JP2008506929A - 水和金属酸化物を用いるリン酸化分子の検出と単離のための方法と組成物 - Google Patents
水和金属酸化物を用いるリン酸化分子の検出と単離のための方法と組成物 Download PDFInfo
- Publication number
- JP2008506929A JP2008506929A JP2007520439A JP2007520439A JP2008506929A JP 2008506929 A JP2008506929 A JP 2008506929A JP 2007520439 A JP2007520439 A JP 2007520439A JP 2007520439 A JP2007520439 A JP 2007520439A JP 2008506929 A JP2008506929 A JP 2008506929A
- Authority
- JP
- Japan
- Prior art keywords
- phosphomolecule
- sample
- metal oxide
- phosphoaffinity
- hydrated metal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229910044991 metal oxide Inorganic materials 0.000 title claims abstract description 191
- 150000004706 metal oxides Chemical class 0.000 title claims abstract description 190
- 238000000034 method Methods 0.000 title claims abstract description 148
- 238000001514 detection method Methods 0.000 title claims description 55
- 238000002955 isolation Methods 0.000 title description 36
- 239000000203 mixture Substances 0.000 title description 28
- 239000000463 material Substances 0.000 claims abstract description 218
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 14
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 14
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 claims abstract description 14
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 205
- 239000002245 particle Substances 0.000 claims description 127
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 105
- 239000004408 titanium dioxide Substances 0.000 claims description 89
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 54
- 239000000499 gel Substances 0.000 claims description 54
- 239000012528 membrane Substances 0.000 claims description 54
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 54
- 230000027455 binding Effects 0.000 claims description 51
- -1 Iron aluminate Chemical class 0.000 claims description 37
- 229910052751 metal Inorganic materials 0.000 claims description 27
- 239000002184 metal Substances 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 27
- SIWVEOZUMHYXCS-UHFFFAOYSA-N oxo(oxoyttriooxy)yttrium Chemical compound O=[Y]O[Y]=O SIWVEOZUMHYXCS-UHFFFAOYSA-N 0.000 claims description 21
- 238000010828 elution Methods 0.000 claims description 20
- 239000002223 garnet Substances 0.000 claims description 20
- 229920001184 polypeptide Polymers 0.000 claims description 20
- 239000004094 surface-active agent Substances 0.000 claims description 20
- MTRJKZUDDJZTLA-UHFFFAOYSA-N iron yttrium Chemical compound [Fe].[Y] MTRJKZUDDJZTLA-UHFFFAOYSA-N 0.000 claims description 16
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 claims description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 15
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
- 238000004949 mass spectrometry Methods 0.000 claims description 14
- 238000001209 resonance light scattering Methods 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 claims description 13
- 239000007788 liquid Substances 0.000 claims description 13
- 239000011324 bead Substances 0.000 claims description 12
- 229920002678 cellulose Polymers 0.000 claims description 11
- 239000001913 cellulose Substances 0.000 claims description 11
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 11
- 229920005989 resin Polymers 0.000 claims description 11
- 239000011347 resin Substances 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 10
- JNDMLEXHDPKVFC-UHFFFAOYSA-N aluminum;oxygen(2-);yttrium(3+) Chemical compound [O-2].[O-2].[O-2].[Al+3].[Y+3] JNDMLEXHDPKVFC-UHFFFAOYSA-N 0.000 claims description 7
- 229910052742 iron Inorganic materials 0.000 claims description 7
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 claims description 7
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical group O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims description 7
- 229910019901 yttrium aluminum garnet Inorganic materials 0.000 claims description 7
- 239000000835 fiber Substances 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 5
- 238000002875 fluorescence polarization Methods 0.000 claims description 5
- 238000002866 fluorescence resonance energy transfer Methods 0.000 claims description 5
- 229910001679 gibbsite Inorganic materials 0.000 claims description 5
- 239000002563 ionic surfactant Substances 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 5
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 claims description 4
- 238000002835 absorbance Methods 0.000 claims description 4
- 229910001680 bayerite Inorganic materials 0.000 claims description 4
- 229910001593 boehmite Inorganic materials 0.000 claims description 4
- 229910052733 gallium Inorganic materials 0.000 claims description 4
- 229910052598 goethite Inorganic materials 0.000 claims description 4
- FAHBNUUHRFUEAI-UHFFFAOYSA-M hydroxidooxidoaluminium Chemical compound O[Al]=O FAHBNUUHRFUEAI-UHFFFAOYSA-M 0.000 claims description 4
- AEIXRCIKZIZYPM-UHFFFAOYSA-M hydroxy(oxo)iron Chemical compound [O][Fe]O AEIXRCIKZIZYPM-UHFFFAOYSA-M 0.000 claims description 4
- YDZQQRWRVYGNER-UHFFFAOYSA-N iron;titanium;trihydrate Chemical compound O.O.O.[Ti].[Fe] YDZQQRWRVYGNER-UHFFFAOYSA-N 0.000 claims description 4
- 238000002372 labelling Methods 0.000 claims description 4
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 claims description 4
- GROMGGTZECPEKN-UHFFFAOYSA-N sodium metatitanate Chemical compound [Na+].[Na+].[O-][Ti](=O)O[Ti](=O)O[Ti]([O-])=O GROMGGTZECPEKN-UHFFFAOYSA-N 0.000 claims description 4
- 238000004416 surface enhanced Raman spectroscopy Methods 0.000 claims description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims description 4
- 229910052726 zirconium Inorganic materials 0.000 claims description 4
- 229910001928 zirconium oxide Inorganic materials 0.000 claims description 4
- XHCLAFWTIXFWPH-UHFFFAOYSA-N [O-2].[O-2].[O-2].[O-2].[O-2].[V+5].[V+5] Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[V+5].[V+5] XHCLAFWTIXFWPH-UHFFFAOYSA-N 0.000 claims description 3
- AJNVQOSZGJRYEI-UHFFFAOYSA-N digallium;oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Ga+3].[Ga+3] AJNVQOSZGJRYEI-UHFFFAOYSA-N 0.000 claims description 3
- 229910001195 gallium oxide Inorganic materials 0.000 claims description 3
- JCDAAXRCMMPNBO-UHFFFAOYSA-N iron(3+);oxygen(2-);titanium(4+) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[Ti+4].[Ti+4].[Fe+3].[Fe+3] JCDAAXRCMMPNBO-UHFFFAOYSA-N 0.000 claims description 3
- 229920002521 macromolecule Polymers 0.000 claims description 3
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 claims description 3
- 229910001935 vanadium oxide Inorganic materials 0.000 claims description 3
- 238000004435 EPR spectroscopy Methods 0.000 claims description 2
- 238000005481 NMR spectroscopy Methods 0.000 claims description 2
- 230000005540 biological transmission Effects 0.000 claims description 2
- 238000000572 ellipsometry Methods 0.000 claims description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims 1
- 238000000559 atomic spectroscopy Methods 0.000 claims 1
- AOWKSNWVBZGMTJ-UHFFFAOYSA-N calcium titanate Chemical compound [Ca+2].[O-][Ti]([O-])=O AOWKSNWVBZGMTJ-UHFFFAOYSA-N 0.000 claims 1
- ADCBYGNHJOLWLB-UHFFFAOYSA-N iron(2+) oxygen(2-) yttrium(3+) Chemical group [Y+3].[O-2].[Fe+2] ADCBYGNHJOLWLB-UHFFFAOYSA-N 0.000 claims 1
- 239000000523 sample Substances 0.000 description 161
- 102000004169 proteins and genes Human genes 0.000 description 77
- 108090000623 proteins and genes Proteins 0.000 description 77
- 235000018102 proteins Nutrition 0.000 description 76
- 239000000243 solution Substances 0.000 description 55
- 108010001441 Phosphopeptides Proteins 0.000 description 46
- 239000012148 binding buffer Substances 0.000 description 33
- 238000000576 coating method Methods 0.000 description 32
- 102000007982 Phosphoproteins Human genes 0.000 description 28
- 108010089430 Phosphoproteins Proteins 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000011248 coating agent Substances 0.000 description 24
- 239000000975 dye Substances 0.000 description 23
- 238000001914 filtration Methods 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000000872 buffer Substances 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 20
- 238000011534 incubation Methods 0.000 description 20
- 238000000151 deposition Methods 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000013459 approach Methods 0.000 description 18
- 238000003556 assay Methods 0.000 description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
- 238000000926 separation method Methods 0.000 description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 230000008021 deposition Effects 0.000 description 16
- 239000011159 matrix material Substances 0.000 description 16
- 230000026731 phosphorylation Effects 0.000 description 16
- 238000006366 phosphorylation reaction Methods 0.000 description 16
- 239000000758 substrate Substances 0.000 description 16
- XROWMBWRMNHXMF-UHFFFAOYSA-J titanium tetrafluoride Chemical compound [F-].[F-].[F-].[F-].[Ti+4] XROWMBWRMNHXMF-UHFFFAOYSA-J 0.000 description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 15
- 230000003993 interaction Effects 0.000 description 15
- 108010058846 Ovalbumin Proteins 0.000 description 14
- 229940092253 ovalbumin Drugs 0.000 description 14
- 210000002966 serum Anatomy 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 239000008367 deionised water Substances 0.000 description 13
- 229910021641 deionized water Inorganic materials 0.000 description 13
- 238000005406 washing Methods 0.000 description 13
- 102000001332 SRC Human genes 0.000 description 12
- 108060006706 SRC Proteins 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000005194 fractionation Methods 0.000 description 12
- 238000005755 formation reaction Methods 0.000 description 11
- 238000001819 mass spectrum Methods 0.000 description 11
- 108090000209 Carbonic anhydrases Proteins 0.000 description 10
- 102000003846 Carbonic anhydrases Human genes 0.000 description 10
- 108010015730 Proto-Oncogene Proteins pp60(c-src) Proteins 0.000 description 10
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 238000010586 diagram Methods 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
- 102000004142 Trypsin Human genes 0.000 description 9
- 108090000631 Trypsin Proteins 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 239000012149 elution buffer Substances 0.000 description 9
- 239000010408 film Substances 0.000 description 9
- 235000019253 formic acid Nutrition 0.000 description 9
- 239000007791 liquid phase Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- 239000012588 trypsin Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 229940098773 bovine serum albumin Drugs 0.000 description 8
- 229910021645 metal ion Inorganic materials 0.000 description 8
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 8
- 108091005981 phosphorylated proteins Proteins 0.000 description 8
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 7
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 7
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 239000002131 composite material Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 229920002401 polyacrylamide Polymers 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 239000000919 ceramic Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000002493 microarray Methods 0.000 description 6
- 239000002105 nanoparticle Substances 0.000 description 6
- 238000012856 packing Methods 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000000717 retained effect Effects 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 230000019491 signal transduction Effects 0.000 description 6
- 239000001632 sodium acetate Substances 0.000 description 6
- 235000017281 sodium acetate Nutrition 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 239000010936 titanium Substances 0.000 description 6
- 108091023037 Aptamer Proteins 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 5
- 239000012736 aqueous medium Substances 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 230000005284 excitation Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000007850 fluorescent dye Substances 0.000 description 5
- 238000001502 gel electrophoresis Methods 0.000 description 5
- 239000006249 magnetic particle Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 229920001155 polypropylene Polymers 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000012488 sample solution Substances 0.000 description 5
- 206010041232 sneezing Diseases 0.000 description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
- 238000001179 sorption measurement Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000010409 thin film Substances 0.000 description 5
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 4
- 102000011632 Caseins Human genes 0.000 description 4
- 108010076119 Caseins Proteins 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 4
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 101100403745 Mus musculus Myot gene Proteins 0.000 description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- 239000004793 Polystyrene Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000005349 anion exchange Methods 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000012159 carrier gas Substances 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 4
- 239000006148 magnetic separator Substances 0.000 description 4
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 229920002223 polystyrene Polymers 0.000 description 4
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 230000009822 protein phosphorylation Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
- 239000011534 wash buffer Substances 0.000 description 4
- 101000741065 Bos taurus Beta-casein Proteins 0.000 description 3
- RPIXXMOFBZXOQR-UHFFFAOYSA-N DND-160 dye Chemical compound C1=CC(OCC(=O)NCCN(C)C)=CC=C1C1=NC=C(C=2C=CN=CC=2)O1 RPIXXMOFBZXOQR-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoserine Chemical compound OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 238000002679 ablation Methods 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- WEUCVIBPSSMHJG-UHFFFAOYSA-N calcium titanate Chemical compound [O-2].[O-2].[O-2].[Ca+2].[Ti+4] WEUCVIBPSSMHJG-UHFFFAOYSA-N 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000033077 cellular process Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000005530 etching Methods 0.000 description 3
- 238000005187 foaming Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000000095 laser ablation inductively coupled plasma mass spectrometry Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000005291 magnetic effect Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000001254 matrix assisted laser desorption--ionisation time-of-flight mass spectrum Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000010339 medical test Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 230000006911 nucleation Effects 0.000 description 3
- 238000010899 nucleation Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 3
- 239000004417 polycarbonate Substances 0.000 description 3
- 229920000515 polycarbonate Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000005020 polyethylene terephthalate Substances 0.000 description 3
- 229920000139 polyethylene terephthalate Polymers 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000012723 sample buffer Substances 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000003381 solubilizing effect Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 229910001428 transition metal ion Inorganic materials 0.000 description 3
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- AFVLVVWMAFSXCK-UHFFFAOYSA-N α-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(C#N)=CC1=CC=C(O)C=C1 AFVLVVWMAFSXCK-UHFFFAOYSA-N 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- QGKMIGUHVLGJBR-UHFFFAOYSA-M (4z)-1-(3-methylbutyl)-4-[[1-(3-methylbutyl)quinolin-1-ium-4-yl]methylidene]quinoline;iodide Chemical compound [I-].C12=CC=CC=C2N(CCC(C)C)C=CC1=CC1=CC=[N+](CCC(C)C)C2=CC=CC=C12 QGKMIGUHVLGJBR-UHFFFAOYSA-M 0.000 description 2
- BQCIDUSAKPWEOX-UHFFFAOYSA-N 1,1-Difluoroethene Chemical compound FC(F)=C BQCIDUSAKPWEOX-UHFFFAOYSA-N 0.000 description 2
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- AIFLGMNWQFPTAJ-UHFFFAOYSA-J 2-hydroxypropanoate;titanium(4+) Chemical compound [Ti+4].CC(O)C([O-])=O.CC(O)C([O-])=O.CC(O)C([O-])=O.CC(O)C([O-])=O AIFLGMNWQFPTAJ-UHFFFAOYSA-J 0.000 description 2
- CDOWNLMZVKJRSC-UHFFFAOYSA-N 2-hydroxyterephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(O)=C1 CDOWNLMZVKJRSC-UHFFFAOYSA-N 0.000 description 2
- PKKJRWITDTTZCL-UHFFFAOYSA-N 2-methyl-2-nitrosopropane Chemical compound CC(C)(C)N=O.CC(C)(C)N=O PKKJRWITDTTZCL-UHFFFAOYSA-N 0.000 description 2
- ACMLKANOGIVEPB-UHFFFAOYSA-N 2-oxo-2H-chromene-3-carboxylic acid Chemical compound C1=CC=C2OC(=O)C(C(=O)O)=CC2=C1 ACMLKANOGIVEPB-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 239000004254 Ammonium phosphate Substances 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 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 2
- 239000005977 Ethylene Substances 0.000 description 2
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 2
- 101000609762 Gallus gallus Ovalbumin Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 102000008192 Lactoglobulins Human genes 0.000 description 2
- 108010060630 Lactoglobulins Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108010062374 Myoglobin Proteins 0.000 description 2
- 102000036675 Myoglobin Human genes 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 229910010413 TiO 2 Inorganic materials 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 235000012501 ammonium carbonate Nutrition 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 2
- 235000019289 ammonium phosphates Nutrition 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 238000007743 anodising Methods 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 239000013060 biological fluid Substances 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- YHWCPXVTRSHPNY-UHFFFAOYSA-N butan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCC[O-].CCCC[O-].CCCC[O-].CCCC[O-] YHWCPXVTRSHPNY-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
- 235000021240 caseins Nutrition 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- VYXSBFYARXAAKO-WTKGSRSZSA-N chembl402140 Chemical compound Cl.C1=2C=C(C)C(NCC)=CC=2OC2=C\C(=N/CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-WTKGSRSZSA-N 0.000 description 2
- 238000000224 chemical solution deposition Methods 0.000 description 2
- 238000005229 chemical vapour deposition Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 238000004042 decolorization Methods 0.000 description 2
- 230000001877 deodorizing effect Effects 0.000 description 2
- 229960003964 deoxycholic acid Drugs 0.000 description 2
- 230000030609 dephosphorylation Effects 0.000 description 2
- 238000006209 dephosphorylation reaction Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 229950006137 dexfosfoserine Drugs 0.000 description 2
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000000834 fixative Substances 0.000 description 2
- 238000001917 fluorescence detection Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052595 hematite Inorganic materials 0.000 description 2
- 239000011019 hematite Substances 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 238000009616 inductively coupled plasma Methods 0.000 description 2
- 229910052809 inorganic oxide Inorganic materials 0.000 description 2
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 2
- LIKBJVNGSGBSGK-UHFFFAOYSA-N iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Fe+3].[Fe+3] LIKBJVNGSGBSGK-UHFFFAOYSA-N 0.000 description 2
- 238000000608 laser ablation Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910000000 metal hydroxide Inorganic materials 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- IYSYLWYGCWTJSG-UHFFFAOYSA-N n-tert-butyl-1-phenylmethanimine oxide Chemical compound CC(C)(C)[N+]([O-])=CC1=CC=CC=C1 IYSYLWYGCWTJSG-UHFFFAOYSA-N 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- RFJIPESEZTVQHZ-UHFFFAOYSA-N oxirane;prop-2-enoic acid Chemical compound C1CO1.OC(=O)C=C RFJIPESEZTVQHZ-UHFFFAOYSA-N 0.000 description 2
- 230000005298 paramagnetic effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000005011 phenolic resin Substances 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 2
- USRGIUJOYOXOQJ-GBXIJSLDSA-N phosphothreonine Chemical compound OP(=O)(O)O[C@H](C)[C@H](N)C(O)=O USRGIUJOYOXOQJ-GBXIJSLDSA-N 0.000 description 2
- 230000010287 polarization Effects 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
- 229920005597 polymer membrane Polymers 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 229920000131 polyvinylidene Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 2
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 2
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000005546 reactive sputtering Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000026267 regulation of growth 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
- 229940043267 rhodamine b Drugs 0.000 description 2
- 239000010979 ruby Substances 0.000 description 2
- 229910001750 ruby Inorganic materials 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 238000003980 solgel method Methods 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005118 spray pyrolysis Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000004575 stone Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- 239000011573 trace mineral Substances 0.000 description 2
- 235000013619 trace mineral Nutrition 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 210000002268 wool Anatomy 0.000 description 2
- 235000021247 β-casein Nutrition 0.000 description 2
- YBEPDTOTOCUWHF-REOHCLBHSA-N (2r)-2-(phosphonoamino)-3-sulfanylpropanoic acid Chemical compound OC(=O)[C@H](CS)NP(O)(O)=O YBEPDTOTOCUWHF-REOHCLBHSA-N 0.000 description 1
- NVFHUBRALOJXMJ-REOHCLBHSA-N (2s)-2-(phosphonoamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NP(O)(O)=O NVFHUBRALOJXMJ-REOHCLBHSA-N 0.000 description 1
- KKGSCLRYTMKKLP-VKHMYHEASA-N (2s)-2-(phosphonoamino)pentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NP(O)(O)=O KKGSCLRYTMKKLP-VKHMYHEASA-N 0.000 description 1
- MOYPZVWCTBPWEH-YFKPBYRVSA-N (2s)-2-amino-3-(1-phosphonoimidazol-4-yl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CN(P(O)(O)=O)C=N1 MOYPZVWCTBPWEH-YFKPBYRVSA-N 0.000 description 1
- GWYFPBKINYGBFG-YFKPBYRVSA-N (2s)-2-amino-6-(phosphonoamino)hexanoic acid Chemical compound OC(=O)[C@@H](N)CCCCNP(O)(O)=O GWYFPBKINYGBFG-YFKPBYRVSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- JCAULFRGWRHHIG-UHFFFAOYSA-N 1-bromo-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-henicosafluorodecane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)Br JCAULFRGWRHHIG-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- NNKSRGUMPLVLGD-UHFFFAOYSA-N 2-[[2-(2-ethylbutoxy)-2,2-diphenylacetyl]-methylamino]ethyl-dimethylazanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1C(C(=O)N(C)CC[NH+](C)C)(OCC(CC)CC)C1=CC=CC=C1 NNKSRGUMPLVLGD-UHFFFAOYSA-N 0.000 description 1
- KXGFMDJXCMQABM-UHFFFAOYSA-N 2-methoxy-6-methylphenol Chemical compound [CH]OC1=CC=CC([CH])=C1O KXGFMDJXCMQABM-UHFFFAOYSA-N 0.000 description 1
- YPCHDSNALSYUDS-UHFFFAOYSA-N 2-phenylchromene-2,3,3,4,4-pentol Chemical compound OC1(O)C(O)(O)C2=CC=CC=C2OC1(O)C1=CC=CC=C1 YPCHDSNALSYUDS-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000206761 Bacillariophyta Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101000984310 Bos taurus Carbonic anhydrase 2 Proteins 0.000 description 1
- FSDBCCIUXPLUIE-UHFFFAOYSA-N C1=C(C(SS1)C(=O)O)[P+](=O)[O-] Chemical compound C1=C(C(SS1)C(=O)O)[P+](=O)[O-] FSDBCCIUXPLUIE-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 1
- 229910015372 FeAl Inorganic materials 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 241000134253 Lanka Species 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 239000012901 Milli-Q water Substances 0.000 description 1
- YXOLAZRVSSWPPT-UHFFFAOYSA-N Morin Chemical compound OC1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 YXOLAZRVSSWPPT-UHFFFAOYSA-N 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 description 1
- 108010068647 P2 peptide Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 101800004191 Peptide P2 Proteins 0.000 description 1
- QLZHNIAADXEJJP-UHFFFAOYSA-N Phenylphosphonic acid Chemical compound OP(O)(=O)C1=CC=CC=C1 QLZHNIAADXEJJP-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000002007 Proto-Oncogene Proteins pp60(c-src) Human genes 0.000 description 1
- 101710122944 Proto-oncogene tyrosine-protein kinase Src Proteins 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- NRCMAYZCPIVABH-UHFFFAOYSA-N Quinacridone Chemical compound N1C2=CC=CC=C2C(=O)C2=C1C=C1C(=O)C3=CC=CC=C3NC1=C2 NRCMAYZCPIVABH-UHFFFAOYSA-N 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical compound OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- GBXZONVFWYCRPT-KVTDHHQDSA-N [(2s,3s,4r,5r)-3,4,5,6-tetrahydroxy-1-oxohexan-2-yl] dihydrogen phosphate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](C=O)OP(O)(O)=O GBXZONVFWYCRPT-KVTDHHQDSA-N 0.000 description 1
- CUPCBVUMRUSXIU-UHFFFAOYSA-N [Fe].OOO Chemical compound [Fe].OOO CUPCBVUMRUSXIU-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010669 acid-base reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- 229950006790 adenosine phosphate Drugs 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000012801 analytical assay Methods 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001098 anti-algal effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 229910052787 antimony Inorganic materials 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 238000001479 atomic absorption spectroscopy Methods 0.000 description 1
- OXAUNDBQHKIUSD-UHFFFAOYSA-N azanium;titanium;fluoride Chemical compound [NH4+].[F-].[Ti] OXAUNDBQHKIUSD-UHFFFAOYSA-N 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000008364 bulk solution Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 239000011797 cavity material Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- VQWFNAGFNGABOH-UHFFFAOYSA-K chromium(iii) hydroxide Chemical compound [OH-].[OH-].[OH-].[Cr+3] VQWFNAGFNGABOH-UHFFFAOYSA-K 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 239000011246 composite particle Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012468 concentrated sample Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000002242 deionisation method Methods 0.000 description 1
- 230000015961 delipidation Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- SYELZBGXAIXKHU-UHFFFAOYSA-N dodecyldimethylamine N-oxide Chemical compound CCCCCCCCCCCC[N+](C)(C)[O-] SYELZBGXAIXKHU-UHFFFAOYSA-N 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000011209 electrochromatography Methods 0.000 description 1
- 238000000804 electron spin resonance spectroscopy Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- MEGHWIAOTJPCHQ-UHFFFAOYSA-N ethenyl butanoate Chemical compound CCCC(=O)OC=C MEGHWIAOTJPCHQ-UHFFFAOYSA-N 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- MSNWSDPPULHLDL-UHFFFAOYSA-K ferric hydroxide Chemical compound [OH-].[OH-].[OH-].[Fe+3] MSNWSDPPULHLDL-UHFFFAOYSA-K 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- 239000003302 ferromagnetic material Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000000198 fluorescence anisotropy Methods 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- DWYMPOCYEZONEA-UHFFFAOYSA-L fluoridophosphate Chemical compound [O-]P([O-])(F)=O DWYMPOCYEZONEA-UHFFFAOYSA-L 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- PHLYOKFVXIVOJC-UHFFFAOYSA-N gallein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C(O)=C1OC1=C(O)C(O)=CC=C21 PHLYOKFVXIVOJC-UHFFFAOYSA-N 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000011799 hole material Substances 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000012052 hydrophilic carrier Substances 0.000 description 1
- 239000012051 hydrophobic carrier Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 239000010842 industrial wastewater Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- 229910021519 iron(III) oxide-hydroxide Inorganic materials 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 238000011898 label-free detection Methods 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- YFVGRULMIQXYNE-UHFFFAOYSA-M lithium;dodecyl sulfate Chemical compound [Li+].CCCCCCCCCCCCOS([O-])(=O)=O YFVGRULMIQXYNE-UHFFFAOYSA-M 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000000504 luminescence detection Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000002923 metal particle Substances 0.000 description 1
- 229910052752 metalloid Inorganic materials 0.000 description 1
- 150000002738 metalloids Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 239000000983 mordant dye Substances 0.000 description 1
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
- 235000007708 morin Nutrition 0.000 description 1
- UNAFTICPPXVTTN-UHFFFAOYSA-N n-dodecyldodecan-1-amine;hydrobromide Chemical compound [Br-].CCCCCCCCCCCC[NH2+]CCCCCCCCCCCC UNAFTICPPXVTTN-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052758 niobium Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000000382 optic material Substances 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000002907 paramagnetic material Substances 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 238000010587 phase diagram Methods 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229920001568 phenolic resin Polymers 0.000 description 1
- FDIKHVQUPVCJFA-UHFFFAOYSA-N phosphohistidine Chemical compound OP(=O)(O)NC(C(=O)O)CC1=CN=CN1 FDIKHVQUPVCJFA-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000008039 phosphoramides Chemical class 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000001799 protein solubilization Methods 0.000 description 1
- 230000007925 protein solubilization Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 229960001327 pyridoxal phosphate Drugs 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000002964 rayon Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 239000012070 reactive reagent Substances 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000009834 selective interaction Effects 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004557 single molecule detection Methods 0.000 description 1
- 238000005245 sintering Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000010897 surface acoustic wave method Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- ZSYPIPFQOQGYHH-UHFFFAOYSA-N tetrahydroxyflavanol Natural products OC1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 ZSYPIPFQOQGYHH-UHFFFAOYSA-N 0.000 description 1
- 238000006863 thiophosphorylation reaction Methods 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- LLZRNZOLAXHGLL-UHFFFAOYSA-J titanic acid Chemical compound O[Ti](O)(O)O LLZRNZOLAXHGLL-UHFFFAOYSA-J 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- AYNNSCRYTDRFCP-UHFFFAOYSA-N triazene Chemical compound NN=N AYNNSCRYTDRFCP-UHFFFAOYSA-N 0.000 description 1
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- GRUMUEUJTSXQOI-UHFFFAOYSA-N vanadium dioxide Chemical compound O=[V]=O GRUMUEUJTSXQOI-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
- RUDFQVOCFDJEEF-UHFFFAOYSA-N yttrium(III) oxide Inorganic materials [O-2].[O-2].[O-2].[Y+3].[Y+3] RUDFQVOCFDJEEF-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
- 239000002888 zwitterionic surfactant Substances 0.000 description 1
- 229910006540 α-FeOOH Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/6818—Hybridisation assays characterised by the detection means involving interaction of two or more labels, e.g. resonant energy transfer
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/22—Affinity chromatography or related techniques based upon selective absorption processes
-
- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6842—Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/16—Phosphorus containing
- Y10T436/163333—Organic [e.g., chemical warfare agents, insecticides, etc.]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
- Y10T436/255—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.] including use of a solid sorbent, semipermeable membrane, or liquid extraction
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Genetics & Genomics (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Bioinformatics & Computational Biology (AREA)
- General Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
【選択図】図5
Description
本明細書に記載するテクノロジーは、サンプルからホスホ分子を単離する方法に関する。一つの態様では、該方法は、(a)ホスホ分子が、ホスホアフィニティ物質に結合して、ホスホ分子−ホスホアフィニティ物質複合体を形成することができる条件下で、サンプルを、水和金属酸化物を含むホスホアフィニティ物質と接触させる工程と、(b)該ホスホ分子−ホスホアフィニティ物質複合体を、該サンプルから分離し、それによって、ホスホ分子をサンプルから単離する工程を包含する。他の態様では、該方法は、(a)ホスホ分子が、ホスホアフィニティ物質に結合して、ホスホ分子−ホスホアフィニティ物質複合体を形成することができる条件下で、サンプルを、水和金属酸化物と担体を含むホスホアフィニティ物質と接触させる工程と、(b)該ホスホ分子−ホスホアフィニティ物質複合体からホスホ分子を溶離して、それによって、該ホスホ分子を該サンプルから単離する工程を包含する。これらの方法はさらに、ホスホ分子をホスホ分子−ホスホアフィニティ物質複合体から分離する工程を包含することができる。
本発明に記載するテクノロジーは、水和金属酸化物を含有するホスホアフィニティ物質を用いて、リン酸化分子を単離及び/又は検出するための方法、組成物及び商業的パッケージに関する。
ホスホペプチドを単離するためのアフィニティカラムは以下のように調製した:15〜25mgの酸化イットリウム(Aldrichカタログ番号205168−10)、イットリウム鉄ガーネット(Aldrichカタログ番号634417−10)または二酸化チタン(Aldrichカタログ番号634662−25)粒子を5インチの使い捨てカラム(Evergreen Scientific、Los Angeles、CA)へ充填した。各カラムを1%(v/v)のギ酸を含有する脱イオン水1mlで2回洗浄した。カラムの内容物をボルテックスミキサーを用いて断続的に混合した。次いで各カラムを結合緩衝液(0.5M酢酸ナトリウム、0.2M塩化ナトリウム、pH5.5)1mlで3回洗浄した。カラムの内容物をボルテックスミキサーを用いて断続的に混合した。
96穴濾過プレート形式のホスホアフィニティ物質は、以下のように調製した:約0.2gの二酸化チタン粒子を10mlの1%ギ酸中で10分間室温にて活性化させ、遠心分離を利用して脱イオン水で数回洗浄してビーズを回収した。予備洗浄したビーズを10mlの脱イオン水に再懸濁し、得られた懸濁液を200μl/ウェルにて96穴のMULTISCREEN DV(Millipore Corporation、Bedford、MA)プレートへピペッティングした。得られた二酸化チタン負荷プレートを、500mM酢酸ナトリウムpH5.5+200mM NaCl緩衝液(結合緩衝液)中でウェルを洗浄することにより予備平衡化させた。
酸化チタンを被覆/含浸させた膜を含むマルチウエルプレートを以下のように調製した:MULTISCREEN96穴(Millipore Corp.、Bedford、MA)プレートを、250μl/ウェルの無水エタノールで3回、次いで250μl/ウェルの脱イオン水(Milli−Q水、Millipore Corp.)で5回洗浄して清浄にした。プレートを60℃で30分間乾燥させた。
ホスホペプチド(P2P)と非リン酸化ペプチド(P2)とを含有する混合物からホスホペプチドを富化した。ペプチドは、先のサンプルで記載した通り、p60 c−srcペプチド(P2)とpp60 c−srcペプチド(P2P)とした。これらの検討には、P2およびP2Pの100μM水溶液を約16μlずつ混合し、結合緩衝液(20%アセトニトリル+20%イソプロパノール+0.1%ギ酸)で1:25に希釈した。得られたペプチドミックス溶液の半量をコレクションプレートの2つのウェルへさらに分注し、非分画陽性対照として除けておいた。ペプチドミックスサンプルの残りの半量を、二酸化チタン被覆MULTISCREEN96穴プレート(実施例4で調製した通り)上で以下のように分画した。等量のサンプルを2つの別個のウェルへ負荷した。二酸化チタンプレートを真空マニホールド中のコレクションプレートの上に乗せ、減圧をかけ(25mmHg未満)、ペプチド溶液を二酸化チタン被覆膜中を通過させ、未結合物質をいずれもコレクションプレートへ回収して分析した。陽性対照サンプルおよび未結合物質サンプルを60℃にて約30分間真空オーブンへ入れ、アセトニトリルとイソプロパノールを蒸発させてから、サンプルをC18 ZipPlate(Millipore、Bedford、MA)上で濃縮した。有機溶剤の蒸発後、濃縮サンプルを0.1%ギ酸で元の液量まで希釈した。二酸化チタン被覆膜上のサンプルを、180μlの結合緩衝液を用いて洗浄した。洗浄工程を5回繰り返した。サンプルを300μlの100mMリン酸アンモニウムpH8.5で溶離し、上述の通り真空マニホールドを用いてコレクションプレートに回収した。これらの実験では、リン酸化および非リン酸化形態のp60 c−src(521−533)ペプチド(以下、それぞれP2およびP2Pと略記)はSynPep Corporation、Dublin、CAより入手した。P2およびP2Pに対して予想されるm/z値は、それぞれ1463Daおよび1543Daである。
約400pmolのリン酸化(P2P)および非リン酸化(P2)合成ペプチドを20μlのヒト血清(Sigma)へ添加することにより、複合ホスホペプチド混合物を調製した。純粋な血清サンプルを陰性対照として使用した。2つのサンプルを本明細書中ではそれぞれ「スパイク(spiked)サンプル」および「非スパイク(non−spiked)サンプル」と呼ぶ。
トリプシン消化ウシβ−カゼインより生成した複合ペプチド混合物からホスホペプチドを単離した。約100μgのウシβ−カゼイン(100mM炭酸アンモニウム緩衝液中、pH8.5)を5μgのトリプシン(Sigma)で16時間消化した。ギ酸を3%の最終濃度まで添加して酵素反応を停止させた。5μlの消化物サンプルを結合緩衝液(実施例5参照)で20倍に希釈し、3種類のカゼイン消化物サンプルを調製した。得られたサンプルを、実施例5に記載の手順に従って、二酸化チタン被覆MULTISCREEN膜プレート上で分画し、分析した。二酸化チタン分画を行わずにZipPlate上で濃縮したサンプルと、カゼイン消化物をMALDI Chip上に直接スポットしたものを対照として使用した。
等重量のウシ血清アルブミン(BSA)、卵白アルブミン、炭酸脱水酵素、ミオグロビンおよびβ−ラクトグロブリンを組み合わせて5種タンパク質混合物(Pmix5)を調製した。Pmix5の原液を結合緩衝液(実施例5)で1:10に希釈した。サンプルの半量を同じく1%TRITON X100を含有する結合緩衝液で1:10に希釈し、タンパク質と二酸化チタンとの非特異的な相互作用を軽減した。
マルチウエルマイクロプレートと自動液体ハンドリング機器とを組み合わせることにより、薬物発見およびリード化合物のスクリーニングにおけるハイスループットサンプル処理のための簡便かつ有力なテクノロジープラットフォームを提供する。マイクロプレート/液体ハンドラープラットフォームにより、多数のサンプルまたはアッセイを同時並行的に処理することが可能となる。ポリスチレン製マルチウエルプレートは、当該プラスチックが正確な成形が容易であり、自動システムによるハンドリングに対して良好な剛性を示し、かつ、プレートの読み取りに必要な光学的透明度をもたらすため、多くの用途にとって一般的である。ポリプロピレン製プレートは、タンパク質および核酸に対する結合能がポリスチレンよりも低いため、ポリメラーゼ連鎖反応(PCR)を伴う用途で一般に採用されている。また、熱伝達を良くするため薄く成形することができる。マルチウエルマイクロプレートは、各種の機能性被膜(例えば、ビオチニル化分子を捕捉するためのストレプトアビジン)を備えたもの、並びに、目的の各種分子の精製を容易にするため基体に各種フィルターを装備したものが入手可能である。
以下に記載するのは、ホスホプロテインまたはホスホペプチド等のリン酸化ポリペプチドを、ホスホアフィニティ物質を用いてSDS−PAGEゲルにて検出するための代表的な手順である。その際、ホスホアフィニティ物質は、粒子または結晶形状の酸化イットリウム、イットリウム・アルミニウム・ガーネットまたは二酸化チタン等の水和金属酸化物である。標準的な手順に従い、タンパク質サンプルをSDS−ポリアクリルアミドゲル電気泳動で分離する。電気泳動後、酸とアルコールとを含有する溶液(例えば、50%メタノール、10%酢酸)中でゲルを固定し、次いで脱イオン水中で洗浄して固定剤溶液を除去する。次いでホスホアフィニティ粒子/結晶を含む溶液へゲルを添加し、2時間〜一晩室温で静かに振盪(即ち、オービタルシェーカーにて約50RPM)しながらインキュベートする。ホスホアフィニティ粒子を含む溶液には、ホスホアフィニティ粒子とホスホプロテインとの結合を容易にし、また、ゲルマトリックスまたはサンプル中の他のアニオン性巨大分子への非選択的結合を最小限に抑えるため、単純なアルコール、緩衝液、塩および/または酸が含まれていてもよい。結合時に使用したのと同様の組成の緩衝液でゲルを洗浄するが、溶液にはホスホアフィニティ粒子を配合しない。あるいは、ゲルを脱イオン水中でインキュベートする。次いで、ホスホアフィニティ粒子に選択的に結合する着色または蛍光色素を含有する溶液中でゲルをインキュベートする。選択した色素は、通常、タンパク質またはゲルマトリックスに対する結合力を殆ど持たないか、全く持たないものである。珪藻類に含まれるシリカに結合することが知られている蛍光色素の一つは、2−(4−ピリジル)−5−((4−(2−ジメチルアミノエチルアミノカルバモイル)メトキシ)フェニル)オキサゾール(PDMPO)であり、この化合物も他の金属酸化物と相互作用して蛍光レポーターとして機能し得る(Shimizuら、2001)。典型的には、スルホン化された色素はタンパク質に結合するため避けるが、低分子のスルホン化化合物を添加すれば、この非特異的相互作用を最小限に抑えることができる。次いでゲルを振盪しながら再度インキュベートし、過剰の色素を除去する。リン酸化ポリペプチドの検出は、目視観測で行うか、あるいは、UV式CCDカメラ検出システム、レーザー式ゲルスキャナー、キセノンアーク式CCDカメラ検出システム、UVトランスイルミネーターと組み合わせたポラロイドカメラ等のデバイス、または、着色もしくは蛍光部分の検出に使用される様々な他のデバイスを用いて行う。高分子膜(例えば、ニトロセルロース膜またはポリビニリデンジフルオリド膜)上に電気ブロットしたホスホプロテインを検出する際にも、同様のアプローチを採用する。一般に、ポリペプチドが検出試薬へ近づきやすくなるため、インキュベーション期間は転写膜の場合には短くなる。
ゲル中またはブロット上でのホスホプロテインまたはホスホペプチドの検出は、ホスホアフィニティ物質と、蛍光体で予め誘導体化しておいたサンプルとを併用することで実施可能である。その際、ホスホアフィニティ物質は、粒子または結晶形状の酸化イットリウム、イットリウム・アルミニウム・ガーネットまたは二酸化チタン等の水和金属酸化物である。タンパク質サンプルを標識する場合、シアニン色素であるCy2、Cy3およびCy5のスクシンイミジルエステルを用いて3種類もの異なる複合タンパク質集団を蛍光標識し、その後これらを混合し、ディファレンスゲル電気泳動(DIGE)(Unluら、1997)と呼ばれる方法を利用して同一の二次元ゲル上を同時に泳動させればよい。二次元ゲルの画像は、3種類もの異なる励起/発光フィルターを用いて取得し、それぞれ違った色を持つ蛍光シグナルの比率を利用してサンプル間のタンパク質の違いを見出す。DIGEにより、2〜3種類のサンプルを同一の電気泳動条件下で分離することが可能となり、ゲル画像の記録と整合の工程が簡略化される。このテクノロジーの応用の一つは、2種類のサンプル間(例えば、薬物処理細胞と対照細胞、または、患部組織と健常組織)の相違を調べることに利用されている。ゲルまたはブロットは、実施例10で上述したように、ホスホアフィニティ粒子中でインキュベート可能である。ある特定の粒子は、蛍光体で標識されたホスホプロテインからのシグナルを消すことができ、粒子とのインキュベーション前後でゲルから発生した蛍光プロファイルを比較することで、得られた2種類の画像の減法分析によりプロファイル中のどのタンパク質がリン酸化したかが判る。タンパク質に固有の蛍光(主にトリプトファンから生じる蛍光)を利用してタンパク質を可視化する場合(Roegenerら、2003)にも、同様のアプローチを使用することができる。
本実施例では、元素分析の分析アプローチのうちの一つである誘導結合プラズマ質量分析(ICP−MS)について記載する。ICP−MSを利用すると、1ppbもの低濃度金属イオンを検出することが可能である。第一イオン化電位が5.986電子ボルトであるアルミニウムのイオン化転化率は、WilburおよびMcCurdy、2001にリンについて記載されたのと同一の実施条件下では99%である。従って、リンの代わりにAl(III)を検出するのにWilburおよびMcCurdy、2001に概説された手順に従うと、検出は16倍向上する。また、金属を特異的に検出することによって、検出ウィンドウをサンプルのバックグラウンドシグナルから隔てることができる。
当該アッセイは、以下のように行う。リン酸化分子の結合パートナーをスポットとして固相担体の表面上に固定化する。結合パートナーは、例えば、抗体、ペプチド、アプタマー等であってよい。スポットは、異なる結合パートナーを含むものでもよく、同一スポットの繰り返しであってもよい。結合パートナーに結合可能なリン酸化分子を含有すると思われるサンプルを固相担体表面へ適用し、固相担体をインキュベートする。従来のマイクロアレイ型の担体と同様、インキュベーションは開放系でも、カバーガラス下でも、または、インキュベーション器具中でも行うことができる。インキュベーション後、サンプルを洗浄して固相担体から過剰の非選択的に結合したホスホアフィニティ粒子や他の分子を除去する。リン酸緩衝生理食塩水等の無機リン酸を含有する緩衝液は、通常避けるが、これは、ホスフェートがホスホアフィニティ粒子の結合と競合する結果、リン酸化分子に結合したホスホアフィニティ粒子の量が減ってしまうからである。
Claims (51)
- サンプルからホスホ分子を単離する方法であって、
(a)サンプルを、水和金属酸化物を含むホスホアフィニティ物質と、ホスホ分子がホスホアフィニティ物質に結合してホスホ分子−ホスホアフィニティ物質複合体を形成することができる条件下で、接触させる工程、この場合該水和金属酸化物はイットリウムを含む;及び
(b)該ホスホ分子−ホスホアフィニティ物質複合体を該サンプルから分離し、それによって、該ホスホ分子を該サンプルから単離する工程
を含む方法。 - サンプルからホスホ分子を単離する方法であって、
(a)サンプルを、水和金属酸化物と担体を含むホスホアフィニティ物質と、ホスホ分子がホスホアフィニティ物質に結合してホスホ分子−ホスホアフィニティ物質複合体を形成することができる条件下で、接触させる工程、この場合該水和金属酸化物はイットリウムを含む;及び
(b)該ホスホ分子−ホスホアフィニティ物質複合体からホスホ分子を溶離して、それによって、該ホスホ分子を該サンプルから単離する工程
を含む方法。 - 該ホスホ分子を該ホスホ分子−ホスホアフィニティ物質複合体から分離することをさらに含む、請求項1又は2に記載の方法。
- 溶離の前に、該ホスホ分子−ホスホアフィニティ物質複合体から未結合サンプル要素を除去することをさらに含む、請求項2記載の方法。
- サンプルからリン酸化ポリペプチドを単離する方法であって、
(a)サンプルを、水和金属酸化物と担体を含むホスホアフィニティ物質と、ホスホ分子がホスホアフィニティ物質に結合してホスホ分子−ホスホアフィニティ物質複合体を形成することができる条件下及び有機溶媒を含む液体媒質中で接触させる工程;
(b)該ホスホ分子−ホスホアフィニティ物質複合体からホスホ分子を溶離して、それによって、該ホスホ分子を該サンプルから単離する工程
を含む方法。 - 該液体媒質がイソプロパノールを含む、請求項5記載の方法。
- 該液体媒質がアセトニトリルを含む、請求項5記載の方法。
- 該溶離が界面活性剤の存在下で行なわれる、請求項5記載の方法。
- 該界面活性剤がイオン性界面活性剤である、請求項5記載の方法。
- サンプル中のホスホ分子を検出する方法であって、
(a)サンプルを、水和金属酸化物を含むホスホアフィニティ物質と、ホスホ分子がホスホアフィニティ物質に結合してホスホ分子−ホスホアフィニティ物質複合体を形成することができる条件下で接触させる工程;及び
(b)該ホスホ分子−ホスホアフィニティ物質複合体の形成を検出して、それによって、該サンプル中のホスホ分子を検出する工程
を含む方法。 - 該検出が、ホスホ分子とホスホアフィニティ物質との間の結合を測定することを含む、請求項10記載の方法。
- 該測定が、吸光度、透過、質量測定、蛍光強度、蛍光偏光、蛍光共鳴エネルギー転移、時間分解蛍光、共鳴光散乱、表面増強ラマン散乱、誘導結合プラズマ質量分光分析、電子常磁性共鳴、屈折率吸光度、核磁気共鳴、マイクロ熱量測定、フーリエ変換赤外分光分析、原子分光分析、表面プラズモン共鳴、屈折率変化、分光偏光測定及び偏光解析法の群から選択されるモードを含む、請求項10記載の方法。
- 該検出が、ホスホ分子−ホスホアフィニティ物質複合体のホスホアフィニティ物質部分を検出することを含む、請求項10記載の方法。
- ホスホアフィニティ物質部分の金属を検出する、請求項10記載の方法。
- 質量分光分析モードを用いて、該金属を検出する、請求項10記載の方法。
- 質量分光分析モードが誘導結合プラズマ質量分光分析である、請求項15記載の方法。
- 該検出前に、該ホスホアフィニティ物質を検出可能なタグで標識することをさらに含む、請求項10記載の方法。
- 該検出可能なタグが蛍光部分である、請求項17記載の方法。
- 該水和金属酸化物が、蛍光部分によって標識されている、請求項10記載の方法。
- 該検出が、ホスホ分子−ホスホアフィニティ物質複合体のホスホ分子部分を検出することを含む、請求項10記載の方法。
- 質量分光分析モードが、誘導結合プラズマ質量分光分析である、請求項10記載の方法。
- 該検出が、蛍光共鳴エネルギー転移を検出することを含む、請求項10記載の方法。
- 蛍光共鳴エネルギー転移が、ホスホ分子上の蛍光タグと、ホスホアフィニティ物質上の蛍光タグとの間で生ずる、請求項10記載の方法。
- 該水和金属酸化物が、酸化アルミニウム、酸化チタン、イットリウム鉄ガーネット、イットリウム・アルミニウム・ガーネット、イットリウム・ガリウム・ガーネット、酸化第二鉄、酸化ガリウム、酸化イットリウム、酸化バナジウム、酸化ジルコニウム、チタン酸鉄、アルミン酸鉄、チタン酸カルシウム、チタン酸ナトリウム、アルミン酸ジルコニウム、針鉄鉱、ギブス石、バイヤライト、ベーマイト、イルメナイト、イルメノルチル、シュードルチル、ルチル、ブロカイト、シュードブロカイト、ゲルキーライト、パイロファン石、エカンドリュウサイト、メラノスチバイト、アルマルコライト、スリランカイト及びアナターゼの群から選択される、請求項10記載の方法。
- 該水和金属酸化物が、酸化イットリウム、イットリウム鉄ガーネット及び二酸化チタンから成る群から選択される、請求項24記載の方法。
- 該水和金属酸化物が、酸化イットリウムである、請求項1、2、5又は10のいずれかに記載の方法。
- 該水和金属酸化物が、イットリウム鉄ガーネットである、請求項1、2、5又は10のいずれかに記載の方法。
- 該水和金属酸化物が、粒子形状である、請求項1、2、5又は10のいずれかに記載の方法。
- ホスホアフィニティ物質がさらに担体を含む、請求項1、2、5又は10のいずれかに記載の方法。
- 該担体が、粒子、ビーズ、ゲル、マトリックス、膜、フィルター、ファイバー、シート、メッシュ、フリット、樹脂、サンプル容器、カラム、ピペット先端、スライドチャンネル及びMALDI−TOFプレートの群から選択される、請求項1、2、5又は10のいずれかに記載の方法。
- 該担体が無機物質を含む、請求項1、2、5又は10のいずれかに記載の方法。
- 該担体が粒子である、請求項1、2、5又は10のいずれかに記載の方法。
- 該粒子がコロイド状金属を含む、請求項32記載の方法。
- 該担体が有機物質を含む、請求項1、2、5又は10のいずれかに記載の方法。
- 該担体がシートである、請求項1、2、5又は10のいずれかに記載の方法。
- 該シートがセルロースを含む、請求項35記載の方法。
- 該担体が検出可能なタグを含む、請求項1、2、5又は10のいずれかに記載の方法。
- 該ホスホ分子がマクロ分子である、請求項1、2、5又は10のいずれかに記載の方法。
- 該ホスホ分子がリン酸化ポリペプチドである、請求項1、2、5又は10のいずれかに記載の方法。
- サンプルが担体を含む、請求項1、2、5又は10のいずれかに記載の方法。
- サンプルが検出可能なタグを含む、請求項1、2、5又は10のいずれかに記載の方法。
- ホスホアフィニティ・ユニットを含む商業的パッケージであって、該ユニットが、水和金属酸化物で被覆された複数の担体シートを含むパッケージ。
- 該水和金属酸化物が酸化チタンである、請求項42記載の商業的パッケージ。
- 該担体シートが膜である、請求項43記載の商業的パッケージ。
- 該担体シートがセルロースを含む、請求項44記載の商業的パッケージ。
- 担体に付着した水和金属酸化物を含む商業的パッケージであって、該水和金属酸化物がイットリウムを含むパッケージ。
- 該水和金属酸化物が酸化イットリウムである、請求項46記載の商業的パッケージ。
- 該水和金属酸化物がイットリウム鉄酸化物である、請求項47記載の商業的パッケージ。
- 本明細書に記載するとおりの、サンプルからリン酸化分子を単離する方法。
- 本明細書に記載するとおりの、サンプルからリン酸化分子を検出する方法。
- 本明細書に記載するとおりの、リン酸化分子を単離する又は検出する方法を実施するための商業的パッケージ。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US52180404P | 2004-07-06 | 2004-07-06 | |
US60/521,804 | 2004-07-06 | ||
US64418105P | 2005-01-14 | 2005-01-14 | |
US60/644,181 | 2005-01-14 | ||
PCT/US2005/023810 WO2006014424A2 (en) | 2004-07-06 | 2005-07-06 | Methods and compositions for detecting and isolating phosphorylated molecules using hydrated metal oxides |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008506929A true JP2008506929A (ja) | 2008-03-06 |
JP4974297B2 JP4974297B2 (ja) | 2012-07-11 |
Family
ID=35787598
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007520439A Active JP4974297B2 (ja) | 2004-07-06 | 2005-07-06 | 水和金属酸化物を用いるリン酸化分子の検出と単離のための方法と組成物 |
Country Status (6)
Country | Link |
---|---|
US (1) | US8945932B2 (ja) |
EP (1) | EP1774276B1 (ja) |
JP (1) | JP4974297B2 (ja) |
AU (1) | AU2005269978B2 (ja) |
CA (1) | CA2611663C (ja) |
WO (1) | WO2006014424A2 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008309547A (ja) * | 2007-06-13 | 2008-12-25 | Hitachi High-Technologies Corp | 修飾ペプチドの分析方法および装置 |
JP2010538299A (ja) * | 2007-09-06 | 2010-12-09 | ウオーターズ・テクノロジーズ・コーポレイシヨン | 機能性高分子の単離方法 |
JP2015004659A (ja) * | 2013-06-20 | 2015-01-08 | 中國醫藥大學 | プレート表面上に二酸化チタンを有するプレート、その製造方法及び使用 |
US11640903B2 (en) | 2021-02-26 | 2023-05-02 | Kioxia Corporation | Analysis apparatus and analysis method |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7685737B2 (en) | 2004-07-19 | 2010-03-30 | Earthrenew, Inc. | Process and system for drying and heat treating materials |
US7024800B2 (en) | 2004-07-19 | 2006-04-11 | Earthrenew, Inc. | Process and system for drying and heat treating materials |
US20090053694A1 (en) * | 2005-12-26 | 2009-02-26 | Kriksunov Leo B | Photochemically Amplified Bioassay |
US7610692B2 (en) | 2006-01-18 | 2009-11-03 | Earthrenew, Inc. | Systems for prevention of HAP emissions and for efficient drying/dehydration processes |
US20070235390A1 (en) * | 2006-04-10 | 2007-10-11 | Boyes Barry E | Titanium-coated sorbents as a separation medium for HPLC of phosphorus-containing materials |
EP2013224A2 (en) * | 2006-04-27 | 2009-01-14 | Syddansk Universitet | Methods for isolation and analysis of sialylated and phosphorylated peptides |
WO2007127988A2 (en) | 2006-04-28 | 2007-11-08 | Perkinelmer Las, Inc. | Detecting phospho-transfer activity |
EP2135093B1 (en) * | 2007-04-16 | 2015-04-15 | Momenta Pharmaceuticals, Inc. | Analysis of phosphorylated glycans, glcopeptides or glycoproteins by imac |
WO2008148645A1 (en) * | 2007-06-07 | 2008-12-11 | Syddansk Universitet | Separation of mono- from multi-phoshorylated peptides |
US20090270278A1 (en) * | 2007-11-06 | 2009-10-29 | Ambergen, Inc. | Methods and compounds for making arrays |
WO2009152893A2 (de) * | 2008-05-26 | 2009-12-23 | Merck Patent Gmbh | Verfahren zur anreicherung von phosphorylierten und/oder glycosylierten analyten |
EP2558858B1 (en) * | 2010-04-13 | 2018-01-10 | Purdue Research Foundation | Reagents and methods for phosphorylation/dephosphorylation analyses |
IN2010CH01529A (ja) * | 2010-06-02 | 2015-08-07 | Indian Inst Technology | |
CN102399555B (zh) * | 2010-09-15 | 2013-07-24 | 海洋王照明科技股份有限公司 | 铝酸盐荧光粉及其制备方法 |
US10079139B2 (en) * | 2011-03-17 | 2018-09-18 | Kent J. Voorhees | Metal oxide laser ionization-mass spectrometry |
CN104168996B (zh) * | 2011-11-24 | 2017-03-15 | 印度理工学院 | 用于水纯化的多层有机模板化‑勃姆石‑纳米结构 |
MX362092B (es) | 2012-04-17 | 2019-01-07 | Indian Institute Of Tech | Deteccion del caudal de agua con clusteres cuanticos. |
KR101293968B1 (ko) * | 2012-05-30 | 2013-08-07 | 고려대학교 산학협력단 | 은 이온 검출용 올리고뉴클레오티드 고정 마이크로 오실레이터 및 이의 공진을 이용한 은 이온 검출방법 |
EP2971280B1 (en) * | 2013-03-15 | 2018-08-29 | Arizona Board of Regents on behalf of Arizona State University | Biosensor microarray compositions and methods |
US9171710B2 (en) * | 2013-09-16 | 2015-10-27 | The Board Of Trustees Of The University Of Alabama | Mass spectrometric analysis using nanoparticle matrices |
US9406490B1 (en) * | 2014-05-02 | 2016-08-02 | Elemental Scientific, Inc. | Determination of metal and metalloid concentrations using ICPMS |
CN108287155A (zh) * | 2017-01-10 | 2018-07-17 | 富士康(昆山)电脑接插件有限公司 | 一种高效检测铜合金中磷含量的方法 |
WO2019195878A1 (en) * | 2018-04-10 | 2019-10-17 | The University Of Sydney | Methods and kits for sample preparation for phosphoproteomics |
EP3775891A4 (en) * | 2018-04-13 | 2022-04-13 | Fluidigm Canada Inc. | STABILIZED CELL DETECTION FOR ELEMENTARY ANALYSIS |
CN108918512B (zh) * | 2018-06-08 | 2021-03-02 | 浙江方圆金属材料检测有限公司 | 一种不锈钢镍含量的检测试剂及检测方法 |
CN110128499A (zh) * | 2019-04-28 | 2019-08-16 | 北京谷海天目生物医学科技有限公司 | 磷酸化肽段富集的方法、检测和定量的方法 |
CN110082421A (zh) * | 2019-06-13 | 2019-08-02 | 中国科学院广州地球化学研究所 | 超微体积液体的激光剥蚀等离子质谱成分分析技术 |
CN112964507B (zh) * | 2021-02-01 | 2021-10-15 | 生态环境部南京环境科学研究所 | 一种集成式地下水淋溶液采集及分析用智能采集分析装置 |
CN115591531B (zh) * | 2022-09-05 | 2023-08-29 | 北方民族大学 | 一种含功能聚合物刷的磷酸化肽吸附剂及其制备与应用 |
CN116850990B (zh) * | 2023-04-28 | 2024-06-07 | 重庆工商大学 | 一种用于高效降解有机污染物的微波辅助改性尖晶石/多孔生物碳催化剂 |
CN117825129B (zh) * | 2024-03-04 | 2024-05-10 | 内蒙古工业大学 | 一种高温高压下测试同位素分馏的实验试件及方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003065031A1 (fr) * | 2002-01-31 | 2003-08-07 | Gl Sciences Incorporated | Procede et dispositif pour analyser de l'acide amine, un peptide, une proteine, une saccharide ou un lipide |
JP2004509638A (ja) * | 2000-09-29 | 2004-04-02 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | 脂質キナーゼの調節因子をスクリーニングするための方法および組成物 |
JP2005017013A (ja) * | 2003-06-24 | 2005-01-20 | Hitachi Maxell Ltd | 生体物質結合用磁性担体 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5395498A (en) * | 1991-11-06 | 1995-03-07 | Gombinsky; Moshe | Method for separating biological macromolecules and means therfor |
AUPP494798A0 (en) * | 1998-07-29 | 1998-08-20 | Pacific Biolink Pty Limited | Protective protein formulation |
JP2003179269A (ja) | 2001-01-24 | 2003-06-27 | Nichia Chem Ind Ltd | 光半導体素子 |
WO2004078724A1 (ja) | 2003-03-03 | 2004-09-16 | Kabushiki Kaisha Nard Kenkyusho | リン酸化ペプチドの標識方法および選択的吸着方法、該方法に使用される錯体化合物、該錯体化合物の製造方法、および該錯体化合物の原料化合物 |
DE10322701B4 (de) | 2003-05-20 | 2006-12-28 | Humboldt-Universität Zu Berlin | Probenträger unter Verwendung eines porösen, Metalloxidpartikel umfassenden Films, Verfahren zur Herstellung eines Probenträgers, Verwendung des Probenträgers sowie Verfahren zum selektiven Nachweis von phosphorylierten/sulfatierten Biopolymeren, insbesondere Peptiden/Proteinen |
US20050017525A1 (en) * | 2003-07-21 | 2005-01-27 | Douziech Maurice J. | Auxiliary handle assembly for hand tool |
WO2005123758A1 (en) * | 2004-06-14 | 2005-12-29 | Michigan State University | Method for the enrichment and characterization of phosphorylated peptides or proteins |
-
2005
- 2005-07-06 WO PCT/US2005/023810 patent/WO2006014424A2/en active Application Filing
- 2005-07-06 EP EP05857278.5A patent/EP1774276B1/en active Active
- 2005-07-06 US US11/571,687 patent/US8945932B2/en active Active
- 2005-07-06 JP JP2007520439A patent/JP4974297B2/ja active Active
- 2005-07-06 AU AU2005269978A patent/AU2005269978B2/en active Active
- 2005-07-06 CA CA2611663A patent/CA2611663C/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004509638A (ja) * | 2000-09-29 | 2004-04-02 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | 脂質キナーゼの調節因子をスクリーニングするための方法および組成物 |
WO2003065031A1 (fr) * | 2002-01-31 | 2003-08-07 | Gl Sciences Incorporated | Procede et dispositif pour analyser de l'acide amine, un peptide, une proteine, une saccharide ou un lipide |
JP2005017013A (ja) * | 2003-06-24 | 2005-01-20 | Hitachi Maxell Ltd | 生体物質結合用磁性担体 |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008309547A (ja) * | 2007-06-13 | 2008-12-25 | Hitachi High-Technologies Corp | 修飾ペプチドの分析方法および装置 |
JP2010538299A (ja) * | 2007-09-06 | 2010-12-09 | ウオーターズ・テクノロジーズ・コーポレイシヨン | 機能性高分子の単離方法 |
JP2015004659A (ja) * | 2013-06-20 | 2015-01-08 | 中國醫藥大學 | プレート表面上に二酸化チタンを有するプレート、その製造方法及び使用 |
US11640903B2 (en) | 2021-02-26 | 2023-05-02 | Kioxia Corporation | Analysis apparatus and analysis method |
Also Published As
Publication number | Publication date |
---|---|
AU2005269978B2 (en) | 2010-02-11 |
EP1774276A2 (en) | 2007-04-18 |
EP1774276A4 (en) | 2007-08-29 |
AU2005269978A1 (en) | 2006-02-09 |
JP4974297B2 (ja) | 2012-07-11 |
CA2611663C (en) | 2014-10-14 |
CA2611663A1 (en) | 2006-02-09 |
WO2006014424A2 (en) | 2006-02-09 |
EP1774276B1 (en) | 2017-06-07 |
WO2006014424A3 (en) | 2006-12-28 |
US20080261321A1 (en) | 2008-10-23 |
US8945932B2 (en) | 2015-02-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4974297B2 (ja) | 水和金属酸化物を用いるリン酸化分子の検出と単離のための方法と組成物 | |
Li et al. | Recent advances in phosphopeptide enrichment: strategies and techniques | |
Xu et al. | Metal oxides in sample pretreatment | |
US8574916B2 (en) | Melamine assay methods and systems | |
Han et al. | Development of phosphopeptide enrichment techniques for phosphoproteome analysis | |
JP4906725B2 (ja) | 試料提示器具 | |
Leitner et al. | Probing the phosphoproteome of HeLa cells using nanocast metal oxide microspheres for phosphopeptide enrichment | |
CA2565844C (en) | Methods for target molecule detection using siderophores and related compositions | |
WO2008148645A1 (en) | Separation of mono- from multi-phoshorylated peptides | |
US20100285596A1 (en) | Methods for isolating functionalized macromolecules | |
AU2005327173A1 (en) | Integration of direct binding sensors with mass spectrometry for functional and structural characterization of molecules | |
Mohammed et al. | Chip-based enrichment and NanoLC− MS/MS analysis of phosphopeptides from whole lysates | |
WO2016115256A1 (en) | Methods relating to improving accuracy of capture object-based assays | |
WO2001083825A2 (en) | Colloid compositions for solid phase biomolecular analytical systems | |
Regnier et al. | Accelerating trypsin digestion: the immobilized enzyme reactor | |
Stolowitz | On‐target and nanoparticle‐facilitated selective enrichment of peptides and proteins for analysis by MALDI‐MS | |
WO2014118778A1 (en) | Low fluorescence utensils | |
Zhang et al. | Robust dual-biomimetic titanium dioxide-cellulose monolith for enrichment of phosphopeptides | |
CN101014852B (zh) | 样品递呈装置 | |
Halvorsen et al. | The utility of molecularly imprinted polymers for mass spectrometric protein and proteomics analysis | |
Zheng et al. | Zirconium-cation-immobilized core/shell (Fe3O4@ Polymer) microspheres as an IMAC material for the selective enrichment of phosphopeptides | |
Salovska et al. | Enrichment strategies for phosphoproteomics: state-of-the-art | |
CN110596375A (zh) | 微孔板、基于微孔板的高灵敏度免疫荧光检测方法 | |
Smith et al. | Metal oxide formation by serine and cysteine proteases | |
Kayili et al. | Sol‐gel materials used in phosphoproteomics and glycoproteomics applications |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080509 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20101118 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101207 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110307 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110314 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110607 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20110914 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111114 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120214 |
|
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: 20120309 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120406 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4974297 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150420 Year of fee payment: 3 |
|
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 |
|
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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |