CN1311717A - 再拉伸的毛细管成像用储器 - Google Patents
再拉伸的毛细管成像用储器 Download PDFInfo
- Publication number
- CN1311717A CN1311717A CN99805597A CN99805597A CN1311717A CN 1311717 A CN1311717 A CN 1311717A CN 99805597 A CN99805597 A CN 99805597A CN 99805597 A CN99805597 A CN 99805597A CN 1311717 A CN1311717 A CN 1311717A
- Authority
- CN
- China
- Prior art keywords
- substrate
- passage
- array
- liquid
- section
- 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.)
- Pending
Links
- 238000003384 imaging method Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 78
- 239000000758 substrate Substances 0.000 claims description 132
- 239000007788 liquid Substances 0.000 claims description 84
- 239000011159 matrix material Substances 0.000 claims description 30
- 108091034117 Oligonucleotide Proteins 0.000 claims description 29
- 239000000523 sample Substances 0.000 claims description 28
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 27
- 239000011521 glass Substances 0.000 claims description 27
- 239000011049 pearl Substances 0.000 claims description 26
- 239000000463 material Substances 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 18
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical group NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 17
- 229920000642 polymer Polymers 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 9
- 230000008021 deposition Effects 0.000 claims description 7
- 229920001169 thermoplastic Polymers 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 238000006116 polymerization reaction Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229920000620 organic polymer Polymers 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000007710 freezing Methods 0.000 claims description 3
- 230000008014 freezing Effects 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 238000003860 storage Methods 0.000 claims description 3
- 239000012472 biological sample Substances 0.000 claims 2
- 229920000592 inorganic polymer Polymers 0.000 claims 2
- 238000010017 direct printing Methods 0.000 claims 1
- 230000008676 import Effects 0.000 claims 1
- 230000000717 retained effect Effects 0.000 claims 1
- 239000012530 fluid Substances 0.000 abstract description 6
- 238000003491 array Methods 0.000 abstract description 4
- 238000012360 testing method Methods 0.000 abstract description 3
- 230000009870 specific binding Effects 0.000 abstract 1
- 238000007639 printing Methods 0.000 description 19
- 238000009736 wetting Methods 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 238000005520 cutting process Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 238000012546 transfer Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 238000005245 sintering Methods 0.000 description 10
- 238000007306 functionalization reaction Methods 0.000 description 8
- 230000036961 partial effect Effects 0.000 description 8
- -1 polypropylene Polymers 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 7
- 239000000853 adhesive Substances 0.000 description 7
- 230000001070 adhesive effect Effects 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 239000005297 pyrex Substances 0.000 description 7
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 6
- 239000003822 epoxy resin Substances 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 150000002430 hydrocarbons Chemical class 0.000 description 6
- 150000007523 nucleic acids Chemical group 0.000 description 6
- 229920000647 polyepoxide Polymers 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000001993 wax Substances 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- URDOJQUSEUXVRP-UHFFFAOYSA-N 3-triethoxysilylpropyl 2-methylprop-2-enoate Chemical class CCO[Si](OCC)(OCC)CCCOC(=O)C(C)=C URDOJQUSEUXVRP-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- 238000002966 oligonucleotide array Methods 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 239000004416 thermosoftening plastic Substances 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- 229920003091 Methocel™ Polymers 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 238000005452 bending Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229910010293 ceramic material Inorganic materials 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000003682 fluorination reaction Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000006112 glass ceramic composition Substances 0.000 description 2
- 239000002241 glass-ceramic Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- DCAYPVUWAIABOU-UHFFFAOYSA-N hexadecane Chemical compound CCCCCCCCCCCCCCCC DCAYPVUWAIABOU-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007641 inkjet printing Methods 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000005499 meniscus Effects 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 239000002751 oligonucleotide probe Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- YCOZIPAWZNQLMR-UHFFFAOYSA-N pentadecane Chemical compound CCCCCCCCCCCCCCC YCOZIPAWZNQLMR-UHFFFAOYSA-N 0.000 description 2
- 238000005498 polishing Methods 0.000 description 2
- 229920000098 polyolefin Polymers 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- 239000004065 semiconductor Substances 0.000 description 2
- 229910000077 silane Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 description 2
- 238000005979 thermal decomposition reaction Methods 0.000 description 2
- YCFBPCFPRWYZFG-UHFFFAOYSA-N trichloro(10-fluorodecyl)silane Chemical compound FCCCCCCCCCC[Si](Cl)(Cl)Cl YCFBPCFPRWYZFG-UHFFFAOYSA-N 0.000 description 2
- IIYFAKIEWZDVMP-UHFFFAOYSA-N tridecane Chemical compound CCCCCCCCCCCCC IIYFAKIEWZDVMP-UHFFFAOYSA-N 0.000 description 2
- FZMJEGJVKFTGMU-UHFFFAOYSA-N triethoxy(octadecyl)silane Chemical compound CCCCCCCCCCCCCCCCCC[Si](OCC)(OCC)OCC FZMJEGJVKFTGMU-UHFFFAOYSA-N 0.000 description 2
- UKRDPEFKFJNXQM-UHFFFAOYSA-N vinylsilane Chemical class [SiH3]C=C UKRDPEFKFJNXQM-UHFFFAOYSA-N 0.000 description 2
- DLKQHBOKULLWDQ-UHFFFAOYSA-N 1-bromonaphthalene Chemical compound C1=CC=C2C(Br)=CC=CC2=C1 DLKQHBOKULLWDQ-UHFFFAOYSA-N 0.000 description 1
- 101710186708 Agglutinin Proteins 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- HIBWGGKDGCBPTA-UHFFFAOYSA-N C=CC1=CC=CC=C1.C=CC1=CC=CC=C1 Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1 HIBWGGKDGCBPTA-UHFFFAOYSA-N 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010071602 Genetic polymorphism Diseases 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 101710146024 Horcolin Proteins 0.000 description 1
- 101710189395 Lectin Proteins 0.000 description 1
- 101710179758 Mannose-specific lectin Proteins 0.000 description 1
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 description 1
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 244000137852 Petrea volubilis Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000910 agglutinin Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000000498 ball milling Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000007705 chemical test Methods 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 238000005253 cladding Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000006063 cullet Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 229920006379 extruded polypropylene Polymers 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000005357 flat glass Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 239000010954 inorganic particle Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000000206 photolithography Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229920005573 silicon-containing polymer Polymers 0.000 description 1
- 238000005549 size reduction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000008646 thermal stress Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- PYJJCSYBSYXGQQ-UHFFFAOYSA-N trichloro(octadecyl)silane Chemical compound CCCCCCCCCCCCCCCCCC[Si](Cl)(Cl)Cl PYJJCSYBSYXGQQ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J4/00—Feed or outlet devices; Feed or outlet control devices
- B01J4/02—Feed or outlet devices; Feed or outlet control devices for feeding measured, i.e. prescribed quantities of reagents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
- B01L3/0244—Drop counters; Drop formers using pins
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
- B01L3/0262—Drop counters; Drop formers using touch-off at substrate or container
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
- B01L3/50857—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates using arrays or bundles of open capillaries for holding samples
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/56—Labware specially adapted for transferring fluids
- B01L3/563—Joints or fittings ; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
-
- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03B—MANUFACTURE, SHAPING, OR SUPPLEMENTARY PROCESSES
- C03B19/00—Other methods of shaping glass
- C03B19/06—Other methods of shaping glass by sintering, e.g. by cold isostatic pressing of powders and subsequent sintering, by hot pressing of powders, by sintering slurries or dispersions not undergoing a liquid phase reaction
-
- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03B—MANUFACTURE, SHAPING, OR SUPPLEMENTARY PROCESSES
- C03B23/00—Re-forming shaped glass
- C03B23/04—Re-forming tubes or rods
- C03B23/047—Re-forming tubes or rods by drawing
-
- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03B—MANUFACTURE, SHAPING, OR SUPPLEMENTARY PROCESSES
- C03B23/00—Re-forming shaped glass
- C03B23/04—Re-forming tubes or rods
- C03B23/06—Re-forming tubes or rods by bending
-
- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03B—MANUFACTURE, SHAPING, OR SUPPLEMENTARY PROCESSES
- C03B37/00—Manufacture or treatment of flakes, fibres, or filaments from softened glass, minerals, or slags
- C03B37/01—Manufacture of glass fibres or filaments
- C03B37/02—Manufacture of glass fibres or filaments by drawing or extruding, e.g. direct drawing of molten glass from nozzles; Cooling fins therefor
- C03B37/025—Manufacture of glass fibres or filaments by drawing or extruding, e.g. direct drawing of molten glass from nozzles; Cooling fins therefor from reheated softened tubes, rods, fibres or filaments, e.g. drawing fibres from preforms
- C03B37/028—Drawing fibre bundles, e.g. for making fibre bundles of multifibres, image fibres
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54306—Solid-phase reaction mechanisms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1065—Multiple transfer devices
- G01N35/1067—Multiple transfer devices for transfer to or from containers having different spacing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00306—Reactor vessels in a multiple arrangement
- B01J2219/00308—Reactor vessels in a multiple arrangement interchangeably mounted in racks or blocks
- B01J2219/0031—Reactor vessels in a multiple arrangement interchangeably mounted in racks or blocks the racks or blocks being mounted in stacked arrangements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00306—Reactor vessels in a multiple arrangement
- B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
- B01J2219/00315—Microtiter plates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00306—Reactor vessels in a multiple arrangement
- B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
- B01J2219/00315—Microtiter plates
- B01J2219/00317—Microwell devices, i.e. having large numbers of wells
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00364—Pipettes
- B01J2219/00367—Pipettes capillary
- B01J2219/00369—Pipettes capillary in multiple or parallel arrangements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00378—Piezoelectric or ink jet dispensers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/005—Beads
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00511—Walls of reactor vessels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00513—Essentially linear supports
- B01J2219/0052—Essentially linear supports in the shape of elongated tubes
- B01J2219/00522—Essentially linear supports in the shape of elongated tubes in a multiple parallel arrangement
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00513—Essentially linear supports
- B01J2219/00524—Essentially linear supports in the shape of fiber bundles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/0054—Means for coding or tagging the apparatus or the reagents
- B01J2219/00547—Bar codes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/0054—Means for coding or tagging the apparatus or the reagents
- B01J2219/00547—Bar codes
- B01J2219/00549—2-dimensional
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00585—Parallel processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00596—Solid-phase processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/0061—The surface being organic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00614—Delimitation of the attachment areas
- B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00623—Immobilisation or binding
- B01J2219/00626—Covalent
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00632—Introduction of reactive groups to the surface
- B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00639—Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium
- B01J2219/00641—Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium the porous medium being continuous, e.g. porous oxide substrates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00646—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports
- B01J2219/00648—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports by the use of solid beads
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00659—Two-dimensional arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00673—Slice arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00722—Nucleotides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/021—Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0819—Microarrays; Biochips
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
- B01L2300/0838—Capillaries
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0893—Geometry, shape and general structure having a very large number of wells, microfabricated wells
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00178—Special arrangements of analysers
- G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
- G01N2035/1037—Using surface tension, e.g. pins or wires
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1065—Multiple transfer devices
- G01N35/1067—Multiple transfer devices for transfer to or from containers having different spacing
- G01N2035/1069—Multiple transfer devices for transfer to or from containers having different spacing by adjusting the spacing between multiple probes of a single transferring head
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1065—Multiple transfer devices
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/2575—Volumetric liquid transfer
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Clinical Laboratory Science (AREA)
- Materials Engineering (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Manufacturing & Machinery (AREA)
- Pathology (AREA)
- Urology & Nephrology (AREA)
- Geochemistry & Mineralogy (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- General Life Sciences & Earth Sciences (AREA)
- Dispersion Chemistry (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Devices For Use In Laboratory Experiments (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
Abstract
本发明涉及用于转移流体的方法和装置,特别是用于生物学测试,包括一个毛细管阵列(10),这些毛细管具有进口端(16)和出口端(18),该出口端(18)比进口端(16)小。该毛细管阵列可通过挤出和再拉伸蜂窝型通道形成。还描述了使用该毛细管阵列所形成的具有不同特异性的结合配体阵列。
Description
本申请要求欧洲专利申请号98401021.5(98年4月27日提交)以及临时申请号60/091707(98年7月3日提交)的权利。
发明领域
本发明涉及一种印刷生物学和化学试验用高密度阵列的装置和方法，以及能用来在不同孔密度的多孔板之间传递样品的装置。
发明背景
杂交是两条核酸链之间的氢键反应，它遵循华生-克里克互补规律。所有其它碱基配对是破坏杂交体稳定的错配。由于一个错配可使杂交体解链温度降低10℃，因此可找到仅完美杂交体才能存在的条件。杂交包括使链接触，其中一条通常固定在固相载体上，而另一条常带有放射性、化学发光或荧光标记，然后洗涤载体将形成的杂交体与未反应的标记链分出。通过检测结合在载体表面的标记来识别杂交体。
寡核苷酸杂交广泛用于确定在核酸中是否存在与寡核苷酸探针互补的序列。在许多情况下，这就能提供不同于传统测序方法且简便、快速、和便宜的选择。杂交不需要核酸克隆和纯化，进行碱基特异性反应，或繁琐的电泳分离。寡核苷酸探针的杂交已成功地用于各种不同目的，例如遗传多态性的分析、遗传病诊断、癌症诊断、病毒和微生物病原体的检测、克隆筛选、基因组作图和片段文库排序。
寡核苷酸阵列是由以规则方式固定在固相载体表面上的许多单独的寡核苷酸种类所构成的，每种寡核苷酸位于一个不同区域，使得各寡核苷酸的位置是已知的。阵列可含有一群选定的寡核苷酸，例如对所有已知的临床上重要病原体特异的探针，或者对遗传病所有已知序列标记特异的探针。这样的阵列可满足诊断实验室的需要。或者，一个阵列可含有给定长度n的所有可能的寡核苷酸。核酸与这种综合性阵列的杂交，可导致列出所有其构成性的n-聚物，这些n-聚物可用来明确地识别基因(例如在法医研究中)、用来确定未知的基因变异体和突变(包括一旦知道其中之一的序列，就可对相关基因组进行测序)、用来重迭克隆、以及用来检查用常规方法确定的序列。最后，通过与综合性阵列的杂交而调查n-聚物，可以提供足够信息用来确定完全未知核酸的序列。
寡核苷酸阵列能通过直接在载体上平行地合成所有寡核苷酸来制备(使用固相化学合成方法，并与如美国专利号5,510,270所述的定点掩膜相结合)。需要具有不重叠窗孔的4片掩膜和4种偶联反应，来使固定的寡核苷酸的长度增加一个核苷酸。在合成的各随后轮次中，使用另一套不同的4片掩膜，而这决定了各特定区域中合成的寡核苷酸的独特序列。使用有效的照相平板印刷技术，已有了每平方厘米中含有多达105种不同寡核苷酸的微型阵列。
另一种制造寡核苷酸阵列的技术，涉及采用如美国专利5,474,796所述的压电泵进行精确的点滴沉积。这种压电泵能将微量液体输送到基片表面上。泵的设计与喷墨打印中所用的泵非常相似。这种微微泵(picopump)能够以3000Hz之内的频率输送50微米直径和65微微升体积的液滴，并且能够准确喷击在250微米的目标上。泵单元装有5个喷嘴阵列头，4 种核苷酸中每一种使用一个喷嘴阵列头，而第五个喷嘴阵列头输送用于偶联的活化剂。在液滴是向下泵射到移动的阵列板的时候，泵单元是静止的。当泵工作时，这种细微液滴就从泵射出并沉积在阵列板上的功能化结合位点。基于微液滴沉积顺序，在各结合位点处合成了不同的寡核苷酸。
另一种使用阵列的方法是用于平行寡核苷酸合成的针浸渍方法，Geysen,J.有机化学，56,6659(1991)。在该方法中，将小量的固相载体与螺线管控制的一些聚丙烯针熔合，然后将这些针浸入含合适试剂的盘中。阵列的密度受该过程的限制。
另一些形成阵列的方法涉及：取得预合成的寡核苷酸序列或者单独制备的水相混合物中的cDNA序列，并将它们个别地或少数几个一起转移到基片上。这可以通过例如用喷墨印刷装置，使附着有液滴的印刷针与基片表面重复接触，从而形成阵列基质，或用笔式绘图仪来完成。在传送103或更多不同序列的混合物到基片的指定位置上时，这些印刷过程受到所需的时间或成本的限制。
发明概述
本发明提供了用于将高密度的生物或化学阵列沉积在基片上的毛细管储器装置、液体沉积工具和方法。该工具由多个末端开口并一起构成基体(matrix)的通道所构成。该基体已被再拉伸和切割，从而使上样端的通道栅距远大于液体输出端的通道栅距。各个通道的上部作为储器，而通过再拉伸过程而形成的另一端在径向上的尺寸使得储器中的液体因输出端的毛细管压力而保留。在沿毛细管储器装置高度方向上的任一点，所有的截面尺寸和面积是均匀减小的。换言之，在任何2个通道的中心取向距离(也称为2个通道的栅距)，以对于任何截面的直径表示为函数，它在整个结构中是恒定的。在另一实施例中，本发明装置的变化形式可用于在不同孔密度的多孔板之间转移样品。
附图简述
图1是本发明装置的三维视图。
图2显示了在再拉伸之前的多个相连的毛细管。
图3是将装置的出口端浸入液体容器中以便将可润湿性赋予通道内部表面的示意图。
图4显示了将装置的出口端截去以暴露非润湿表面。
图5是通过蜂窝状模具挤出材料预制件时的三维视图。
图6是已被随后再拉伸的挤出坯体的三维视图。
图7是已被随后再拉伸并经固化程序的挤出坯体的侧视图。
图8是从图7中装置的再拉伸部分切下的一系列坯体的三维视图。
图9是图8中的坯体正被刀片切割时的三维视图。
图10是本发明的3块高密度阵列板的三维视图。
图11是一种将液体样品从多孔板转移至本发明的毛细管储器装置的方法的分解图。
图12是用于将液体样品沉积于接受板时图11装置的三维视图。
图13是在两端有密封装置的本发明毛细管储器装置的截面图。
图14是本发明一种毛细管储器装置的一个通道的截面图。
图15是采用本发明毛细管储器装置的印刷机的三维视图。
图16是图15中针板(pin plate)与毛细管储器装置出口端接触时的部分截面图。
图17是图16中针板从毛细管储器装置出口端移开后的部分截面图。
图18是在将液体物质沉积在基片上之后，图15-17中针板的部分截面图。
图19是本发明印刷工具的部分截面图。
图20是本发明另一种印刷工具的部分截面图。
图21是本发明又一种印刷工具的部分截面图。
图22是当一个材料板坯与其他类似板坯装配以形成一个坯体时的部分剖视图。
图23是在熔合之前，多个板坯相互叠放在一起时的部分剖视图。
图24是通过熔合图23中的板坯而形成的坯体的部分剖视图。
发明详述
印刷工具
玻璃和有机聚合物的再拉伸过程是众所周知的，而且已用于制造精密的、具有复杂截面的管道、薄板和纤维束。本发明以独特方式运用预制的再拉伸技术，形成了具有通道阵列的容器，这些通道可各自输送少量体积的液体至基片、印刷用针板之上，或输送至多孔板的孔中。术语“再拉伸”是光学纤维领域的技术术语，指预制件直径的减小过程。出于本申请目的，该术语与其他已知的本领域术语同义，其中包括“拉延”和“拉伸”。
再拉伸技术始于多单元的挤出坯体(也被称为“蜂窝状基件”)或一组相连的毛细管。再拉伸技术的一个重要方面是，可轻易将具有复杂的截面结构(对应于最终产品的复杂截面结构)的较大的玻璃或聚合物构件拉伸形成所需尺寸。在再拉伸或拉伸过程中，所有的截面尺寸和面积都均匀地减少，而存在的公差保持恒定。因此，现举例说明，公差为1％的1英寸尺寸(即公差为±0.01英寸)按10∶1减小时，就形成0.1英寸的尺寸和±0.001英寸的公差。再次按10∶1减小时，就形成0.01英寸的尺寸和±0.0001英寸的公差。
为了用玻璃、玻璃陶瓷、或陶瓷材料形成毛细管储器装置，人们必须使用热塑性粘合剂如石蜡或美国专利5,602,197中所述的粘合剂(该专利在此引用作为参考)，并将粘合剂与无机粉末状材料(较佳地为CorningIncorporated出售的PYREX 7761粉末)混合，其中玻璃原料颗粒大小为10微米左右。该有机/无机混合物接着通过在室温操作的反向旋转的双螺杆挤出机而挤出。所用的模具决定了挤出材料的尺寸。较佳地，挤出后，形成了直径2-7英寸的正方形或圆形通道的，单块的蜂窝状预制件，它具有15-40密耳厚的通道壁和20-400通道(或单元)/平方英寸前表面。预制件可以任何形状挤出，包括截面形状为圆形、长方形或正方形。通道的截面形状可以是由模具决定的任何形状。有机粘合剂必须被小心去除，即通过缓慢加热至足够温度从而导致有机粘合剂的挥发和热分解掉。通过小心选择和控制混合物的流变学特性、无机物体积含量和粘合剂的热分解/挥发特性，可以避免塌陷和其他变形。在去除粘合剂后，接着烧结充填着的颗粒预制件，使粉末颗粒熔合并保持预制件的形状。为了避免通道壁的塌陷，烧结条件必须严密检控。PYREX 7761的烧结温度约为675℃。在该温度下，会发生玻璃颗粒的粘合并且预制件会均匀地发生10-15％的收缩。生成的是玻璃、玻璃陶瓷或陶瓷材料，这取决于烧结程序和最初原料粉末的组成。对于用于本发明，宜改变烧结程序和粉末组成，从而产生基本上相同的，高密度和无断裂孔隙的通道壁。形成的蜂窝状坯体具有多个平行的、延伸贯穿的通道(或称单元)。该坯体可以是任何长度，这由将其从挤出机上切下时的切割位置所决定。
实施例-挤出和烧结
表1显示了PYREX 7761玻璃的组成。无机粉末是用PYREX 7761碎玻璃制成的，经过了粉碎、磁分离、球磨(氧化铝)和超声波筛选(-325目)。
表1
| 组份 | 重量百分比(％) |
| SiO2 | 78.92 |
| K2O | 2.76 |
| B2O3 | 18.27 |
表2显示了挤出用混合物的批料组成。
表2
| 成分 | 重量(克) |
| PYREX 7761粉末 | 7938 |
| 油酸 | 80 |
| Dow F-40M METHOCEL | 558 |
| 水(DI) | 1985 |
在LITTLEFORD混合机中，将无机粉末、METHOCEL和油酸混合在一起，然后在LANCASTER混合机中与加入的水一起研磨。混合物再通过抽真空和面条式挤出(3次)而进一步混合。最后，批料通过模具挤出，形成多单元的预制件，从挤出物上切下预制件，以备烧结。
表3显示了用于烧结预制件的炉程序。在烧结过程中预制件被垂直悬挂以减少弧形弯曲。
表3
| 烧结炉程序 |
| (1)室温至300℃,50℃/小时 |
| (2)300℃至500℃,20℃/小时 |
| (3)550℃至700℃,50℃/小时 |
| (4)在700℃保持2小时 |
| (5)700℃至室温(关闭电源) |
一旦预制件被烧结，形成的构件就被加热并进行再拉伸减缩。再拉伸在比玻璃转变温度高大约20-100℃下进行。对于PYREX 7761，经烧结的坯体被再加热至870℃，维持约1.5小时，以便在待拉伸的坯体区段内部达到+/-20 ℃的温度均一性。再拉伸步骤分2步进行：第一步，将坯体悬挂成通道呈垂直方向；然后将一部分挤出坯体夹住，并让坯体重量向下拉伸未夹住的部分。第二步，在未夹住部分上施加一恒力以进一步协助拉伸。一旦挤出坯体被拉伸至预定直径(这取决于对装置出口端的截面尺寸要求)，就通过降低温度而使该过程停止。这一降温退火步骤宜在1小时内进行，使温度降至20℃。作为例子，为了将180毫米长、截面直径为22毫米的柱形坯体拉伸至截面直径为4.2毫米，该坯体必须在长度上拉伸约920毫米。较佳地，在再拉伸后，毛细管储器装置的长度为拉伸前坯体直径的2-3倍，以便优化各通道的保持液体的毛细管性能。
在生产弯曲的储器装置中，如某些情况下所需，拉伸的坯体的待弯曲部分被维持在约850℃温度。从炉中取出该坯体，弯曲成合适的角度(如180℃)。在弯曲后，坯体被置于退火炉中，冷却至室温以免产生热应力。
在约1小时期间退火冷却至约20℃后，无论弯曲或未弯曲的坯体，都在坯体的尺寸减缩的区段上切割，形成储器装置的出口端，并且还可在上样或进口端处用例如金刚石锯切割。切割宜在有内部水流的情况下进行，以防止玻璃碎片或碎屑留在通道中。然后，通过用12微米、3微米、1微米和0.3微米的抛光砂纸进行连续的抛光，来修整坯体的出口端。如果装置是用于印刷极小体积的液体液滴，那么使装置的出口端达到约±2微米的平坦度是至关重要的。装置还可通过在约450℃的火中进一步修整1小时。
任选地，当使用例如美国专利5,602,197中所公开的粘合剂时，也可以在挤出预制件之后但在去除粘合剂和烧结之前对预制件进行再拉伸。在这种情况下的再拉伸与对热塑性聚合物进行的再拉伸相同，因为待拉伸的预制件或预制件的区段被再加热至软化或部分熔融状态，从而可通过牵拉而再拉伸预制件。使用这种技术的一个优点是，可以使用在无机状态下无法再拉伸的无机颗粒，例如氧化锆、氧化铝等。
在用热塑性聚合物制造毛细管储器装置的例子中，首先通过在热塑性材料的熔融温度工作的双螺杆挤出机和模具而挤出聚合物，例如在约180℃挤出聚丙烯。储器装置的通道密度和壁厚度与上述的玻璃实施例中基本上相同。一旦坯体被挤出，就如上那样进行聚合物再拉伸，此时可能需要从外部加热坯体或待再拉伸的区段至例如150℃(例如对于聚丙烯)。再拉伸还可需要对聚合物坯体的内部加热，例如通过强制热空气方式，以便消除在再拉伸过程中坯体内部的温度梯度。尽管已用聚烯烃(具体地为聚丙烯)演示了挤出过程，然而正如本领域技术人员所认识的那样，任何热塑性聚合物都可用于该方法。
尽管圆柱形挤出对于粉末状玻璃和塑料都比较容易进行，然而优选的是正方形或长方形的挤出，以便形成能够沉积出直线阵列的工具。
聚合物和粉末状玻璃的挤出理想地是用垂直挤出法进行。垂直挤出有助于减少因重力效应而导致的壁塌陷问题。然而，水平挤出法在大规模生产情况下是优选的。
另一种对挤出的含许多单元的坯体进行拉伸的方法是，用固化时有类似于湿批料的塑性的熔融蜡来填入挤出预制件的开口的单元。然后，冷却后的坯体由湿的挤出单元预制件和单元中固化的塑性蜡构成，使其在室温下通过尺寸减小模具。通过将复合坯体部分地通过模具，可以获得具有所需的从大单元变成小单元的坯体。之后，使蜡熔融并去除；再以正常方式干燥、烧结和修整单元坯体。适用于该技术的蜡是具有高的针穿硬度(15+)的微晶烃蜡。这种备选的拉伸技术在一起转让的美国专利申请60/068,230(该申请在此引用作为参考)中有更详细的公开。
图1显示了作为本发明主题的毛细管储器装置10。在一优选例中，该装置理想地包括方形通道12基体，沿着该构件的每个外壁14有100个通道，总共有10000个通道。装置的上方是装置的液体加样或入口端16。入口端的暴露面被称为入口面。装置的入口端16的每一侧约为112.5毫米。在该例子中整个入口面的表面积约为12,656平方毫米。该构件已经被再拉伸过，使得基体出口端18上每侧的长度约为22毫米。出口端的暴露面被称为出口面。出口面的表面积约为484平方毫米。装置10中每个通道12是自含式的(self contained)并且以与截面总表面积减小近似的比例减小其截面面积。因此，如图1所示，顶表面处宽度或栅距为1.125毫米的通道在底表面处的宽度或栅距约为0.22毫米。单个通道的截面表面积，其占沿垂直放置的装置高度的任一点垂直于高度方向所截取的截面面积的比例，是近似恒定的。当装置被再拉伸时，壁厚度占截面总面积的比例可能会轻微上升，但是通道的数目以及基体中由通道至通道间中心栅距所界定的每个通道的相对位置是恒定的。换言之，该装置有多个末端开口的、从入口面延伸至出口面的通道，其中至少在预定长度上，每个通道的直径、截面面积和壁厚度都同样程度地减小。
另一种制造毛细管储器装置的方法是在多个板坯的表面上刻出或压出通道，将这些板坯一层层叠放好形成具有多个通道的坯体，然后熔合这些板坯，并再拉伸整个构件。用这种方法产生坯体的情况示于图22和23。图22显示了板坯130的一部分的截面图。板坯130有在上表面134中形成的多个均匀间隔的平行通道132。通道可以用各种不同的已知技术形成。如果材料是玻璃，通道可蚀刻出、压出、或通过精确轧制而形成。如果材料是聚合物，板坯可通过例如注塑技术形成。图23显示了相互叠放的多个板坯130的部分截面图。每个板坯130的底表面136封闭了紧挨其下方的板坯的通道132。没有通道的顶部坯体138封闭了最上面的板坯通道。然后，整个构件被加热至某一温度，使板坯熔合在一起，从而形成能够被再拉伸的坯体140，如图24所示。用这种技术可形成具有任何数目、任何尺寸或形状的通道的板坯。
几乎所有用热塑性材料制成的、具有形成的贯穿其中的多个平行通道的坯体，都可被再拉伸以形成本发明的装置。
应注意，另一种制造毛细管储器装置的方法是将多个单独的管或毛细管粘合在一起。这些管可以粘合在一起，形成具有任何数目管子的管束。该管束再以与经挤出和再拉伸坯体相同的方式进行再拉伸和修整。图2显示了在再拉伸之后这种毛细管22束的出口端20。管22与图1装置的通道12起相同作用。但是在具体引用这些附图说明装置时，术语通道和管具有相同含义。
作为说明可行性的例子，22根管子22以7、8和7根管子一列的方式被粘合在一起。然后，再拉伸9毫米管子的基体，使得管和管中心间距变为350微米，而每个管中毛细管出口开口的直径为180微米。
用于暴露出图1或图2装置的出口面的平面切割，宜为非润湿性的切割。例如，在图2中，管子内部24宜具有润湿性表面，而管子末端26宜为非润湿性的。类似地，图1装置中通道12的内壁是润湿性的，但是壁末端是非润湿性的。因为每个通道具有润湿性的通道内壁和非润湿性的末端，因此液滴倾向于挂在每个通道的末端。此外，该装置中整个出口平面的非润湿性表面，可防止各通道在出口端处的干扰。
无论装置是用挤出坯体或装配坯体再拉伸而成，还是用粘合的毛细管制成，都可用相同方式获得出口面的润湿特性。在用对水中等润湿的材料(如聚苯乙烯)或对水不润湿的材料(如聚烯烃如聚乙烯或聚丙烯)制造的装置中，为了获得出口面的润湿性，可以通过氧化处理来改善润湿性。例如，可将氧化性的化学蚀刻剂(如硫酸或铬酸)引入通道内部。一种使通道内部受氧化性蚀刻剂或者其他任何可涂覆内部通道的液体处理的方法，示于图3-5中。图3显示了来自容器30的液体28是如何涂覆图2装置的出口端20处管22的内部。接着，以垂直于通道长度的方向，用切割机切割该装置，如图4所示。切割后，暴露出天然的非润湿的或润湿性较差的聚合物出口面。图4显示了图2装置的出口端20正被切割机32进行平面切割的情况。切割后暴露出非润湿的管末端26，而管内部24仍然是润湿的，因为涂层接受到来自容器30的液体。切下的管碎片34被弃去。
对于用天然润湿性材料(如玻璃对水是润湿性的)制成的装置，已经被切割并修整过的装置出口部分，可以对着涂有非润湿性涂料(如具有CF3末端的硅烷、十八烷基三乙氧基硅烷(OTS)、或聚二甲基硅氧烷)的橡胶印模进行挤压。将硅烷转移至装置的出口面，使表面变得非润湿。由玻璃制成的通道内部是天然润湿性的。或者，可将出口端浸入赋予非润湿性能的溶液中，例如氟代癸基三氯硅烷溶液，同时将气流注入毛细管毛细管阵列的入口端，以防止溶液进入通道内部。用这种方法，出口面可获得非润湿特性，而通道内部因不被涂覆从而仍保留其润湿特性。
一旦形成，无论是用有机聚合物还是用玻璃制成的装置，其使用操作是基本上相同的。在使用操作中，将液体被上样于装置的入口端。入口与宏观的液体上样是相容的，并且上样可以通过各种不同的已知装置实现，包括：移液管、注射器、泵、多重移液管或注射器、漏斗等。较佳地，在入口端处通道之间的中心间距宜对应于多孔板(例如1536孔板)的中心间距。用这种方法，可通过将液体压出1536孔板中每个孔底部的小洞，可将含于1536孔板中每个孔中的液体上样于毛细管储器装置中对应的通道。每个通道是自含式的，因此可将10000种不同的液体上样于该装置。重要的是，应注意通道数目是完全可变的，而数字10000仅仅被选作优选情况的例子而已。
每个通道的体积由其内部尺寸(包括装置的高度)决定。理想地，每个通道含有5-500微升，但任何体积都是可能的，这由下列可变尺寸决定：顶部和底部的通道栅距，以及装置的高度。
理想地，在出口端的通道栅距使得液体能靠毛细作用力而留在每个通道中。这样，液体就会留在每个通道中直至有某种外力将其压出。一种将液体挤压通过毛细管的方法，是通过使用光子压力来调控毛细管。在这种例子中，如法国专利申请#中所述，通过光学纤维和通过每个毛细管窗口的微透镜来传送光脉冲。光子脉冲会使指定的每个毛细管的出口端的液滴排除出。用于从毛细管的出口端排出液体的其他方法包括：外部压力(如在出口处的真空或在入口端的正压力)、机械压力、声压、磁压、加热或其他可在通道中产生恒定排出量的方法。
在一优选例中，每个通道填有位于液体基质中的不同结合体(bindingentity)。“结合体”通常被称为生物分子或合成分子，它通过共价键或非共价键对另一分子有特异性的亲和力。较佳地，特异性结合体含有(或者天然地或通过修饰而含有)功能性化学基团(伯胺、巯基、醛等)、共有序列(核酸)、表位(抗体)、半抗原、或配体，这使得该结合体可与基片表面上共同的官能团发生共价反应或非共价结合。特异性结合体包括(但并不限于)：脱氧核糖核酸(DNA)、核糖核酸(RNA)、合成的寡核苷酸、抗体、蛋白质、肽、凝集素、修饰的多糖、合成的复合大分子、功能化的纳米结构物、合成的聚合物、修饰的/保护的核苷酸/核苷、修饰的/保护的氨基酸、荧光团、生色团、配体、螯合剂、和半抗原。出于本公开内容的目的，术语“生物分子”和“结合体”可互换使用。
应注意，关于本装置的发明申请并不局限于生物材料，相反可扩展至任何能够处于液体形式或悬浮液中的化学物质，其中包括(但并不限于)：乳剂、颗粒悬浮液、和凝聚层。事实上，用PYREX玻璃制成的储器装置能够印刷加热至500℃的液体的阵列。这暗示可用于化学应用，例如印刷室温半导体、分配热的颜料或热的蜡、以及其他的纳米技术的微元件。
含有结合体的液体宜为丙烯酰胺单体，但是也可以是任何生物相容性的可聚合材料。丙烯酰胺提供了固定DNA或其他生物分子所需的必要的交联作用。在一优选例中，将10000种不同的丙烯酰胺溶液(每种含有核苷酸序列稍微不同的寡聚物)，通过前述的多孔板、多孔移液管、注射器等而上样于每个通道中。通过使用光子压力、外部压力等，可使每个通道同时排出液滴。液滴与基片接触，并发生沉积。接着，丙烯酰胺宜在沉积于基片之后立刻通过紫外辐射而聚合。形成的聚合液滴阵列的特征是，基片上液滴之间的距离与装置出口面上通道之间的栅距基本上相同。每个液滴占据整体阵列中一个可识别的位置，而每个液滴中的生物分子被共价地结合于聚合的丙烯酰胺。在这种例子中，生物分子(寡核苷酸)被共价地结合于一起沉积的聚合后的丙烯酰胺。
一切基片都可用于本发明。基片可以是生物的、非生物的、有机的、无机的、或它们的任何组合，可以以颗粒、条带、沉淀物、凝胶、薄板、管道、球体、珠、多孔珠、容器、毛细管、垫、薄片、薄膜、板、载玻片、膜等形式存在。基片可以有任何方便的形状，如圆盘、正方形、长方形、球形等。基片宜为平坦的，但是可采用各种不同的其他表面结构。例如，基片可以含有凸起或凹陷的区域，并在这些区域沉积液体。此外，基片可以是已蚀刻出一些通道的玻璃、聚合物或膜，或者它含有用化学蚀刻剂变得多孔的区域。基片及其表面宜形成刚性载体，在该载体上可沉积具有合适表面能量并含有结合体的液体，而且该载体宜用例如γ-氨基丙基三乙氧基硅烷或甲基丙烯酰氧丙基三乙氧基硅烷等有机硅烷进行过功能化处理。
在一优选例中，基片是平玻璃，较佳地是表面凹凸特征小于10纳米的硼硅酸盐玻璃。尽管未图案处理的板对于液体排列而言是优选的，但是玻璃基片的表面可涂有非润湿剂，如氟代癸基三氯硅烷或十八烷基三氯硅烷。涂层可用已知的光蚀刻而选择性地去除，或用掩模技术而选择性施涂。较佳地，提供未涂覆因而润湿的位置阵列。在润湿/非润湿位置阵列中的间隔，宜对应于毛细管储器装置出口面上各通道之间的间隔。用这种方式，液滴仅需与基片上暴露的润湿位置接触就可转移液滴。通过物理或化学方法，将液滴抽拉至润湿位置的中心。干扰现象通过基片的润湿特性而加以消除。或者，用图案蚀刻法在基片中和基片表面之下产生一些位置，这些位置构成多孔玻璃区域矩阵，这也可用于消除干扰可能性。液滴可以沉积在这些多孔区域，而这些区域宜与毛细管储器装置出口面上的通道间距对齐。
印刷方法
用直接来自毛细管储器装置并含有寡核苷酸的丙烯酰胺液体印刷出矩阵，其间距小于200微米，此时需要特殊的程序以减少相邻液滴发生扩散和混合，即减少干扰。印刷方法包括步骤：提供一在出口面和侧壁经过非润湿氟化处理的毛细管储器装置；在毛细管储器装置的至少一个通道中注入丙烯酰胺/生物分子混合溶液；提供功能化玻璃基片，例如涂有例如甲基丙烯酰氧丙基三乙氧基硅烷等有机硅烷的基片；和在零或负毛细管压力的情况下，通过与基片接触而转移毛细管储器装置中每个通道出口处的液滴。
丙烯酰胺/寡核苷酸溶液的中等表面张力约为52mN/m，并且与用甲基丙烯酰氧丙基三乙氧基硅烷功能化处理过的玻璃基片有较小的接触角，例如约50度。接触角是表面能量的直接衡量值。对于50度的接触角，基片上间隔100微米或更小的各液滴是不可能在固化之前避免液滴混合的。此外，一旦转移，则低于90度的接触角会在毛细管储器装置和玻璃基片之间产生正毛细管压力，这导致液滴中的寡核苷酸扩散进入毛细管储器装置出口面和基片之间的空隙中。因此，为了减少液滴转移过程中的干扰，负或零毛细管压力是优选的。为了在装置和基片之间形成负或零毛细管压力，在储器装置出口面和基片表面上都需要接触角等于或大于90度。对于毛细管储器装置，前面描述的氟化处理就可满足这种条件。
对于基片，合适的接触角可这样实现：将液滴从毛细管装置在一种空气以外的、与液滴液体不混溶的环境液体介质中转移到功能化基片上。因为寡核苷酸在水性溶液中，因此烷或烃类可满足这种不可混溶性。作为例子，用胺功能化处理过的基片与寡核苷酸/丙烯酰胺溶液的接触角，可从空气环境中的50度增加至十二烷环境中的100度。在这些条件下，寡核苷酸/丙烯酰胺液滴的扩散被限制，并且毛细管压力是负的。通过将基片浸入烃.化溶液，基片的表面张力会显著低于空气。寡核苷酸/丙烯酰胺溶液与储器装置的通道的接触角也会增加，从而产生有利于液滴转移的条件。
在转移之后，不混溶的液体环境还可提供无氧的环境，让寡核苷酸/丙烯酰胺液滴固化在基片上。这是优于在空气中进行液滴转移的重要优点，因为丙烯酰胺聚合对氧气的抑制作用是非常敏感的。
为了增大功能化基片与寡核苷酸/丙烯酰胺溶液的接触角至90度或更大，在表面张力约35mN/m(20℃)的不可混溶液体介质中进行液滴转移是优选的。
已观察到，在开始从毛细管储器装置转移液滴之前，将功能化基片在烃环境中存放1小时是有利的。有了这个步骤，就可以使用在20℃时表面张力(K)为25mN/m或更大的烃化液体。对于将寡核苷酸/丙烯酰胺液滴沉积在基片上，表4非排除性地列出了用于提供合适环境的烃类。
表4
烃类 20℃时表面张力K(mN/m)
十二烷 25.4
十三烷 26.0
十四烷 26.6
十五烷 27.1
十六烷 27.5
环己烷 25.2
十氢萘 31.1
溴萘 44.4
应注意，将液滴在不可混溶的液体环境中从一种介质转移至另一种介质上，可以使用多种不同的液滴化学法或基片，并且可根据液滴的化学性质以及基片的化学性质而加以改变。只要在转移低表面张力的液体以防止液滴在基片上扩散的场合，都可使用。在液滴固化后，就基片板加热至约60-65℃，以便蒸发掉溶剂和/或环境烃物质。
一种避免使用负毛细管压力环境的方法是制造一种储器装置，它被设计成在出口端维持恒定的液面。在解释“这是如何实现”这一基本概念时，将注意力集中于装置中的一个通道。在该例子中，储器在再拉伸后被弯曲，从而使出口面和入口面处于同一水平面，而整个装置是U形的。此外，每个独立的通道是U形的，如图14所示(图14是装置中一个通道的截面图)，并且在入口端82具有预定的半径(r2)，在出口端84具有预定的半径(r1)。取决于毛细管压力、液体密度和接触角所决定的头高，液体或者在通道出口端形成小珠，或者在通道中形成弯液面。出于本公开的目的，无论液体为珠状与否是不重要的，但是在下面实施例中，液体在通道中形成弯液面。
例如，印刷针板的针被插入装置出口端处的通道中，采集一液滴，然后再与基片接触，从而形成阵列。
如观察的那样，r2大于r1。诸如待印刷的DNA探针溶液等液体，被上样至通道入口端82。半径稍小于r1的针通过浸入通道出口端84而与液体接触。体积为v的液滴通过针表面上的表面张力作用从通道中取出，然后转移至基片上。因为毛细管压力，通道中的液面在出口端不会下降。在装置入口端的液面会下降已被移去的液滴体积，而在装置出口端的液面保持不变。这种现象是通道出口端与入口端之间的毛细管压力造成的。毛细管压力等于2γ(1/r1-1/r2)，式中r1＜r2，且γ是液体表面张力。该压力使得在通道的出口端移去v体积的液体，而不影响出口端的液面。液面会在装置的入口靖下降，同时维持装置出口端处不变，直至在毛细管两端的高度差H达到下式表示的毛细管高度：2γ/ρg(1/r1-1/r2)，其中ρ是液体密度而g为重力加速度常数(9.81m/s2)。在出口端液面开始下降之前，可从通道中取出的总体积V由下列等式给出：V=2πr2 2γ(1/r1-1/r2)/ρg。因此，从该通道中可以转移至印刷针的次数等于V/v。
应注意，没有必要使入口端和出口端处于同一水平面。出口端可以低于入口端，但是在两个末端之间的距离h应小于毛细管高度H。当出口端和入口端在同一平面(h=0)时，V为最大值。
作为例子，假设入口端和出口端在同一平面(h=0)时，r1=50微米，r2=300微米，γ=50×10-3N/m，而ρ=103kg/m3。那么，在维持通道出口端液面不变时，可利用的DNA探针溶液V等于48微升。如果用于将液体从装置出口端转移至基片板的印刷板具有半径40微米数量级的针，那么单个液滴的体积为80pl。因此，在通道出口端的液面保持不变的情况下，该通道可允许600,000次针转移液体。
显而易见，完整的储器装置可以由多个所述的U形通道构成。毛细管的数目对应于所需阵列中的位置数目。使用这种弯曲装置的印刷工具90的例子示于图15。弯曲的储器装置92被安装在封闭单元94中，使得装置的出口面96和入口面98基本处于同一平面。在有弹性的不锈钢弯曲件(flextem)102上安装了一印刷针阵列，它具有对齐排列的针矩阵，从而使矩阵中的每个针能够插入储器装置92的出口面96的对应通道中。一根绳104将杠杆106连接于弯曲件102的上表面，使得该杠杆运作时，针板100与装置的出口面96接触，每根针进入每个通道，与其中的液体接触，随后退出。图16显示了当图15的针板100与装置的出口面96相互接近时的截面部分。各个针101与各个通道105的液体103接触。将针板100从通道105中取出，从而从每个通道中牵拉出液滴107。液滴被附着在针101的末端，如图17所示。在液滴107被取出后，在每个通道105顶部的液面维持不变。然后，将合适制备的基片置于针板100下方；之后，让针板与基片表面接触，从而沉积出液滴阵列。图18显示了基片108的部分截面图，其中针板100已将众多液滴110沉积在基片上。
为了在储器的出口端获得恒定的液面，没有必要一定使用U形结构。在图19中显示了图15中含有U形储器装置的印刷工具的截面图。在图20-21中示出了另两种毛细管储器设计。图19的U形储器92具有半径300微米的入口面98,50微米的出口面96，长度为200-400毫米，可理想地用于盛装50-100微升液体并且可印刷约50,000-1,000,000个液滴(80pl/滴)。图20是一种具有圆锥设计120的储器装置，其中构成装置的通道的入口端被注入选定的液体混合物。该装置然后被颠倒，使装置的出口端122朝上。因为毛细管压力，液体会被留在通道中，而液面会在装置的出口端保持恒定，甚至在从通道中取出液滴之后。用这种设计，假设与上面相同的出口面和入口面半径，但通道长度为20-50毫米，则每个毛细管储器(通道)含2-10微升印刷液体，它相当于约20,000-100,000个液滴(80pl/滴)。
图21显示了装置的另一种设计。该设计可比图19的通道装置储藏更大的体积，但是比U形设计所允许的体积小。该L形装置124的工作方式基本上相同，即通过装置的入口面126注入每个储器，然后用例如针板从装置的出口端128取出液滴。与上面的实施例相同，在出口端处的液面保持恒定。用这种设计，假设与上面相同的出口面和入口面半径，但通道长度为50-200毫米，则每个毛细管储器(通道)含10-50微升印刷液体，它相当于约100,000-500,000个液滴(80pl/滴)。
然而应注意，可将更小体积的液体上样于这些装置；而液体会被毛细管压力推向装置的出口端。所述的体积范围仅仅是建议的体积，因而并不局限于每个具体例子。
印刷珠
通常，诸如寡核苷酸或肽之类的生物分子是在低度交联的聚苯乙烯珠或其他聚合物载体上，用S.R.Wilson和A.W.Czarnick,CombinatorialChemistry,Synthesis and Appplication(1997)中所述和引用的方法合成的。这种合成被称为固相合成，用这种方式，可以合成和鉴别出由生物分子或其他顺序地或组合地产生的分子所构成的极大的文库。合成的生物分子通常在合成过程结束时从珠上切割下。
在这种例子中，用固相合成法合成的分子并不从载体珠上切下。取而代之的是，它们与合适的溶剂一起掺入到悬浮液中，以形成可印刷的液体。为了保留维持于悬浮液中的能力，同时仍减少任何可能的立体作用问题，生物分子宜在直径为0.3-0.6微米的珠上合成。
用上面公开的方法，将悬浮液印刷在基片上。优选地和作为例子，基片是具有乙烯基硅烷涂层的玻璃基片，而且珠是在二乙烯基苯中交联的乙烯基苯。毛细管储器装置的每个通道中注入不同的共价连于多个珠的已知生物分子，从而在任一通道中存在连于多个珠的众多相同的生物分子。含有这些珠的悬浮液，或者在基片表面，或者在基片的微孔或通道中按预定的位置印刷成阵列。一旦被印刷，乙烯基硅烷中的乙烯基就与珠中的苯乙烯(乙烯基苯)发生共价反应，从而将珠固定于基片表面。分子本身被固定在珠上。可以设想，珠或基片也可使用其他材料，以便利用这种共价的珠-基片固定相互作用的优点。
在另一例子中，分子在珠上合成，而珠的大小使得一次仅有一颗珠子可通过装置中各通道的出口。用这种方式，在阵列的每个位置上可印刷单个珠子。每个独立的珠含有至少一个附着其上的分子，而珠本身附着在基片上。在该例子中，珠的大小取决于印刷中所用的毛细管储器装置出口端处的通道直径。
在另一例子中，未反应的珠子被沉积在基片上，形成一阵列。然后在被固定的珠子上进行组合的或顺序的合成。
薄片阵列
本发明的另一例子涉及一技术，它消除了在毛细管储器装置和基片之间操作液体的需要。在该例子中，毛细管储器装置宜具有1000个或更多通道，并且宜由有机聚合物(如聚苯乙烯)再拉伸成预定尺寸(如图6所示)，并且被伸长从而在出口端42形成截面大小基本均匀的、缩小的直线部分40。然后，形成的再拉伸装置48的每个通道中注入液体。每种液体是由特定结合体和热激活型固化聚合物如环氧树脂(EPON)构成的不同混合物。作为例子，每个通道可含有与环氧树脂混合的、不同种类的胺化寡核苷酸或cDNA。环氧树脂的环氧基会与胺发生共价反应，形成交联的聚合物网络。对于每个独立的通道选择不同种类的已知寡核苷酸或cDNA片段并与环氧树脂混合。将各种不同混合物引入多个通道，整个装置在例如40℃固化6小时，或更佳地在室温下固化2天，从而限制聚合反应所导致的气体产生。图7显示了处于固化步骤的图6的装置。固化可以通过例如γ辐射、蓝光、温度激活或室温下的固化而进行。
在固化后，将尺寸减小的部分40与装置的其余部分切开，并且较佳地冷冻至-40℃，低于聚合物的玻璃相转变温度。冷冻步骤可使环氧树脂基质和聚合物变脆，从而有助于形成整齐的断裂切口。当刀片通过时，断裂切割可降低相邻通道间发生干扰污染的机会。此外，阵列的变形或扭曲也可用这种切割技术加以避免。
接着，如图8所示，尺寸减小的部分40被切成一些坯体50。图9显示了用断面X射线照相术切割工具52(如金刚石刀片或玻璃刀片)从冷冻的坯体50上切下非常薄的薄片54。每个薄片52的厚度宜为4-10微米，尽管任何薄片厚度都是可能的。作为注入通道的结果，每个薄片还含有例如10,000种悬浮在固化环氧树脂基质中的不同结合体。薄片获得了板的形状，包括由通道壁形成的框架网络并且界定了包含空间。每个包含空间具有侧壁和敞开的顶部和底部，并且不同种类的已知结合体占据着每个包含空间。
在切片之后，通过例如超声波焊接或胶合方式，将薄片54粘合于最好平坦且最好的由玻璃或有机聚合物制成的基片56，如图10所示。通道的壁起着边界作用，以消除样品之间的干扰。此外，毛细管储器装置的材料宜为不透光的，更佳地是黑色的。用这种方式，可以减少不同样品之间在荧光、化学发光或比色分析中经常造成的光学干扰。可以使用条形码57作为记录阵列中每个孔或位置上的内容。通过例如斜边缘之类的特征(未示出)，可以保证薄片在基片上的正确排列。
一旦粘合于基片，薄片可以被包装以便运输以及随后用于各种不同的研究或诊断程序。
应注意，在上述方法中，含有共价连于珠子的合成生物分子的液体悬浮液，可以与树脂一起使用以注入通道，从而在固化后成为聚合物网络的一部分。
分析板的格式变换
本发明的另一实施例涉及在分析板格式变换中的用途。多年来，制造的实验室的多孔板的结构为1孔至96孔。多孔板的孔通常被用作进行各种测试、使组织培养物生长、筛选药物或进行分析或诊断工作的反应容器。工业标准的多孔板是8×12矩阵的96孔(相互垂直的8孔一列和12孔一列)。此外，96孔板的高度、长度和宽度是标准化的。这种标准化导致开发出大量的辅助性设备，它们是专为96孔格式开发的。这些设备包括对8、12或96倍数的孔中一次性地加入或取出精确体积液体的装置。最近，随着样品尺寸已经缩小到微升水平以及对每块板中的更大测试数目需求的日益增加，在板上的孔数目同样会增加，例如从384孔至1536孔以及更多。为了与现有的辅助设备相容，标准的板足迹(footprint)仍保持不变，然而孔密度上升了。更高密度的板主要是板上具有多个、数目为标准的96的倍数的孔。这些板的孔间距是96孔板的中心孔间距的几分之一。
科学家面对的一种挑战，是如何将已经在较低密度的板(如96孔板)中制备的样品，快速有效地转移至在同样单位面积上有更多孔的板中(例如1536孔板)。参见图11，制造了一种再拉伸的毛细管装置，其尺寸使得能快速和容易地从96孔板转移至1536孔板。装置的入口端60的尺寸与工业标准的96孔板的尺寸(3.370英寸×5.035英寸)基本上相同。96个通道62以8×12矩阵(相互垂直的8孔一列和12孔一列)方式隔开。通道与中心间距约为0.355英寸的96孔板的孔对齐。该装置以16∶1的缩减比例进行再拉伸，使得出口端64处的通道之间的中心间距基本上等于1536孔板中各孔之间的中心间距(0.089英寸)。1536孔板的孔是以48×32矩阵方式排列的(相互垂直的8孔一列和12孔一列)。这需要16块96孔板来注满1536孔板。被转移的样品会具有有序的方向。换言之，1536孔板可以被分成4行×4列的矩阵，在矩阵中的每个位置含有来自一个96孔板的、具有最初取向的样品。
在图11中，96孔过滤板68在装置的入口端60上方对齐。96孔过滤板的样品被上样至每个通道62。然后，将装置的出口端64移至1536孔板66的一部分的上方，如图12所示，使出口端64上的通道与1536孔板的孔对齐。然后，将样品从每个通道排入板66的各孔中。
装置的出口端可以配有多个注射器针头或移液管尖，以协助转移。
使用这种转移方法，对于在例如收集化合物文库的多个拷贝过程中分配大量样品是特别有利的。
用作转移工具的毛细管装置，可以同样良好地用于96孔板和384孔板之间的转移。在这种情况下，再拉伸过程中的缩减比为4∶1。384孔板可含有来自2×2矩阵的4个96孔板的样品。毛细管装置可用于将任何孔数目的多孔板中的样品转移至在单位面积上有更多孔数目的板。该装置甚至可反向使用，例如将样品从1536孔板转移至96孔板。
此外，还可以采用封闭装置，来覆盖装置的上样端(即入口端)以及装置出口端。这种封闭可防止蒸发并创造有利的储藏条件。封闭装置的例子包括：弹簧盖(snap-on lip)、热封包装、橡皮塞、压封条、或任何本领域已知的其他密封装置。
此外，格式变换工具可用于384孔板和1536孔板；甚至从1536孔板转移至平基片上。格式变换工具可在任何两种不同孔密度的板之间使用，只要由板中孔栅距所确定的矩阵符合相同的比例。
用本文所公开的再拉伸和印刷技术，可以用来进行半导体元件的显微制造。
尽管出于阐述目的详细描述了本发明，应理解这种细节仅仅用于阐述目的，并且本领域技术人员在不背离下列权利要求所界定的本发明范围和精神的情况下，可以作出各种改动。
Claims (43)
1．一种将一阵列沉积于基片上的装置，其特征在于，所述装置包括：
多个通道，它们共同形成一基体，该基体具有预定截面面积的顶部和底部，各通道具有壁，这些壁界定了预定截面面积的敞开进口和预定截面面积的敞开出口；
所述进口的截面面积比所述出口的截面面积大；以及
任一通道截面面积占所述基体截面面积的比例，在所述顶部和所述底部是基本相同的，而且液体能依靠毛细管力保留在至少一根通道中。
2．如权利要求1所述的装置，其特征在于，所述通道具有润湿性表面的内壁，而所述底部具有非润湿性表面。
3．如权利要求1所述的装置，其特征在于，所述装置在所述顶部和所述底部具有可除去的盖。
4．如权利要求1所述的装置，其特征在于，所述装置用有机聚合物制造。
5．如权利要求1所述的装置，其特征在于，所述装置用无机聚合物制造。
6．如权利要求5所述的装置，其特征在于，所述无机聚合物是玻璃。
7．如权利要求1所述的装置，其特征在于，所述基体的所述底部约为1英寸见方。
8．如权利要求1所述的装置，其特征在于，所述基体含有约10,000根通道。
9．一种将液体从第一块多孔板转移至第二块多孔板的工具，其中所述第一块多孔板具有预定的单位面积孔密度，所述第二块多孔板具有成比例的、更大的单位面积孔密度，其特征在于，所述工具包括：
多个通道，它们共同形成基体，该基体具有预定截面面积的顶部和底部，各通道具有壁，这些壁界定了预定截面面积的敞开入口面和预定截面面积的敞开出口面；
所述基体的形状使得所述基体底部的截面面积比所述基体顶部的截面面积小；
所述通道的所述入口面具有与所述第一块多孔板的所述孔间距基本相同的间距，从而使所述孔与所述入口面匹配；以及
所述通道的所述出口面具有与所述第二块多孔板的所述孔间距基本相同的间距，从而使所述第二块多孔板的所述孔部分与所述出口面匹配。
10．如权利要求9所述的工具，其特征在于，所述基体含有96根平行通道。
11．如权利要求9所述的工具，其特征在于，所述基体含有384根平行通道。
12．如权利要求9所述的工具，其特征在于，所述基体含有1536根平行通道。
13．一种将液滴阵列沉积在基片表面的方法，其特征在于，所述方法包括步骤：
a)提供如权利要求1所的工具
b)将液体加入至少一根所述通道内
c)将从至少一个所述出口出来的至少一滴所述液体，与所述基片表面接触。
14．如权利要求13所述的方法，其特征在于，所述液体含有当活化时能够聚合的固化剂。
15．如权利要求14所述的方法，其特征在于，所述固化剂是丙烯酰胺。
16．如权利要求15所述的方法，其特征在于，所述方法包括在所述沉积后立即固化液体的步骤。
17．一种产生具有多个从入口面延伸到出口面的、末端开口的通道的坯体的方法，其中至少在预定长度上，各通道的直径、截面面积、和壁厚度基本上相同程度地缩减，其特征在于，所述方法包括步骤：
a)将材料通过多通道模挤出，以产生具有预定截面形状的多通道蜂窝结构；以及，
b)再拉伸至少一部分所述蜂窝结构体。
18．如权利要求17所述的方法，其特征在于，所述方法还包括步骤：以垂直于所述通道的方向切开所述结构体的再拉伸部分，以露出截面面积小于所述挤出的蜂窝结构截面面积的面。
19．如权利要求17所述的方法，其特征在于，所述截面形状是圆形的。
20．如权利要求18所述的方法，其特征在于，所述截面形状是矩形的。
21．一种将生物学样品阵列沉积于基片的方法，其特征在于，所述方法包括步骤：
a)提供一种装置，所述装置具有多根从入口面延伸到出口面的、末端开口的通道，其中至少在一段长度上各通道直径、截面面积、和壁厚度基本上同等地缩小；
b)用能在适宜条件下固化的液体注入至少一根所述通道；
c)使所述液体固化；以及
d)对所述装置的区段进行切片。
22．如权利要求21所述的方法，其特征在于，所述方法还包括步骤：在所述切片步骤后，将所述切片的部分粘于所述基片。
23．如权利要求21所述的方法，其特征在于，所述方法还包括步骤：在所述固化步骤之后和所述切开步骤之前，冷冻该装置。
24．如权利要求22所述的方法，其特征在于，所述方法还包括步骤：在所述结合步骤后使切片的部分融化。
25．如权利要求23所述的方法，其特征在于，所述切片的部分厚度为4-10微米。
26．如权利要求23所述的方法，其特征在于，所述切片步骤用显微切片机进行。
27．如权利要求23所述的方法，其特征在于，所述粘合是超声波粘合。
28．如权利要求23所述的方法，其特征在于，所述基片是光学透明的。
29．如权利要求23所述的方法，其特征在于，所述基片由玻璃构成。
30．如权利要求23所述的方法，其特征在于，所述基片由热塑性聚合物构成。
31．如权利要求23所述的方法，其特征在于，所述装置由不透明材料构成。
32．如权利要求23所述的方法，其特征在于，所述液体含有结合体。
33．如权利要求31所述的方法，其特征在于，所述结合体是寡核苷酸。
34．一种制造用于将生物样品或化学样品印到基片表面的工具的方法，其特征在于，所述方法包括步骤：
a)将材料通过模具挤出，以形成具有多根平行通道的坯体；以及
b)再拉伸所述坯体，以使所述坯体的周长缩小。
35．一种结合体的阵列，其特征在于，所述阵列包括：
a)具有多个预定附着位置的基片；
b)各位置包括多颗珠，所述珠具有多个与其共价结合的同种已知生物分子；
c)各位置代表一种不同分子；以及
d)所述珠与所述基片共价结合。
36．一种坯体，其特征在于，所述坯体具有多根在其中延伸的平行通道，至少一根通道具有包含在其中的结合体。
37．一片薄片，其特征在于，所述薄片包括：
框架网络，它界定了多个包含空间，所述的包含空间具有侧壁、敞开的顶部和底部，以及占据各所述包含空间的不同结合体。
38．一个结合体的阵列，其特征在于，所述阵列包括：
一个基片，
一个固定在所述基片上的聚合物矩阵，该矩阵确定了多个样品位置，以及
至少一个所述位置中所含的样品。
39．一个结合体的阵列，其特征在于，所述阵列包括：
基片表面的多个孔，所述孔具有侧壁，
占据各所述孔的不同结合体。
40．如权利要求38所述的阵列，其特征在于，所述孔在所述基片上的密度是至少103个孔/平方厘米所述表面的表面积。
41．一个结合体的阵列，其特征在于，所述阵列包括：
一基本平坦的第一板；
一第二板，它具有多个末端开口的孔；
占据各所述末端开口的孔的不同结合体，并且所述第二块板与第一块板结合。
42．一个结合体的阵列，其特征在于，所述阵列包括：
如权利要求36所述的薄片，以及
一基片，所述薄片附着于所述基片。
43.一种直接印刷过程，其特征在于，所述过程包括：
a)提供一种装置，所述装置具有多根从入口面延伸到出口面的、末端开口的通道，其中至少在预定长度上，各通道直径、截面面积、和壁厚度基本同等地缩小；
b)在该毛细管储藏装置的至少一根通道中注入液体；
c)提供一基片；
d)在0℃或负毛细管压力的环境下，将来自装置中至少一根通道的输出端的液滴与基片接触，从而转移该液滴到基片上。
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98401021A EP0955084B1 (en) | 1998-04-27 | 1998-04-27 | Method of depositing an array of biological samples using a redrawn capillary reservoir |
| EP98401021.5 | 1998-04-27 | ||
| US9170798P | 1998-07-03 | 1998-07-03 | |
| US60/091,707 | 1998-07-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1311717A true CN1311717A (zh) | 2001-09-05 |
Family
ID=8235351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99805597A Pending CN1311717A (zh) | 1998-04-27 | 1999-04-09 | 再拉伸的毛细管成像用储器 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6596237B1 (zh) |
| EP (2) | EP0955084B1 (zh) |
| JP (1) | JP2002513136A (zh) |
| CN (1) | CN1311717A (zh) |
| AU (2) | AU3552499A (zh) |
| CA (1) | CA2327664A1 (zh) |
| DE (1) | DE69835342T2 (zh) |
| WO (2) | WO1999055460A1 (zh) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103524031A (zh) * | 2013-09-13 | 2014-01-22 | 中国建筑材料科学研究总院 | 一种玻璃微细管阵列的制备方法 |
| CN108841009A (zh) * | 2018-07-07 | 2018-11-20 | 盐城师范学院 | 一种异孔共价有机框架材料的制备方法 |
| CN111018327A (zh) * | 2018-10-09 | 2020-04-17 | 贺利氏石英玻璃有限两合公司 | 毛细管及其制造方法 |
| CN111432931A (zh) * | 2017-11-30 | 2020-07-17 | 康宁股份有限公司 | 拉伸吹塑的移液器及形成其的系统和方法 |
Families Citing this family (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6762061B1 (en) | 1998-07-03 | 2004-07-13 | Corning Incorporated | Redrawn capillary imaging reservoir |
| US6736633B1 (en) | 1998-12-17 | 2004-05-18 | Corning Incorporated | Burner manifold apparatus for use in a chemical vapor deposition process |
| US6129896A (en) * | 1998-12-17 | 2000-10-10 | Drawn Optical Components, Inc. | Biosensor chip and manufacturing method |
| WO2000049382A2 (en) | 1999-02-16 | 2000-08-24 | The Perkin-Elmer Corporation | Bead dispensing system |
| KR20020010573A (ko) * | 1999-02-18 | 2002-02-04 | 알프레드 엘. 미첼슨 | 실리카 수트 압출로부터의 티타늄-함유 실리카 유리허니컴 구조물 |
| EP1177092A4 (en) * | 1999-02-18 | 2004-11-17 | Corning Inc | HONEYCOMB SILICA GLASS STRUCTURE MADE BY EXTRUSION OF SILICA SOOT |
| US6627157B1 (en) | 1999-03-04 | 2003-09-30 | Ut-Battelle, Llc | Dual manifold system and method for fluid transfer |
| WO2000053736A1 (en) | 1999-03-05 | 2000-09-14 | Mitsubishi Rayon Co., Ltd. | Carriers having biological substance |
| DE19913076A1 (de) | 1999-03-23 | 2000-10-19 | Hahn Schickard Ges | Vorrichtung und Verfahren zum Aufbringen von Mikrotröpfchen auf ein Substrat |
| GB2368640B (en) * | 1999-08-13 | 2003-09-17 | Cartesian Technologies Inc | Apparatus for liquid sample handling |
| GB2353093B (en) * | 1999-08-13 | 2003-09-17 | Glaxo Group Ltd | Apparatus for liquid sample handling |
| SE9903002D0 (sv) * | 1999-08-25 | 1999-08-25 | Alphahelix Ab | Device and method for handling small volume samples and/or reaction mixtures |
| AU7090600A (en) * | 1999-09-02 | 2001-03-26 | Corning Incorporated | Porous substrates for dna arrays |
| WO2001019518A1 (en) * | 1999-09-13 | 2001-03-22 | Aclara Biosciences, Inc. | Surface tension loading inertial release droplet device and method |
| AU7868900A (en) * | 1999-10-08 | 2001-04-23 | Bio-Informatics Group, Inc. | Volume-reducing liquid arrayer and associated methods |
| EP1239961A2 (en) * | 1999-12-17 | 2002-09-18 | Motorola, Inc. | Devices and methods for making bioarrays |
| US6406840B1 (en) * | 1999-12-17 | 2002-06-18 | Biomosaic Systems, Inc. | Cell arrays and the uses thereof |
| US20020151040A1 (en) | 2000-02-18 | 2002-10-17 | Matthew O' Keefe | Apparatus and methods for parallel processing of microvolume liquid reactions |
| EP1257355A2 (en) | 2000-02-22 | 2002-11-20 | Genospectra, Inc. | Microarray fabrication techniques and apparatus |
| US6594432B2 (en) | 2000-02-22 | 2003-07-15 | Genospectra, Inc. | Microarray fabrication techniques and apparatus |
| FR2806646A1 (fr) * | 2000-03-22 | 2001-09-28 | Francois Geli | Micro-arrays ou macro-arrays multiblocs avec laboratoires sur puces integres |
| CA2410238A1 (en) * | 2000-06-19 | 2001-12-27 | Carlton Brooks | Methods and devices for enhancing bonded substrate yields and regulating temperature |
| DE10034570A1 (de) * | 2000-07-14 | 2002-01-31 | Max Delbrueck Centrum | Verfahren zur Herstellung von Mikroarray-Chips mit Nukleinsäuren, Proteinen oder anderen Testsubstanzen |
| US20020055111A1 (en) * | 2000-08-25 | 2002-05-09 | Shiping Chen | Three-dimensional probe carriers |
| US20100261159A1 (en) | 2000-10-10 | 2010-10-14 | Robert Hess | Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof |
| EP1330306A2 (en) * | 2000-10-10 | 2003-07-30 | BioTrove, Inc. | Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof |
| US20020072111A1 (en) | 2000-12-13 | 2002-06-13 | Clarkin James P. | Drawn microchannel array devices and method of analysis using same |
| US6386219B1 (en) | 2001-02-01 | 2002-05-14 | Agilent Technologies, Inc. | Fluid handling system and method of manufacture |
| JP2002286735A (ja) * | 2001-03-28 | 2002-10-03 | Canon Inc | プローブ担体製造用の液体吐出装置、プローブ担体の製造装置及びプローブ担体の製造方法 |
| CN1385518A (zh) * | 2001-04-23 | 2002-12-18 | 株式会社百尼尔 | 生物学试料的微细排列用点样装置及该装置中使用的点样针 |
| EP1273346A1 (fr) | 2001-07-05 | 2003-01-08 | Seyonic SA | Dispensateur de fluide multi-canal |
| US7332328B2 (en) * | 2001-09-07 | 2008-02-19 | Corning Incorporated | Microcolumn-platform based array for high-throughput analysis |
| US20030124549A1 (en) * | 2001-10-11 | 2003-07-03 | Xerox Corporation | Devices and methods for detecting genetic sequences |
| US20030148539A1 (en) * | 2001-11-05 | 2003-08-07 | California Institute Of Technology | Micro fabricated fountain pen apparatus and method for ultra high density biological arrays |
| EP1323465A1 (en) * | 2001-12-31 | 2003-07-02 | Corning Incorporated | Flexible high density array print head with systems and methods for aligning pin plate, reservoir and substrate with respect to each other |
| EP1323474A1 (en) | 2001-12-31 | 2003-07-02 | Corning Incorporated | Device and process for simultaneous transfer of liquids |
| US6924107B2 (en) * | 2002-01-28 | 2005-08-02 | Bio-Informatics Group, Inc. | Four dimensional biochip design for high throughput applications and methods of using the four dimensional biochip |
| CA2521999A1 (en) | 2002-12-20 | 2004-09-02 | Biotrove, Inc. | Assay apparatus and method using microfluidic arrays |
| US20040129676A1 (en) * | 2003-01-07 | 2004-07-08 | Tan Roy H. | Apparatus for transfer of an array of liquids and methods for manufacturing same |
| US7025935B2 (en) * | 2003-04-11 | 2006-04-11 | Illumina, Inc. | Apparatus and methods for reformatting liquid samples |
| US8652774B2 (en) * | 2003-04-16 | 2014-02-18 | Affymetrix, Inc. | Automated method of manufacturing polyer arrays |
| US7407630B2 (en) | 2003-09-19 | 2008-08-05 | Applera Corporation | High density plate filler |
| US7998435B2 (en) | 2003-09-19 | 2011-08-16 | Life Technologies Corporation | High density plate filler |
| US20070014694A1 (en) * | 2003-09-19 | 2007-01-18 | Beard Nigel P | High density plate filler |
| US8277760B2 (en) | 2003-09-19 | 2012-10-02 | Applied Biosystems, Llc | High density plate filler |
| US20050232821A1 (en) * | 2003-09-19 | 2005-10-20 | Carrillo Albert L | High density plate filler |
| US20050226782A1 (en) * | 2003-09-19 | 2005-10-13 | Reed Mark T | High density plate filler |
| JP2007507721A (ja) * | 2003-09-30 | 2007-03-29 | クロンバ，インコーポレーテッド | クロマトグラフィー及びサンプル調製のためのマルチキャピラリーカラム |
| US20070017870A1 (en) | 2003-09-30 | 2007-01-25 | Belov Yuri P | Multicapillary device for sample preparation |
| DE102004062280A1 (de) * | 2003-12-29 | 2005-07-28 | Siemens Ag | Verfahren und Vorrichtung zum Dispensieren von Flüssigkeiten im Mikroraster |
| CA2559171A1 (en) | 2004-03-12 | 2005-09-29 | Biotrove, Inc. | Nanoliter array loading |
| WO2005094995A1 (de) * | 2004-03-31 | 2005-10-13 | Epr Labautomation Ag | Verfahren und vorrichtung zum speichern und dispensieren von kleinen flüssigkeitsmengen |
| DE102004031167A1 (de) * | 2004-06-28 | 2006-01-12 | Infineon Technologies Ag | Verfahren zur Herstellung von Biochips aus porösen Substraten |
| US20060105453A1 (en) | 2004-09-09 | 2006-05-18 | Brenan Colin J | Coating process for microfluidic sample arrays |
| US7572640B2 (en) | 2004-09-28 | 2009-08-11 | Singulex, Inc. | Method for highly sensitive detection of single protein molecules labeled with fluorescent moieties |
| US8685711B2 (en) | 2004-09-28 | 2014-04-01 | Singulex, Inc. | Methods and compositions for highly sensitive detection of molecules |
| US9040305B2 (en) | 2004-09-28 | 2015-05-26 | Singulex, Inc. | Method of analysis for determining a specific protein in blood samples using fluorescence spectrometry |
| WO2006102296A2 (en) * | 2005-03-22 | 2006-09-28 | Applera Corporation | High density plate filler |
| US8383059B2 (en) * | 2005-09-30 | 2013-02-26 | University Of Utah Research Foundation | Microfluidic interface for highly parallel addressing of sensing arrays |
| EP3156799B1 (en) | 2006-04-04 | 2024-01-24 | Novilux, LLC | Analyzer and method for highly sensitive detection of analytes |
| US7838250B1 (en) | 2006-04-04 | 2010-11-23 | Singulex, Inc. | Highly sensitive system and methods for analysis of troponin |
| EP2016394A4 (en) | 2006-04-04 | 2013-04-24 | Singulex Inc | METHOD AND COMPOSITIONS FOR HIGHLY SENSITIVE ANALYSIS OF MARKERS AND DETECTION OF MOLECULES |
| US7767135B2 (en) * | 2007-10-19 | 2010-08-03 | Corning Incorporated | Method of forming a sintered microfluidic device |
| JP2011508219A (ja) | 2007-12-19 | 2011-03-10 | シンギュレックス・インコーポレイテッド | 単一分子検出走査分析器およびその使用方法 |
| US20110092686A1 (en) * | 2008-03-28 | 2011-04-21 | Pelican Group Holdings, Inc. | Multicapillary sample preparation devices and methods for processing analytes |
| DE102008050092A1 (de) * | 2008-10-06 | 2010-04-08 | Hach Lange Gmbh | Mobile Wasser-Analyseanordnung |
| EP2440936A4 (en) | 2009-06-08 | 2013-03-13 | Singulex Inc | GROUPS OF HIGHLY SENSITIVE BIOMARKERS |
| US8101913B2 (en) * | 2009-09-11 | 2012-01-24 | Ut-Battelle, Llc | Method of making large area conformable shape structures for detector/sensor applications using glass drawing technique and postprocessing |
| FR2957529B1 (fr) * | 2010-03-19 | 2012-04-06 | Saint Gobain Ct Recherches | Structure filtrante comprenant un materiau de bouchage ameliore |
| EP2566971B1 (en) | 2010-05-06 | 2019-03-27 | Singulex, Inc. | Methods for diagnosing, staging, predicting risk for developing and identifying treatment responders for rheumatoid arthritis |
| WO2012159632A1 (en) * | 2011-05-26 | 2012-11-29 | Vestergaard Frandsen Sa | Sintered glass for release of nutrients or other agents |
| US9180449B2 (en) | 2012-06-12 | 2015-11-10 | Hach Company | Mobile water analysis |
| US10300450B2 (en) | 2012-09-14 | 2019-05-28 | Carterra, Inc. | Method and device for depositing a substance on a submerged surface |
| EP2969177A1 (en) * | 2013-03-15 | 2016-01-20 | Massachusetts Institute of Technology | Deposition and imaging of particles on planar substrates |
| US11300486B1 (en) * | 2016-11-23 | 2022-04-12 | Array Science, Llc | Apparatus for producing high yield cores for use in a microarray block, method for using same |
| CN110369011A (zh) * | 2019-06-25 | 2019-10-25 | 东南大学 | 基于液压驱动的微量液体转移装置、控制设备及控制方法 |
Family Cites Families (105)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3568735A (en) | 1968-06-26 | 1971-03-09 | Cooke Eng Co | Laboratory microtitration dispensing apparatus |
| US4010019A (en) * | 1971-11-19 | 1977-03-01 | American Optical Corporation | Method of making microchannel plates |
| US3863507A (en) | 1973-03-16 | 1975-02-04 | Coulter Electronics | Sample mixing and metering apparatus |
| LU77642A1 (zh) | 1976-07-09 | 1977-10-03 | ||
| US4199013A (en) | 1977-04-01 | 1980-04-22 | Packard Instrument Company, Inc. | Liquid sample aspirating and/or dispensing system |
| NL7704460A (nl) | 1977-04-22 | 1978-10-24 | Vitatron Scientific Bv | Analyse-automaat. |
| US4140018A (en) | 1977-09-07 | 1979-02-20 | Science Spectrum, Inc. | Programmable action sampler system |
| US4216245A (en) * | 1978-07-25 | 1980-08-05 | Miles Laboratories, Inc. | Method of making printed reagent test devices |
| US4416400A (en) | 1978-10-24 | 1983-11-22 | Dougherty Brothers Company | One piece dispenser |
| JPS55161238U (zh) | 1979-05-04 | 1980-11-19 | ||
| US4276048A (en) | 1979-06-14 | 1981-06-30 | Dynatech Ag | Miniature reaction container and a method and apparatus for introducing micro volumes of liquid to such a container |
| SE8004687L (sv) | 1980-06-25 | 1981-12-26 | Clinicon Ab | Automatisk analysapparat |
| DE3047265C2 (de) * | 1980-12-16 | 1985-08-22 | Deutsches Krebsforschungszentrum, 6900 Heidelberg | Einrichtung zur Überführung von Probengefäßen in Auffanggefäße |
| US4422151A (en) | 1981-06-01 | 1983-12-20 | Gilson Robert E | Liquid handling apparatus |
| US4461328A (en) * | 1982-06-04 | 1984-07-24 | Drummond Scientific Company | Pipette device |
| JPS59120437A (ja) | 1982-12-28 | 1984-07-12 | Shin Etsu Polymer Co Ltd | シリコ−ンゴムロ−ルの製造方法 |
| US4483925A (en) | 1982-12-30 | 1984-11-20 | Becton, Dickinson And Company | Liquid removal device |
| DE3407849A1 (de) | 1984-02-29 | 1985-08-29 | Alois 3201 Algermissen Höft | Verfahren und einrichtung zum gleichzeitigen aufbringen einer vielzahl von fluessigkeitsproben auf einen objekttraeger |
| DE3410508C2 (de) * | 1984-03-22 | 1986-06-26 | Kernforschungsanlage Jülich GmbH, 5170 Jülich | Serien-Abfüllgerät zum Befüllen der Becher einer Mikrobecherplatte |
| US4621655A (en) * | 1985-03-04 | 1986-11-11 | Hydril Company | Marine riser fill-up valve |
| US4731335A (en) | 1985-09-13 | 1988-03-15 | Fisher Scientific Company | Method for treating thin samples on a surface employing capillary flow |
| US4853020A (en) * | 1985-09-30 | 1989-08-01 | Itt Electro Optical Products, A Division Of Itt Corporation | Method of making a channel type electron multiplier |
| US4906439A (en) * | 1986-03-25 | 1990-03-06 | Pb Diagnostic Systems, Inc. | Biological diagnostic device and method of use |
| US5000921A (en) | 1986-10-24 | 1991-03-19 | Hanaway Richard W | Multiple pipette samples |
| JPS63199432A (ja) * | 1987-02-16 | 1988-08-17 | Toshiba Corp | Ｃｖｄ装置用ガス分散ヘツド |
| US4914022A (en) * | 1987-10-21 | 1990-04-03 | Amc Cancer Research Center | Method for preparing multiple tissue samples for microscopic investigation and testing |
| US5055263A (en) | 1988-01-14 | 1991-10-08 | Cyberlab, Inc. | Automated pipetting system |
| DE3805414C1 (zh) * | 1988-02-22 | 1989-09-07 | Secon Gesellschaft Fuer Separations- Und Concentrationstechnik Mbh, 3402 Dransfeld, De | |
| US5700637A (en) | 1988-05-03 | 1997-12-23 | Isis Innovation Limited | Apparatus and method for analyzing polynucleotide sequences and method of generating oligonucleotide arrays |
| US5008082A (en) | 1988-08-25 | 1991-04-16 | Eastman Kodak Company | Analyzers using linear sample trays with random access |
| US5095213A (en) | 1988-11-03 | 1992-03-10 | Syntex (U.S.A.) Inc. | Method of using an opaque plastic microscope slide for epi-fluorescent microscopy |
| US5166889A (en) | 1989-01-10 | 1992-11-24 | Medical Robotics, Inc. | Robotic liquid sampling system |
| US5602197A (en) | 1989-05-30 | 1997-02-11 | Corning Incorporated | Reversible polymer gel binders for powder forming |
| US5547839A (en) * | 1989-06-07 | 1996-08-20 | Affymax Technologies N.V. | Sequencing of surface immobilized polymers utilizing microflourescence detection |
| US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| US5744101A (en) | 1989-06-07 | 1998-04-28 | Affymax Technologies N.V. | Photolabile nucleoside protecting groups |
| US5262128A (en) | 1989-10-23 | 1993-11-16 | The United States Of America As Represented By The Department Of Health And Human Services | Array-type multiple cell injector |
| US5041266A (en) | 1989-12-21 | 1991-08-20 | Hoffmann-La Roche Inc. | Tray for immunometric determinations |
| CA2008831C (en) | 1990-01-29 | 1996-03-26 | Patrick T.T. Wong | Method of detecting the presence of anomalies in biological tissues and cells in natural and cultured form by infrared spectroscopy |
| DE4024545A1 (de) | 1990-08-02 | 1992-02-06 | Boehringer Mannheim Gmbh | Verfahren und vorrichtung zum dosierten zufuehren einer biochemischen analysefluessigkeit auf ein target |
| US5188148A (en) | 1990-12-21 | 1993-02-23 | Millipore Corporation | Conduit plate for fluid delivery system |
| US5525302A (en) | 1991-02-01 | 1996-06-11 | Astle; Thomas W. | Method and device for simultaneously transferring plural samples |
| US5763170A (en) | 1991-04-16 | 1998-06-09 | Amersham International Plc | Method for forming an array of biological particles |
| US5506098A (en) | 1991-09-04 | 1996-04-09 | Daikin Industries, Ltd. | In situ hybridization method |
| US5474796A (en) | 1991-09-04 | 1995-12-12 | Protogene Laboratories, Inc. | Method and apparatus for conducting an array of chemical reactions on a support surface |
| US5265327A (en) * | 1991-09-13 | 1993-11-30 | Faris Sadeg M | Microchannel plate technology |
| US5632957A (en) * | 1993-11-01 | 1997-05-27 | Nanogen | Molecular biological diagnostic systems including electrodes |
| NL9101953A (nl) | 1991-11-21 | 1993-06-16 | Seed Capital Investments | Testinrichting omvattende een plaat met een veelvoud van putjes met een bijbehorende doseerinrichting, alsmede een kit die deze inrichtingen omvat en toepassing van de inrichtingen. |
| JPH05177831A (ja) * | 1991-12-27 | 1993-07-20 | Rohm Co Ltd | インクジェットプリントヘッド及びそれを備える電子機器 |
| US5188733A (en) * | 1992-02-26 | 1993-02-23 | Trustees Of Boston University | Apparatus and process for effecting sequential peptide syntheses |
| US5585275A (en) * | 1992-09-02 | 1996-12-17 | Arris Pharmaceutical Corporation | Pilot apparatus for peptide synthesis and screening |
| US5334352A (en) | 1992-09-23 | 1994-08-02 | Icn Biomedicals, Inc. | Manifold construction |
| US5508200A (en) * | 1992-10-19 | 1996-04-16 | Tiffany; Thomas | Method and apparatus for conducting multiple chemical assays |
| US5583211A (en) * | 1992-10-29 | 1996-12-10 | Beckman Instruments, Inc. | Surface activated organic polymers useful for location - specific attachment of nucleic acids, peptides, proteins and oligosaccharides |
| JP2974537B2 (ja) * | 1993-04-07 | 1999-11-10 | 株式会社日立製作所 | キャピラリーアレー、電気泳動方法及び電気泳動装置 |
| US5577444A (en) | 1993-06-22 | 1996-11-26 | Yamahachi Chemical Co., Ltd. | Hand stamp |
| RU2041263C1 (ru) | 1993-08-11 | 1995-08-09 | Геннадий Моисеевич Ершов | Способ микродозирования водных растворов веществ на носитель и устройство для его осуществления |
| CA2174140C (en) * | 1993-10-28 | 2004-04-06 | Kenneth L. Beattie | Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions |
| US5972545A (en) | 1993-11-03 | 1999-10-26 | Corning Incorporated | Method of printing a color filter |
| US5624775A (en) | 1994-02-16 | 1997-04-29 | Corning Incorporated | Apparatus and method for printing a color filter |
| US6015880A (en) * | 1994-03-16 | 2000-01-18 | California Institute Of Technology | Method and substrate for performing multiple sequential reactions on a matrix |
| US5738996A (en) * | 1994-06-15 | 1998-04-14 | Pence, Inc. | Combinational library composition and method |
| US5807522A (en) | 1994-06-17 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for fabricating microarrays of biological samples |
| US5498545A (en) | 1994-07-21 | 1996-03-12 | Vestal; Marvin L. | Mass spectrometer system and method for matrix-assisted laser desorption measurements |
| US5551487A (en) | 1995-03-10 | 1996-09-03 | Hewlett-Packard Company | Micro-dispenser for preparing assay plates |
| US5560811A (en) * | 1995-03-21 | 1996-10-01 | Seurat Analytical Systems Incorporated | Capillary electrophoresis apparatus and method |
| US5723320A (en) | 1995-08-29 | 1998-03-03 | Dehlinger; Peter J. | Position-addressable polynucleotide arrays |
| US5678165A (en) * | 1995-12-06 | 1997-10-14 | Corning Incorporated | Plastic formable mixtures and method of use therefor |
| GB9521775D0 (en) * | 1995-10-24 | 1996-01-03 | Pa Consulting Services | Microwell plates |
| FR2741357B1 (fr) | 1995-11-22 | 1998-01-16 | Corning Inc | Procede de fabrication d'une plaquette de support d'un reseau bidimensionnel de micropuits, notamment pour essais ou cultures biologiques |
| US5763263A (en) * | 1995-11-27 | 1998-06-09 | Dehlinger; Peter J. | Method and apparatus for producing position addressable combinatorial libraries |
| US5649576A (en) * | 1996-02-26 | 1997-07-22 | Pharmacopeia, Inc. | Partitioning device |
| US6074609A (en) * | 1996-04-24 | 2000-06-13 | Glaxo Wellcome Inc. | Systems for arraying beads |
| CA2257287A1 (en) * | 1996-05-30 | 1997-12-04 | D. Lansing Taylor | Miniaturized cell array methods and apparatus for cell-based screening |
| US5770151A (en) | 1996-06-05 | 1998-06-23 | Molecular Dynamics, Inc. | High-speed liquid deposition device for biological molecule array formation |
| AU3508197A (en) * | 1996-06-27 | 1998-01-14 | Cellstat Technologies, Inc | High-throughput screening method and apparatus |
| DE19628178C1 (de) | 1996-07-12 | 1997-09-18 | Bruker Franzen Analytik Gmbh | Verfahren zum Beladen von Probenträgern für Massenspektrometer |
| DE19628928A1 (de) * | 1996-07-18 | 1998-01-22 | Basf Ag | Feste Träger für analytische Meßverfahren, ein Verfahren zu ihrer Herstellung sowie ihre Verwendung |
| US5798035A (en) * | 1996-10-03 | 1998-08-25 | Pharmacopeia, Inc. | High throughput solid phase chemical synthesis utilizing thin cylindrical reaction vessels useable for biological assay |
| FR2754469B1 (fr) | 1996-10-10 | 1998-12-04 | Corning Inc | Outil de transport de gouttes de liquide et procede de transfert de gouttes a l'aide d'un tel outil |
| WO1998015355A2 (en) | 1996-10-10 | 1998-04-16 | Corning Incorporated | Tool and method for transfer of drops |
| WO1998016830A2 (en) * | 1996-10-16 | 1998-04-23 | The President And Fellows Of Harvard College | Droplet assay system |
| US6875620B1 (en) * | 1996-10-31 | 2005-04-05 | Agilent Technologies, Inc. | Tiling process for constructing a chemical array |
| US5774779A (en) | 1996-11-06 | 1998-06-30 | Materials And Electrochemical Research (Mer) Corporation | Multi-channel structures and processes for making such structures |
| US6054325A (en) | 1996-12-02 | 2000-04-25 | Glaxo Wellcom Inc. | Method and apparatus for transferring and combining distinct chemical compositions with reagents |
| US6083763A (en) | 1996-12-31 | 2000-07-04 | Genometrix Inc. | Multiplexed molecular analysis apparatus and method |
| US5772966A (en) | 1997-01-24 | 1998-06-30 | Maracas; George N. | Assay dispensing apparatus |
| FR2760838B1 (fr) | 1997-03-13 | 1999-05-21 | Corning Inc | Circuit fluidique integre d'execution d'un processus de preparation ou d'analyse d'un echantillon de matiere fluide, son procede de fabrication et appareil d'exploitation de ce circuit |
| US6090251A (en) | 1997-06-06 | 2000-07-18 | Caliper Technologies, Inc. | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
| FR2764705A1 (fr) | 1997-06-17 | 1998-12-18 | Corning Costar Corp | Procede et appareil de transfert et de distribution de petits volumes de liquide |
| US6051190A (en) | 1997-06-17 | 2000-04-18 | Corning Incorporated | Method and apparatus for transferring and dispensing small volumes of liquid and method for making the apparatus |
| US6231813B1 (en) * | 1997-09-16 | 2001-05-15 | Invitrogen Corporation | Gel loading adapter |
| JP4564165B2 (ja) | 1997-10-31 | 2010-10-20 | アプライド バイオシステムズ， エルエルシー | アレイ（群）を作製するための方法および装置 |
| US5882930A (en) | 1997-11-10 | 1999-03-16 | Hyseq, Inc. | Reagent transfer device |
| ES2209222T3 (es) | 1997-11-14 | 2004-06-16 | Gen-Probe Incorporated | Estacion de trabajo de ensayos. |
| KR20010024749A (ko) | 1997-12-19 | 2001-03-26 | 알프레드 엘. 미첼슨 | 셀형 하니콤 구조의 제조 |
| US5974969A (en) | 1998-02-04 | 1999-11-02 | Brother Kogyo Kabushiki Kaisha | Stamp unit with ink pack filled with ink |
| JPH11295323A (ja) | 1998-04-13 | 1999-10-29 | Matsushita Electric Ind Co Ltd | 自動分注装置および分注方法 |
| US6350618B1 (en) | 1998-04-27 | 2002-02-26 | Corning Incorporated | Redrawn capillary imaging reservoir |
| US6309891B1 (en) | 1998-09-09 | 2001-10-30 | Incyte Genomics, Inc. | Capillary printing systems |
| US6162341A (en) * | 1998-09-11 | 2000-12-19 | The Perkin-Elmer Corporation | Multi-channel capillary electrophoresis device including sheath-flow cuvette and replacable capillary array |
| US6255116B1 (en) | 1998-12-17 | 2001-07-03 | Smithkline Beecham Corporation | Apparatus and process for arraying beads |
| US6221653B1 (en) | 1999-04-27 | 2001-04-24 | Agilent Technologies, Inc. | Method of performing array-based hybridization assays using thermal inkjet deposition of sample fluids |
| US6189450B1 (en) | 1999-10-15 | 2001-02-20 | Shiny Shih | Ink refillable stamp |
| US6610253B2 (en) | 2000-05-31 | 2003-08-26 | Autosplice, Inc. | Liquid pin transfer assembly with common pin bias |
-
1998
- 1998-04-27 DE DE69835342T patent/DE69835342T2/de not_active Expired - Fee Related
- 1998-04-27 EP EP98401021A patent/EP0955084B1/en not_active Expired - Lifetime
-
1999
- 1999-04-09 EP EP99917389A patent/EP1075327A4/en not_active Withdrawn
- 1999-04-09 CA CA002327664A patent/CA2327664A1/en not_active Abandoned
- 1999-04-09 JP JP2000545647A patent/JP2002513136A/ja not_active Withdrawn
- 1999-04-09 WO PCT/US1999/007844 patent/WO1999055460A1/en active Application Filing
- 1999-04-09 AU AU35524/99A patent/AU3552499A/en not_active Abandoned
- 1999-04-09 CN CN99805597A patent/CN1311717A/zh active Pending
- 1999-04-26 US US09/299,766 patent/US6596237B1/en not_active Expired - Fee Related
- 1999-04-27 WO PCT/US1999/008956 patent/WO1999055461A1/en active Application Filing
- 1999-04-27 AU AU37604/99A patent/AU3760499A/en not_active Abandoned
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103524031A (zh) * | 2013-09-13 | 2014-01-22 | 中国建筑材料科学研究总院 | 一种玻璃微细管阵列的制备方法 |
| CN111432931A (zh) * | 2017-11-30 | 2020-07-17 | 康宁股份有限公司 | 拉伸吹塑的移液器及形成其的系统和方法 |
| CN111432931B (zh) * | 2017-11-30 | 2022-04-26 | 康宁股份有限公司 | 拉伸吹塑的移液器及形成其的系统和方法 |
| CN108841009A (zh) * | 2018-07-07 | 2018-11-20 | 盐城师范学院 | 一种异孔共价有机框架材料的制备方法 |
| CN108841009B (zh) * | 2018-07-07 | 2021-09-14 | 盐城师范学院 | 一种异孔共价有机框架材料的制备方法 |
| CN111018327A (zh) * | 2018-10-09 | 2020-04-17 | 贺利氏石英玻璃有限两合公司 | 毛细管及其制造方法 |
| CN111018327B (zh) * | 2018-10-09 | 2022-06-28 | 贺利氏石英玻璃有限两合公司 | 毛细管及其制造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| DE69835342T2 (de) | 2007-08-23 |
| WO1999055461A1 (en) | 1999-11-04 |
| AU3760499A (en) | 1999-11-16 |
| EP0955084B1 (en) | 2006-07-26 |
| JP2002513136A (ja) | 2002-05-08 |
| US6596237B1 (en) | 2003-07-22 |
| EP1075327A4 (en) | 2006-01-25 |
| AU3552499A (en) | 1999-11-16 |
| CA2327664A1 (en) | 1999-11-04 |
| EP1075327A1 (en) | 2001-02-14 |
| EP0955084A1 (en) | 1999-11-10 |
| WO1999055460A1 (en) | 1999-11-04 |
| DE69835342D1 (de) | 2006-09-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1311717A (zh) | 再拉伸的毛细管成像用储器 | |
| US6350618B1 (en) | Redrawn capillary imaging reservoir | |
| Feng et al. | Droplet microarrays: from surface patterning to high‐throughput applications | |
| US6762061B1 (en) | Redrawn capillary imaging reservoir | |
| CN100496749C (zh) | 对微阵列和其他微型装置进行高浓度点沉积的点样装置及方法 | |
| US6884626B1 (en) | Redrawn capillary imaging reservoir | |
| US20100204065A1 (en) | Microarray using laminar flow and method of preparing the same | |
| CN107107058A (zh) | 高清晰度微液滴打印机 | |
| AU780441B2 (en) | Improved low fluorescence nylon/glass composites for micro-analytical diagnostic applications | |
| Li et al. | An oligonucleotide synthesizer based on a microreactor chip and an inkjet printer | |
| CN112920941A (zh) | 一种多层三维数字核酸扩增芯片及其制作与使用方法 | |
| WO2001098781A1 (fr) | Microjeu ordonne de substances associees a des organismes | |
| CN114390948B (zh) | 微流控芯片、生产方法及用途 | |
| CN109370891B (zh) | 一种生物芯片及其制备方法 | |
| EP1002570A1 (en) | Capillary transfer device for high density arrays | |
| CN215799530U (zh) | 一种多层三维数字核酸扩增芯片 | |
| Chen et al. | Surface-tension-confined droplet microfluidics☆ | |
| EP3933411A1 (en) | Microfluidic device and sample analysis method | |
| EP2012126A1 (en) | Porous biological assay substrate and method for producing such substrate | |
| US20070117139A1 (en) | Method of manufacturing probe carrier | |
| Ueda et al. | Patterned superhydrophobic surfaces | |
| EP2260936B1 (de) | Verfahren zur ortsspezifischen Synthese von Nukleinsäuren auf festen Trägern | |
| Benoit | Flow-through microchannel DNA chips | |
| US20020015960A1 (en) | Method of preparing nucleic acid microchips | |
| CN102628081A (zh) | 一种微流体自驱动原位压印生物芯片新方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |