CN1643379A - 具有可变的发射强度与发射频率的发光球形非自发光硅胶颗粒 - Google Patents
具有可变的发射强度与发射频率的发光球形非自发光硅胶颗粒 Download PDFInfo
- Publication number
- CN1643379A CN1643379A CN03807087.1A CN03807087A CN1643379A CN 1643379 A CN1643379 A CN 1643379A CN 03807087 A CN03807087 A CN 03807087A CN 1643379 A CN1643379 A CN 1643379A
- Authority
- CN
- China
- Prior art keywords
- particle
- silica gel
- luminescent substance
- luminescent
- luminous
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002245 particle Substances 0.000 title claims abstract description 81
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 239000000741 silica gel Substances 0.000 title claims abstract description 25
- 229910002027 silica gel Inorganic materials 0.000 title claims abstract description 25
- 239000000126 substance Substances 0.000 claims abstract description 56
- 238000004020 luminiscence type Methods 0.000 claims abstract description 5
- 239000011159 matrix material Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 30
- -1 alkoxy silane Chemical compound 0.000 claims description 27
- 239000000463 material Substances 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 18
- 239000004054 semiconductor nanocrystal Substances 0.000 claims description 16
- 102000004169 proteins and genes Human genes 0.000 claims description 15
- 150000007523 nucleic acids Chemical class 0.000 claims description 14
- 229910000077 silane Inorganic materials 0.000 claims description 14
- 102000039446 nucleic acids Human genes 0.000 claims description 12
- 108020004707 nucleic acids Proteins 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000006185 dispersion Substances 0.000 claims description 11
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 11
- 230000005540 biological transmission Effects 0.000 claims description 9
- 238000005516 engineering process Methods 0.000 claims description 9
- 239000012074 organic phase Substances 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- 239000000084 colloidal system Substances 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 7
- 238000012360 testing method Methods 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000004458 analytical method Methods 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000003745 diagnosis Methods 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- 238000005352 clarification Methods 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 3
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 3
- 239000013522 chelant Substances 0.000 claims description 3
- 238000005401 electroluminescence Methods 0.000 claims description 3
- 150000004676 glycans Chemical class 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 229920000620 organic polymer Polymers 0.000 claims description 3
- 229920001282 polysaccharide Polymers 0.000 claims description 3
- 239000005017 polysaccharide Substances 0.000 claims description 3
- 102000005962 receptors Human genes 0.000 claims description 3
- 108020003175 receptors Proteins 0.000 claims description 3
- 230000004936 stimulating effect Effects 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 claims description 3
- 108010047357 Luminescent Proteins Proteins 0.000 claims description 2
- 102000006830 Luminescent Proteins Human genes 0.000 claims description 2
- 108010090804 Streptavidin Proteins 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 239000000975 dye Substances 0.000 claims description 2
- 239000011554 ferrofluid Substances 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 229910052761 rare earth metal Inorganic materials 0.000 claims description 2
- 150000002910 rare earth metals Chemical class 0.000 claims description 2
- 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 claims 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 2
- 108090001008 Avidin Proteins 0.000 claims 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims 1
- 229960002685 biotin Drugs 0.000 claims 1
- 235000020958 biotin Nutrition 0.000 claims 1
- 239000011616 biotin Substances 0.000 claims 1
- 229910052802 copper Inorganic materials 0.000 claims 1
- 239000010949 copper Substances 0.000 claims 1
- 238000007865 diluting Methods 0.000 claims 1
- 150000003233 pyrroles Chemical group 0.000 claims 1
- 238000012163 sequencing technique Methods 0.000 claims 1
- 229910052709 silver Inorganic materials 0.000 claims 1
- 239000004332 silver Substances 0.000 claims 1
- 239000003550 marker Substances 0.000 abstract description 2
- 238000005538 encapsulation Methods 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 238000001514 detection method Methods 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 7
- 238000011953 bioanalysis Methods 0.000 description 7
- 239000002105 nanoparticle Substances 0.000 description 7
- 239000002096 quantum dot Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 5
- 239000012491 analyte Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000002159 nanocrystal Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- UHYPYGJEEGLRJD-UHFFFAOYSA-N cadmium(2+);selenium(2-) Chemical compound [Se-2].[Cd+2] UHYPYGJEEGLRJD-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical group 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- SBIBMFFZSBJNJF-UHFFFAOYSA-N selenium;zinc Chemical compound [Se]=[Zn] SBIBMFFZSBJNJF-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002604 ultrasonography Methods 0.000 description 4
- 229910004613 CdTe Inorganic materials 0.000 description 3
- 238000000018 DNA microarray Methods 0.000 description 3
- 108091005461 Nucleic proteins Proteins 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910052769 Ytterbium Inorganic materials 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 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 3
- 238000007306 functionalization reaction Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- HOGDNTQCSIKEEV-UHFFFAOYSA-N n'-hydroxybutanediamide Chemical compound NC(=O)CCC(=O)NO HOGDNTQCSIKEEV-UHFFFAOYSA-N 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 239000004065 semiconductor Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 description 3
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ACNUVXZPCIABEX-UHFFFAOYSA-N 3',6'-diaminospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(N)C=C1OC1=CC(N)=CC=C21 ACNUVXZPCIABEX-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- 229910052691 Erbium Inorganic materials 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 229910004262 HgTe Inorganic materials 0.000 description 2
- 229910052689 Holmium Inorganic materials 0.000 description 2
- 229910000673 Indium arsenide Inorganic materials 0.000 description 2
- GPXJNWSHGFTCBW-UHFFFAOYSA-N Indium phosphide Chemical compound [In]#P GPXJNWSHGFTCBW-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 229910052775 Thulium Inorganic materials 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- 229910007709 ZnTe Inorganic materials 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000002458 cell surface marker Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000013016 damping Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 2
- 238000001879 gelation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- RPQDHPTXJYYUPQ-UHFFFAOYSA-N indium arsenide Chemical compound [In]#[As] RPQDHPTXJYYUPQ-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 229910052747 lanthanoid Inorganic materials 0.000 description 2
- 150000002602 lanthanoids Chemical class 0.000 description 2
- MRELNEQAGSRDBK-UHFFFAOYSA-N lanthanum(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[La+3].[La+3] MRELNEQAGSRDBK-UHFFFAOYSA-N 0.000 description 2
- 239000006249 magnetic particle Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000003499 nucleic acid array Methods 0.000 description 2
- 150000002924 oxiranes Chemical group 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 238000006068 polycondensation reaction Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000151 polyglycol Polymers 0.000 description 2
- 239000010695 polyglycol Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 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 2
- HQHVZNOWXQGXIX-UHFFFAOYSA-J sodium;yttrium(3+);tetrafluoride Chemical compound [F-].[F-].[F-].[F-].[Na+].[Y+3] HQHVZNOWXQGXIX-UHFFFAOYSA-J 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- TYIZUJNEZNBXRS-UHFFFAOYSA-K trifluorogadolinium Chemical compound F[Gd](F)F TYIZUJNEZNBXRS-UHFFFAOYSA-K 0.000 description 2
- BYMUNNMMXKDFEZ-UHFFFAOYSA-K trifluorolanthanum Chemical compound F[La](F)F BYMUNNMMXKDFEZ-UHFFFAOYSA-K 0.000 description 2
- YUYCVXFAYWRXLS-UHFFFAOYSA-N trimethoxysilane Chemical compound CO[SiH](OC)OC YUYCVXFAYWRXLS-UHFFFAOYSA-N 0.000 description 2
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 1
- IZFHEQBZOYJLPK-SSDOTTSWSA-N (R)-dihydrolipoic acid Chemical compound OC(=O)CCCC[C@@H](S)CCS IZFHEQBZOYJLPK-SSDOTTSWSA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical class CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- KSCAZPYHLGGNPZ-UHFFFAOYSA-N 3-chloropropyl(triethoxy)silane Chemical compound CCO[Si](OCC)(OCC)CCCCl KSCAZPYHLGGNPZ-UHFFFAOYSA-N 0.000 description 1
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
- SJECZPVISLOESU-UHFFFAOYSA-N 3-trimethoxysilylpropan-1-amine Chemical compound CO[Si](OC)(OC)CCCN SJECZPVISLOESU-UHFFFAOYSA-N 0.000 description 1
- WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 description 1
- XPKVSFHMZHXKIX-UHFFFAOYSA-N 9h-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1.C1=CC=C2CC3=CC=CC=C3OC2=C1 XPKVSFHMZHXKIX-UHFFFAOYSA-N 0.000 description 1
- 229910015808 BaTe Inorganic materials 0.000 description 1
- 229910004813 CaTe Inorganic materials 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- PQMOXTJVIYEOQL-UHFFFAOYSA-N Cumarin Natural products CC(C)=CCC1=C(O)C(C(=O)C(C)CC)=C(O)C2=C1OC(=O)C=C2CCC PQMOXTJVIYEOQL-UHFFFAOYSA-N 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 229920003656 Daiamid® Polymers 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 244000187656 Eucalyptus cornuta Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229910001218 Gallium arsenide Inorganic materials 0.000 description 1
- 229910000530 Gallium indium arsenide Inorganic materials 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- FSOGIJPGPZWNGO-UHFFFAOYSA-N Meomammein Natural products CCC(C)C(=O)C1=C(O)C(CC=C(C)C)=C(O)C2=C1OC(=O)C=C2CCC FSOGIJPGPZWNGO-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 229910017680 MgTe Inorganic materials 0.000 description 1
- 229910052779 Neodymium Inorganic materials 0.000 description 1
- KJJVVRLOVRVINC-UHFFFAOYSA-N O.[S-2].[Y+3] Chemical compound O.[S-2].[Y+3] KJJVVRLOVRVINC-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 229910052777 Praseodymium Inorganic materials 0.000 description 1
- 102000004330 Rhodopsin Human genes 0.000 description 1
- 108090000820 Rhodopsin Proteins 0.000 description 1
- 241000854711 Shinkai Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 229910004411 SrTe Inorganic materials 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 1
- 229920002359 Tetronic® Polymers 0.000 description 1
- MZZINWWGSYUHGU-UHFFFAOYSA-J ToTo-1 Chemical compound [I-].[I-].[I-].[I-].C12=CC=CC=C2C(C=C2N(C3=CC=CC=C3S2)C)=CC=[N+]1CCC[N+](C)(C)CCC[N+](C)(C)CCC[N+](C1=CC=CC=C11)=CC=C1C=C1N(C)C2=CC=CC=C2S1 MZZINWWGSYUHGU-UHFFFAOYSA-J 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- GRRMZXFOOGQMFA-UHFFFAOYSA-J YoYo-1 Chemical compound [I-].[I-].[I-].[I-].C12=CC=CC=C2C(C=C2N(C3=CC=CC=C3O2)C)=CC=[N+]1CCC[N+](C)(C)CCC[N+](C)(C)CCC[N+](C1=CC=CC=C11)=CC=C1C=C1N(C)C2=CC=CC=C2O1 GRRMZXFOOGQMFA-UHFFFAOYSA-J 0.000 description 1
- NWGKJDSIEKMTRX-BFWOXRRGSA-N [(2r)-2-[(3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)C1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-BFWOXRRGSA-N 0.000 description 1
- MCVAAHQLXUXWLC-UHFFFAOYSA-N [O-2].[O-2].[S-2].[Gd+3].[Gd+3] Chemical compound [O-2].[O-2].[S-2].[Gd+3].[Gd+3] MCVAAHQLXUXWLC-UHFFFAOYSA-N 0.000 description 1
- MCEBKLYUUDGVMD-UHFFFAOYSA-N [SiH3]S(=O)=O Chemical compound [SiH3]S(=O)=O MCEBKLYUUDGVMD-UHFFFAOYSA-N 0.000 description 1
- BTKXSYWWRGMQHR-UHFFFAOYSA-N [amino(diethoxy)silyl]oxyethane Chemical compound CCO[Si](N)(OCC)OCC BTKXSYWWRGMQHR-UHFFFAOYSA-N 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 1
- 229910052768 actinide Inorganic materials 0.000 description 1
- 150000001255 actinides Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- DMFBEUCTHCSNKZ-UHFFFAOYSA-I barium(2+);yttrium(3+);pentafluoride Chemical compound [F-].[F-].[F-].[F-].[F-].[Y+3].[Ba+2] DMFBEUCTHCSNKZ-UHFFFAOYSA-I 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- GAURFLBIDLSLQU-UHFFFAOYSA-N diethoxy(methyl)silicon Chemical compound CCO[Si](C)OCC GAURFLBIDLSLQU-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- 239000007863 gel particle Substances 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- WPYVAWXEWQSOGY-UHFFFAOYSA-N indium antimonide Chemical group [Sb]#[In] WPYVAWXEWQSOGY-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000005497 microtitration Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
- QEFYFXOXNSNQGX-UHFFFAOYSA-N neodymium atom Chemical compound [Nd] QEFYFXOXNSNQGX-UHFFFAOYSA-N 0.000 description 1
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- GFKJCVBFQRKZCJ-UHFFFAOYSA-N oxygen(2-);yttrium(3+);trisulfide Chemical compound [O-2].[O-2].[O-2].[S-2].[S-2].[S-2].[Y+3].[Y+3].[Y+3].[Y+3] GFKJCVBFQRKZCJ-UHFFFAOYSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000223 polyglycerol Polymers 0.000 description 1
- 229920000307 polymer substrate Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920005606 polypropylene copolymer Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000003361 porogen Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- PUDIUYLPXJFUGB-UHFFFAOYSA-N praseodymium atom Chemical compound [Pr] PUDIUYLPXJFUGB-UHFFFAOYSA-N 0.000 description 1
- KOODSCBKXPPKHE-UHFFFAOYSA-N propanethioic s-acid Chemical class CCC(S)=O KOODSCBKXPPKHE-UHFFFAOYSA-N 0.000 description 1
- 238000003498 protein array Methods 0.000 description 1
- 238000000575 proteomic method Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- 238000010557 suspension polymerization reaction Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229940105963 yttrium fluoride Drugs 0.000 description 1
- RBORBHYCVONNJH-UHFFFAOYSA-K yttrium(iii) fluoride Chemical compound F[Y](F)F RBORBHYCVONNJH-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- 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
- G01N33/54346—Nanoparticles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
-
- 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
- G01N33/588—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with semiconductor nanocrystal label, e.g. quantum dots
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Nanotechnology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Materials Engineering (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Luminescent Compositions (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Silicon Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
本发明涉及一种通过在硅胶基体中包封一种或多种不同发光物质制备的,具有高发光性的球形透明硅胶颗粒。通过改变发光物质的浓度和通过包封具有不同发射频率的物质,该颗粒可以在生物分析和诊断中作为复合编码和生物标记体系被使用。
Description
技术领域
本发明涉及一种发光强度可变的发光、球形微米或纳米颗粒,及该颗粒的制备方法和应用。
发光被定义为通过能量吸收而被预先激发的物质在全部光谱范围内的光发射。荧光和磷光也在此范围内。
当前发光物质以荧光或磷光物质的形式在生物化学和医学分析与诊断的整个领域内被常规地用于鉴别如蛋白质、肽、毒素或核酸的分析物,并且用作标记显示细胞、细胞小室,或检测生物学过程。
背景技术
一种对发光方法十分有趣和创新的使用是用于鉴别生物分子的所谓的芯片技术。在当今的生物分析和诊断领域中,芯片技术作为以栅格形排列有大量具有已知结构的生物分子传感器(核酸、蛋白质或肽)的平的、玻璃或聚合物载体或者基质,也称作生物芯片,而被熟知。通过与生物芯片一起孵育先前由例如组织或细胞获得的发光标记的蛋白质或核酸样品,在其表面上具有与样品互补的化学-物理结构的点上形成特异性结合。由于样品的发光标记会引起在形成结合的点上具有可检测的发光,因而对样品的化学和物理结构提供了直接的信息。由于大量的传感器被固定在芯片上,芯片技术对于在医药开发过程中测试分子库是一种很有用的工具。
由于芯片技术的品质和适用性直接依赖于发光标记的检测灵敏度和光谱特异性,已往进行了大量开发以制造新的、改进的发光体系,从而使得生物鉴定的检测极限被显著地降低。发光物质的开发集中于两类物质。一类是发光分子,这类发光分子中最普通的是Fluorescein、Rhodamin、Phycoerythrin、Coumarin、Cy3、Cy5、TAMRA、ROX、Oregon Green、Ethidiumbromid、Texas Red和Dabcyl(这些均为商品名称)。另一类化合物主要为由周期系中IIB和VIA族、IIIA和VA族或IVA族的半导体纳米晶体,这类纳米晶体中最普通的为CdS、CdSe、CdTe、ZnS和ZnSe。这些半导体纳米晶体的一个独特特征是一方面高的量子效率,另一方面又不象常规发光染色那样易于退色。更值得注意的使得在文献中称作为“量子点”的该化合物成为常规荧光染色的有趣替代的一点是量子点的吸收和发射性能取决于其大小。具体地是指随着颗粒尺寸的减小,发射光谱向短波范围移动,反之亦然。
对于使用发光效应的生物测定的发展,开启了不仅基于物质的选择而且基于颗粒大小进行不同发光标记的另外的可能性。这也为生物芯片领域中生物分子的光学编码提供了理想的基础。
在生物分析中荧光标记的应用在许多相关文献中已有叙述。
美国专利4,777,123描述了一种免疫测定原理,该原理揭示了两种不同荧光团标记的受体的应用,从而在检测的配体的存在下由第一个被激发的荧光团转移到第二个荧光团的能量减少。
美国专利5,324,633的主题为使用光子计数器或共焦显微镜检测与生物高聚物结合的荧光标记受体的生物芯片法。
美国专利5,066,580中描述了在被标记的抗体的协助下用于细胞检测的具有450~650nm的激发频率的氧杂蒽(xanthene)荧光染料。在美国专利3,998,943、3,996,345、4,174,384、4,199,559和4,261,968中公开了配体受体测定,该测定的基本原理为用发射性能依靠于配体-受体结合的荧光染色标记受体和/或配体。
美国专利5,319,209公开了其中适于测量细胞中离子浓度的苯并呋喃-异酞酸酯形式的荧光传感器。
具有相应的光学特性的半导体纳米晶体和/或量子点的制备是现有技术并在相关的文献中以不同方式被报道:Kortan等,美国化学学会杂志(J.Am.Chem.Soc.)Vol 112,1327,1990;Colvin等,自然(Nature),Vol.370,354,1994;Murray等,美国化学学会杂志(J.Am.Chem.Soc.)Vol.115,8706,1993;Hirai等,物理化学B杂志(J.Phys.Chem.B),Vol.103,4228,1999;Dabbousi等,物理化学B杂志(J.Phys.Chem.B),Vol.101,9463,1997;Hines等,物理化学杂志(J.Phys.Chem.)Vol.100,468,1996;Danek等,化学材料(Chem.Mater.)Vol.8,173,1996;Steigerwald等,美国化学学会杂志(J.Am.Chem.Soc.)(1988)110:3046-3050和Lianos等,化学物理快报(Chem.Phys.Lett.)Vol.125,299,1986。
但是,对于在生物分析中发光物质的使用而言,仅实际的合成并不是决定性的,重要的是在发光标记和相应生物物质之间的共价键的可能性。使用发光染料,首先以N-羟基琥珀酰亚胺基酯或异硫氰酸酯的形式被引入的功能基团起到与生物分子的氨基结合的作用。另一方面,量子点总是按照两种方法被功能化:一方面,表面用如巯基丙酸、二氢硫辛酸、巯基乙酸、巯基硅烷的功能巯基化合物转化,该化合物随后优选通过羧基功能与相应的生物分子连接(Gerion等,物理化学杂志(J.Phys.Chem.)Vol.105,8861,2001);Mattoussi等,美国化学学会杂志(J.Am.Chem.Soc.)Vol.122,12142,2000);Chan等,科学(Science)Vol 281,2016,1998);Mitchell等,美国化学学会杂志(J.Am.Chem.Soc.)Vol.121,8122,1999)),或者量子点被包封在聚合物基质或枝形聚合物(dendrimer)中(“覆盖”)。Lemon等,(美国化学学会杂志(J.Am.Chem.Soc.)Vol.122,12886,2000),Sooklal等,(先进材料(Adv.Mater.)Vol.10,1083,1998)和Lakowicz等,(物理化学杂志(J.Phys.Chem.)Vol.103,7613,1999)描述了在聚酰胺胺枝形聚合物的协助下半导体纳米晶体的包封。使用共聚苯乙烯乙烯(polystyrene-co-vinyl)吡啶、聚苯乙烯、硅胶或聚月桂酰甲基丙烯酸酯的包封由以下文献公开:Zhao等,(化学材料(Chem.Mater.)Vol.14,1418,2002);Han等,(自然生物技术(Nature Biotech.),Vol.19,631,2001);Correa-Duarte等,(化学物理快报(Chem.Phys.Letters,)Vol.286,497,1998);Chang等,(美国化学学会杂志(J.Am.Chem.Soc.)Vol.116,6739,1994)和Lee等,(先进材料(Adv.Mater.),Vol.12,1102,2000)。美国专利6,114,038和5,906,670的主要内容为被包封在含巯基的组分和二氨基羧酸中的量子点以及用喷射系统在气相中制备的半导体纳米晶体。
美国专利6,207,397、5,251,018、5,751,018、5,262,357和5,505,928涉及了能够与亲和性配体结合的III-V族和II-VI族半导体纳米晶体的制备。
美国专利6,326,144和6,207,229的主要内容为具有与生物成分的亲和键的被包覆的半导体纳米晶体以及用ZnS、ZnSe、CdS或CdSe包覆的单分散的光发射纳米晶体。
美国专利5,293,050和5,354,707涉及用于电路的硅的光发射半导体层,其中第二硅层含有至少一个量子点。
美国专利5,525,377描述了用于阴极射线管或电致发光显示器的被聚甲基丙烯酸甲酯涂敷的掺杂半导体化合物的20~100纳米颗粒。
美国专利5,537,000中涉及了使用ZnS、ZnSe、ZnTe、CdS、CdSe、CdTe、HgS、HgSe、HgTe、GaS、InAs、InP和InSb形式的半导体纳米晶体作为电子传输介质制备电致发光设备,当被施加电压后,该电致发光设备可以发射出不同波长的可见光。美国专利5,541,948的主要内容为包含II和VI族元素的掺杂了过渡金属的激光强化晶体。
美国专利5,585,640公开了掺杂了发光纳米晶体的玻璃基质。制备掺杂的预制玻璃形式需要超过1000℃的温度。
美国专利5,770,299公开了用作绘画的颜料的包含CdS和/或III-V族组分的半导体纳米晶体或II-VI族半导体纳米晶体。
美国专利5,789,162公开了在商业硅胶小球上的荧光标记的肽库的固相合成。
美国专利5,990,479涉及涂敷硅烷衍生物并能够与亲和性分子键合的生物应用发光半导体纳米晶体传感器。
美国专利5,043,265公开了作为免疫球蛋白和聚核苷酸的标记的ZnS-Ag和Y2O2S-Eu形式的发光颗粒。
美国专利5,985,353的主要内容为在分散于核酸或蛋白质形式的惰性凝胶聚合物中的阳离子交换剂存在下由过渡金属、镧系元素或锕系元素制备纳米颗粒。与交换剂键合的阳离子通过加入相应的阴离子被沉淀为纳米颗粒。
美国专利4,666,862和Oi等(J.Cell.Biol.Vol.93,891 1982)公开了能够降低激发和发射频率之间的光谱重叠程度,相当于显著的斯托克司频移(Stokes shift),的藻胆蛋白标记物。
另外一组光发射物质是所谓的上转换磷光颗粒(up-convertingphosphor),其独特特征为发射与激发辐射相反的短波辐射。这种类型的物质主要地包含氧和/或硫和/或氟与镧系元素或钇的化合物。
如果被用于生物测定中,则这些物质具有吸收和发射频率不受如载体颗粒或微量滴定载玻片的载体系统的自身荧光干扰的优点。当使用任何类型的载体系统时,在当今的生物分析中该自身荧光现象仍会引起问题。
美国专利5,674,698和5,698,397公开了通过激光激发被用于生物学和其他测定中的一系列掺杂上转换磷光颗粒形式如氟化钠钇、氟化镧、氟化钆和氧硫化钇的分子传感器。
美国专利5,132,242中公开了密封在聚丙烯酸酯微载体中的上转换磷光颗粒,该微载体对于激发和发射频率是透明的并且能够通过功能基团而加入与蛋白质的共价键。
Corstjens等,(Clin.Chem.Vol.47,1885,2001)和Niedbala等,(分析生物化学(Anal.Biochem.)Vol.293,22,2001)公开了用于测定核酸序列和免疫测定的上转换磷光颗粒。Hampl等,(分析生物化学(Anal.Biochem.)Vol.288,176,2001)公开了硅烷涂敷的上转换磷光颗粒。
美国专利6,004,530的主要内容为可被用作检测生物物质的发光金属卟啉。
在现有技术水平中已知的单一分子或纳米晶体形式的发光标记具有缺陷,即该发光标记的使用,尤其是在生物测定中,在所需的时间和步骤方面需要复杂的制备。因而与复杂步骤相关的合成或制备时间为几小时到几天(参见美国专利5,132,242):在氮气惰性气氛中操作,蒸馏,在有机介质中操作。因而,这些在任何情况下均存在有机聚合物的产物具有显著的自身荧光,参见上面列出的Han等的参考文献。
已知的发光体系的最严重的局限是对每个要被标记的生物分子,一般地只有一个或很少的几个发光颗粒(半导体纳米晶体或上转换磷光颗粒晶体)可以被键合。结果,这种限制显著地降低了生物测定的检测灵敏度。对于发光分子情况也相似,同样仅有少数发光颗粒可与每个生物分子键合,所以很难检测到从被标记的生物分子发射出的信号。此外,连接发光物质到生物分子(如,抗体)上可能会引起后者失活。然而,已经被开发为替代物的发光标记的微粒或纳米颗粒均具有与难以生产、使用和检测的颗粒的表面相连接的发光标记,参见Fornusek和Vetvicka,在CRC Critical Reviews in Therapeutic Drug Carrier Systems,2,pp.137-174,1986中的“用于细胞表面标记示踪的作为诊断工具的聚合小球(Polymeric Microspheres as Diagnostic Tools for Cell SurfaceMarker Tracing)”。该文献对这种技术做了综合性的评述,其他引用文献为:Kaplan等(Biochimica et Biophysica Acta,Vol.728,112,1983)以及美国专利3,853,987、4,035,316、4,105,598、4,108,972、4,224,198和4,326,008。
发明内容
本发明的目的之一是避免已知现有技术水平的发光载体体系的缺点并提供包含复合发光物质的具有适当多孔性的透明、非自发荧光的微粒和亚微颗粒。由于可以在分子和纳米颗粒或胶体两种形式中包封大量的发光剂,在生物分析和诊断中生物分子的检测灵敏度已经被极大地提高,甚至达到可以检测单个分子的水平。然而,几种具有可变发射性能的发光物质的包封使得生物分子的光学编码有多种变化。
该目标按照本发明通过在不会影响基本物质的实质发光性能的硅胶透明基质中包封发光物质而实现。
更进一步,该目标按照本发明通过反向悬浮法(inverse suspensionmethod)完成,因而含有硅胶溶胶和发光物质的混合物被分散在不与水混溶的有机相中,然后被缩聚。通过该方法可以制备出包含包封的发光物质的立体交联的、珠状聚合物载体。
具体实施方式
硅溶胶根据普遍已知的现有技术的方法,即在稀释的无机酸的帮助下通过烷氧基硅烷的水解而被制备出来(Dave等ImmobilizedBiomolecules in Analysis,编辑Cass和Ligler,Oxford University出版社,1998;WO 02/09125 A1)。脂肪醇的硅原酸酯可被用作烷氧基硅烷,优选为甲基、乙基或丙基酯,单独或以混合物的形式。相应的发光物质在第二个步骤中被加入到硅溶胶中。为了能够更均匀地混合异质的溶胶-发光物质混合物,反应在超声浴中进行或使用超声极(ultrasonicsonotrode),处理通常持续半分钟。由这种方法获得的胶体分散混合物然后一般通过搅拌被分散在与水不混溶的有机溶剂中。形成的珠状溶胶滴然后通过随后加入稀释的碱缩聚成为立体交联硅胶。
溶胶和有机分散相的极性特征被选择一方面能够制备稳定的悬浮液,另一方面使得添加的发光物质对溶胶具有高亲合力,以至于在溶胶和有机相之间有清晰的分界,结果使加入的发光化合物只被均匀的分散在溶胶相中。
根据配方,包括硅胶溶胶制备的整个制备方法需要约20~50分钟。
发光颗粒的合成开始于按照已知方法通过在酸性水溶性的环境中水解适当的烷氧基硅烷制备的硅溶胶。具有C1到C3酯基的原硅酸被优选地用于该方法及产物。令人惊异的是,这与具有确定浓度的硅烷一起使得完全透明颗粒得以制备。在最初的配方中烷氧基硅烷的浓度为40~90%体积,优选的为65~80%体积。在酸性水溶液的存在下使硅烷受到超声的作用从而制备澄清的溶胶,该酸性水溶液在硅烷配方中的体积百分比一般在10~40%并且其浓度一般在0.01到0.5摩尔/升之间。超声处理的时间依赖酸浓度确定为5~20分钟。通过该方法获得的硅溶胶可以在深冷温度下(大约-18℃)中储存多天,或者也可以被立即处理。
本发明的硅胶技术的另一个特点是所获得颗粒的多孔性可以在宽的范围内变动,这是一个任何其它已知现有技术不具备的特点。
颗粒载体介质的多孔性对于所有的生物检测或分离过程中起到决定性作用,这是因为分析物的特异性的检测能力依赖于其与固定在载体上的配体和/或受体的结合。这种结合过程的程度和质量直接受载体的可接近表面的影响。后者直接由载体的多孔性决定。令人惊异的是,这可以借助于按照本发明的产物和方法通过向溶胶加入特定物质加以调节。这些一般被称为生孔剂(porogen)的物质在分散前被加入到溶胶中。被作为添加物使用的物质优选是不影响载体的吸收-发射性能的物质。这些物质的例子包括:聚乙二醇、聚乙烯醇、聚丙烯酸、聚氨基酸、多糖,蛋白质或聚乙烯吡咯烷酮,本发明不局限于这些物质。它们在分散和交联过程中被包封在球形颗粒中。相对于溶胶相而言,以1~10%水溶液存在的有机聚合物溶液的体积百分比为1~20%。
另外用于调节多孔性的参数源于对各种二、三或四取代的硅烷组分的组合的选择。从而,纯粹四取代酯的凝胶通常具有比通过添加二或三取代酯化合物而制备的溶胶或凝胶更低的多孔性。二或三功能酯基化合物的选择性混合物使孔径在50~200nm之间。相对于整个硅烷浓度,二和三功能硅烷的浓度一般在1~10%,优选为1~5%体积。
本发明的产物和方法的另一个重要方面是可以同时通过机械搅拌的类型和方式以及硅溶胶的粘度来控制颗粒的大小。众所周知,颗粒的大小是在悬浮聚合期间通过搅拌速度加以调节,其调节方式为颗粒尺寸问题随搅拌速度的增加而下降。这些因素的相互关系也适用于本发明,即>1000rpm的搅拌速度一般会使得颗粒尺寸<50μm,搅拌速度>5000rpm则颗粒尺寸<10μm。为了获得更细的亚微米级颗粒,就需要例如根据转子-定子原理(rotor-stator principle)工作并且转子速度>10000rpm(例如,Ultra-Turrax)的分散工具。超声处理也使颗粒尺寸在0.5~10μm的范围内。
除了纯粹的机械因素,溶胶的粘度对颗粒的大小也有决定性的影响。降低溶胶粘度一般会导致颗粒大小类似的降低,反之亦然:升高粘度导致颗粒尺寸的增加。获得按照本发明的具有0.5~50μm的理想颗粒尺寸的产物所需的粘度在5~300cp之间。
在制备了具有理想特性的溶胶后,相应的发光标记物在下一步骤中被加入并与溶胶均匀地混合,优选应用超声波处理。这些可以在吸收了一定波长的辐射后以不同于吸收频率的频率发射出光子并且能够达到与硅胶溶胶的均匀混合的化合物可以被用作发光物质。
多种这类物质已经在所列的参考文献中被描述。发光分子和标记的例子有:荧光黄(Fluorescein)、若丹明(Rhodamin)、香豆素(Coumarin)、丹磺酰氯(Dansylchlorid)、溴乙菲啶(Ethidiumbromid)、Texas Red、藻红蛋白、Oregon Green或Cascade Blue以及具有下列商品名的化合物:BODIPY、SYBR Green、TOTO-1或YOYO-1以及这些产品的衍生物,本发明的产物并不局限于此。例如MgS、MgSe、MgTe、CaS、CaSe、CaTe、SrS、SrSe、SrTe、BaS、BaSe、BaTe、ZnS、ZnSe、ZnTe、CdS、CdSe,CdTe,HgS,HgSe或HgTe的II-VI族系列化合物以及例如GaAs、InGaAs、InP或InAs的III-V族纳米晶体均可被用作半导体纳米晶体。例如锗的IVA族半导体也是适合的。
上转换磷光颗粒的适当例子为稀土或IIIB族元素的化合物,例如氟化钠钇、氟化镧、硫氧化镧、硫氧化钇、氟化钇、镓酸钇、氟化钆、氟化钡钇、硫氧化钆以及掺杂了活化剂对(activator pair)如镱/铒、镱/铥或镱/钬的上述类型的化合物。其它适合的上转换磷光颗粒包括铒、钕、铥、钬和镨的螯合化合物。发光蛋白质如视紫红蛋白质、绿荧光蛋白质(GFP)和金属卟啉也可以相似的方式被用作发光物质。
被加入的发光物质的浓度可以依据相应生物分析或诊断的要求在宽范围内变化。为了实现清楚地发光,为标记物质的1~10%重量的浓度通常就足够了。这些浓度超过了常规测定中每个分析物可使用的发光标记浓度的几个数量级。
硅溶胶与多种物质极佳的可混溶性意外地使得磁性胶体和/或纳米颗粒形式的磁性化合物可以与发光物质一起同时被包封。这产生了可同时起到发光效果和磁性分离的作用的全新的特性组合。这就为高效生物测定的发展开辟了全新的前景,通过该高效生物测定使得以前只在聚合物或玻璃基质上进行的先前的阵列无法测定的极大量的生物分子(“分子库”)得以被测定。可以被使用的磁性物质为已知的含亚铁、含铁或超顺磁性物质以及铁磁流体,其中许多已经在相关的文献中被描述:巴西专利1439031,Shinkai等,生物催化(Biocatalysis)Vol 5,61,1991;Kondo等,微生物生物技术应用(Appl.Microbiol.Biotechn.)Vol.41,99,1994。磁性胶体的浓度全部经过挑选以使得涉及到发光标记的吸收和发射性能的颗粒的透明性不会受到影响。其一般在相对于硅胶颗粒重量的10~30%。
在该方法的第三个步骤中,硅胶-发光标记混合物通过搅拌被分散在有机相中。这些不与水互溶且可以使硅溶胶稳定分散的溶剂是合适的分散剂。这类分散剂从现有技术可知并在以下文献中被描述:WO02/09125以及Laane等(“有机介质中的生物催化(Biocatalysis inOrganic Media)”,Laane等,编辑,Elsevier,Amsterdam,pp 65,1987)。符合这些要求的溶剂包括己烷、三氯乙烯、石油醚、甲苯、氯仿、1,1,1-三氯乙烷、四氯化碳、庚烷。密度大约为1g/cm3的上述溶液的混合物也很适于分散。有机相与水溶胶的体积比例一般在8∶1~30∶1。
考虑到更窄的颗粒大小分布和更好的分散性能,一种或多种表面活性剂、分散稳定剂或乳化剂型的表面活性物质可以被加入到有机相中。这些物质的例子包括:丙烯氧化物-乙烯氧化物的嵌段共聚物、聚羟基脂肪酸-聚乙二醇嵌段共聚物、聚乙二醇-醚衍生物、脱水山梨糖醇脂肪酸酯、蓖麻油衍生物的嵌段共聚物、聚乙二醇-蓖麻油衍生物、聚氧乙烯脱水山梨糖醇脂肪酸酯、烷基苯基聚乙二醇衍生物、聚丙三醇酯、改性聚酯、聚氧丙烯乙二胺嵌段共聚物、聚乙二醇、聚氧乙烯衍生物、聚氧乙烯醇衍生物。这种类型的物质在市场上的商品名为:Renex、Estol、Prisorine、Hypermer、Pluronic、Tween、Eumulgin、Pripol、Tetronic、Brij、Lameform、Arlacel、Span、Dehymuls、Synperonic或Triton。有关颗粒的产生的表面活性剂的浓度在体积和/或重量的0.1~15%之间,优选地为0.5~6%。
在该方法的最后一个步骤中,在分散过程中溶胶与稀释的碱混合,所以前者浓缩聚合为固体凝胶。溶胶一般在数秒钟(3~20秒)内被固定成预期的凝胶颗粒。因此,机械分散处理只进行几秒钟。所选的碱浓度越高,凝胶化和同时的机械分散处理就越短。1~12%水溶液形式的氨被优选地用作碱,其它的碱如NaOH、二乙胺或KOH也可以使用。碱与溶胶的体积比一般在1∶2~1∶4之间。
非常快速的凝胶化反应的结果是,包括发光标记包封的整个颗粒制备过程可以在一个小时内完成。这相对于全部制备发光颗粒的常规方法节省了高达90%的时间。
制备过程后用乙醇和水洗涤数次。所获得的磁性载体一般被储存在水中。所获得的硅胶颗粒可以被直接用于进一步的功能化。
为了使发光颗粒与所有作为目标物质的相应的生物分子,如蛋白质、抗体、肽、酶、核酸、低聚糖,受体、生物配体或分析物传感器相结合,使用了普通已知的硅胶和/或硅烷化载体的活化和连接方法。这些方法包括与具有例如氨基、环氧基、含巯基的、异硫氰酸酯、丙烯酸或卤素基团的功能烷氧基硅烷反应。这种活化和连接剂的例子包括:3-氨基丙基-三乙氧基硅烷、3-氨基丙基-三甲氧基硅烷、3-缩水甘油基-丙氧基三甲氧基硅烷、3-缩水甘油基丙氧基甲基二乙氧基硅烷、3-巯基丙基三甲氧基硅烷、3-异氰硫基丙基三乙氧基硅烷、甲基丙烯基丙氧基三乙氧基硅烷、氯丙基三乙氧基硅烷。通过使用氨基羧酸、戊二醛对前面所述的烷氧基硅烷的衍化或者以酸或碱水解环氧基团向羟基衍生物引入羧基、羟基或醛基的方法已被现有技术所公开。相似地,按照已知方法环氧活化的载体与羧酸、亚硫酸、硫代硫酸、氨基取代的羧酸如次氮基三乙酸或亚胺基乙酰乙酸之间的反应也会产生金属螯合物载体。通过光活化剂,如含有芳基叠氮(arylazine)或偶氮甲烷(diazirin)功能团的,活化硅胶颗粒是较容易做到的,该光活化剂首先通过紫外光照射被连接到载体上,然后可与生物配体和/或生物分子反应。该类型的物质包括:N-羟基琥珀酰亚胺基-4-叠氮苯甲酸、[2-硝基-4-[3-(三氟甲基)-3H-偶氮甲烷-3-基]苯氧基]乙酰基-N-羟基琥珀酰亚胺酸、N-羟基琥珀酰亚胺基-(4-叠氮苯基)-1,3`-二硫代丙酸、N-[m-[3-(三氟甲基)偶氮甲烷-3-基]苯基]-4-顺丁烯二酰亚胺丁酰胺(maleimidobutyramide)。
在这里不需要对各种活化、功能化和连接进行详细描述,因为特定的反应方法是普遍已知的并可以在任何时候被本领域技术人员所使用(参见,Vansant等,“二氧化硅表面的特性和化学修饰(Characterizationand Chemical Modification of the Silica Surface)”,由Delmon和Yates编辑,Elsevier,Amsterdam,1997;“磁性载体的科学与临床应用(Scientificand Clinical Applications of Magnetic Carriers)”,Hfeli等(编者),PlenumPress,New York,1997;Shriver-Lake,“分析中的固定生物分子(Immobilized Biomolecules in Analysis)”,Cass和Ligler,编辑,OxfordUniversity Press,1998;WO 99/01766;Lottspeich和Zorbas编辑,“Bioanalytik”,Spektrum Verlag,Heidelberg,1998)。基本实施例不应被看作是公开范围的限制。
按照本发明的发光颗粒的应用覆盖所有使用显色反应、发光或放射性以检测或定量特定物质或分析物的生物分析和诊断的领域。其例子包括放射或酶免疫形式的免疫分析、核酸检测、蛋白质组分析、DNA测序、噬菌体显示(phage display)、细胞标记、核酸阵列或细胞标记。此外,颗粒发光标记物可被用于流式细胞仪或被荧光激活细胞分选仪(FACS)或用于测试DNA或蛋白质库。
随后的实施例更详细地叙述了本发明的产物和方法,但本发明并不仅限于这些实施例。
实施例1
室温下5ml四甲氧基硅烷和2ml的0.05M HCl一同在超声浴中置于超声波下10分钟,所获得的2ml澄清的溶胶与1ml的0.05%若丹明B溶液混合,混合物然后被加入到含有0.4ml的Korantin(BASF)的25ml己烷中。该配比用分散装置(Ultra-Turrax)以20000rpm分散3秒钟。在加入1ml的1%的氨水溶液后再分散5秒钟。5分钟后颗粒通过两分钟的离心被沉淀。过量的部分被倾析掉并用乙醇,丙酮和水漂洗三次,每次大约10ml。得到了颗粒大小为1~3μm的发光颗粒。
获得的颗粒随后用无水甲苯洗涤数次,然后在氩气气氛中与5ml无水甲苯和2ml的3-缩水甘油基丙氧基三甲氧基硅烷在90℃搅拌下反应3小时。然后用甲苯和丙酮漂洗5次。100mg所获得的产物再用0.5摩尔pH为8.5的磷酸缓冲液洗涤三次,并且随后在溶解有10mg链霉抗生物素蛋白的2ml相同的缓冲液中40℃下孵育5小时。然后产物经离心步骤每次用0.05M pH为7.2的磷酸缓冲液洗涤5次。为了阻断任何剩余的环氧基团,被结合的产物在包含0.1%血清白蛋白的1%乙醇胺溶液中室温下储存24小时。然后用pH为8.0的0.05 Tris/HCl缓冲液洗涤数次。
从而制备出能够用于结合或标记生物素化的生物分子的产物。
实施例2
与实施例1类似地制备的2ml硅溶胶与根据Sooklal等(Adv.Mater.,Vol.10,1083,1998)的说明合成的平均颗粒大小为138nm的10mgCdS半导体纳米晶体混合,然后在室温下置于超声波中2分钟。混合物在溶解有2.5%体积的Span 60和溶解有0.5%体积的Tween 80的25ml甲苯中用Ultra-Turrax在20000rpm下被分散5秒钟。加入1ml 6%氨水溶液后,被继续分散5秒钟。然后类似于实施例1,颗粒被分离并制备。获得了发射最大值为510nm的平均颗粒大小为3.6μm的发光颗粒。
为了活化颗粒,在[2-硝基-4-[3-(三氟甲基)-3H-偶氮甲烷-3-基]苯氧基]乙酰基-N-羟基琥珀酰亚胺酸(配比:5mg溶解于0.5ml乙醇-水(1∶1)中)的存在下用stratalinker UV 2400(Stratagene)照射75mg发光颗粒20分钟。包含氨基的生物分子、配体或受体例如核酸、蛋白质或抗体都可根据已知方法(Matson和Little,J.Chromatogr.,Vol.458,67,1988)在用乙醇和水洗涤之后与活化的产物结合。
实施例3
0.5ml四乙氧基硅烷与0.1ml的水和0.08ml的0.1M HCl混合,在室温下超声浴中置于超声波下10分钟。所获得的0.2ml的溶胶与根据Hampl的描述(Anal.Biochem.,Vol.288,176,2001)制备的5mg(YYbEr)2O2S混合,并在超声浴中处理5分钟。然后加入30mg磁性粉末(Bayferrox 318M,Bayer,FRG)到混合物中。混合物再被置于超声波下2分钟。混合物然后通过在12000rpm的搅拌(Ultra-Turrax)被分散于溶解有2%体积的Dehymuls HRE7和0.5%体积的Prisorine 3700的3ml三氯乙烯中。0.08ml的6%氨水溶液在分散中被加入。化合物再搅拌5秒钟。获得的发光颗粒的分离和制备与实施例1类似。
得到了平均颗粒大小为6.7μm的发光颗粒。
在各次磁性分离之后,产物在被用干燥甲苯洗涤5次之前被真空干燥3小时,随后在加入3ml甲苯和0.25ml的3-丙氨基三乙氧基硅烷后沸腾回流12小时。磁性颗粒被再次磁性分离并用大约5ml的甲苯和氯仿洗涤3次。然后该磁性颗粒在真空中干燥数小时。然后35℃下在4ml的pH为9.0的0.1M碳酸钠缓冲液中,氨基修饰的产物用6%戊二醛溶液转化。然后该产物用pH为7.2的0.1M磷酸缓冲液彻底地漂洗。
根据已知方法,具有氨基基团的生物分子例如蛋白质、肽、核酸或在5′端有取代氨基的低聚核苷酸,能够与所获得的醛基功能化的发光颗粒结合。以这种方式被功能化的发光颗粒可以在蛋白质或核酸阵列中被用作传感器。
Claims (25)
1、发光硅胶颗粒,在透明硅胶基质中包含一种或多种发光物质。
2、根据权利要求1的颗粒,其特征在于该颗粒不是自发光的。
3、根据权利要求1或2的颗粒,其特征在于所述的发光物质被包封在该颗粒中。
4、根据前面权利要求任意一项的颗粒,其特征在于发光物质选自显示荧光、磷光、化学发光、电致发光或能量转换发光的物质的组。
5、根据前面权利要求任意一项的颗粒,其特征在于发光物质的浓度为1~10wt%。
6、根据前面权利要求任意一项的颗粒,其特征在于发光物质显示不同的发射频率。
7、根据前面权利要求任意一项的颗粒,其特征在于发光物质是激发频率高于发射频率的分子。
8、根据权利要求1到6中任意一项的颗粒,其特征在于发光物质包括IIIA和VA族,IIB和VIA族或IVA族的元素形成的半导体纳米晶体。
9、根据权利要求8的颗粒,其特征在于发光半导体纳米晶体被加入铜和/或银添加剂。
10、根据权利要求1到6中任意一项的颗粒,其特征在于发光物质具有比发射频率低的激发频率。
11、根据权利要求10的颗粒,其特征在于发光物质是稀土和/或钇与第VIA和/或VIIA族元素的微晶化合物。
12、根据前面权利要求中任意一项的颗粒,其特征在于发光物质是金属螯合化合物,其中心原子选自VIII,IB,IIB族或稀土族。
13、根据前面权利要求中任意一项的颗粒,其特征在于发光物质为吡咯染料。
14、根据权利要求1到6的颗粒,其特征在于发光物质为发光蛋白质。
15、根据权利要求1到14中任意一项的颗粒,其中额外包含或包封了磁性胶体。
16、根据权利要求15的颗粒,其特征在于磁性胶体选自包含亚铁、铁和超顺磁性化合物以及铁磁流体的组。
17、根据权利要求15或16的颗粒,其特征在于磁性胶体以相对颗粒重量10~50%的浓度存在。
18、根据前面权利要求中任意一项的颗粒,其特征在于硅胶具有可以与选自包含蛋白质、肽、细胞受体、核酸、核酸片断、多聚糖、低聚糖、抗体、抗体片断、链霉抗生物素蛋白、抗生物素蛋白、生物素和酶的组的生物分子结合的功能基团,或者能够与一种或多种这些生物分子联合的功能基团。
19、制备根据权利要求1到18中任意一项的发光硅胶颗粒的方法,其特征在于
a)由稀释的酸和烷氧基硅烷构成的混合物被浓缩为澄清的硅溶胶;
b)澄清硅溶胶被均匀地与一种或多种发光物质混合;
c)溶胶-发光物质混合物被分散在不与水混溶的有机相中;和
d)溶胶-发光物质混合物通过在分散过程中或分散之后加入碱被交联。
20、根据权利要求19的发光透明硅胶颗粒的制备方法,其特征在于10~50%重量的含亚铁、含铁或超顺磁性的物质被加入到溶胶-发光物质混合物中。
21、根据权利要求19和20的发光硅胶颗粒的制备方法,其特征在于不与水混溶的有机相包含0.1~15%体积浓度的一种或多种表面活性物质。
22、根据权利要求19到21中任意一项的发光硅胶颗粒的制备方法,其特征在于溶胶与有机相的体积比为1∶5到1∶30。
23、根据权利要求19到22中任意一项的发光硅胶颗粒的制备方法,其特征在于分散交联过程需要2~30秒。
24、根据权利要求19到23中任意一项的发光硅胶颗粒的制备方法,其特征在于1~20%体积比的有机聚合物、多聚糖或蛋白质的水溶液在分散前与溶胶混合。
25、根据权利要求1到18中的任意一项的发光硅胶颗粒在核酸、核酸片断、蛋白质、肽、抗体、抗体片断、细胞、细胞受体、生物素化的生物分子的分析和/或诊断,以及在芯片技术中作为传感器测试蛋白质或核酸库,或者在核酸测序中的应用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10214019A DE10214019A1 (de) | 2002-03-30 | 2002-03-30 | Lumineszierende, sphärische, nicht autofluoreszierende Silicagel-Partikel mit veränderbaren Emissionsintensitäten und -frequenzen |
DE10214019.7 | 2002-03-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1643379A true CN1643379A (zh) | 2005-07-20 |
Family
ID=28050954
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN03807087.1A Pending CN1643379A (zh) | 2002-03-30 | 2003-03-27 | 具有可变的发射强度与发射频率的发光球形非自发光硅胶颗粒 |
Country Status (8)
Country | Link |
---|---|
US (1) | US20050147974A1 (zh) |
EP (1) | EP1490691B1 (zh) |
JP (1) | JP2005528466A (zh) |
CN (1) | CN1643379A (zh) |
AT (1) | ATE421696T1 (zh) |
AU (1) | AU2003223998A1 (zh) |
DE (2) | DE10214019A1 (zh) |
WO (1) | WO2003083481A2 (zh) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012055069A1 (en) * | 2010-10-27 | 2012-05-03 | Capitalbio Corporation | Luminophore-labeled molecules coupled with particles for microarray-based assays |
US9803236B2 (en) | 2010-08-06 | 2017-10-31 | Tsinghua University | Microarray-based assay integrated with particles for analyzing molecular interactions |
US10167499B2 (en) | 2013-12-05 | 2019-01-01 | Capitalbio Technoloogy Corporation | Luminophore-labeled molecules coupled with particles for microarray-based assays |
WO2021017904A1 (en) * | 2019-07-31 | 2021-02-04 | Auiset Biotechnology Co. Ltd. | Fabrication of fluorescent nanoparticles and their conjugates for in vitro and in vivo diagnostics |
CN114032086A (zh) * | 2020-12-25 | 2022-02-11 | 武汉大学 | 一种长余辉纳米探针组合在检测细菌生物被膜中的应用 |
CN115261013A (zh) * | 2022-07-01 | 2022-11-01 | 西安邮电大学 | 一种稀土发光材料及其制备方法与应用 |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0400235D0 (en) * | 2004-01-07 | 2004-02-11 | Univ Sunderland | Nanoparticles as agents for imaging finger prints |
US7368086B2 (en) * | 2004-10-29 | 2008-05-06 | Invitrogen Corporation | Functionalized fluorescent nanocrystals, and methods for their preparation and use |
US20090061226A1 (en) * | 2004-12-07 | 2009-03-05 | Yissum Research Development Company Of The Hebrew | Spherical composites entrapping nanoparticles, processes of preparing same and uses thereof |
JP4982687B2 (ja) * | 2004-12-09 | 2012-07-25 | 株式会社テクノネットワーク四国 | 標識分子含有シリカ球の調製方法 |
JP2006305485A (ja) * | 2005-04-28 | 2006-11-09 | Hitachi Maxell Ltd | 磁性担体の製造方法 |
AU2006277712B2 (en) | 2005-08-09 | 2012-01-19 | University Of Sunderland | Hydrophobic silica particles and methods of making same |
WO2007074722A1 (ja) * | 2005-12-27 | 2007-07-05 | The Furukawa Electric Co., Ltd. | 蛍光ナノシリカ粒子、ナノ蛍光材料、それを用いたバイオチップ及びそのアッセイ法 |
US20090239767A1 (en) * | 2006-09-19 | 2009-09-24 | Konica Minolta Medical & Graphic, Inc. | Biomolecule detection reagent and method for detecting biomolecule using reagent |
US8053744B2 (en) * | 2009-04-13 | 2011-11-08 | Src, Inc. | Location analysis using nucleic acid-labeled tags |
FR2952436B1 (fr) * | 2009-11-10 | 2014-10-31 | Commissariat Energie Atomique | Materiau et procede pour pieger, detecter et quantifier des composes aromatiques heterocycliques et autres. |
JP5275518B2 (ja) * | 2010-02-02 | 2013-08-28 | ヴェンタナ メディカル システムズ, インク. | 蛍光粒子を安定化するための組成物及び方法 |
US20130150265A1 (en) * | 2010-02-09 | 2013-06-13 | Robert Balog | Chemical synthesis using up-converting phosphor technology and high speed flow cytometry |
US8703493B2 (en) | 2010-06-15 | 2014-04-22 | Src, Inc. | Location analysis using fire retardant-protected nucleic acid-labeled tags |
US8716027B2 (en) | 2010-08-03 | 2014-05-06 | Src, Inc. | Nucleic acid-labeled tags associated with odorant |
FR2993798B1 (fr) * | 2012-07-25 | 2015-03-06 | Commissariat Energie Atomique | Procede de marquage d'un substrat metallique par incorporation de particules inorganiques luminescentes |
DE102014110573A1 (de) | 2014-07-25 | 2016-01-28 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Mit einer Signatur auf Basis von superparamagnetischen und/oder weichmagnetischen Nanopartikeln versehener Gegenstand, Verfahren zu dessen Herstellung und Verwendung von superparamagnetischen und/oder weichmagnetischen Nanopartikeln zum Sichern von Gegenständen gegen Fälschung und Nachahmung |
CN105419778B (zh) * | 2015-12-22 | 2017-11-14 | 重庆益新阳工贸有限公司 | 一种含有石蜡的量子点复合材料及其制备方法 |
CN105419777B (zh) * | 2015-12-22 | 2018-08-14 | 莫婉玲 | 一种含有脂肪酸脂的量子点复合材料及其制备方法 |
CN108701521B (zh) | 2016-02-29 | 2020-12-04 | 洛德公司 | 用于磁流变流体的添加剂 |
US10941057B2 (en) * | 2017-04-28 | 2021-03-09 | U.S. Environmental Protection Agency | Highly tunable fluorescent core-shell particles for environmental release simulation and tracking applications |
CN109540878B (zh) * | 2018-11-12 | 2021-07-27 | 安庆师范大学 | 一种检测钡离子的试剂盒及其检测方法 |
Family Cites Families (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3853987A (en) * | 1971-09-01 | 1974-12-10 | W Dreyer | Immunological reagent and radioimmuno assay |
US3998943A (en) * | 1973-10-02 | 1976-12-21 | Syva Company | Double receptor fluorescent immunoassay |
US4108972A (en) * | 1974-03-15 | 1978-08-22 | Dreyer William J | Immunological reagent employing radioactive and other tracers |
DE2426919C3 (de) * | 1974-06-04 | 1981-07-16 | Philippe Edouard Jean Leon Alexis Puteaux Gravisse | PhotolumineszierendesBaumaterial und ein Verfahren zu dessen Herstellung |
US3996345A (en) * | 1974-08-12 | 1976-12-07 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4199559A (en) * | 1974-08-12 | 1980-04-22 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4174384A (en) * | 1975-06-30 | 1979-11-13 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4035316A (en) * | 1975-11-24 | 1977-07-12 | California Institute Of Technology | Cell specific, variable density, polymer microspheres |
US4326008A (en) * | 1976-08-27 | 1982-04-20 | California Institute Of Technology | Protein specific fluorescent microspheres for labelling a protein |
US4235869A (en) * | 1978-05-16 | 1980-11-25 | Syva Company | Assay employing a labeled Fab-fragment ligand complex |
US4224198A (en) * | 1978-05-26 | 1980-09-23 | California Institute Of Technology | Protein specific polymeric immunomicrospheres |
US4261968A (en) * | 1979-05-10 | 1981-04-14 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4666862A (en) * | 1984-08-14 | 1987-05-19 | Ortho Diagnostic Systems Inc. | Fluorescent energy transfer with phycobiliproteins |
JPS61246748A (ja) * | 1985-04-24 | 1986-11-04 | Konishiroku Photo Ind Co Ltd | ハロゲン化銀カラ−写真感光材料 |
DE3677364D1 (de) * | 1985-08-05 | 1991-03-07 | Univ Leiden | Markierte makromolekuele; verfahren zu ihrer herstellung und ihre verwendung in immunologischen oder immunocytochemischen testen. |
US5132242A (en) * | 1987-07-15 | 1992-07-21 | Cheung Sau W | Fluorescent microspheres and methods of using them |
US5066580A (en) * | 1988-08-31 | 1991-11-19 | Becton Dickinson And Company | Xanthene dyes that emit to the red of fluorescein |
KR930011971B1 (ko) * | 1991-01-29 | 1993-12-23 | 삼성전자 주식회사 | 색신호 경계면 보정장치 |
US5770358A (en) * | 1991-09-18 | 1998-06-23 | Affymax Technologies N.V. | Tagged synthetic oligomer libraries |
JP2970967B2 (ja) * | 1991-11-20 | 1999-11-02 | 浜松ホトニクス株式会社 | 蛍光性プローブ試薬を用いた細胞内イオン濃度測定法 |
JPH07502479A (ja) * | 1991-11-22 | 1995-03-16 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 自己集合性単一層を使って固体無機表面に共有結合した半導体微少結晶 |
US5505928A (en) * | 1991-11-22 | 1996-04-09 | The Regents Of University Of California | Preparation of III-V semiconductor nanocrystals |
US5262357A (en) * | 1991-11-22 | 1993-11-16 | The Regents Of The University Of California | Low temperature thin films formed from nanocrystal precursors |
US5324633A (en) * | 1991-11-22 | 1994-06-28 | Affymax Technologies N.V. | Method and apparatus for measuring binding affinity |
US5698397A (en) * | 1995-06-07 | 1997-12-16 | Sri International | Up-converting reporters for biological and other assays using laser excitation techniques |
US5674698A (en) * | 1992-09-14 | 1997-10-07 | Sri International | Up-converting reporters for biological and other assays using laser excitation techniques |
US5293050A (en) * | 1993-03-25 | 1994-03-08 | International Business Machines Corporation | Semiconductor quantum dot light emitting/detecting devices |
US6048616A (en) * | 1993-04-21 | 2000-04-11 | Philips Electronics N.A. Corp. | Encapsulated quantum sized doped semiconductor particles and method of manufacturing same |
GB9323498D0 (en) * | 1993-11-15 | 1994-01-05 | Isis Innovation | Making particles of uniform size |
US5527711A (en) * | 1993-12-13 | 1996-06-18 | Hewlett Packard Company | Method and reagents for binding chemical analytes to a substrate surface, and related analytical devices and diagnostic techniques |
US5537000A (en) * | 1994-04-29 | 1996-07-16 | The Regents, University Of California | Electroluminescent devices formed using semiconductor nanocrystals as an electron transport media and method of making such electroluminescent devices |
US5541948A (en) * | 1994-11-28 | 1996-07-30 | The Regents Of The University Of California | Transition-metal doped sulfide, selenide, and telluride laser crystal and lasers |
US5985353A (en) * | 1994-12-01 | 1999-11-16 | University Of Massachusetts Lowell | Biomolecular synthesis of quantum dot composites |
US5585640A (en) * | 1995-01-11 | 1996-12-17 | Huston; Alan L. | Glass matrix doped with activated luminescent nanocrystalline particles |
DE19541028C2 (de) * | 1995-11-05 | 1998-01-22 | Daimler Benz Ag | Effektlack mit Pigmenten, die eine Kennzeichnung tragen, sowie Verfahren zu seiner Herstellung |
US6207397B1 (en) * | 1996-04-18 | 2001-03-27 | Ariad Pharmaceuticals, Inc. | In vitro fluorescence polarization assay |
US6004530A (en) * | 1996-06-04 | 1999-12-21 | Roche Diagnostics Gmbh | Use of metallo-porphyrin conjugates for the detection of biological substances |
DE19730359A1 (de) * | 1997-07-15 | 1999-01-21 | Boehringer Mannheim Gmbh | Integriertes Verfahren und System zur Amplifizierung und zum Nachweis von Nukleinsäuren |
US7348181B2 (en) * | 1997-10-06 | 2008-03-25 | Trustees Of Tufts College | Self-encoding sensor with microspheres |
US6322901B1 (en) * | 1997-11-13 | 2001-11-27 | Massachusetts Institute Of Technology | Highly luminescent color-selective nano-crystalline materials |
US5990479A (en) * | 1997-11-25 | 1999-11-23 | Regents Of The University Of California | Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US6326144B1 (en) * | 1998-09-18 | 2001-12-04 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
US6114038A (en) * | 1998-11-10 | 2000-09-05 | Biocrystal Ltd. | Functionalized nanocrystals and their use in detection systems |
-
2002
- 2002-03-30 DE DE10214019A patent/DE10214019A1/de not_active Withdrawn
-
2003
- 2003-03-27 CN CN03807087.1A patent/CN1643379A/zh active Pending
- 2003-03-27 DE DE50311117T patent/DE50311117D1/de not_active Expired - Lifetime
- 2003-03-27 WO PCT/EP2003/003163 patent/WO2003083481A2/de active Application Filing
- 2003-03-27 JP JP2003580862A patent/JP2005528466A/ja active Pending
- 2003-03-27 US US10/509,712 patent/US20050147974A1/en not_active Abandoned
- 2003-03-27 EP EP03720372A patent/EP1490691B1/de not_active Expired - Lifetime
- 2003-03-27 AT AT03720372T patent/ATE421696T1/de not_active IP Right Cessation
- 2003-03-27 AU AU2003223998A patent/AU2003223998A1/en not_active Abandoned
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9803236B2 (en) | 2010-08-06 | 2017-10-31 | Tsinghua University | Microarray-based assay integrated with particles for analyzing molecular interactions |
WO2012055069A1 (en) * | 2010-10-27 | 2012-05-03 | Capitalbio Corporation | Luminophore-labeled molecules coupled with particles for microarray-based assays |
US9310375B2 (en) | 2010-10-27 | 2016-04-12 | Capitalbio Corporation | Luminophore-labeled molecules coupled with particles for microarray-based assays |
US10167499B2 (en) | 2013-12-05 | 2019-01-01 | Capitalbio Technoloogy Corporation | Luminophore-labeled molecules coupled with particles for microarray-based assays |
US10982267B2 (en) | 2013-12-05 | 2021-04-20 | Capitalbio Technology Corporation | Luminophore-labeled molecules coupled with particles for microarray-based assays |
WO2021017904A1 (en) * | 2019-07-31 | 2021-02-04 | Auiset Biotechnology Co. Ltd. | Fabrication of fluorescent nanoparticles and their conjugates for in vitro and in vivo diagnostics |
CN114032086A (zh) * | 2020-12-25 | 2022-02-11 | 武汉大学 | 一种长余辉纳米探针组合在检测细菌生物被膜中的应用 |
CN114032086B (zh) * | 2020-12-25 | 2023-11-17 | 武汉大学 | 一种长余辉纳米探针组合在检测细菌生物被膜中的应用 |
CN115261013A (zh) * | 2022-07-01 | 2022-11-01 | 西安邮电大学 | 一种稀土发光材料及其制备方法与应用 |
Also Published As
Publication number | Publication date |
---|---|
ATE421696T1 (de) | 2009-02-15 |
AU2003223998A8 (en) | 2003-10-13 |
EP1490691A2 (de) | 2004-12-29 |
AU2003223998A1 (en) | 2003-10-13 |
WO2003083481A2 (de) | 2003-10-09 |
WO2003083481A3 (de) | 2004-03-25 |
DE50311117D1 (de) | 2009-03-12 |
JP2005528466A (ja) | 2005-09-22 |
US20050147974A1 (en) | 2005-07-07 |
DE10214019A1 (de) | 2003-10-16 |
EP1490691B1 (de) | 2009-01-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1643379A (zh) | 具有可变的发射强度与发射频率的发光球形非自发光硅胶颗粒 | |
US20200150120A1 (en) | Portable electronic device, system, and method for analyte detection | |
JP7402244B2 (ja) | 単分子定量検出方法及び検出システム | |
Yao et al. | FloDots: luminescent nanoparticles | |
JP4716337B2 (ja) | フローサイトメトリーによる細胞の検出・分取システム、及び検出・分取方法 | |
US6783699B2 (en) | Europium-containing fluorescent nanoparticles and methods of manufacture thereof | |
CN1389539A (zh) | 纳米微粒、微球及其生物荧光探针的制备和应用 | |
CN1183999C (zh) | 核壳型纳米颗粒 | |
EP1666560A1 (en) | Novel fine fluorescent particle | |
EP3054283A1 (en) | Method for detecting target substance | |
US20100048416A1 (en) | Encoded microsphere | |
CN1265197C (zh) | β-二酮-三价铕配合物纳米荧光探针及其制备和应用 | |
JP2022528043A (ja) | 量子ドット含有ナノ粒子及びその製造方法 | |
JPWO2008035569A1 (ja) | 生体分子検出用試薬及びそれを用いた生体分子検出方法 | |
JP3721097B2 (ja) | 分子認識蛍光体、それを用いた標的物質の測定方法 | |
JP4245415B2 (ja) | 分子認識蛍光体の製造方法 | |
CN113125420B (zh) | 基于化学发光的多元分析光子晶体芯片及其制备方法和应用 | |
Zhao et al. | Fluorescent nanoparticle for bacteria and DNA detection | |
JP2003270154A (ja) | 蛍光色素分子含有シリカ球 | |
CN1186634C (zh) | 荧光稀土络合物硅纳米颗粒类标记物及其制备方法 | |
WO2002099425A2 (en) | Polymeric bead probe with nanocrystal, manufacture and use of the same | |
Sathe et al. | Development of dual-function microbeads embedded with quantum dots and iron oxide nanocrystals for biomedical applications |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
ASS | Succession or assignment of patent right |
Owner name: BEZDOLNYJ NIKOLAJ I Free format text: FORMER OWNER: MULLER-SHULTE DETLEF P. Effective date: 20061208 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20061208 Address after: Aachen Applicant after: Magnamedics GmbH Address before: Aachen, Federal Republic of Germany Applicant before: Detlef P Miller - Shure |
|
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |