JP6456969B2 - 膨張顕微鏡法 - Google Patents
膨張顕微鏡法 Download PDFInfo
- Publication number
- JP6456969B2 JP6456969B2 JP2016553349A JP2016553349A JP6456969B2 JP 6456969 B2 JP6456969 B2 JP 6456969B2 JP 2016553349 A JP2016553349 A JP 2016553349A JP 2016553349 A JP2016553349 A JP 2016553349A JP 6456969 B2 JP6456969 B2 JP 6456969B2
- Authority
- JP
- Japan
- Prior art keywords
- sample
- swellable material
- hydrogel
- labeled
- polyelectrolyte
- 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.)
- Active
Links
- 238000000386 microscopy Methods 0.000 title claims description 25
- 239000000463 material Substances 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 64
- 239000000017 hydrogel Substances 0.000 claims description 30
- 239000002243 precursor Substances 0.000 claims description 28
- 239000000178 monomer Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- 229920000867 polyelectrolyte Polymers 0.000 claims description 17
- 238000003384 imaging method Methods 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 12
- 230000008961 swelling Effects 0.000 claims description 11
- 238000011065 in-situ storage Methods 0.000 claims description 9
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 230000006862 enzymatic digestion Effects 0.000 claims description 7
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 claims description 7
- 239000004094 surface-active agent Substances 0.000 claims description 7
- PQUXFUBNSYCQAL-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1F PQUXFUBNSYCQAL-UHFFFAOYSA-N 0.000 claims description 6
- 239000011837 N,N-methylenebisacrylamide Substances 0.000 claims description 6
- 238000012760 immunocytochemical staining Methods 0.000 claims description 6
- 229920000058 polyacrylate Polymers 0.000 claims description 6
- 229940047670 sodium acrylate Drugs 0.000 claims description 6
- 239000004971 Cross linker Substances 0.000 claims description 5
- 239000003125 aqueous solvent Substances 0.000 claims description 4
- 238000006116 polymerization reaction Methods 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000003125 immunofluorescent labeling Methods 0.000 claims 5
- 238000011532 immunohistochemical staining Methods 0.000 claims 5
- 230000000977 initiatory effect Effects 0.000 claims 3
- 230000008823 permeabilization Effects 0.000 claims 3
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims 2
- 229940048053 acrylate Drugs 0.000 claims 2
- 239000000523 sample Substances 0.000 description 84
- 239000000872 buffer Substances 0.000 description 14
- 229920000642 polymer Polymers 0.000 description 14
- 102000029749 Microtubule Human genes 0.000 description 13
- 108091022875 Microtubule Proteins 0.000 description 13
- 210000004688 microtubule Anatomy 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 11
- 239000000499 gel Substances 0.000 description 11
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 230000029087 digestion Effects 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 7
- 239000000975 dye Substances 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 101150075063 HOMER1 gene Proteins 0.000 description 6
- 102000010029 Homer Scaffolding Proteins Human genes 0.000 description 6
- 210000004748 cultured cell Anatomy 0.000 description 6
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 210000000225 synapse Anatomy 0.000 description 5
- 102000005853 Clathrin Human genes 0.000 description 4
- 108010019874 Clathrin Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 229930193282 clathrin Natural products 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 238000012634 optical imaging Methods 0.000 description 4
- 230000001242 postsynaptic effect Effects 0.000 description 4
- 230000003518 presynaptic effect Effects 0.000 description 4
- 238000009877 rendering Methods 0.000 description 4
- 238000009987 spinning Methods 0.000 description 4
- 241000283074 Equus asinus Species 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 230000001054 cortical effect Effects 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- -1 methacryloyl group Chemical group 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 206010037888 Rash pustular Diseases 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 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
- 230000008901 benefit Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000006059 cover glass Substances 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 210000003520 dendritic spine Anatomy 0.000 description 2
- 210000001947 dentate gyrus Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 238000007431 microscopic evaluation Methods 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 208000029561 pustule Diseases 0.000 description 2
- 238000010526 radical polymerization reaction Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010869 super-resolution microscopy Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241001414828 Aonidiella aurantii Species 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 101150052863 THY1 gene Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical class NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229960004198 guanidine Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010952 in-situ formation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 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
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical class CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002052 molecular layer Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000001454 recorded image Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/36—Embedding or analogous mounting of samples
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6841—In situ hybridisation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/0004—Microscopes specially adapted for specific applications
- G02B21/002—Scanning microscopes
- G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
- G02B21/0052—Optical details of the image generation
- G02B21/0072—Optical details of the image generation details concerning resolution or correction, including general design of CSOM objectives
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/36—Embedding or analogous mounting of samples
- G01N2001/364—Embedding or analogous mounting of samples using resins, epoxy
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- General Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Pathology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Optics & Photonics (AREA)
- Biomedical Technology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Sampling And Sample Adjustment (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201461943045P | 2014-02-21 | 2014-02-21 | |
US61/943,045 | 2014-02-21 | ||
PCT/US2015/016788 WO2015127183A2 (en) | 2014-02-21 | 2015-02-20 | Expansion microscopy |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018202178A Division JP2019056708A (ja) | 2014-02-21 | 2018-10-26 | 膨張顕微鏡法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017511883A JP2017511883A (ja) | 2017-04-27 |
JP6456969B2 true JP6456969B2 (ja) | 2019-01-23 |
Family
ID=53879241
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016553349A Active JP6456969B2 (ja) | 2014-02-21 | 2015-02-20 | 膨張顕微鏡法 |
JP2018202178A Pending JP2019056708A (ja) | 2014-02-21 | 2018-10-26 | 膨張顕微鏡法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018202178A Pending JP2019056708A (ja) | 2014-02-21 | 2018-10-26 | 膨張顕微鏡法 |
Country Status (4)
Country | Link |
---|---|
US (1) | US10309879B2 (pt-PT) |
EP (1) | EP3108218A4 (pt-PT) |
JP (2) | JP6456969B2 (pt-PT) |
WO (1) | WO2015127183A2 (pt-PT) |
Families Citing this family (83)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10501791B2 (en) | 2011-10-14 | 2019-12-10 | President And Fellows Of Harvard College | Sequencing by structure assembly |
WO2014163886A1 (en) * | 2013-03-12 | 2014-10-09 | President And Fellows Of Harvard College | Method of generating a three-dimensional nucleic acid containing matrix |
ES2991004T3 (es) | 2011-12-22 | 2024-12-02 | Harvard College | Métodos para la detección de analitos |
EP4249605B1 (en) | 2011-12-22 | 2024-08-28 | President And Fellows Of Harvard College | Methods for analyte detection |
WO2013184754A2 (en) | 2012-06-05 | 2013-12-12 | President And Fellows Of Harvard College | Spatial sequencing of nucleic acids using dna origami probes |
SG11201509962QA (en) | 2013-06-04 | 2016-01-28 | Harvard College | Rna-guideded transcriptional regulation |
CN105473744B (zh) | 2013-06-25 | 2020-06-19 | 普罗格诺西斯生物科学公司 | 采用微流控装置的空间编码生物分析 |
US10179932B2 (en) | 2014-07-11 | 2019-01-15 | President And Fellows Of Harvard College | Methods for high-throughput labelling and detection of biological features in situ using microscopy |
WO2016018963A1 (en) | 2014-07-30 | 2016-02-04 | President And Fellows Of Harvard College | Probe library construction |
FI3901281T3 (fi) | 2015-04-10 | 2023-01-31 | Biologisten näytteiden spatiaalisesti eroteltu moninkertainen nukleiinihappoanalyysi | |
US10526649B2 (en) | 2015-04-14 | 2020-01-07 | Massachusetts Institute Of Technology | Augmenting in situ nucleic acid sequencing of expanded biological samples with in vitro sequence information |
US10059990B2 (en) | 2015-04-14 | 2018-08-28 | Massachusetts Institute Of Technology | In situ nucleic acid sequencing of expanded biological samples |
US11408890B2 (en) | 2015-04-14 | 2022-08-09 | Massachusetts Institute Of Technology | Iterative expansion microscopy |
US10317321B2 (en) | 2015-08-07 | 2019-06-11 | Massachusetts Institute Of Technology | Protein retention expansion microscopy |
WO2017027367A1 (en) * | 2015-08-07 | 2017-02-16 | Massachusetts Institute Of Technology | Nanoscale imaging of proteins and nucleic acids via expansion microscopy |
GB2559526B (en) | 2015-11-03 | 2021-02-17 | Harvard College | Method and apparatus for volumetric imaging of a three-dimensional nucleic acid containing matrix |
WO2017147435A1 (en) * | 2016-02-25 | 2017-08-31 | Massachusetts Institute Of Technology | Methods for expanding clinical tissue specimens |
US20170276578A1 (en) * | 2016-03-22 | 2017-09-28 | University Of Washington | Expansion microscopy methods and kits |
CN116200465A (zh) | 2016-04-25 | 2023-06-02 | 哈佛学院董事及会员团体 | 用于原位分子检测的杂交链反应方法 |
WO2017190101A1 (en) * | 2016-04-29 | 2017-11-02 | Massachusetts Institute Of Technology | Methods for reversible and tunable tissue magnification |
US11352667B2 (en) | 2016-06-21 | 2022-06-07 | 10X Genomics, Inc. | Nucleic acid sequencing |
EP4582805A2 (en) | 2016-08-31 | 2025-07-09 | President And Fellows Of Harvard College | Methods of generating libraries of nucleic acid sequences for detection via fluorescent in situ sequencing |
EP4428536A3 (en) | 2016-08-31 | 2024-12-04 | President and Fellows of Harvard College | Methods of combining the detection of biomolecules into a single assay using fluorescent in situ sequencing |
EP3538867B1 (en) * | 2016-11-08 | 2024-01-03 | President and Fellows of Harvard College | Multiplexed imaging using merfish, expansion microscopy, and related technologies |
WO2018136856A1 (en) | 2017-01-23 | 2018-07-26 | Massachusetts Institute Of Technology | Multiplexed signal amplified fish via splinted ligation amplification and sequencing |
WO2018157074A1 (en) | 2017-02-24 | 2018-08-30 | Massachusetts Institute Of Technology | Methods for diagnosing neoplastic lesions |
WO2018157048A1 (en) * | 2017-02-24 | 2018-08-30 | Massachusetts Institute Of Technology | Methods for examining podocyte foot processes in human renal samples using conventional optical microscopy |
CN106959240B (zh) * | 2017-03-28 | 2019-09-24 | 华中科技大学 | 一种反复膨胀过程实现大块组织体的膨胀透明方法 |
WO2018218150A1 (en) | 2017-05-26 | 2018-11-29 | President And Fellows Of Harvard College | Systems and methods for high-throughput image-based screening |
WO2019009300A1 (ja) * | 2017-07-06 | 2019-01-10 | 公立大学法人大阪府立大学 | 生体組織透明化法及びその試薬 |
US11180804B2 (en) | 2017-07-25 | 2021-11-23 | Massachusetts Institute Of Technology | In situ ATAC sequencing |
WO2019068880A1 (en) | 2017-10-06 | 2019-04-11 | Cartana Ab | RNA MATRIX LIGATION |
WO2019075091A1 (en) | 2017-10-11 | 2019-04-18 | Expansion Technologies | MULTIPLEXED IN SITU HYBRIDIZATION OF TISSUE SECTIONS FOR SPATIALLY RESOLVED TRANSCRIPTOMIC WITH EXPANSION MICROSCOPY |
US11479811B2 (en) | 2017-11-21 | 2022-10-25 | Expansion Technologies | Expansion microscopy compatible and multiplexed in situ hybridization of formalin fixed paraffin embedded tissue sections for spatially resolved transcriptomics |
WO2019156957A1 (en) | 2018-02-06 | 2019-08-15 | Massachusetts Institute Of Technology | Swellable and structurally homogenous hydrogels and methods of use thereof |
US10915729B2 (en) | 2018-02-20 | 2021-02-09 | The Regents Of The University Of Michigan | Three-dimensional cell and tissue image analysis for cellular and sub-cellular morphological modeling and classification |
JP7082364B2 (ja) * | 2018-03-02 | 2022-06-08 | 日本電信電話株式会社 | フィルム状ソフトマテリアル、蛍光フィルム基材及びフィルム状ソフトマテリアルの製造方法、並びに応力計測方法 |
US20210149174A1 (en) * | 2018-04-25 | 2021-05-20 | The Regents Of The University Of California | Histology-grade three-dimensional imaging of tissue using microscopy with ultraviolet surface excitation |
US11414701B2 (en) | 2018-05-24 | 2022-08-16 | The Broad Institute, Inc. | Multimodal readouts for quantifying and sequencing nucleic acids in single cells |
WO2019241662A1 (en) | 2018-06-15 | 2019-12-19 | Carnegie Mellon University | Improved expansion microscopy methods and kits |
CN119480607A (zh) | 2018-06-18 | 2025-02-18 | 富鲁达加拿大公司 | 用于分析生物样本的设备 |
WO2020013833A1 (en) | 2018-07-13 | 2020-01-16 | Massachusetts Institute Of Technology | Dimethylacrylamide (dmaa) hydrogel for expansion microscopy (exm) |
SG11202101934SA (en) | 2018-07-30 | 2021-03-30 | Readcoor Llc | Methods and systems for sample processing or analysis |
US11549135B2 (en) | 2018-09-14 | 2023-01-10 | The Broad Institute, Inc. | Oligonucleotide-coupled antibodies for single cell or single complex protein measurements |
KR102368585B1 (ko) * | 2018-09-28 | 2022-03-03 | 서울대학교산학협력단 | 온도에 따라 가역적 팽창/초기화가 가능한 하이드로젤을 이용한 생체조직 이미징 |
WO2020076976A1 (en) | 2018-10-10 | 2020-04-16 | Readcoor, Inc. | Three-dimensional spatial molecular indexing |
WO2020142490A1 (en) | 2018-12-31 | 2020-07-09 | Expansion Technologies | Expansion microscopy compatible anchorable h&e staining for histopathology |
WO2020172247A1 (en) * | 2019-02-22 | 2020-08-27 | Massachusetts Institute Of Technology | Iterative direct expansion microscopy |
CN110006862B (zh) * | 2019-03-29 | 2020-09-08 | 华中科技大学 | 膨胀切削显微成像方法及适用于该方法的超吸水水凝胶 |
CN113906147B (zh) | 2019-05-31 | 2024-09-13 | 10X基因组学有限公司 | 检测目标核酸分子的方法 |
US11287422B2 (en) | 2019-09-23 | 2022-03-29 | Element Biosciences, Inc. | Multivalent binding composition for nucleic acid analysis |
US12265004B2 (en) | 2019-11-05 | 2025-04-01 | Massachusetts Institute Of Technology | Membrane probes for expansion microscopy |
US11802822B2 (en) | 2019-12-05 | 2023-10-31 | Massachusetts Institute Of Technology | Multiplexed expansion (MultiExM) pathology |
GB201919032D0 (en) | 2019-12-20 | 2020-02-05 | Cartana Ab | Method of detecting an analyte |
US12110548B2 (en) | 2020-02-03 | 2024-10-08 | 10X Genomics, Inc. | Bi-directional in situ analysis |
CN115485391A (zh) | 2020-02-17 | 2022-12-16 | 10X基因组学有限公司 | 染色质相互作用的原位分析 |
CA3168202A1 (en) | 2020-02-21 | 2021-08-26 | Felice Alessio BAVA | Methods and compositions for integrated in situ spatial assay |
US12188085B2 (en) | 2020-03-05 | 2025-01-07 | 10X Genomics, Inc. | Three-dimensional spatial transcriptomics with sequencing readout |
US12209273B2 (en) | 2020-06-12 | 2025-01-28 | 10X Genomics, Inc. | Nucleic acid assays using click chemistry bioconjugation |
WO2022015600A2 (en) | 2020-07-13 | 2022-01-20 | Singular Genomics Systems, Inc. | Methods of sequencing complementary polynucleotides |
WO2022032195A2 (en) | 2020-08-06 | 2022-02-10 | Singular Genomics Systems, Inc. | Spatial sequencing |
US11492662B2 (en) | 2020-08-06 | 2022-11-08 | Singular Genomics Systems, Inc. | Methods for in situ transcriptomics and proteomics |
US20220049303A1 (en) | 2020-08-17 | 2022-02-17 | Readcoor, Llc | Methods and systems for spatial mapping of genetic variants |
US12297499B2 (en) | 2020-08-17 | 2025-05-13 | 10X Genomics, Inc. | Multicomponent nucleic acid probes for sample analysis |
US12071667B2 (en) | 2020-11-04 | 2024-08-27 | 10X Genomics, Inc. | Sequence analysis using meta-stable nucleic acid molecules |
US11333588B1 (en) | 2020-12-07 | 2022-05-17 | Nebulum Technologies Co., Ltd. | Matrix-assisted methods and compositions to prepare biological samples for super-resolution imaging |
CN112881671A (zh) * | 2021-01-11 | 2021-06-01 | 东南大学 | 一种基于高密度荧光标记法的细胞微管膨胀显微成像方法 |
US12060603B2 (en) | 2021-01-19 | 2024-08-13 | 10X Genomics, Inc. | Methods for internally controlled in situ assays using padlock probes |
KR102762387B1 (ko) * | 2021-02-24 | 2025-02-05 | 한국과학기술원 | 화학적 염색과 팽창 이미징 기법의 최적화 방법 |
US12275984B2 (en) | 2021-03-02 | 2025-04-15 | 10X Genomics, Inc. | Sequential hybridization and quenching |
WO2022235764A1 (en) | 2021-05-05 | 2022-11-10 | Singular Genomics Systems, Inc. | Multiomic analysis device and methods of use thereof |
CA3224093A1 (en) | 2021-07-30 | 2023-02-02 | Jorge Ivan Hernandez Neuta | Methods and compositions for synchronizing reactions in situ |
US12139751B2 (en) | 2021-07-30 | 2024-11-12 | 10X Genomics, Inc. | Circularizable probes for in situ analysis |
US20250034623A1 (en) | 2021-10-25 | 2025-01-30 | Singular Genomics Systems, Inc. | Manipulating and detecting biological samples |
EP4505177A1 (en) | 2022-04-01 | 2025-02-12 | 10x Genomics, Inc. | Compositions and methods for targeted masking of autofluorescence |
EP4522769A1 (en) | 2022-05-11 | 2025-03-19 | 10X Genomics, Inc. | Compositions and methods for in situ sequencing |
DE102022112065B3 (de) | 2022-05-13 | 2023-08-24 | Abberior Instruments Gmbh | Verfahren, vorrichtung und computerprogramm zur mikroskopischen probenabbildung |
WO2023245190A1 (en) | 2022-06-17 | 2023-12-21 | 10X Genomics, Inc. | Catalytic de-crosslinking of samples for in situ analysis |
EP4511510A1 (en) | 2022-08-16 | 2025-02-26 | 10X Genomics, Inc. | Ap50 polymerases and uses thereof |
KR20240042887A (ko) * | 2022-09-26 | 2024-04-02 | 연세대학교 산학협력단 | 고배율의 세포 확대 분석을 위한 세포 필름, 이의 제조용 조성물 및 제조 방법 |
US12319956B2 (en) | 2023-07-31 | 2025-06-03 | 10X Genomics, Inc. | Methods and systems for targeted RNA cleavage and target RNA-primed rolling circle amplification |
WO2025147667A1 (en) | 2024-01-05 | 2025-07-10 | Element Biosciences, Inc. | Target probe complexes and analyte detection complexes for in situ detecting and identifying target analytes |
WO2025165512A1 (en) | 2024-02-02 | 2025-08-07 | Element Biosciences, Inc. | Amplification-free probe complexes for detection of target analytes |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6107081A (en) * | 1999-02-05 | 2000-08-22 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Uni-directional cell stretching device |
KR100713786B1 (ko) * | 1999-04-27 | 2007-05-07 | 바이오 래드 래버러토리스 인코오포레이티드 | 기체상 이온 분광계용 탐침 |
US6287870B1 (en) * | 1999-08-20 | 2001-09-11 | Robert A. Levine | Method and assembly for separating formed constituents from a liquid constituent in a complex biologic fluid sample |
US6878384B2 (en) * | 2001-03-13 | 2005-04-12 | Microvention, Inc. | Hydrogels that undergo volumetric expansion in response to changes in their environment and their methods of manufacture and use |
JP3812829B2 (ja) * | 2002-08-22 | 2006-08-23 | 独立行政法人科学技術振興機構 | 組織の包埋剤、樹脂包埋体及び樹脂包埋体の製造方法 |
JP2005291759A (ja) * | 2004-03-31 | 2005-10-20 | Michimasa Kishimoto | 二次元画像による病症診断システム |
JP4374435B2 (ja) * | 2004-07-28 | 2009-12-02 | 国立大学法人 大分大学 | 高親水性高分子による組織包埋方法。 |
JP5185291B2 (ja) * | 2007-02-01 | 2013-04-17 | イムンディアグノスティック アクチェンゲゼルシャフト | 血清あるいは血漿中のビタミンdの直接決定 |
JP5058676B2 (ja) * | 2007-05-18 | 2012-10-24 | 株式会社アイエスティー | 生体標本の作製方法 |
JP2010537633A (ja) * | 2007-08-30 | 2010-12-09 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | コンプライアント表面のマルチウェル培養プレート |
US20100041128A1 (en) | 2008-01-08 | 2010-02-18 | Medtrain Technologies, Llc | Microfluidic Device for Application of Shear Stress and Tensile Strain |
BRPI0906724A2 (pt) * | 2008-01-30 | 2019-05-07 | Geron Corp | artigo de cultura celular e triagem |
JP4956839B2 (ja) | 2008-02-13 | 2012-06-20 | 国立大学法人 大分大学 | 高親水性高分子モノマー水溶液による組織包埋方法 |
US20090241681A1 (en) * | 2008-03-27 | 2009-10-01 | Andrew Machauf | Hydrogel-based mems biosensor |
WO2009142661A1 (en) | 2008-05-20 | 2009-11-26 | The Regents Of The University Of California | Analysis of ex vivo cells for disease state detection and therapeutic agent selection and monitoring |
US20130045503A1 (en) | 2010-03-12 | 2013-02-21 | Riken | Clearing reagent for biological material, and use thereof |
WO2012142664A1 (en) * | 2011-04-20 | 2012-10-26 | Monash University | Method and device for trapping and analysing cells and the like |
JP5967528B2 (ja) | 2012-06-22 | 2016-08-10 | 国立研究開発法人理化学研究所 | 生物材料を透明化する方法および生物材料用透明化処理キット |
AU2013300171B2 (en) * | 2012-08-09 | 2017-09-14 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for preparing biological specimens for microscopic analysis |
CA2924478A1 (en) * | 2013-09-20 | 2015-03-26 | California Institute Of Technology | Methods for phenotyping of intact whole tissues |
-
2015
- 2015-02-20 JP JP2016553349A patent/JP6456969B2/ja active Active
- 2015-02-20 US US14/627,310 patent/US10309879B2/en active Active
- 2015-02-20 WO PCT/US2015/016788 patent/WO2015127183A2/en active Application Filing
- 2015-02-20 EP EP15751396.1A patent/EP3108218A4/en not_active Withdrawn
-
2018
- 2018-10-26 JP JP2018202178A patent/JP2019056708A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
WO2015127183A3 (en) | 2016-02-04 |
US20160116384A1 (en) | 2016-04-28 |
JP2019056708A (ja) | 2019-04-11 |
WO2015127183A2 (en) | 2015-08-27 |
EP3108218A4 (en) | 2017-11-15 |
US10309879B2 (en) | 2019-06-04 |
JP2017511883A (ja) | 2017-04-27 |
EP3108218A2 (en) | 2016-12-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6456969B2 (ja) | 膨張顕微鏡法 | |
EP3928074B1 (en) | Method for iterative direct expansion microscopy | |
Wassie et al. | Expansion microscopy: principles and uses in biological research | |
US11408890B2 (en) | Iterative expansion microscopy | |
Chang et al. | Iterative expansion microscopy | |
Gao et al. | Q&A: expansion microscopy | |
Wen et al. | Current progress in expansion microscopy: chemical strategies and applications | |
CN104350372B (zh) | 用于制备供显微镜分析的生物样本的方法和组合物 | |
CA3015363A1 (en) | Methods for expanding clinical tissue specimens | |
US12265004B2 (en) | Membrane probes for expansion microscopy | |
US20210190652A1 (en) | Multiplexed Expansion (MultiExM) Pathology | |
Fang et al. | Three-dimensional single-cell transcriptome imaging of thick tissues | |
Cho et al. | Expansion microscopy | |
Wunderlich et al. | Superresolving the kidney—a practical comparison of fluorescence nanoscopy of the glomerular filtration barrier | |
Faulkner et al. | An introduction to the methodology of expansion microscopy | |
Wang et al. | Nanoscale fluorescence imaging of biological ultrastructure via molecular anchoring and physical expansion | |
Li et al. | Chemical reactivation of fluorescein isothiocyanate immunofluorescence-labeled resin-embedded samples | |
Gao et al. | Expansion STED microscopy (ExSTED) | |
Kang et al. | Expansion Microscopy with a Thermally Adjustable Expansion Factor Using Thermoresponsive Biospecimen–Hydrogel Hybrids | |
Truckenbrodt et al. | Simple multi-color super-resolution by X10 microscopy | |
Klimas et al. | Basics of expansion microscopy | |
JP2022506723A (ja) | 核酸に基づくバーコーディング | |
Zhang et al. | Subdiffraction Imaging of Cleared and Expanded Large-Scale Tissues | |
Rathi et al. | Plasmon-Enhanced Expansion Microscopy | |
Tian et al. | Rapid lightsheet fluorescence imaging of whole Drosophila brains at nanoscale resolution by potassium acrylate-based expansion microscopy |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20170803 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170814 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20171107 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20171221 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180206 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20180705 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181026 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20181029 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20181116 |
|
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: 20181207 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181219 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6456969 Country of ref document: JP 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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |