2006-01-12 | Hong Cai | Rapid haplotyping by single molecule detection |
EP1286913A2 (en) | 2000-05-24 | 2003-03-05 | Micronics, Inc. | Microfluidic concentration gradient loop |
US6645432B1 (en) | 2000-05-25 | 2003-11-11 | President & Fellows Of Harvard College | Microfluidic systems including three-dimensionally arrayed channel networks |
US20060263888A1 (en) | 2000-06-02 | 2006-11-23 | Honeywell International Inc. | Differential white blood count on a disposable card |
US6632606B1 (en) | 2000-06-12 | 2003-10-14 | Aclara Biosciences, Inc. | Methods for single nucleotide polymorphism detection |
ES2259666T3 (es) | 2000-06-21 | 2006-10-16 | Bioarray Solutions Ltd | Analisis molecular de multiples analitos usando series de particulas aleatorias con especificidad de aplicacion. |
EP1309404A2 (en) | 2000-08-07 | 2003-05-14 | Nanostream, Inc. | Fluidic mixer in microfluidic system |
US6773566B2 (en) | 2000-08-31 | 2004-08-10 | Nanolytics, Inc. | Electrostatic actuators for microfluidics and methods for using same |
US6610499B1 (en) | 2000-08-31 | 2003-08-26 | The Regents Of The University Of California | Capillary array and related methods |
WO2002022878A1 (en) | 2000-09-14 | 2002-03-21 | Caliper Technologies Corp. | Microfluidic devices and methods for performing temperature mediated reactions |
WO2002023163A1 (en) | 2000-09-15 | 2002-03-21 | California Institute Of Technology | Microfabricated crossflow devices and methods |
EP1364052A2 (en) | 2000-10-10 | 2003-11-26 | Diversa Corporation | High throughput or capillary-based screening for a bioactivity or biomolecule |
JP2002155305A (ja) | 2000-11-14 | 2002-05-31 | Akira Kawasaki | 単分散粒子の製造装置及び単分散粒子の製造方法及びその製造方法で製造された単分散粒子 |
CA2332186A1 (en) | 2001-02-08 | 2002-08-08 | Her Majesty In Right Of Canada As Represented By The Minister Of Agricul Ture And Agri-Food Canada | Replicative in vivo gene targeting |
US7670559B2 (en) | 2001-02-15 | 2010-03-02 | Caliper Life Sciences, Inc. | Microfluidic systems with enhanced detection systems |
WO2002068383A2 (en) | 2001-02-22 | 2002-09-06 | Anika Therapeutics, Inc. | Thiol-modified hyaluronan |
WO2002068104A1 (en) | 2001-02-23 | 2002-09-06 | Japan Science And Technology Corporation | Process for producing emulsion and microcapsules and apparatus therefor |
US20150329617A1 (en) | 2001-03-14 | 2015-11-19 | Dynal Biotech Asa | Novel MHC molecule constructs, and methods of employing these constructs for diagnosis and therapy, and uses of MHC molecules |
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 |
EP1377811B1 (en) | 2001-04-03 | 2008-07-16 | Micronics, Inc. | Split focusing cytometer |
US7138267B1 (en) | 2001-04-04 | 2006-11-21 | Epicentre Technologies Corporation | Methods and compositions for amplifying DNA clone copy number |
US20030027221A1 (en) | 2001-04-06 | 2003-02-06 | Scott Melissa E. | High-throughput screening assays by encapsulation |
US7572642B2 (en) | 2001-04-18 | 2009-08-11 | Ambrigen, Llc | Assay based on particles, which specifically bind with targets in spatially distributed characteristic patterns |
EP1399580B1 (en) | 2001-05-26 | 2008-10-08 | One Cell Systems, Inc. | Secretion of proteins by encapsulated cells |
US6880576B2 (en) | 2001-06-07 | 2005-04-19 | Nanostream, Inc. | Microfluidic devices for methods development |
US7179423B2 (en) | 2001-06-20 | 2007-02-20 | Cytonome, Inc. | Microfluidic system including a virtual wall fluid interface port for interfacing fluids with the microfluidic system |
US6613523B2 (en) | 2001-06-29 | 2003-09-02 | Agilent Technologies, Inc. | Method of DNA sequencing using cleavable tags |
US7682353B2 (en) | 2001-06-29 | 2010-03-23 | Coloplast A/S | Catheter device |
US7077152B2 (en) | 2001-07-07 | 2006-07-18 | Nanostream, Inc. | Microfluidic metering systems and methods |
CA2454573A1 (en) | 2001-07-20 | 2003-01-30 | California Institute Of Technology | Protein and nucleic acid expression systems |
US6767731B2 (en) | 2001-08-27 | 2004-07-27 | Intel Corporation | Electron induced fluorescent method for nucleic acid sequencing |
US7297485B2 (en) | 2001-10-15 | 2007-11-20 | Qiagen Gmbh | Method for nucleic acid amplification that results in low amplification bias |
US20030089605A1 (en) | 2001-10-19 | 2003-05-15 | West Virginia University Research Corporation | Microfluidic system for proteome analysis |
US6783647B2 (en) | 2001-10-19 | 2004-08-31 | Ut-Battelle, Llc | Microfluidic systems and methods of transport and lysis of cells and analysis of cell lysate |
US20030149307A1 (en) | 2001-10-24 | 2003-08-07 | Baxter International Inc. | Process for the preparation of polyethylene glycol bis amine |
US20030182068A1 (en) | 2001-10-30 | 2003-09-25 | Battersby Bronwyn J. | Device and methods for directed synthesis of chemical libraries |
GB0127564D0 (en) | 2001-11-16 | 2002-01-09 | Medical Res Council | Emulsion compositions |
US7335153B2 (en) | 2001-12-28 | 2008-02-26 | Bio Array Solutions Ltd. | Arrays of microparticles and methods of preparation thereof |
WO2003057010A2 (en) | 2002-01-04 | 2003-07-17 | Board Of Regents, The University Of Texas System | Droplet-based microfluidic oligonucleotide synthesis engine |
AU2003202026A1 (en) | 2002-01-16 | 2003-09-02 | Dynal Biotech Asa | Method for isolating nucleic acids and protein from a single sample |
KR100459870B1 (ko) | 2002-02-22 | 2004-12-04 | 한국과학기술원 | 트랜스포존과 Cre/loxP 부위 특이적 재조합 방법을 이용하는 염색체의 특정부위가 제거된 미생물 변이주 제조방법 |
AU2003226679A1 (en) | 2002-03-20 | 2003-09-29 | Innovativebio.Biz | Microcapsules with controlable permeability encapsulating a nucleic acid amplification reaction mixture and their use as reaction compartments for parallels reactions |
PT2151250E (pt) | 2002-05-06 | 2013-12-09 | Endocyte Inc | Agentes de formação de imagem direccionados para vitamina |
EP2278338B1 (en) | 2002-05-09 | 2020-08-26 | The University of Chicago | Device and method for pressure-driven plug transport and reaction |
US7901939B2 (en) | 2002-05-09 | 2011-03-08 | University Of Chicago | Method for performing crystallization and reactions in pressure-driven fluid plugs |
US7527966B2 (en) | 2002-06-26 | 2009-05-05 | Transgenrx, Inc. | Gene regulation in transgenic animals using a transposon-based vector |
JP2006507921A (ja) | 2002-06-28 | 2006-03-09 | 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 | 流体分散のための方法および装置 |
EP1543157A4 (en) | 2002-07-24 | 2006-11-15 | Ptc Therapeutics Inc | METHODS FOR IDENTIFYING SMALL MOLECULES MODULATING PREMATURE TRANSLATION TERMINATION AND DEGRADATION OF INDUCED MRNA BY NON-SENSE MUTATION |
IL151660A0 (en) | 2002-09-09 | 2003-04-10 | Univ Ben Gurion | Method for isolating and culturing unculturable microorganisms |
JP4201203B2 (ja) | 2002-09-30 | 2008-12-24 | エフ.ホフマン−ラ ロシュ アーゲー | チミジル酸シンターゼ遺伝子の遺伝子型判別のためのオリゴヌクレオチド |
US20040081962A1 (en) | 2002-10-23 | 2004-04-29 | Caifu Chen | Methods for synthesizing complementary DNA |
US6979713B2 (en) | 2002-11-25 | 2005-12-27 | 3M Innovative Properties Company | Curable compositions and abrasive articles therefrom |
US20040248299A1 (en) | 2002-12-27 | 2004-12-09 | Sumedha Jayasena | RNA interference |
EP1587946B1 (en) | 2003-01-17 | 2009-07-08 | The Trustees Of Boston University | Haplotype analysis |
ES2396245T3 (es) | 2003-01-29 | 2013-02-20 | 454 Life Sciences Corporation | Método de amplificación y secuenciamiento de ácidos nucleicos |
US8420386B2 (en) | 2003-02-10 | 2013-04-16 | Max-Delbruck-Centrum Fur Molekulare Medizin (Mdc) | Transposon-based targeting system |
US7041481B2 (en) | 2003-03-14 | 2006-05-09 | The Regents Of The University Of California | Chemical amplification based on fluid partitioning |
US7316903B2 (en) | 2003-03-28 | 2008-01-08 | United States Of America As Represented By The Department Of Health And Human Services | Detection of nucleic acid sequence variations using phase Mu transposase |
US20060078893A1 (en) | 2004-10-12 | 2006-04-13 | Medical Research Council | Compartmentalised combinatorial chemistry by microfluidic control |
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 |
RU2541809C2 (ru) | 2003-04-04 | 2015-02-20 | Зоетис Пи ЛЛК | Микрофлюидизированные эмульсии "масло в воде" и композиции вакцины |
US20100035254A1 (en) | 2003-04-08 | 2010-02-11 | Pacific Biosciences Of California, Inc. | Composition and method for nucleic acid sequencing |
EP2266687A3 (en) | 2003-04-10 | 2011-06-29 | The President and Fellows of Harvard College | Formation and control of fluidic species |
US20060275915A1 (en) | 2003-05-16 | 2006-12-07 | Global Technologies (Nz) Ltd. | Method and apparatus for mixing sample and reagent in a suspension fluid |
DE112004001376D2 (de) | 2003-05-19 | 2006-04-13 | Knoell Hans Forschung Ev | Vorrichtung und Verfahren zur Strukturierung von Flüssigkeiten und zum zudosieren von Reaktionsflüssigkeiten zu in Separationsmedium eingebetteten Flüssigkeitskompartimenten |
WO2004105734A1 (en) | 2003-05-28 | 2004-12-09 | Valorisation Recherche, Societe En Commandite | Method of preparing microcapsules |
WO2004113877A1 (en) | 2003-06-13 | 2004-12-29 | The General Hospital Corporation | Microfluidic systems for size based removal of red blood cells and platelets from blood |
GB2403475B (en) | 2003-07-01 | 2008-02-06 | Oxitec Ltd | Stable integrands |
GB0315438D0 (en) | 2003-07-02 | 2003-08-06 | Univ Manchester | Analysis of mixed cell populations |
WO2005010145A2 (en) | 2003-07-05 | 2005-02-03 | The Johns Hopkins University | Method and compositions for detection and enumeration of genetic variations |
CN104069784B (zh) | 2003-08-27 | 2017-01-11 | 哈佛大学 | 流体物种的电子控制 |
JP4988345B2 (ja) | 2003-09-04 | 2012-08-01 | ザ・ユナイテッド・ステイツ・オブ・アメリカ・アズ・リプレゼンティッド・バイ・ザ・デパートメント・オブ・ヴェテランズ・アフェアーズ | 眼用ハイドロゲルナノコンポジット |
US7354706B2 (en) | 2003-09-09 | 2008-04-08 | The Regents Of The University Of Colorado, A Body Corporate | Use of photopolymerization for amplification and detection of a molecular recognition event |
US20090004739A1 (en) | 2003-09-22 | 2009-01-01 | Taku Demura | Efficient Method of Preparing Dna Inverted Repeat |
DK1691196T3 (da) | 2003-09-25 | 2013-04-15 | Vivalis | Chip med mikrobrøndsarray og fremgangsmåde til fremstilling heraf |
JP2007512811A (ja) | 2003-11-10 | 2007-05-24 | インベスチゲン, インコーポレイテッド | 検出のための核酸を調製する方法 |
WO2005049787A2 (en) | 2003-11-24 | 2005-06-02 | Yeda Research And Development Co.Ltd. | Compositions and methods for in vitro sorting of molecular and cellular libraries |
US8071364B2 (en) | 2003-12-24 | 2011-12-06 | Transgenrx, Inc. | Gene therapy using transposon-based vectors |
US20050181379A1 (en) | 2004-02-18 | 2005-08-18 | Intel Corporation | Method and device for isolating and positioning single nucleic acid molecules |
CN1950519A (zh) | 2004-02-27 | 2007-04-18 | 哈佛大学的校长及成员们 | 聚合酶群落荧光原位测序珠子 |
KR100552706B1 (ko) | 2004-03-12 | 2006-02-20 | 삼성전자주식회사 | 핵산 증폭 방법 및 장치 |
US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
EP1735668A2 (en) | 2004-04-13 | 2006-12-27 | President And Fellows Of Harvard College | Methods and apparatus for manipulation and/or detection of biological samples and other objects |
US7799553B2 (en) | 2004-06-01 | 2010-09-21 | The Regents Of The University Of California | Microfabricated integrated DNA analysis system |
US7700281B2 (en) | 2004-06-30 | 2010-04-20 | Usb Corporation | Hot start nucleic acid amplification |
US7968085B2 (en) | 2004-07-05 | 2011-06-28 | Ascendis Pharma A/S | Hydrogel formulations |
CN1648671B (zh) | 2005-02-06 | 2012-09-26 | 成都夸常医学工业有限公司 | 多反应器分析芯片检测方法和分析芯片及检测装置 |
US7608434B2 (en) | 2004-08-04 | 2009-10-27 | Wisconsin Alumni Research Foundation | Mutated Tn5 transposase proteins and the use thereof |
WO2006030993A1 (en) | 2004-09-14 | 2006-03-23 | Jin-Ho Choy | Information code system using dna sequences |
US7892731B2 (en) | 2004-10-01 | 2011-02-22 | Radix Biosolutions, Ltd. | System and method for inhibiting the decryption of a nucleic acid probe sequence used for the detection of a specific nucleic acid |
US7968287B2 (en) | 2004-10-08 | 2011-06-28 | Medical Research Council Harvard University | In vitro evolution in microfluidic systems |
WO2007001448A2 (en) | 2004-11-04 | 2007-01-04 | Massachusetts Institute Of Technology | Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals |
WO2006051552A2 (en) | 2004-11-15 | 2006-05-18 | Yeda Research And Development Co. Ltd. At The Weizmann Institute Of Science | Directed evolution and selection using in vitro compartmentalization |
US7329493B2 (en) | 2004-12-22 | 2008-02-12 | Asiagen Corporation | One-tube nested PCR for detecting Mycobacterium tuberculosis |
WO2006078841A1 (en) | 2005-01-21 | 2006-07-27 | President And Fellows Of Harvard College | Systems and methods for forming fluidic droplets encapsulated in particles such as colloidal particles |
US7579153B2 (en) | 2005-01-25 | 2009-08-25 | Population Genetics Technologies, Ltd. | Isothermal DNA amplification |
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 |
US7604938B2 (en) | 2005-02-18 | 2009-10-20 | Canon U.S. Life Sciences, Inc. | Devices and methods for monitoring genomic DNA of organisms |
US8062391B2 (en) | 2005-02-21 | 2011-11-22 | Kagoshima University | Method for purifying biodiesel fuel |
EP1861194A2 (en) | 2005-03-04 | 2007-12-05 | The President and Fellows of Harvard College | Method and apparatus for forming multiple emulsions |
US9040237B2 (en) | 2005-03-04 | 2015-05-26 | Intel Corporation | Sensor arrays and nucleic acid sequencing applications |
US20070054119A1 (en) | 2005-03-04 | 2007-03-08 | Piotr Garstecki | Systems and methods of forming particles |
JP2006289250A (ja) | 2005-04-08 | 2006-10-26 | Kao Corp | マイクロミキサー及びそれを用いた流体混合方法 |
EP1885890A4 (en) | 2005-05-26 | 2010-01-20 | Univ Boston | QUANTIFICATION OF NUCLEIC ACIDS AND PROTEINS VIA OLIGONUCLEOTIDE MASS LABELS |
ATE528644T1 (de) | 2005-06-07 | 2011-10-15 | Centre Nat Rech Scient | Verwendung ionischer matrizen zur analyse von gewebeabschnitten durch maldi-massenspektrometrie |
US8407013B2 (en) | 2005-06-07 | 2013-03-26 | Peter K. Rogan | AB initio generation of single copy genomic probes |
CA2611671C (en) | 2005-06-15 | 2013-10-08 | Callida Genomics, Inc. | Single molecule arrays for genetic and chemical analysis |
US20090264299A1 (en) | 2006-02-24 | 2009-10-22 | Complete Genomics, Inc. | High throughput genome sequencing on DNA arrays |
JP2006349060A (ja) | 2005-06-16 | 2006-12-28 | Ntn Corp | ボールねじ |
US8828209B2 (en) | 2005-06-22 | 2014-09-09 | The Research Foundation For The State University Of New York | Massively parallel 2-dimensional capillary electrophoresis |
WO2007002567A2 (en) | 2005-06-23 | 2007-01-04 | Nanosphere, Inc. | Selective isolation and concentration of nucleic acids from complex samples |
JP4927730B2 (ja) | 2005-07-05 | 2012-05-09 | 一般財団法人化学及血清療法研究所 | 改変トランスポゾンベクター及びその利用方法 |
JP5051490B2 (ja) | 2005-07-08 | 2012-10-17 | 独立行政法人産業技術総合研究所 | マクロ生体材料を内包する無機マイクロカプセルおよびその製造方法 |
US20070020640A1 (en) | 2005-07-21 | 2007-01-25 | Mccloskey Megan L | Molecular encoding of nucleic acid templates for PCR and other forms of sequence analysis |
FR2888912B1 (fr) | 2005-07-25 | 2007-08-24 | Commissariat Energie Atomique | Procede de commande d'une communication entre deux zones par electromouillage, dispositif comportant des zones isolables les unes des autres et procede de realisation d'un tel dispositif |
EP1924704B1 (en) | 2005-08-02 | 2011-05-25 | Rubicon Genomics, Inc. | Compositions and methods for processing and amplification of dna, including using multiple enzymes in a single reaction |
WO2007024840A2 (en) | 2005-08-22 | 2007-03-01 | Critical Therapeutics, Inc. | Method of quantitating nucleic acids by flow cytometry microparticle-based array |
JP2007074967A (ja) | 2005-09-13 | 2007-03-29 | Canon Inc | 識別子プローブ及びそれを用いた核酸増幅方法 |
CA2622719A1 (en) | 2005-09-16 | 2007-07-26 | The Regents Of The University Of California | A colorimetric bio-barcode amplification assay for analyte detection |
US7960104B2 (en) | 2005-10-07 | 2011-06-14 | Callida Genomics, Inc. | Self-assembled single molecule arrays and uses thereof |
EP1954838B1 (en) | 2005-11-14 | 2014-02-26 | Life Technologies Corporation | Coded molecules for detecting target analytes |
US20070134277A1 (en) | 2005-12-09 | 2007-06-14 | Children's Medical Center Corporation | Pharmaceutical formulation for sulfur-containing drugs in liquid dosage forms |
EP1963392B2 (en) | 2005-12-15 | 2012-08-01 | Akzo Nobel Coatings International BV | Multilayer coating system |
US20070141718A1 (en) | 2005-12-19 | 2007-06-21 | Bui Huy A | Reduction of scan time in imaging mass spectrometry |
US7932037B2 (en) | 2007-12-05 | 2011-04-26 | Perkinelmer Health Sciences, Inc. | DNA assays using amplicon probes on encoded particles |
CA2636855C (en) | 2006-01-11 | 2016-09-27 | Raindance Technologies, Inc. | Microfluidic devices and methods of use in the formation and control of nanoreactors |
US7537897B2 (en) | 2006-01-23 | 2009-05-26 | Population Genetics Technologies, Ltd. | Molecular counting |
WO2007087310A2 (en) | 2006-01-23 | 2007-08-02 | Population Genetics Technologies Ltd. | Nucleic acid analysis using sequence tokens |
AU2007210152A1 (en) | 2006-01-27 | 2007-08-09 | President And Fellows Of Harvard College | Fluidic droplet coalescence |
EP3591068A1 (en) | 2006-02-02 | 2020-01-08 | The Board of Trustees of the Leland Stanford Junior University | Non-invasive fetal genetic screening by digital analysis |
WO2007092538A2 (en) | 2006-02-07 | 2007-08-16 | President And Fellows Of Harvard College | Methods for making nucleotide probes for sequencing and synthesis |
GB0603251D0 (en) | 2006-02-17 | 2006-03-29 | Isis Innovation | DNA conformation |
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 |
WO2007111937A1 (en) | 2006-03-23 | 2007-10-04 | Applera Corporation | Directed enrichment of genomic dna for high-throughput sequencing |
JP4921829B2 (ja) | 2006-03-30 | 2012-04-25 | 株式会社東芝 | 微粒子の製造装置、乳化剤保持部、微粒子の製造方法および分子膜の製造方法 |
US20090181864A1 (en) | 2006-03-31 | 2009-07-16 | Nam Trung Nguyen | Active control for droplet-based microfluidics |
AU2007237909A1 (en) | 2006-04-19 | 2007-10-25 | Applied Biosystems, Llc. | Reagents, methods, and libraries for gel-free bead-based sequencing |
US7811603B2 (en) | 2006-05-09 | 2010-10-12 | The Regents Of The University Of California | Microfluidic device for forming monodisperse lipoplexes |
EP2047910B1 (en) | 2006-05-11 | 2012-01-11 | Raindance Technologies, Inc. | Microfluidic device and method |
ES2620398T3 (es) | 2006-05-22 | 2017-06-28 | Nanostring Technologies, Inc. | Sistemas y métodos para analizar nanoindicadores |
EP2029781A4 (en) | 2006-05-26 | 2010-06-30 | Althea Technologies Inc | BIOCHEMICAL ANALYSIS OF PARTITIONED CELLS |
FR2901717A1 (fr) | 2006-05-30 | 2007-12-07 | Centre Nat Rech Scient | Procede de traitement de gouttes dans un circuit microfluidique. |
EP4108780A1 (en) | 2006-06-14 | 2022-12-28 | Verinata Health, Inc. | Rare cell analysis using sample splitting and dna tags |
US8715934B2 (en) | 2006-06-19 | 2014-05-06 | The Johns Hopkins University | Single-molecule PCR on microparticles in water-in-oil emulsions |
WO2008005675A2 (en) | 2006-06-30 | 2008-01-10 | Applera Corporation | Emulsion pcr and amplicon capture |
EP1878501A1 (en) | 2006-07-14 | 2008-01-16 | Roche Diagnostics GmbH | Instrument for heating and cooling |
EP2077912B1 (en) | 2006-08-07 | 2019-03-27 | The President and Fellows of Harvard College | Fluorocarbon emulsion stabilizing surfactants |
CN104774275A (zh) | 2006-09-25 | 2015-07-15 | 阿彻-丹尼尔斯-米德兰德公司 | 超吸收性的经表面处理的羧烷基化多糖及其制备方法 |
US7935518B2 (en) | 2006-09-27 | 2011-05-03 | Alessandra Luchini | Smart hydrogel particles for biomarker harvesting |
WO2008052138A2 (en) | 2006-10-25 | 2008-05-02 | The Regents Of The University Of California | Inline-injection microdevice and microfabricated integrated dna analysis system using same |
US7910302B2 (en) | 2006-10-27 | 2011-03-22 | Complete Genomics, Inc. | Efficient arrays of amplified polynucleotides |
US20110045462A1 (en) | 2006-11-14 | 2011-02-24 | The Regents Of The University Of California | Digital analysis of gene expression |
DK2518162T3 (en) | 2006-11-15 | 2018-06-18 | Biospherex Llc | Multi-tag sequencing and ecogenomic analysis |
US20080242560A1 (en) | 2006-11-21 | 2008-10-02 | Gunderson Kevin L | Methods for generating amplified nucleic acid arrays |
WO2008072540A1 (ja) | 2006-12-13 | 2008-06-19 | National University Corporation Nagoya University | Tol1因子のトランスポザーゼ及びそれを用いたDNA導入システム |
US7844658B2 (en) | 2007-01-22 | 2010-11-30 | Comcast Cable Holdings, Llc | System and method for providing an application to a device |
US20080176768A1 (en) | 2007-01-23 | 2008-07-24 | Honeywell Honeywell International | Hydrogel microarray with embedded metal nanoparticles |
WO2008093098A2 (en) | 2007-02-02 | 2008-08-07 | Illumina Cambridge Limited | Methods for indexing samples and sequencing multiple nucleotide templates |
US8003312B2 (en) | 2007-02-16 | 2011-08-23 | The Board Of Trustees Of The Leland Stanford Junior University | Multiplex cellular assays using detectable cell barcodes |
FI20075124A0 (fi) | 2007-02-21 | 2007-02-21 | Valtion Teknillinen | Menetelmä ja testikitti nukleotidivariaatioiden toteamiseksi |
US9029085B2 (en) | 2007-03-07 | 2015-05-12 | President And Fellows Of Harvard College | Assays and other reactions involving droplets |
US20080228268A1 (en) | 2007-03-15 | 2008-09-18 | Uluru, Inc. | Method of Formation of Viscous, Shape Conforming Gels and Their Uses as Medical Prosthesis |
US7776927B2 (en) | 2007-03-28 | 2010-08-17 | President And Fellows Of Harvard College | Emulsions and techniques for formation |
WO2008134153A1 (en) | 2007-04-23 | 2008-11-06 | Advanced Liquid Logic, Inc. | Bead-based multiplexed analytical methods and instrumentation |
CN101293191B (zh) | 2007-04-25 | 2011-11-09 | 中国科学院过程工程研究所 | 一种琼脂糖凝胶微球的制备方法 |
CN101720359A (zh) | 2007-06-01 | 2010-06-02 | 454生命科学公司 | 从多重混合物中识别个别样本的系统和方法 |
WO2009005680A1 (en) | 2007-06-29 | 2009-01-08 | President And Fellows Of Harvard College | Methods and apparatus for manipulation of fluidic species |
WO2009011808A1 (en) | 2007-07-13 | 2009-01-22 | President And Fellows Of Harvard College | Droplet-based selection |
WO2009015296A1 (en) | 2007-07-24 | 2009-01-29 | The Regents Of The University Of California | Microfabricated dropley generator |
US20130084243A1 (en) | 2010-01-27 | 2013-04-04 | Liliane Goetsch | Igf-1r specific antibodies useful in the detection and diagnosis of cellular proliferative disorders |
US8563527B2 (en) | 2007-08-20 | 2013-10-22 | Pharmain Corporation | Oligonucleotide core carrier compositions for delivery of nucleic acid-containing therapeutic agents, methods of making and using the same |
US8268564B2 (en) | 2007-09-26 | 2012-09-18 | President And Fellows Of Harvard College | Methods and applications for stitched DNA barcodes |
WO2009048532A2 (en) | 2007-10-05 | 2009-04-16 | President And Fellows Of Harvard College | Formation of particles for ultrasound application, drug release, and other uses, and microfluidic methods of preparation |
US20090099040A1 (en) | 2007-10-15 | 2009-04-16 | Sigma Aldrich Company | Degenerate oligonucleotides and their uses |
US20100086914A1 (en) | 2008-10-03 | 2010-04-08 | Roche Molecular Systems, Inc. | High resolution, high throughput hla genotyping by clonal sequencing |
WO2009061372A1 (en) | 2007-11-02 | 2009-05-14 | President And Fellows Of Harvard College | Systems and methods for creating multi-phase entities, including particles and/or fluids |
US8592150B2 (en) | 2007-12-05 | 2013-11-26 | Complete Genomics, Inc. | Methods and compositions for long fragment read sequencing |
CN101918590B (zh) | 2007-12-10 | 2013-03-27 | 高晓莲 | 核酸测序 |
US7771944B2 (en) | 2007-12-14 | 2010-08-10 | The Board Of Trustees Of The University Of Illinois | Methods for determining genetic haplotypes and DNA mapping |
EP2235210B1 (en) | 2007-12-21 | 2015-03-25 | President and Fellows of Harvard College | Methods for nucleic acid sequencing |
EP3699291A1 (en) | 2008-01-17 | 2020-08-26 | Sequenom, Inc. | Single molecule nucleic acid sequence analysis processes and compositions |
EP2252625B1 (en) | 2008-02-07 | 2017-12-20 | Pacific Biosciences of California, Inc. | Cis reactive oxygen quenchers integrated into linkers |
JP5468271B2 (ja) | 2008-02-08 | 2014-04-09 | 花王株式会社 | 微粒子分散液の製造方法 |
US20090203531A1 (en) | 2008-02-12 | 2009-08-13 | Nurith Kurn | Method for Archiving and Clonal Expansion |
US9068181B2 (en) | 2008-05-23 | 2015-06-30 | The General Hospital Corporation | Microfluidic droplet encapsulation |
GB0810051D0 (en) | 2008-06-02 | 2008-07-09 | Oxford Biodynamics Ltd | Method of diagnosis |
WO2009148598A1 (en) | 2008-06-05 | 2009-12-10 | President And Fellows Of Harvard College | Polymersomes, colloidosomes, liposomes, and other species associated with fluidic droplets |
US8198028B2 (en) | 2008-07-02 | 2012-06-12 | Illumina Cambridge Limited | Using populations of beads for the fabrication of arrays on surfaces |
US8388945B2 (en) | 2008-07-11 | 2013-03-05 | Eth Zurich | Degradable microcapsules |
WO2010009365A1 (en) | 2008-07-18 | 2010-01-21 | Raindance Technologies, Inc. | Droplet libraries |
US10722562B2 (en) | 2008-07-23 | 2020-07-28 | Immudex Aps | Combinatorial analysis and repair |
US20100062494A1 (en) | 2008-08-08 | 2010-03-11 | President And Fellows Of Harvard College | Enzymatic oligonucleotide pre-adenylation |
US8383345B2 (en) | 2008-09-12 | 2013-02-26 | University Of Washington | Sequence tag directed subassembly of short sequencing reads into long sequencing reads |
US20110218123A1 (en) | 2008-09-19 | 2011-09-08 | President And Fellows Of Harvard College | Creation of libraries of droplets and related species |
US20120252015A1 (en) | 2011-02-18 | 2012-10-04 | Bio-Rad Laboratories | Methods and compositions for detecting genetic material |
US9156010B2 (en) | 2008-09-23 | 2015-10-13 | Bio-Rad Laboratories, Inc. | Droplet-based assay system |
US8709762B2 (en) | 2010-03-02 | 2014-04-29 | Bio-Rad Laboratories, Inc. | System for hot-start amplification via a multiple emulsion |
CA2735899A1 (en) | 2008-09-25 | 2010-04-01 | Cephalon, Inc. | Liquid formulations of bendamustine |
US8361299B2 (en) | 2008-10-08 | 2013-01-29 | Sage Science, Inc. | Multichannel preparative electrophoresis system |
DK2376517T3 (da) | 2008-10-24 | 2013-02-11 | Epict Technologies Corp | Transposon-ende-sammensætninger og fremgangsmåder til at modificere nukleinsyrer |
US9080211B2 (en) | 2008-10-24 | 2015-07-14 | Epicentre Technologies Corporation | Transposon end compositions and methods for modifying nucleic acids |
US20100113296A1 (en) | 2008-11-05 | 2010-05-06 | Joel Myerson | Methods And Kits For Nucleic Acid Analysis |
US8748103B2 (en) | 2008-11-07 | 2014-06-10 | Sequenta, Inc. | Monitoring health and disease status using clonotype profiles |
SG171916A1 (en) | 2008-12-02 | 2011-07-28 | Bio Rad Laboratories | Chromatin structure detection |
EP3290531B1 (en) | 2008-12-19 | 2019-07-24 | President and Fellows of Harvard College | Particle-assisted nucleic acid sequencing |
KR101065807B1 (ko) | 2009-01-23 | 2011-09-19 | 충남대학교산학협력단 | 액적 기반의 미세유체 칩을 이용한 마이크로 캡슐 제조방법 |
US9347092B2 (en) | 2009-02-25 | 2016-05-24 | Roche Molecular System, Inc. | Solid support for high-throughput nucleic acid analysis |
JP5457222B2 (ja) | 2009-02-25 | 2014-04-02 | エフ.ホフマン−ラ ロシュ アーゲー | 小型化ハイスループット核酸分析 |
BRPI1008965B1 (pt) | 2009-03-13 | 2018-12-18 | Harvard College | método para aumento de escala de dispositivos microfluídicos e sistema para a formação de gotículas em canais microfluídicos em paralelo |
WO2010104604A1 (en) | 2009-03-13 | 2010-09-16 | President And Fellows Of Harvard College | Method for the controlled creation of emulsions, including multiple emulsions |
EP2230312A1 (en) | 2009-03-19 | 2010-09-22 | Helmholtz-Zentrum für Infektionsforschung GmbH | Probe compound for detecting and isolating enzymes and means and methods using the same |
WO2010111231A1 (en) | 2009-03-23 | 2010-09-30 | Raindance Technologies, Inc. | Manipulation of microfluidic droplets |
US20120010091A1 (en) | 2009-03-30 | 2012-01-12 | Illumina, Inc. | Gene expression analysis in single cells |
AU2010232439C1 (en) | 2009-04-02 | 2017-07-13 | Fluidigm Corporation | Multi-primer amplification method for barcoding of target nucleic acids |
FR2945545B1 (fr) | 2009-05-14 | 2011-08-05 | Univ Aix Marseille Ii | Methode de detection d'adn procaryote extrait d'un echantillon de selles |
FR2945819B1 (fr) | 2009-05-19 | 2011-06-17 | Commissariat Energie Atomique | Dispositif et procede d'isolement de cibles biologiques ou chimiques |
US8574835B2 (en) | 2009-05-29 | 2013-11-05 | Life Technologies Corporation | Scaffolded nucleic acid polymer particles and methods of making and using |
CA2765427A1 (en) | 2009-06-15 | 2010-12-23 | Complete Genomics, Inc. | Methods and compositions for long fragment read sequencing |
US9524369B2 (en) | 2009-06-15 | 2016-12-20 | Complete Genomics, Inc. | Processing and analysis of complex nucleic acid sequence data |
EP4019977A1 (en) | 2009-06-26 | 2022-06-29 | President and Fellows of Harvard College | Fluid injection |
US20110028412A1 (en) | 2009-08-03 | 2011-02-03 | Cappellos, Inc. | Herbal enhanced analgesic formulations |
US20110033548A1 (en) | 2009-08-05 | 2011-02-10 | E.I. Du Pont De Nemours And Company | Degradable crosslinked aminated dextran microspheres and methods of use |
WO2011021102A2 (en) | 2009-08-20 | 2011-02-24 | Population Genetics Technologies Ltd | Compositions and methods for intramolecular nucleic acid rearrangement |
BR112012004382A2 (pt) | 2009-09-01 | 2016-03-22 | Koninkl Philips Electronics Nv | dispositivo para a seleção específica de moléculas-alvo, método para selecionar especificamente moléculas-alvo e uso de um dispositivo |
JP5869482B2 (ja) | 2009-09-02 | 2016-02-24 | 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 | ジェッティングおよび他の技術を使用して生成された多重エマルジョン |
EP2940153B1 (en) | 2009-09-02 | 2020-05-13 | Bio-Rad Laboratories, Inc. | System for mixing fluids by coalescence of multiple emulsions |
US9625454B2 (en) | 2009-09-04 | 2017-04-18 | The Research Foundation For The State University Of New York | Rapid and continuous analyte processing in droplet microfluidic devices |
JP5954876B2 (ja) | 2009-10-13 | 2016-07-20 | ナノストリング テクノロジーズ, インコーポレイテッド | ナノレポーターによるタンパク質の検出 |
GB0918564D0 (en) | 2009-10-22 | 2009-12-09 | Plasticell Ltd | Nested cell encapsulation |
EP3461558B1 (en) | 2009-10-27 | 2021-03-17 | President and Fellows of Harvard College | Droplet creation techniques |
WO2011056872A2 (en) | 2009-11-03 | 2011-05-12 | Gen9, Inc. | Methods and microfluidic devices for the manipulation of droplets in high fidelity polynucleotide assembly |
RU2573409C2 (ru) | 2009-11-04 | 2016-01-20 | Дзе Юниверсити Оф Бритиш Коламбиа | Содержащие нуклеиновые кислоты липидные частицы и относящиеся к ним способы |
EP2504448B1 (en) | 2009-11-25 | 2016-10-19 | Bio-Rad Laboratories, Inc. | Methods and compositions for detecting genetic material |
CA2767028A1 (en) | 2009-11-25 | 2011-06-03 | Quantalife, Inc. | Methods and compositions for detecting genetic material |
US9023769B2 (en) | 2009-11-30 | 2015-05-05 | Complete Genomics, Inc. | cDNA library for nucleic acid sequencing |
US8835358B2 (en) | 2009-12-15 | 2014-09-16 | Cellular Research, Inc. | Digital counting of individual molecules by stochastic attachment of diverse labels |
WO2011074960A1 (en) | 2009-12-17 | 2011-06-23 | Keygene N.V. | Restriction enzyme based whole genome sequencing |
EP2517025B1 (en) | 2009-12-23 | 2019-11-27 | Bio-Rad Laboratories, Inc. | Methods for reducing the exchange of molecules between droplets |
US8889416B2 (en) * | 2010-01-21 | 2014-11-18 | California Institute Of Technology | Methods and devices for micro-isolation, extraction, and/or analysis of microscale components |
JP5901046B2 (ja) | 2010-02-19 | 2016-04-06 | 国立大学法人 千葉大学 | OATP1B3mRNAの新規な選択的スプライシングバリアント |
CA2767182C (en) | 2010-03-25 | 2020-03-24 | Bio-Rad Laboratories, Inc. | Droplet generation for droplet-based assays |
PT2556171E (pt) * | 2010-04-05 | 2015-12-21 | Prognosys Biosciences Inc | Ensaios biológicos codificados espacialmente |
US20110287947A1 (en) * | 2010-05-18 | 2011-11-24 | University Of Southern California | Tethered Conformation Capture |
US20120000777A1 (en) | 2010-06-04 | 2012-01-05 | The Regents Of The University Of California | Devices and methods for forming double emulsion droplet compositions and polymer particles |
US8703493B2 (en) | 2010-06-15 | 2014-04-22 | Src, Inc. | Location analysis using fire retardant-protected nucleic acid-labeled tags |
US20120003657A1 (en) | 2010-07-02 | 2012-01-05 | Samuel Myllykangas | Targeted sequencing library preparation by genomic dna circularization |
WO2012005595A2 (en) * | 2010-07-09 | 2012-01-12 | Wouter Leonard De Laat | V3-d genomic region of interest sequencing strategies |
WO2012012037A1 (en) | 2010-07-19 | 2012-01-26 | New England Biolabs, Inc. | Oligonucleotide adaptors: compositions and methods of use |
CN103202812B (zh) | 2010-08-09 | 2015-10-28 | 南京大学 | 一种制备用于体内递送药理活性物质的蛋白纳米粒的方法 |
CN103328007B (zh) | 2010-09-16 | 2016-09-21 | 北卡罗来纳州大学查珀尔希尔分校 | 作为药物试剂、化学试剂和生物试剂的递送载剂和前药的不对称双官能甲硅烷基单体及其颗粒 |
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 |
US9187783B2 (en) | 2010-10-04 | 2015-11-17 | Genapsys, Inc. | Systems and methods for automated reusable parallel biological reactions |
US9999886B2 (en) | 2010-10-07 | 2018-06-19 | The Regents Of The University Of California | Methods and systems for on demand droplet generation and impedance based detection |
CA2814049C (en) | 2010-10-08 | 2021-07-13 | President And Fellows Of Harvard College | High-throughput single cell barcoding |
US10392726B2 (en) | 2010-10-08 | 2019-08-27 | President And Fellows Of Harvard College | High-throughput immune sequencing |
US20130225623A1 (en) | 2010-10-27 | 2013-08-29 | Mount Sinai School Of Medicine | Methods of Treating Psychiatric or Neurological Disorders with MGLUR Antagonists |
US9074251B2 (en) | 2011-02-10 | 2015-07-07 | Illumina, Inc. | Linking sequence reads using paired code tags |
EP2635679B1 (en) | 2010-11-05 | 2017-04-19 | Illumina, Inc. | Linking sequence reads using paired code tags |
US8829171B2 (en) | 2011-02-10 | 2014-09-09 | Illumina, Inc. | Linking sequence reads using paired code tags |
EP2652155B1 (en) | 2010-12-16 | 2016-11-16 | Gigagen, Inc. | Methods for massively parallel analysis of nucleic acids in single cells |
GB201101429D0 (en) | 2011-01-27 | 2011-03-16 | Biocompatibles Uk Ltd | Drug delivery system |
US8765455B2 (en) | 2011-01-27 | 2014-07-01 | Lawrence Livermore National Security, Llc | Chip-based droplet sorting |
AU2012211081B2 (en) | 2011-01-28 | 2016-02-04 | Illumina, Inc. | Oligonucleotide replacement for di-tagged and directional libraries |
WO2012106546A2 (en) | 2011-02-02 | 2012-08-09 | University Of Washington Through Its Center For Commercialization | Massively parallel continguity mapping |
AU2012214312A1 (en) * | 2011-02-09 | 2013-08-22 | Bio-Rad Laboratories, Inc. | Analysis of nucleic acids |
WO2012129363A2 (en) | 2011-03-24 | 2012-09-27 | President And Fellows Of Harvard College | Single cell nucleic acid detection and analysis |
GB2489714B (en) | 2011-04-05 | 2013-11-06 | Tracesa Ltd | Fluid Identification Method |
US20140141442A1 (en) * | 2011-04-05 | 2014-05-22 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Linear dna amplification |
GB201106254D0 (en) * | 2011-04-13 | 2011-05-25 | Frisen Jonas | Method and product |
SI2702146T1 (sl) | 2011-04-28 | 2019-06-28 | The Board Of Trustees Of The Leland Stanford Junior University | Identifikacija polinukleotidov, povezanih z vzorcem |
CN106912197B (zh) | 2011-04-28 | 2022-01-25 | 生命技术公司 | 用于多重pcr的方法和组合物 |
WO2012157684A1 (ja) | 2011-05-16 | 2012-11-22 | 地方独立行政法人 大阪府立病院機構 | 血中dnaの定量的検出による悪性新生物の病勢の進行を評価する方法 |
US9005935B2 (en) | 2011-05-23 | 2015-04-14 | Agilent Technologies, Inc. | Methods and compositions for DNA fragmentation and tagging by transposases |
KR20140034242A (ko) | 2011-05-23 | 2014-03-19 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 다중 에멀젼을 포함하는 에멀젼의 제어 |
EP2714938B1 (en) | 2011-05-27 | 2017-11-15 | President and Fellows of Harvard College | Methods of amplifying whole genome of a single cell |
US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
US9150916B2 (en) | 2011-06-24 | 2015-10-06 | Beat Christen | Compositions and methods for identifying the essential genome of an organism |
US8927218B2 (en) | 2011-06-27 | 2015-01-06 | Flir Systems, Inc. | Methods and compositions for segregating target nucleic acid from mixed nucleic acid samples |
US8975302B2 (en) | 2011-07-07 | 2015-03-10 | Life Technologies Corporation | Polymer particles, nucleic acid polymer particles and methods of making and using the same |
US20130017978A1 (en) | 2011-07-11 | 2013-01-17 | Finnzymes Oy | Methods and transposon nucleic acids for generating a dna library |
US9605304B2 (en) | 2011-07-20 | 2017-03-28 | The Hong Kong Polytechnic University | Ultra-stable oligonucleotide-gold and-silver nanoparticle conjugates and method of their preparation |
US20130189700A1 (en) | 2011-07-25 | 2013-07-25 | Bio-Rad Laboratories, Inc. | Breakage of an emulsion containing nucleic acid |
EP2737089B1 (en) | 2011-07-29 | 2017-09-06 | Bio-rad Laboratories, Inc. | Library characterization by digital assay |
US9725765B2 (en) | 2011-09-09 | 2017-08-08 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for obtaining a sequence |
US9514272B2 (en) | 2011-10-12 | 2016-12-06 | Complete Genomics, Inc. | Identification of DNA fragments and structural variations |
US9469874B2 (en) | 2011-10-18 | 2016-10-18 | The Regents Of The University Of California | Long-range barcode labeling-sequencing |
US20130109576A1 (en) | 2011-10-28 | 2013-05-02 | Anthony P. Shuber | Methods for detecting mutations |
US9385791B2 (en) | 2011-11-04 | 2016-07-05 | Intel Corporation | Signaling for configuration of downlink coordinated multipoint communications |
EP2786019B1 (en) | 2011-11-16 | 2018-07-25 | International Business Machines Corporation | Microfluidic device with deformable valve |
US10689643B2 (en) | 2011-11-22 | 2020-06-23 | Active Motif, Inc. | Targeted transposition for use in epigenetic studies |
US9938524B2 (en) | 2011-11-22 | 2018-04-10 | Active Motif, Inc. | Multiplex isolation of protein-associated nucleic acids |
EP4108782B1 (en) | 2011-12-22 | 2023-06-07 | President and Fellows of Harvard College | Compositions and methods for analyte detection |
US20150125865A1 (en) | 2011-12-23 | 2015-05-07 | Gigagen, Inc. | Methods And Apparatuses For Droplet Mixing |
CN106883334B (zh) | 2012-02-09 | 2019-06-18 | 生命技术公司 | 亲水性聚合物颗粒及其制备方法 |
WO2013122996A1 (en) | 2012-02-14 | 2013-08-22 | The Johns Hopkins University | Mirna analysis methods |
EP2814472A4 (en) | 2012-02-15 | 2015-11-04 | Wisconsin Alumni Res Found | DITHIOAMINE REDUCING AGENTS |
US10202628B2 (en) | 2012-02-17 | 2019-02-12 | President And Fellows Of Harvard College | Assembly of nucleic acid sequences in emulsions |
EP2817418B1 (en) | 2012-02-24 | 2017-10-11 | Raindance Technologies, Inc. | Labeling and sample preparation for sequencing |
NO2694769T3 (ja) | 2012-03-06 | 2018-03-03 | ||
EP2647426A1 (en) * | 2012-04-03 | 2013-10-09 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Replication of distributed nucleic acid molecules with preservation of their relative distribution through hybridization-based binding |
CA2870160C (en) | 2012-04-16 | 2021-08-24 | Biological Dynamics, Inc. | Nucleic acid sample preparation |
US20130296173A1 (en) | 2012-04-23 | 2013-11-07 | Complete Genomics, Inc. | Pre-anchor wash |
EP3514243B1 (en) | 2012-05-21 | 2022-08-17 | The Scripps Research Institute | Methods of sample preparation |
JP6558830B2 (ja) | 2012-06-15 | 2019-08-14 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | 複数転写産物のハイスループットシークエンシング |
US20150376609A1 (en) | 2014-06-26 | 2015-12-31 | 10X Genomics, Inc. | Methods of Analyzing Nucleic Acids from Individual Cells or Cell Populations |
US9701998B2 (en) | 2012-12-14 | 2017-07-11 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US9951386B2 (en) | 2014-06-26 | 2018-04-24 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US20150005199A1 (en) | 2012-08-14 | 2015-01-01 | 10X Technologies, Inc. | Compositions and methods for sample processing |
US20140378322A1 (en) | 2012-08-14 | 2014-12-25 | 10X Technologies, Inc. | Compositions and methods for sample processing |
US10221442B2 (en) | 2012-08-14 | 2019-03-05 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US20150005200A1 (en) | 2012-08-14 | 2015-01-01 | 10X Technologies, Inc. | Compositions and methods for sample processing |
US20140378349A1 (en) | 2012-08-14 | 2014-12-25 | 10X Technologies, Inc. | Compositions and methods for sample processing |
US20140378345A1 (en) | 2012-08-14 | 2014-12-25 | 10X Technologies, Inc. | Compositions and methods for sample processing |
EP2898096B1 (en) | 2012-09-21 | 2024-02-14 | The Broad Institute, Inc. | Methods for labeling of rnas |
US9644199B2 (en) | 2012-10-01 | 2017-05-09 | Agilent Technologies, Inc. | Immobilized transposase complexes for DNA fragmentation and tagging |
GB201217772D0 (en) | 2012-10-04 | 2012-11-14 | Base4 Innovation Ltd | Sequencing method |
CN107541546B (zh) | 2012-10-15 | 2021-06-15 | 生命技术公司 | 用于标靶核酸富集的组合物、方法、系统和试剂盒 |
CA2886974C (en) * | 2012-10-17 | 2021-06-29 | Spatial Transcriptomics Ab | Methods and product for optimising localised or spatial detection of gene expression in a tissue sample |
EP2911664B1 (en) | 2012-10-25 | 2019-05-08 | The General Hospital Corporation | Combination therapies for the treatment of alzheimer's disease and related disorders |
CA2889862C (en) | 2012-11-05 | 2021-02-16 | Rubicon Genomics, Inc. | Barcoding nucleic acids |
WO2014074611A1 (en) | 2012-11-07 | 2014-05-15 | Good Start Genetics, Inc. | Methods and systems for identifying contamination in samples |
CN105026576A (zh) | 2012-12-03 | 2015-11-04 | 以琳生物药物有限公司 | 单链多核苷酸扩增方法 |
US20140242664A1 (en) | 2012-12-12 | 2014-08-28 | The Broad Institute, Inc. | Engineering of systems, methods and optimized guide compositions for sequence manipulation |
CA2894694C (en) | 2012-12-14 | 2023-04-25 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
EP2752664A1 (en) | 2013-01-07 | 2014-07-09 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Label-free method for the detection of analytes |
US9683230B2 (en) | 2013-01-09 | 2017-06-20 | Illumina Cambridge Limited | Sample preparation on a solid support |
CA2900481A1 (en) | 2013-02-08 | 2014-08-14 | 10X Genomics, Inc. | Polynucleotide barcode generation |
WO2014138711A1 (en) | 2013-03-08 | 2014-09-12 | Bio-Rad Laboratories, Inc. | Compositions, methods and systems for polymerase chain reaction assays |
DK3553175T3 (da) | 2013-03-13 | 2021-08-23 | Illumina Inc | Fremgangsmåde til fremstilling af et nukleinsyresekvenseringsbibliotek |
US9273349B2 (en) | 2013-03-14 | 2016-03-01 | Affymetrix, Inc. | Detection of nucleic acids |
EP2971080B1 (en) | 2013-03-15 | 2018-01-03 | Expedeon, S.L. | Methods for amplification and sequencing using thermostable tthprimpol |
AU2014233373B2 (en) | 2013-03-15 | 2019-10-24 | Verinata Health, Inc. | Generating cell-free DNA libraries directly from blood |
CA2907050C (en) | 2013-03-15 | 2023-09-26 | Prognosys Biosciences, Inc. | Methods for detecting peptide/mhc/tcr binding |
GB2525568B (en) | 2013-03-15 | 2020-10-14 | Abvitro Llc | Single cell barcoding for antibody discovery |
US20140274729A1 (en) | 2013-03-15 | 2014-09-18 | Nugen Technologies, Inc. | Methods, compositions and kits for generation of stranded rna or dna libraries |
US9328382B2 (en) | 2013-03-15 | 2016-05-03 | Complete Genomics, Inc. | Multiple tagging of individual long DNA fragments |
CN105431575B (zh) | 2013-05-09 | 2017-08-29 | 生物辐射实验室股份有限公司 | 磁性免疫数字pcr试验 |
AU2014268710B2 (en) | 2013-05-23 | 2018-10-18 | The Board Of Trustees Of The Leland Stanford Junior University | Transposition into native chromatin for personal epigenomics |
WO2014201273A1 (en) | 2013-06-12 | 2014-12-18 | The Broad Institute, Inc. | High-throughput rna-seq |
CA2915033C (en) | 2013-06-12 | 2023-08-29 | The General Hospital Corporation | Methods, kits, and systems for multiplexed detection of target molecules and uses thereof |
BR112015031608A2 (pt) | 2013-06-17 | 2017-08-22 | Massachusetts Inst Technology | Aplicação e uso dos sistemas crispr-cas, vetores e composições para direcionamento e terapia hepáticos |
US20160208323A1 (en) | 2013-06-21 | 2016-07-21 | The Broad Institute, Inc. | Methods for Shearing and Tagging DNA for Chromatin Immunoprecipitation and Sequencing |
WO2014210223A1 (en) | 2013-06-25 | 2014-12-31 | Prognosys Biosciences, Inc. | Spatially encoded biological assays using a microfluidic device |
KR102436171B1 (ko) | 2013-06-27 | 2022-08-24 | 10엑스 제노믹스, 인크. | 샘플 처리를 위한 조성물 및 방법 |
US9840718B2 (en) | 2013-07-12 | 2017-12-12 | University Of South Alabama | Minimal piggyBac vectors for genome integration |
SG10201806890VA (en) | 2013-08-28 | 2018-09-27 | Cellular Res Inc | Massively parallel single cell analysis |
CN105764490B (zh) | 2013-09-24 | 2020-10-09 | 加利福尼亚大学董事会 | 用于生物测定和诊断的胶囊封装的传感器和感测系统及其制造和使用方法 |
GB201317301D0 (en) | 2013-09-30 | 2013-11-13 | Linnarsson Sten | Method for capturing and encoding nucleic acid from a plurality of single cells |
WO2015065924A2 (en) | 2013-10-28 | 2015-05-07 | Massachusetts Institute Of Technology | Hydrogel microstructures with immiscible fluid isolation for small reaction volumes |
US9834814B2 (en) * | 2013-11-22 | 2017-12-05 | Agilent Technologies, Inc. | Spatial molecular barcoding of in situ nucleic acids |
CA2933387C (en) * | 2013-12-11 | 2023-05-02 | The Regents Of The University Of California | Methods for labeling dna fragments to reconstruct physical linkage and phase |
US20140315755A1 (en) | 2013-12-26 | 2014-10-23 | Tao Chen | Genome-wide Antisense Oligonucleotide and RNAi |
ES2912183T3 (es) | 2013-12-30 | 2022-05-24 | Atreca Inc | Análisis de ácidos nucleicos asociados a células individuales utilizando códigos de barras de ácidos nucleicos |
WO2015113725A1 (en) | 2014-02-03 | 2015-08-06 | Thermo Fisher Scientific Baltics Uab | Method for controlled dna fragmentation |
CN105531408B (zh) * | 2014-02-13 | 2019-09-10 | 生物辐射实验室股份有限公司 | 染色体构象划分产物捕获 |
WO2015131110A1 (en) | 2014-02-27 | 2015-09-03 | Igenomx International Genomics Corporation | Methods for analysis of somatic mobile elements, and uses thereof |
AU2015243445B2 (en) | 2014-04-10 | 2020-05-28 | 10X Genomics, Inc. | Fluidic devices, systems, and methods for encapsulating and partitioning reagents, and applications of same |
TWI682997B (zh) | 2014-04-15 | 2020-01-21 | 美商伊路米納有限公司 | 用於改善插入序列傾向及增加dna輸入耐受度之經修飾的轉位酶 |
US20150298091A1 (en) | 2014-04-21 | 2015-10-22 | President And Fellows Of Harvard College | Systems and methods for barcoding nucleic acids |
CN107075543B (zh) | 2014-04-21 | 2021-11-16 | 哈佛学院院长及董事 | 用于条形码化核酸的系统和方法 |
US10975371B2 (en) | 2014-04-29 | 2021-04-13 | Illumina, Inc. | Nucleic acid sequence analysis from single cells |
WO2015179706A1 (en) | 2014-05-23 | 2015-11-26 | Fluidigm Corporation | Haploidome determination by digitized transposons |
JP5949832B2 (ja) | 2014-05-30 | 2016-07-13 | ダイキン工業株式会社 | 空調システム |
AU2015271324B2 (en) | 2014-06-06 | 2019-09-12 | Herlev Hospital | Determining antigen recognition through barcoding of MHC multimers |
US9534215B2 (en) | 2014-06-11 | 2017-01-03 | Life Technologies Corporation | Systems and methods for substrate enrichment |
US11585806B2 (en) | 2014-06-13 | 2023-02-21 | Immudex Aps | General detection and isolation of specific cells by binding of labeled molecules |
CN114214314A (zh) | 2014-06-24 | 2022-03-22 | 生物辐射实验室股份有限公司 | 数字式pcr条码化 |
US20150376605A1 (en) | 2014-06-26 | 2015-12-31 | 10X Genomics, Inc. | Methods and Compositions for Sample Analysis |
US20150376700A1 (en) | 2014-06-26 | 2015-12-31 | 10X Genomics, Inc. | Analysis of nucleic acid sequences |
JP2017526046A (ja) | 2014-06-26 | 2017-09-07 | 10エックス ゲノミクス,インコーポレイテッド | 核酸配列アセンブルのプロセス及びシステム |
US10017759B2 (en) | 2014-06-26 | 2018-07-10 | Illumina, Inc. | Library preparation of tagged nucleic acid |
US20160024558A1 (en) | 2014-07-23 | 2016-01-28 | 10X Genomics, Inc. | Nucleic acid binding proteins and uses thereof |
EP3191605B1 (en) | 2014-09-09 | 2022-07-27 | The Broad Institute, Inc. | A droplet-based method and apparatus for composite single-cell nucleic acid analysis |
AU2015318011B2 (en) | 2014-09-15 | 2020-07-23 | Abvitro Llc | High-throughput nucleotide library sequencing |
IL299976A (en) | 2014-10-17 | 2023-03-01 | Illumina Cambridge Ltd | Continuity-preserving transposition |
US20160122817A1 (en) | 2014-10-29 | 2016-05-05 | 10X Genomics, Inc. | Methods and compositions for targeted nucleic acid sequencing |
SG11201705615UA (en) | 2015-01-12 | 2017-08-30 | 10X Genomics Inc | Processes and systems for preparing nucleic acid sequencing libraries and libraries prepared using same |
CN115011670A (zh) | 2015-02-04 | 2022-09-06 | 加利福尼亚大学董事会 | 通过在离散实体中条形码化对核酸进行测序 |
EP3262188B1 (en) | 2015-02-24 | 2021-05-05 | 10X Genomics, Inc. | Methods for targeted nucleic acid sequence coverage |
EP3262407B1 (en) | 2015-02-24 | 2023-08-30 | 10X Genomics, Inc. | Partition processing methods and systems |
EP3277838A1 (en) | 2015-03-30 | 2018-02-07 | Verily Life Sciences LLC | Methods for combining single cell profiling with combinatorial nanoparticle conjugate library screening |
CN107532207B (zh) | 2015-04-10 | 2021-05-07 | 空间转录公司 | 生物样本的空间区别、多重核酸分析 |
EP3283641B1 (en) | 2015-04-14 | 2019-11-27 | Koninklijke Philips N.V. | Spatial mapping of molecular profiles of biological tissue samples |
CN107532218A (zh) | 2015-05-18 | 2018-01-02 | 10X基因组学有限公司 | 稳定化还原剂及其使用方法 |
CN107580627A (zh) | 2015-05-18 | 2018-01-12 | 10X基因组学有限公司 | 用于生物化学反应和分析中的流动固相组合物 |
WO2016187717A1 (en) | 2015-05-26 | 2016-12-01 | Exerkine Corporation | Exosomes useful for genome editing |
WO2016191618A1 (en) | 2015-05-27 | 2016-12-01 | Jianbiao Zheng | Methods of inserting molecular barcodes |
EP3314015A1 (en) | 2015-06-24 | 2018-05-02 | Oxford Biodynamics Limited | Detection of chromosome interactions |
JP2018527947A (ja) | 2015-07-17 | 2018-09-27 | 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 | 核酸配列増幅方法 |
PT3334841T (pt) | 2015-08-12 | 2020-01-30 | Cemm Forschungszentrum Fuer Molekulare Medizin Gmbh | Métodos para estudar ácidos nucleicos |
US11156611B2 (en) | 2015-09-24 | 2021-10-26 | Abvitro Llc | Single cell characterization using affinity-oligonucleotide conjugates and vessel barcoded polynucleotides |
FR3042658B1 (fr) | 2015-10-15 | 2017-10-27 | Renault Sas | Dispositif de gestion thermique d'un groupe motopropulseur electrique. |
WO2017075294A1 (en) | 2015-10-28 | 2017-05-04 | The Board Institute Inc. | Assays for massively combinatorial perturbation profiling and cellular circuit reconstruction |
WO2017075265A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute, Inc. | Multiplex analysis of single cell constituents |
WO2017087910A1 (en) | 2015-11-19 | 2017-05-26 | 10X Genomics, Inc. | Transformable tagging compositions, methods, and processes incorporating same |
SG11201804086VA (en) | 2015-12-04 | 2018-06-28 | 10X Genomics Inc | Methods and compositions for nucleic acid analysis |
US20170260584A1 (en) | 2016-02-11 | 2017-09-14 | 10X Genomics, Inc. | Cell population analysis using single nucleotide polymorphisms from single cell transcriptomes |
US11680253B2 (en) | 2016-03-10 | 2023-06-20 | The Board Of Trustees Of The Leland Stanford Junior University | Transposase-mediated imaging of the accessible genome |
US10858699B2 (en) | 2016-08-30 | 2020-12-08 | Integrated Dna Technologies, Inc. | Cleavable hairpin primers |
CN109923216A (zh) | 2016-08-31 | 2019-06-21 | 哈佛学院董事及会员团体 | 将生物分子的检测组合到使用荧光原位测序的单个试验的方法 |
EP4026905B1 (en) | 2016-10-19 | 2024-04-17 | 10X Genomics, Inc. | Methods for barcoding nucleic acid molecules from individual cells or cell populations |
GB201619458D0 (en) | 2016-11-17 | 2017-01-04 | Spatial Transcriptomics Ab | Method for spatial tagging and analysing nucleic acids in a biological specimen |
CN110139932A (zh) | 2016-12-19 | 2019-08-16 | 生物辐射实验室股份有限公司 | 液滴加标的相邻性保留的标签化dna |
US10011872B1 (en) | 2016-12-22 | 2018-07-03 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
EP4029939B1 (en) | 2017-01-30 | 2023-06-28 | 10X Genomics, Inc. | Methods and systems for droplet-based single cell barcoding |
-
2016
- 2016-12-02 SG SG11201804086VA patent/SG11201804086VA/en unknown
- 2016-12-02 DK DK21157421.5T patent/DK3882357T3/da active
- 2016-12-02 ES ES21157421T patent/ES2926495T3/es active Active
- 2016-12-02 WO PCT/US2016/064611 patent/WO2017096158A1/en active Application Filing
- 2016-12-02 PT PT211574215T patent/PT3882357T/pt unknown
- 2016-12-02 US US15/367,660 patent/US10774370B2/en active Active
- 2016-12-02 EP EP22181577.2A patent/EP4144861A1/en active Pending
- 2016-12-02 CN CN202211197364.4A patent/CN115369161A/zh active Pending
- 2016-12-02 EP EP16822294.1A patent/EP3384048B1/en active Active
- 2016-12-02 DE DE202016009134.5U patent/DE202016009134U1/de active Active
- 2016-12-02 SG SG10202108763UA patent/SG10202108763UA/en unknown
- 2016-12-02 JP JP2018524457A patent/JP6954899B2/ja active Active
- 2016-12-02 CN CN201680070638.XA patent/CN108431232B/zh active Active
- 2016-12-02 EP EP21157421.5A patent/EP3882357B1/en active Active
- 2016-12-02 KR KR1020187018978A patent/KR20180081164A/ko not_active Application Discontinuation
-
2018
- 2018-05-31 IL IL259736A patent/IL259736A/en unknown
- 2018-11-14 US US16/191,343 patent/US11473125B2/en active Active
-
2020
- 2020-09-14 US US17/020,684 patent/US20210238660A1/en not_active Abandoned
-
2021
- 2021-03-08 US US17/195,514 patent/US11624085B2/en active Active
- 2021-09-30 JP JP2021161303A patent/JP7182679B2/ja active Active
-
2022
- 2022-09-12 US US17/943,064 patent/US11873528B2/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20120220494A1 (en) * | 2011-02-18 | 2012-08-30 | Raindance Technolgies, Inc. | Compositions and methods for molecular labeling |
JP2014512826A (ja) * | 2011-04-25 | 2014-05-29 | バイオ−ラド ラボラトリーズ インコーポレイテッド | 核酸分析のための方法および組成物 |
WO2013134261A1 (en) * | 2012-03-05 | 2013-09-12 | President And Fellows Of Harvard College | Systems and methods for epigenetic sequencing |
JP2015528283A (ja) * | 2012-08-14 | 2015-09-28 | テンエックス・ジェノミクス・インコーポレイテッド | マイクロカプセル組成物および方法 |
WO2015071748A1 (en) * | 2013-11-18 | 2015-05-21 | Erasmus Universiteit Medisch Centrum Rotterdam | Method for analysing the interaction of nucleotide sequences in a three-dimensional dna structure |
Also Published As
Publication number | Publication date |
---|---|
EP3384048A1 (en) | 2018-10-10 |
PT3882357T (pt) | 2022-09-05 |
JP2018537086A (ja) | 2018-12-20 |
US20210238660A1 (en) | 2021-08-05 |
WO2017096158A1 (en) | 2017-06-08 |
US20170159109A1 (en) | 2017-06-08 |
EP4144861A1 (en) | 2023-03-08 |
US20190085380A1 (en) | 2019-03-21 |
EP3882357B1 (en) | 2022-08-10 |
CN115369161A (zh) | 2022-11-22 |
KR20180081164A (ko) | 2018-07-13 |
ES2926495T3 (es) | 2022-10-26 |
US11473125B2 (en) | 2022-10-18 |
IL259736A (en) | 2018-07-31 |
US11624085B2 (en) | 2023-04-11 |
EP3384048B1 (en) | 2021-03-24 |
SG11201804086VA (en) | 2018-06-28 |
DE202016009134U1 (de) | 2022-09-02 |
US20230073186A1 (en) | 2023-03-09 |
US20210246490A1 (en) | 2021-08-12 |
CN108431232B (zh) | 2022-10-14 |
SG10202108763UA (en) | 2021-09-29 |
US10774370B2 (en) | 2020-09-15 |
CN108431232A (zh) | 2018-08-21 |
EP3882357A1 (en) | 2021-09-22 |
JP6954899B2 (ja) | 2021-10-27 |
US11873528B2 (en) | 2024-01-16 |
DK3882357T3 (da) | 2022-08-29 |
JP7182679B2 (ja) | 2022-12-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6954899B2 (ja) | 核酸の解析のための方法及び組成物 | |
US20220403464A1 (en) | Methods and Compositions for Targeted Nucleic Acid Sequence Coverage | |
US11739368B2 (en) | Methods and compositions for targeted nucleic acid sequencing | |
US11952626B2 (en) | Probe-based analysis of nucleic acids and proteins | |
KR20230003659A (ko) | 폴리뉴클레오티드 바코드 생성 | |
US20220403375A1 (en) | Methods for enriching nucleic acid libraries for target molecules that do not produce artefactual antisense reads | |
US20240002914A1 (en) | Probe-based analysis of nucleic acids and proteins |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211101 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20211101 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20221027 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20221121 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7182679 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |