JP5189292B2 - 生物分析物の検出方法における微粒子標識の使用 - Google Patents
生物分析物の検出方法における微粒子標識の使用 Download PDFInfo
- Publication number
- JP5189292B2 JP5189292B2 JP2006539689A JP2006539689A JP5189292B2 JP 5189292 B2 JP5189292 B2 JP 5189292B2 JP 2006539689 A JP2006539689 A JP 2006539689A JP 2006539689 A JP2006539689 A JP 2006539689A JP 5189292 B2 JP5189292 B2 JP 5189292B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- cell
- solid support
- membrane
- particulate
- 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.)
- Expired - Fee Related
Links
- 238000001514 detection method Methods 0.000 title description 27
- 210000004027 cell Anatomy 0.000 claims description 260
- 238000000034 method Methods 0.000 claims description 119
- 239000002245 particle Substances 0.000 claims description 115
- 239000012528 membrane Substances 0.000 claims description 78
- 239000000427 antigen Substances 0.000 claims description 66
- 108091007433 antigens Proteins 0.000 claims description 63
- 102000036639 antigens Human genes 0.000 claims description 63
- 239000011859 microparticle Substances 0.000 claims description 48
- 102000004127 Cytokines Human genes 0.000 claims description 30
- 108090000695 Cytokines Proteins 0.000 claims description 30
- 239000007787 solid Substances 0.000 claims description 30
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 27
- 230000001413 cellular effect Effects 0.000 claims description 26
- 230000028327 secretion Effects 0.000 claims description 25
- 210000004408 hybridoma Anatomy 0.000 claims description 24
- 229940079593 drug Drugs 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 23
- 108060003951 Immunoglobulin Proteins 0.000 claims description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims description 20
- 102000018358 immunoglobulin Human genes 0.000 claims description 20
- 239000003086 colorant Substances 0.000 claims description 19
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 17
- 230000009870 specific binding Effects 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 15
- 230000003248 secreting effect Effects 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 229940072221 immunoglobulins Drugs 0.000 claims description 8
- 210000003850 cellular structure Anatomy 0.000 claims description 6
- 230000002596 correlated effect Effects 0.000 claims description 4
- 230000000717 retained effect Effects 0.000 claims description 4
- 230000035699 permeability Effects 0.000 claims description 3
- 239000010419 fine particle Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 description 78
- 235000018102 proteins Nutrition 0.000 description 76
- 102000004169 proteins and genes Human genes 0.000 description 76
- 238000003556 assay Methods 0.000 description 66
- 239000000523 sample Substances 0.000 description 55
- 239000002096 quantum dot Substances 0.000 description 32
- 230000027455 binding Effects 0.000 description 26
- 210000001519 tissue Anatomy 0.000 description 23
- 108020004414 DNA Proteins 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 239000012491 analyte Substances 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 238000010186 staining Methods 0.000 description 17
- 239000000975 dye Substances 0.000 description 15
- 239000000499 gel Substances 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 241000894007 species Species 0.000 description 13
- 238000013459 approach Methods 0.000 description 12
- 238000002820 assay format Methods 0.000 description 12
- 238000002372 labelling Methods 0.000 description 12
- 238000012216 screening Methods 0.000 description 12
- 239000004793 Polystyrene Substances 0.000 description 11
- 229920002223 polystyrene Polymers 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 238000012512 characterization method Methods 0.000 description 10
- 210000002242 embryoid body Anatomy 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 229920000609 methyl cellulose Polymers 0.000 description 9
- 239000001923 methylcellulose Substances 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 230000035945 sensitivity Effects 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 102000000588 Interleukin-2 Human genes 0.000 description 8
- 108010002350 Interleukin-2 Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 8
- 238000001962 electrophoresis Methods 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- UHYPYGJEEGLRJD-UHFFFAOYSA-N cadmium(2+);selenium(2-) Chemical class [Se-2].[Cd+2] UHYPYGJEEGLRJD-UHFFFAOYSA-N 0.000 description 7
- 238000005251 capillar electrophoresis Methods 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000003102 growth factor Substances 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 239000012472 biological sample Substances 0.000 description 6
- 239000007850 fluorescent dye Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 239000004816 latex Substances 0.000 description 6
- 229920000126 latex Polymers 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 6
- 238000001712 DNA sequencing Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000009792 diffusion process Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 230000005284 excitation Effects 0.000 description 5
- 238000005194 fractionation Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 238000004020 luminiscence type Methods 0.000 description 5
- 230000005012 migration Effects 0.000 description 5
- 238000013508 migration Methods 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 239000011148 porous material Substances 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 4
- 108090000978 Interleukin-4 Proteins 0.000 description 4
- 239000003463 adsorbent Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000001502 gel electrophoresis Methods 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 210000001161 mammalian embryo Anatomy 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- -1 procedures Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 108700028369 Alleles Proteins 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- 108090001008 Avidin Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108010002616 Interleukin-5 Proteins 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 238000002105 Southern blotting Methods 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- VYXSBFYARXAAKO-WTKGSRSZSA-N chembl402140 Chemical compound Cl.C1=2C=C(C)C(NCC)=CC=2OC2=C\C(=N/CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-WTKGSRSZSA-N 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000005684 electric field Effects 0.000 description 3
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 239000004065 semiconductor Substances 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 238000011510 Elispot assay Methods 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 108091005461 Nucleic proteins Chemical group 0.000 description 2
- 238000001069 Raman spectroscopy Methods 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 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 description 2
- 238000001261 affinity purification Methods 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 210000005056 cell body Anatomy 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000000412 dendrimer Substances 0.000 description 2
- 229920000736 dendritic polymer Polymers 0.000 description 2
- 230000013020 embryo development Effects 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000011544 gradient gel Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000000370 laser capture micro-dissection Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 238000007837 multiplex assay Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 210000001322 periplasm Anatomy 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000007398 protein translocation Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000012128 staining reagent Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 229910004613 CdTe Inorganic materials 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 229910000673 Indium arsenide Inorganic materials 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 241000711408 Murine respirovirus Species 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 238000001237 Raman spectrum Methods 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000011358 absorbing material Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000837 carbohydrate group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 238000003568 cytokine secretion assay Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000007274 generation of a signal involved in cell-cell signaling Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000012203 high throughput assay Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- RPQDHPTXJYYUPQ-UHFFFAOYSA-N indium arsenide Chemical compound [In]#[As] RPQDHPTXJYYUPQ-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007641 inkjet printing Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 238000000491 multivariate analysis Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000002159 nanocrystal Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 210000000633 nuclear envelope Anatomy 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 210000001216 paracrine cell Anatomy 0.000 description 1
- 230000008775 paternal effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 238000001296 phosphorescence spectrum Methods 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000002810 primary assay Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000007441 retrograde transport Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 210000002955 secretory cell Anatomy 0.000 description 1
- SBIBMFFZSBJNJF-UHFFFAOYSA-N selenium;zinc Chemical compound [Se]=[Zn] SBIBMFFZSBJNJF-UHFFFAOYSA-N 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- TXDNPSYEJHXKMK-UHFFFAOYSA-N sulfanylsilane Chemical class S[SiH3] TXDNPSYEJHXKMK-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/06—Investigating concentration of particle suspensions
- G01N15/0606—Investigating concentration of particle suspensions by collecting particles on a support
- G01N15/0618—Investigating concentration of particle suspensions by collecting particles on a support of the filter type
- G01N15/0625—Optical scan of the deposits
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6456—Spatial resolved fluorescence measurements; Imaging
- G01N21/6458—Fluorescence microscopy
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44704—Details; Accessories
- G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
- G01N27/44721—Arrangements for investigating the separated zones, e.g. localising zones by optical means
- G01N27/44726—Arrangements for investigating the separated zones, e.g. localising zones by optical means using specific dyes, markers or binding molecules
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
-
- 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
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
- G01N33/5047—Cells of the immune system
- G01N33/505—Cells of the immune system involving T-cells
-
- 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
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
- G01N33/5047—Cells of the immune system
- G01N33/5052—Cells of the immune system involving B-cells
-
- 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
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
-
- 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
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/585—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
- G01N2021/6441—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks with two or more labels
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
- G01N2030/8827—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials involving nucleic acids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- 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
- Y10T436/11—Automated chemical analysis
- Y10T436/112499—Automated chemical analysis with sample on test slide
-
- 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
- Y10T436/13—Tracers or tags
-
- 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
- Y10T436/25125—Digestion or removing interfering materials
-
- 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
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Optics & Photonics (AREA)
- Dispersion Chemistry (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Electrochemistry (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Description
本発明は、識別可能な種類の範囲にわたって特有の色が調整され得るシグナル生成部分を含むサブミクロンサイズの微粒子標識を利用し、それによって様々な多重アッセイ法が可能になる方法に関する。本発明はまた、多重粒子が好ましいが限定的ではない態様を提供するアッセイ法に関する。本発明はまた、新規薬剤の臨床試験および処置手順に対する個々の対象の反応の評価の分野に関する。
本出願は、2003年11月5日に出願した米国特許仮出願第60/517,651号および2003年11月5日に出願した同第60/517,713号に関する。これらの書類の内容は参照により本明細書に組み入れられる。
試料を様々な試薬に対する反応性について試験することが望ましい場合が多い。例えば、サイトカイン分泌プロファイリングでは、特定の組織から分泌されたタンパク質が、関心対象と考えられるファミリーメンバーが数十から数百ある抗原ファミリーに対して産生された一群の抗体と免疫反応する能力が必要とされる。この場合、抗体-抗原複合体の存在の検出は通常、標識が複合体中の抗体に結合しているか、または標識が結合している二次抗体を一次抗体に結合させることを必要とする。次いで、標識の検出によって試料中の抗体-抗原複合体の存在が確認される。
本発明は、顕微鏡を用いて単一細胞を調べる改良方法を提供する。本発明の方法を使用することで、いくつかの態様においては他の細胞と比較して、個々の細胞の組成物のプロフィールを容易に得ることができる。このような試験の特定の適用には、臨床状況における結果の取得および処置手順の評価が含まれる。この方法によって、所望の特徴を有する単一細胞の同定も可能になり、細胞の遺伝子成分を改変するまたは細胞を不死化するなど、細胞をさらに操作することができる。本発明の改良方法では、試験した単一細胞の生存能を維持すること、および必要に応じてさらなる操作のために細胞を回収することも一般に可能である。
本発明のアッセイ法のいくつかでは、細胞の様々な表面抗原、細胞内抗原、および/または分泌タンパク質に基づいて個々の細胞の表現型を同定するために、微粒子標識および顕微鏡観察技法を利用する。そのようなアッセイには以下のものが含まれる:様々な条件下における単一細胞の多変量サイトカイン分泌プロフィールの特徴づけ;分泌された免疫グロブリンの互いのまたは一群の抗原に対する特異性および他の特徴(アイソタイプなど)の特徴づけ;血管新生および再生を含むパターン化された組織増殖に付随する組織環境の特徴づけ;複数の細胞型が、識別可能な微粒子標識に結合した細胞型特異的抗体との結合により、または標識の物理的捕捉により個々に認識され得る自動化病理学(組織染色);タンパク質の細胞内局在性の特徴づけ;単一細胞レベルでのmRNA発現の特徴づけ;インサイチューでの、もしくはマイクロアレイでスポットした、またはクロマトグラフィーもしくは電気泳動による分画後の、破壊した細胞のタンパク質、核酸、炭水化物、または脂質内容物の特徴づけ;内部陽性対照と比較した、試験対の生物学的特異的相互作用の親和性の特徴づけ。
1つの例示的なアッセイ法では、微粒子標識を用いて単一細胞から分泌されたタンパク質を特徴づける。分泌タンパク質の一般的なアッセイ形式はELISPOT法(スポットでのELISA法)として知られている。基本的な技法は数十年もの間知られているが、ELISPOTアッセイ法におけるいくつかの改良点が米国特許第6,410,252号に記載されている(主に分泌タンパク質の捕獲表面としての膜の使用)。ELISPOTアッセイ法はこれまでは、1つまたは2つの分泌タンパク質を決定するように設計されていた。最初に、関心対象の分泌タンパク質に対する抗体を含む捕獲表面を調製するか、または表面自体を非特異的捕獲媒体として使用する。検出試薬として微粒子標識を用いる場合、その後の最終的な多重化は無限であるため、その実験における関心対象の分泌タンパク質と同じ数の捕獲抗体または他の特異的結合パートナーをウェル表面上に堆積させることができる。次いで、細胞懸濁液をマイクロプレートウェル上に堆積させる。必要に応じて特定の細胞刺激物をウェルに添加し、関心対象の細胞応答を誘発する。インキュベーション期間の後にウェルを洗浄し、細胞を除去し、ウェル表面上のそれぞれの抗体に結合している関心対象の分泌タンパク質を残しておく(細胞の「分泌フットプリント」)。従来のELISAPOTアッセイ法では、アルカリホスファターゼまたは西洋ワサビペルオキシダーゼなどの高増幅検出タグと結合させた抗体を使用して、捕獲されたタンパク質をプロービングし、その後酵素基質を添加することがシグナルを発生させる。
単一のBリンパ球またはハイブリドーマから分泌されるIgGもまた、本発明の方法を用いて解析し得る。B細胞集団または個々のB細胞を多くの抗原に対して同時にスクリーニングし、特異性および親和性について選択することができる。抗体単離において有用であるためには、単にそれらの表現型を実証するだけでなく、解析後に分泌細胞を回収することが重要である。この性質は、細胞を膜上で支持し、分泌されたタンパク質が膜を通過した後にこれを捕獲することによって達成される。
サイトカイン分泌は、複数の異なる種類のT細胞(ナイーブ、記憶、キラー)、および樹状細胞などの他の免疫系細胞型の表現型である。これらの様々な細胞型を区別する表面抗原マーカーが認められている。したがって、サイトカイン分泌プロフィールを細胞表面マーカーと関連づけることは有用である。分泌プロフィールは膜上にプレーティングした細胞で行うことができるため、細胞はさらなる解析のために依然として利用できる。
疾患状態および治療手順による処置に対するその反応は、細胞内のタンパク質移行、表面抗原プロフィールの変化、および分泌プロフィールの変化を含む様々なパラメータにより特徴づけられる。疾患状態に特徴的な細胞はこのような典型的なパターンを示し得る−例えば、任意の特定の種類の腫瘍に関する腫瘍細胞は、表面抗原の特徴的なパターンを有する;処置の進行は、このパターンを有する細胞の運命によってモニタリングすることができる。以下の例は、臨床試料に適用した場合に、本発明の方法によって可能となる特徴づけの種類を例証する。
多重染色の有用性は血液試料中の細胞型の規定に限定されず、より広範に任意の組織学的状況に適用できる。自動化病理学を単純化するために細胞型を区別するには、例えば、細胞表面抗原ばかりでなく任意の抗原を使用することができる。例えば、抗体と結合した微粒子標識で組織切片を染色し、これを顕微鏡で観察し得る。核膜抗原、ゴルジ体、および微小管を含む種々の細胞内抗原が区別され得る。ちょうど腫瘍細胞が正常抗原を異常な配置で提示し得るように、中間段階の幹細胞もそのように提示し得る(実際に、いくつかの腫瘍はこの種類の幹細胞の制御障害の結果であると考えられている)。多変量染色手順により正常細胞を同定することで、そのような異常な細胞がより容易に発見される。
5,000を超える遺伝子が分泌タンパク質をコードしていると考えられている。そのほんの一部が十分に特徴づけられているにすぎない。自己分泌およびパラ分泌細胞シグナル伝達におけるそれらの役割は、上記の「組織染色」において考察した方法により研究することができるが、しかしそれはどの因子がどの組織に関連しているかをいくらか予備的に同定した上で初めて可能となる。試験すべき1つの性質は、栄養または増殖促進効果である。推定栄養因子が多くの異なる細胞型に及ぼす影響を試験するための効率的なアプローチは、胚様体をその因子に曝露することである。米国特許第5,914,268号に記載されているように、8細胞期の哺乳動物胚を、適切なタンパク質因子を含む培地中に解離すると、未分化幹細胞として分裂増殖が起こる。必要な因子を退薬すると、細胞は凝集塊、典型的には約500個の細胞の中実または中空の球を形成し、分化へと進行する。多くの細胞型が形成されるが、それは組織化されていない様式による。単一の96ウェルマイクロプレートウェルは、これらの胚様体を数百個維持し得る。増殖因子を発見する目的で、マウス(またはヒト)を単一マイクロプレートウェルに効率的に圧縮する。この縮小化を利用するためには、数十から数百の細胞型を定量する高感度な手段が必要である。微粒子標識を標識として使用すれば、特異的抗体が利用できる細胞型をすべて試験することができる。抗原は細胞表面であっても細胞内であってもよい。同様に、細胞表面抗原により、さらなる解析のための細胞を回収することが容易になる。
分画方法は、大きさ、電荷、ならびに移動相(移動する気体または液体)および固定相(多孔質固体もしくはゲルまたは固体支持体上にコーティングされた液体を含む吸着剤)に対する物質の相対的親和性を含む固有の分子特性の相違に基づいて物質の混合物を分離するために使用する多様な技法を伴う。後者の場合、それぞれの物質が移動相に沿って運ばれる速度は、その溶解度(液体移動相における)または蒸気圧(気体移動相における)および吸着剤に対するその親和性に依存する。電荷または大きさなどの他の物理的特性に基づく関連技法には、これらに限定されるわけではないが、1Dゲル、2Dゲル、アガロースゲル、およびキャピラリー電気泳動が含まれる。
Claims (10)
- 以下の段階を含む、様々な細胞試料のそれぞれから放出される様々な成分の該各成分の有無、もしくは該各成分の量、および/または該様々な細胞試料のそれぞれの細胞から放出される成分の少なくとも一つの有無もしくは量を決定する方法:
該細胞を破壊するか、または該細胞から細胞成分を分泌させることで該成分を放出させ、放出された細胞成分を固体支持体上に堆積させかつ固定させ、該固体支持体に堆積した放出されかつ固定された細胞成分を、異なる色を有する、直径10〜500 nmの様々な微粒子標識と接触させる段階であって、異なる色の微粒子標識それぞれが、放出された細胞成分またはその一部に対する特異的な結合パートナーと結合しており、かつ、放出された細胞成分と結合している微粒子標識は保持されるが、放出された細胞成分と結合していない微粒子標識は保持されない、段階;
放出された細胞成分に結合していない微粒子標識を除去する段階;ならびに
顕微鏡観察手段により、該固体支持体上の該放出された細胞成分と結合している個々の微粒子標識の数および性質を観察する段階、
ここで、
(a)該様々な細胞試料のそれぞれが、固体支持体上に重層した膜であって放出された細胞成分に対して透過性を有するが細胞に対しては透過性を有さない膜上の指定された位置に支持されており、かつ細胞成分が、膜を透過して固体支持体上に堆積されかつ固定され、それによって膜上の様々な細胞試料のそれぞれの位置と固体支持体上における位置とが相関づけられる;または
(b)該様々な細胞試料のそれぞれが、固体支持体上の異なる位置に堆積し、固定されている。 - 放出された、異なる成分のそれぞれの量に基づき、該放出された成分に関する、様々な細胞試料のそれぞれのプロフィールが取得され、該プロフィールがn次元空間における位置により表され、nは特異的結合パートナー含有微粒子標識が提供されている成分の数である、請求項1記載の方法。
- 細胞がT細胞であり、成分が少なくとも3つの異なるサイトカインを含む;または
疾患状態を評価すべき対象のT細胞集団を代表する少なくとも50個のT細胞に対して行われる;または
細胞が初代B細胞、不死化B細胞、もしくはハイブリドーマであり、決定すべき成分が特定の抗原もしくはエピトープに特異的な抗体である、
請求項1または2に記載の方法。 - 細胞が初代B細胞、不死化B細胞、もしくはハイブリドーマであり、その有無もしくは量を決定すべき成分が特定の抗原もしくはエピトープに特異的な抗体である、請求項3記載の方法。
- 放出された成分の該微粒子標識との該接触の前に、該様々な細胞試料のそれぞれを薬剤または他の外部刺激に曝露する段階、ならびに、
該細胞試料を該薬剤または刺激に曝露していない条件下で観察される微粒子標識の数および性質を、該細胞試料を該薬剤または外部刺激に曝露した場合に観察される微粒子標識の数および性質と比較し、それにより該薬剤または外部刺激が該細胞に及ぼす影響を決定する段階をさらに含む、請求項1または2記載の方法。 - 該様々な細胞試料のそれぞれが、固体支持体上に重層した膜であって分泌された成分に対して透過性を有するが細胞に対しては透過性を有さない膜上に支持されており、かつ
細胞成分が、膜を透過して固体支持体上に堆積させられ、
それによって膜上の様々な細胞試料のそれぞれの位置と固体支持体における位置とが相関づけられる、請求項1〜5のいずれか一項記載の方法。 - 該様々な細胞試料のそれぞれが、固体支持体上の異なる位置に堆積している、請求項1〜5のいずれか一項記載の方法。
- 以下の段階を含む、所望の特異性および親和性を有する免疫グロブリンを分泌する細胞を同定するための方法:
(a)固体支持体上に様々な細胞試料のそれぞれを提供する段階、ここで該細胞は該固体支持体上に免疫グロブリンを分泌し、該固体支持体は任意で免疫グロブリン用捕獲試薬を含み、ここで、
(i)該様々な細胞試料のそれぞれが、該固体支持体上の指定した位置に堆積されかつ固定され、その位置上に該細胞は免疫グロブリンを分泌する、または
(ii)該様々な細胞試料のそれぞれが、固体支持体上に重層した膜であって分泌された免疫グロブリンに対して透過性を有するが細胞に対しては透過性を有さない膜上の指定された位置に支持されており、かつ免疫グロブリンが、膜を透過して固体支持体上に堆積されかつ固定され、該固体支持体は任意で免疫グロブリン用捕獲試薬を含み、それによって膜上の様々な細胞試料のそれぞれの位置と固体支持体における位置とが相関づけられる;
(b)該固体支持体上の位置を、それぞれが識別可能な微粒子標識で標識された、様々なエピトープおよび/または抗原と接触させる段階、ここで該様々なエピトープおよび/または抗原は、免疫グロブリンが結合する、所望のエピトープおよび/または抗原、ならびに望ましくないエピトープおよび/または抗原を含む;
(c)所望のエピトープおよび/または抗原と結合するが望ましくないエピトープおよび/または抗原とは結合しない免疫グロブリンを含む、該固体支持体上の任意の位置を選択する段階;および
(d)選択した位置で免疫グロブリンを分泌する細胞を有する細胞試料を同定する段階。 - 前記方法によって同定された細胞を不死化する段階を更に含む、請求項8記載の方法。
- 免疫グロブリンをコードするDNAがクローニングされる、請求項8記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US51765103P | 2003-11-05 | 2003-11-05 | |
US51771303P | 2003-11-05 | 2003-11-05 | |
US60/517,713 | 2003-11-05 | ||
US60/517,651 | 2003-11-05 | ||
PCT/US2004/037077 WO2005045396A2 (en) | 2003-11-05 | 2004-11-04 | Use of particulate labels in bionalyte detection methods |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2007510929A JP2007510929A (ja) | 2007-04-26 |
JP5189292B2 true JP5189292B2 (ja) | 2013-04-24 |
Family
ID=34576807
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006539689A Expired - Fee Related JP5189292B2 (ja) | 2003-11-05 | 2004-11-04 | 生物分析物の検出方法における微粒子標識の使用 |
Country Status (7)
Country | Link |
---|---|
US (2) | US7413868B2 (ja) |
EP (1) | EP1687633B1 (ja) |
JP (1) | JP5189292B2 (ja) |
AU (1) | AU2004288228B2 (ja) |
CA (1) | CA2543977C (ja) |
IL (2) | IL175212A (ja) |
WO (1) | WO2005045396A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11359175B2 (en) | 2015-09-29 | 2022-06-14 | Tokyo Ohka Kogyo Co., Ltd. | Substrate, structure, structure-manufacturing method, cell-sorting method, cell-manufacturing method, and secretion-producing method |
Families Citing this family (64)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0923933A (ja) * | 1995-07-13 | 1997-01-28 | Roasu Kk | パソコン用ラック等における補助テーブル |
JP4690418B2 (ja) * | 2004-11-10 | 2011-06-01 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 多相ナノ粒子 |
US8043480B2 (en) * | 2004-11-10 | 2011-10-25 | The Regents Of The University Of Michigan | Methods for forming biodegradable nanocomponents with controlled shapes and sizes via electrified jetting |
US7947772B2 (en) * | 2004-11-10 | 2011-05-24 | The Regents Of The University Of Michigan | Multiphasic nano-components comprising colorants |
EP2264512B1 (en) | 2004-11-24 | 2014-06-04 | Battelle Memorial Institute | Method and apparatus for detection of rare cells |
US9733315B2 (en) * | 2005-07-27 | 2017-08-15 | University Of Houston | Nanomagnetic detector array for biomolecular recognition |
WO2007022530A2 (en) * | 2005-08-16 | 2007-02-22 | The Children's Mercy Hospital | Quantification of microsphere suspension hybridization and uses thereof |
JP4740700B2 (ja) * | 2005-09-15 | 2011-08-03 | 一般社団法人オンチップ・セロミクス・コンソーシアム | 生体物質解析チップ、生体物質解析キットおよびこれらを用いる生体物質解析法 |
WO2007035633A2 (en) | 2005-09-16 | 2007-03-29 | President & Fellows Of Harvard College | Screening assays and methods |
JP4684915B2 (ja) * | 2006-02-27 | 2011-05-18 | 独立行政法人産業技術総合研究所 | 生体分子の親和性解析装置及び該装置を使用する生体分子間の親和性を解析する方法 |
US7858386B2 (en) * | 2006-03-07 | 2010-12-28 | The United States Of America As Represented By The Secretary Of The Navy | Method of controlling quantum dot photoluminescence and other intrinsic properties through biological specificity |
SE531233C2 (sv) * | 2006-03-28 | 2009-01-27 | Hemocue Ab | Anordning och förfarande för detektion av fluorecensmärkta biologiska komponenter |
WO2007149310A2 (en) * | 2006-06-16 | 2007-12-27 | The Regents Of The University Of Michigan | Multiphasic biofunctional nano-components and methods for use thereof |
JP2009544014A (ja) * | 2006-07-12 | 2009-12-10 | トレリス バイオサイエンス、インク. | セルスポット・アプリケーション |
WO2008051985A2 (en) * | 2006-10-23 | 2008-05-02 | Oregon Health & Science University | Method for separation and identification of biomolecules using unconventional gel electrophoresis and detection of single nanoparticle probes |
US8244021B2 (en) | 2006-12-20 | 2012-08-14 | Ventana Medical Systems, Inc. | Quantitative, multispectral image analysis of tissue specimens stained with quantum dots |
WO2008124525A1 (en) * | 2007-04-03 | 2008-10-16 | Vanderbilt University | Nanoparticles with molecular recognition elements |
AU2008316703B2 (en) | 2007-10-25 | 2012-09-27 | Trellis Bioscience, Inc. | Anti-RSV G protein antibodies |
DE102007052517A1 (de) | 2007-10-29 | 2009-04-30 | Autoimmun Diagnostika Gmbh | ELISPOT-Verfahren mit zwei Filtersystemen |
JP4980944B2 (ja) * | 2008-02-12 | 2012-07-18 | 富士フイルム株式会社 | 免疫学的測定方法 |
JP2009258034A (ja) * | 2008-04-21 | 2009-11-05 | Fujifilm Corp | 表面プラズモン放射光検出方法および装置、表面プラズモン放射光検出用試料セルおよびキット |
ES2452473T3 (es) * | 2008-04-29 | 2014-04-01 | Psychemedics Corporation | Ensayo de múltiples analitos en fase sólida para fármacos psicóticos y sus metabolitos |
WO2010002993A1 (en) | 2008-07-01 | 2010-01-07 | Genocea Biosciences, Inc. | Antigen screening system |
WO2010011641A2 (en) * | 2008-07-21 | 2010-01-28 | The Regents Of The University Of Michigan | Microphasic micro-components and methods for controlling morphology via electrified jetting |
US9119578B2 (en) | 2011-04-29 | 2015-09-01 | Seventh Sense Biosystems, Inc. | Plasma or serum production and removal of fluids under reduced pressure |
WO2010101626A1 (en) | 2009-03-02 | 2010-09-10 | Seventh Sense Biosystems, Inc. | Techniques and devices associated with blood sampling |
WO2010127181A1 (en) | 2009-04-29 | 2010-11-04 | Trellis Bioscience, Inc. | Improved antibodies immunoreactive with heregulin-coupled her3 |
GB0912230D0 (en) * | 2009-07-14 | 2009-08-26 | Imp Innovations Ltd | Method and apparatus for determining analyte parameters or recording analyte information |
WO2011094573A1 (en) | 2010-01-28 | 2011-08-04 | Seventh Sense Biosystems, Inc. | Monitoring or feedback systems and methods |
CA2839420C (en) | 2010-06-16 | 2023-06-13 | Lawrence M. Kauvar | High affinity human antibodies to human cytomegalovirus (cmv) gb protein |
CN106397584A (zh) | 2010-06-17 | 2017-02-15 | 特瑞利斯生物科学有限责任公司 | 可用于被动流感免疫的抗体 |
WO2011163347A2 (en) | 2010-06-23 | 2011-12-29 | Seventh Sense Biosystems, Inc. | Sampling devices and methods involving relatively little pain |
US20120016308A1 (en) | 2010-07-16 | 2012-01-19 | Seventh Sense Biosystems, Inc. | Low-pressure packaging for fluid devices |
US20130158482A1 (en) | 2010-07-26 | 2013-06-20 | Seventh Sense Biosystems, Inc. | Rapid delivery and/or receiving of fluids |
WO2012021801A2 (en) | 2010-08-13 | 2012-02-16 | Seventh Sense Biosystems, Inc. | Systems and techniques for monitoring subjects |
JP5915531B2 (ja) * | 2010-08-30 | 2016-05-11 | コニカミノルタ株式会社 | 組織評価方法 |
US8497138B2 (en) * | 2010-09-30 | 2013-07-30 | Genetix Limited | Method for cell selection |
WO2012054841A2 (en) | 2010-10-22 | 2012-04-26 | The Regents Of The University Of Michigan | Optical devices with switchable particles |
US8808202B2 (en) | 2010-11-09 | 2014-08-19 | Seventh Sense Biosystems, Inc. | Systems and interfaces for blood sampling |
EP3106092A3 (en) | 2011-04-29 | 2017-03-08 | Seventh Sense Biosystems, Inc. | Systems and methods for collecting fluid from a subject |
KR102237667B1 (ko) | 2011-04-29 | 2021-04-12 | 세븐쓰 센스 바이오시스템즈, 인크. | 유체들의 전달 및/또는 수용 |
US20130158468A1 (en) | 2011-12-19 | 2013-06-20 | Seventh Sense Biosystems, Inc. | Delivering and/or receiving material with respect to a subject surface |
MX367743B (es) | 2011-12-05 | 2019-09-04 | Trellis Bioscience Llc | Anticuerpos utiles para la inmunizacion pasiva de influenza. |
EP2708890B1 (en) * | 2012-09-14 | 2015-11-18 | Molecular Devices (New Milton) Ltd | Method of selecting a monoclonal cell colony |
CN103074436B (zh) * | 2013-01-25 | 2014-07-16 | 宁波海尔施基因科技有限公司 | 一种指导5-氟尿嘧啶用药的多重基因检测试剂盒及其检测方法 |
US11274144B2 (en) | 2013-06-13 | 2022-03-15 | Research Institute At Nationwide Children's Hospital | Compositions and methods for the removal of biofilms |
US9745366B2 (en) | 2013-09-23 | 2017-08-29 | University Of Southern California | Compositions and methods for the prevention of microbial infections |
US10233234B2 (en) | 2014-01-13 | 2019-03-19 | Trellis Bioscience, Llc | Binding moieties for biofilm remediation |
US20150086561A1 (en) | 2013-09-26 | 2015-03-26 | Trellis Bioscience, Llc | Binding moieties for biofilm remediation |
US11248040B2 (en) | 2013-09-26 | 2022-02-15 | Trellis Bioscience, Llc | Binding moieties for biofilm remediation |
AU2014324761B2 (en) | 2014-01-13 | 2020-04-30 | Trellis Bioscience, Llc | Binding moieties for biofilm remediation |
CN106795216B (zh) | 2014-02-04 | 2021-04-20 | 抗非特公司 | 可用于被动流感免疫的抗体及其组合物、组合和使用方法 |
EP3114211A4 (en) | 2014-03-07 | 2017-11-22 | Institute for Systems Biology | Point of care assays to detect the status of tuberculosis infection |
EP3268434A4 (en) * | 2015-03-12 | 2019-03-27 | Becton, Dickinson and Company | UV ABSORBENT POLYMER DYES AND METHOD OF USE THEREOF |
US10940204B2 (en) | 2015-07-31 | 2021-03-09 | Research Institute At Nationwide Children's Hospital | Peptides and antibodies for the removal of biofilms |
WO2017066719A2 (en) | 2015-10-14 | 2017-04-20 | Research Institute At Nationwide Children's Hospital | Hu specific interfering agents |
WO2017132627A2 (en) | 2016-01-29 | 2017-08-03 | Achaogen, Inc. | Screening methods for identifying antibodies that bind cell surface epitopes |
JP7514621B2 (ja) | 2017-01-04 | 2024-07-11 | リサーチ インスティチュート アット ネイションワイド チルドレンズ ホスピタル | Dnabiiワクチンおよび強化された活性を有する抗体 |
CA3049114A1 (en) | 2017-01-04 | 2018-07-12 | Lauren O. Bakaletz | Antibody fragments for the treatment of biofilm-related disorders |
WO2018140827A1 (en) | 2017-01-27 | 2018-08-02 | Achaogen, Inc. | Reporter microorganisms and uses thereof |
MX2019011148A (es) | 2017-03-20 | 2019-10-17 | Genocea Biosciences Inc | Metodos de tratamiento. |
CN107192818B (zh) * | 2017-05-23 | 2018-06-29 | 重庆天之助生物科技有限公司 | 一种微粒子色度聚类分析方法及试剂盒 |
CN108195801B (zh) * | 2017-11-17 | 2020-11-24 | 北京林业大学 | 单分子水平观测气孔保卫细胞膜蛋白分布和动态的方法 |
CN114152604A (zh) * | 2020-09-07 | 2022-03-08 | 南京大学 | 一种用于细胞成像的无试剂电致化学发光检测方法 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9211176D0 (en) | 1992-05-27 | 1992-07-08 | Central Blood Lab Authority | Assay |
US5369036A (en) | 1992-07-02 | 1994-11-29 | Becton, Dickinson And Company | Enhancement of signal in immunoassays using microparticles which contain different detectable substances |
US6410252B1 (en) * | 1995-12-22 | 2002-06-25 | Case Western Reserve University | Methods for measuring T cell cytokines |
ATE357663T1 (de) | 1996-04-25 | 2007-04-15 | Genicon Sciences Corp | Teilchenförmiges markierungsmittel verwendendes analytassay |
US6790652B1 (en) * | 1998-01-08 | 2004-09-14 | Bioimage A/S | Method and apparatus for high density format screening for bioactive molecules |
US6642062B2 (en) | 1998-09-03 | 2003-11-04 | Trellis Bioinformatics, Inc. | Multihued labels |
DE19983691T1 (de) * | 1998-10-29 | 2001-11-29 | Cell Works Inc | Charakterisierung mehrerer Marker von Einzelzellen |
US6972198B2 (en) * | 1999-02-26 | 2005-12-06 | Cyclacel, Ltd. | Methods and compositions using protein binding partners |
US6673554B1 (en) | 1999-06-14 | 2004-01-06 | Trellie Bioinformatics, Inc. | Protein localization assays for toxicity and antidotes thereto |
CA2403708A1 (en) * | 2000-03-22 | 2001-09-27 | Quantum Dot Corporation | Methods of using semiconductor nanocrystals in bead-based nucleic acid assays |
AU2001227280A1 (en) * | 2000-04-10 | 2001-10-23 | The Scripps Research Institute | Proteomic analysis using activity-based probe libraries |
WO2003003015A2 (en) * | 2001-06-28 | 2003-01-09 | Advanced Research And Technology Institute, Inc. | Methods of preparing multicolor quantum dot tagged beads and conjugates thereof |
DE10209788A1 (de) * | 2002-02-26 | 2003-09-11 | Foerderver Inst Fuer Medizinte | Vorrichtung und Verfahren zur Bestimmung der relativen Syntheseleistung einzelner Zellen und/oder von Positionskoordinaten |
US7598093B2 (en) * | 2003-07-23 | 2009-10-06 | Ctl Analyzers, Llc | Nanoparticle and microparticle based detection of cellular products |
-
2004
- 2004-11-03 US US10/981,130 patent/US7413868B2/en not_active Expired - Fee Related
- 2004-11-04 AU AU2004288228A patent/AU2004288228B2/en not_active Ceased
- 2004-11-04 WO PCT/US2004/037077 patent/WO2005045396A2/en active Application Filing
- 2004-11-04 EP EP04818350.3A patent/EP1687633B1/en not_active Not-in-force
- 2004-11-04 CA CA2543977A patent/CA2543977C/en not_active Expired - Fee Related
- 2004-11-04 JP JP2006539689A patent/JP5189292B2/ja not_active Expired - Fee Related
-
2006
- 2006-04-26 IL IL175212A patent/IL175212A/en not_active IP Right Cessation
-
2008
- 2008-08-08 US US12/188,976 patent/US7939344B2/en active Active
-
2011
- 2011-06-01 IL IL213298A patent/IL213298A/en not_active IP Right Cessation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11359175B2 (en) | 2015-09-29 | 2022-06-14 | Tokyo Ohka Kogyo Co., Ltd. | Substrate, structure, structure-manufacturing method, cell-sorting method, cell-manufacturing method, and secretion-producing method |
Also Published As
Publication number | Publication date |
---|---|
EP1687633A2 (en) | 2006-08-09 |
US20090221434A1 (en) | 2009-09-03 |
US20050106641A1 (en) | 2005-05-19 |
CA2543977A1 (en) | 2005-05-19 |
WO2005045396A2 (en) | 2005-05-19 |
IL175212A (en) | 2011-06-30 |
EP1687633B1 (en) | 2014-12-17 |
IL175212A0 (en) | 2006-09-05 |
US7939344B2 (en) | 2011-05-10 |
EP1687633A4 (en) | 2007-11-14 |
IL213298A0 (en) | 2011-07-31 |
US7413868B2 (en) | 2008-08-19 |
AU2004288228A1 (en) | 2005-05-19 |
WO2005045396A3 (en) | 2005-09-15 |
AU2004288228B2 (en) | 2010-07-01 |
IL213298A (en) | 2014-04-30 |
JP2007510929A (ja) | 2007-04-26 |
CA2543977C (en) | 2013-08-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5189292B2 (ja) | 生物分析物の検出方法における微粒子標識の使用 | |
JP6971219B2 (ja) | 横断組織切片のユーザー定義領域における複数のタンパク質の同時定量 | |
KR102608653B1 (ko) | 절편화된 조직의 사용자-한정된 영역에서의 유전자 발현의 동시적인 정량화 | |
US6492125B2 (en) | Method to assess library X library interactions | |
US8969009B2 (en) | Identification of discriminant proteins through antibody profiling, methods and apparatus for identifying an individual | |
JP4222756B2 (ja) | 固相生体分子分析調製同定システム用コロイド組成物 | |
CN1144561A (zh) | 用于生物反应的高度特异性的表面,制备它们的方法及其使用方法 | |
JP2003505701A (ja) | アレーサイトメトリー | |
US9588117B2 (en) | Detecting cells secreting a protein of interest | |
AU771927B2 (en) | Multihued labels | |
JP2009544014A (ja) | セルスポット・アプリケーション | |
JP2003522962A (ja) | 半導体ナノクリスタルを使用するマイクロアレイ法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20071030 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100203 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100427 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100510 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100803 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110221 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110512 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110519 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110819 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120425 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20120613 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20120613 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120712 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120720 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121024 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20121128 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121225 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130104 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130124 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160201 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |