WO2022011313A1 - Modification of metallic surfaces with phosphonic acids - Google Patents
Modification of metallic surfaces with phosphonic acids Download PDFInfo
- Publication number
- WO2022011313A1 WO2022011313A1 PCT/US2021/041177 US2021041177W WO2022011313A1 WO 2022011313 A1 WO2022011313 A1 WO 2022011313A1 US 2021041177 W US2021041177 W US 2021041177W WO 2022011313 A1 WO2022011313 A1 WO 2022011313A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- metallic surface
- optionally substituted
- poly
- functionalized
- functionalized metallic
- Prior art date
Links
- 230000004048 modification Effects 0.000 title claims abstract description 58
- 238000012986 modification Methods 0.000 title claims abstract description 58
- 150000003009 phosphonic acids Chemical class 0.000 title description 4
- -1 phosphonate ester Chemical class 0.000 claims abstract description 416
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 267
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 126
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims abstract description 115
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 100
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 72
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims abstract description 58
- 229910052737 gold Inorganic materials 0.000 claims abstract description 58
- 239000010931 gold Substances 0.000 claims abstract description 58
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 50
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 49
- 239000010948 rhodium Substances 0.000 claims abstract description 49
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 48
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 46
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 46
- 239000000017 hydrogel Substances 0.000 claims description 132
- 229910052751 metal Inorganic materials 0.000 claims description 95
- 239000002184 metal Substances 0.000 claims description 95
- 239000000463 material Substances 0.000 claims description 87
- 229910052799 carbon Inorganic materials 0.000 claims description 76
- 125000005647 linker group Chemical group 0.000 claims description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 55
- 229920000642 polymer Polymers 0.000 claims description 52
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 45
- 125000002947 alkylene group Chemical group 0.000 claims description 44
- 239000000523 sample Substances 0.000 claims description 41
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 38
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 38
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 32
- 125000004450 alkenylene group Chemical group 0.000 claims description 29
- 125000004419 alkynylene group Chemical group 0.000 claims description 29
- 238000002493 microarray Methods 0.000 claims description 29
- 108020004707 nucleic acids Proteins 0.000 claims description 29
- 150000007523 nucleic acids Chemical class 0.000 claims description 29
- 102000039446 nucleic acids Human genes 0.000 claims description 29
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- 229910052710 silicon Inorganic materials 0.000 claims description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- 229920001600 hydrophobic polymer Polymers 0.000 claims description 27
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 26
- 230000003647 oxidation Effects 0.000 claims description 26
- 238000007254 oxidation reaction Methods 0.000 claims description 26
- 150000004820 halides Chemical class 0.000 claims description 25
- 238000010438 heat treatment Methods 0.000 claims description 24
- 229910004749 OS(O)2 Inorganic materials 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 23
- 150000001345 alkine derivatives Chemical class 0.000 claims description 23
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 23
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 23
- 125000003107 substituted aryl group Chemical group 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 22
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 22
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 21
- 150000001336 alkenes Chemical class 0.000 claims description 21
- 125000000129 anionic group Chemical group 0.000 claims description 21
- 150000001540 azides Chemical class 0.000 claims description 21
- 229910052719 titanium Inorganic materials 0.000 claims description 21
- 239000010936 titanium Substances 0.000 claims description 21
- 239000012445 acidic reagent Substances 0.000 claims description 20
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 20
- 239000010703 silicon Substances 0.000 claims description 20
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims description 19
- 229910052782 aluminium Inorganic materials 0.000 claims description 19
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 19
- 229910052742 iron Inorganic materials 0.000 claims description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 19
- 229910052726 zirconium Inorganic materials 0.000 claims description 19
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 18
- 125000002091 cationic group Chemical group 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 18
- 229940079593 drug Drugs 0.000 claims description 18
- 229920000193 polymethacrylate Polymers 0.000 claims description 18
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 18
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 17
- 150000002118 epoxides Chemical class 0.000 claims description 17
- 229910052725 zinc Inorganic materials 0.000 claims description 17
- 239000011701 zinc Substances 0.000 claims description 17
- 238000012377 drug delivery Methods 0.000 claims description 16
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
- 125000001165 hydrophobic group Chemical group 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 108090000623 proteins and genes Proteins 0.000 claims description 16
- 102000004169 proteins and genes Human genes 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 15
- 150000004676 glycans Chemical class 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 15
- 229920002401 polyacrylamide Polymers 0.000 claims description 15
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 13
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 13
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 13
- 229910052802 copper Inorganic materials 0.000 claims description 13
- 239000010949 copper Substances 0.000 claims description 13
- 150000002466 imines Chemical class 0.000 claims description 13
- 150000002576 ketones Chemical class 0.000 claims description 13
- 229910052759 nickel Inorganic materials 0.000 claims description 13
- 229920000765 poly(2-oxazolines) Polymers 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 150000001266 acyl halides Chemical class 0.000 claims description 12
- 238000000151 deposition Methods 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical class OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 11
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 229910052698 phosphorus Inorganic materials 0.000 claims description 11
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 11
- 229920000058 polyacrylate Polymers 0.000 claims description 11
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 150000003461 sulfonyl halides Chemical class 0.000 claims description 11
- 239000012620 biological material Substances 0.000 claims description 10
- 229910017052 cobalt Inorganic materials 0.000 claims description 10
- 239000010941 cobalt Substances 0.000 claims description 10
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 10
- 239000012948 isocyanate Substances 0.000 claims description 10
- 150000002513 isocyanates Chemical class 0.000 claims description 10
- 150000002540 isothiocyanates Chemical class 0.000 claims description 10
- 150000002923 oximes Chemical class 0.000 claims description 10
- 229920000233 poly(alkylene oxides) Polymers 0.000 claims description 10
- 229920001282 polysaccharide Polymers 0.000 claims description 10
- 239000005017 polysaccharide Substances 0.000 claims description 10
- 230000008685 targeting Effects 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 239000004698 Polyethylene Substances 0.000 claims description 9
- 229910052804 chromium Inorganic materials 0.000 claims description 9
- 239000011651 chromium Substances 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 9
- 239000002105 nanoparticle Substances 0.000 claims description 9
- 229920000573 polyethylene Polymers 0.000 claims description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 8
- 239000004743 Polypropylene Substances 0.000 claims description 8
- 239000004793 Polystyrene Substances 0.000 claims description 8
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 8
- 230000003373 anti-fouling effect Effects 0.000 claims description 8
- 239000011324 bead Substances 0.000 claims description 8
- 239000011859 microparticle Substances 0.000 claims description 8
- 238000009832 plasma treatment Methods 0.000 claims description 8
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 claims description 8
- 229920001155 polypropylene Polymers 0.000 claims description 8
- 229920002223 polystyrene Polymers 0.000 claims description 8
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 8
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 8
- 229910052709 silver Inorganic materials 0.000 claims description 8
- 239000004332 silver Substances 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 7
- 239000004599 antimicrobial Substances 0.000 claims description 7
- 238000001704 evaporation Methods 0.000 claims description 7
- 229920001451 polypropylene glycol Polymers 0.000 claims description 7
- 229920001291 polyvinyl halide Polymers 0.000 claims description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 6
- 229920002319 Poly(methyl acrylate) Polymers 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 229920002125 Sokalan® Polymers 0.000 claims description 6
- 229920006318 anionic polymer Polymers 0.000 claims description 6
- 125000000732 arylene group Chemical group 0.000 claims description 6
- 239000003124 biologic agent Substances 0.000 claims description 6
- 238000006664 bond formation reaction Methods 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 239000004020 conductor Substances 0.000 claims description 6
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 6
- 239000003779 heat-resistant material Substances 0.000 claims description 6
- 239000000696 magnetic material Substances 0.000 claims description 6
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 235000021317 phosphate Nutrition 0.000 claims description 6
- 229920003213 poly(N-isopropyl acrylamide) Polymers 0.000 claims description 6
- 229920001485 poly(butyl acrylate) polymer Polymers 0.000 claims description 6
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 6
- 229920000120 polyethyl acrylate Polymers 0.000 claims description 6
- 125000005717 substituted cycloalkylene group Chemical group 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 239000004952 Polyamide Substances 0.000 claims description 5
- 150000007942 carboxylates Chemical class 0.000 claims description 5
- 210000004027 cell Anatomy 0.000 claims description 5
- 230000000295 complement effect Effects 0.000 claims description 5
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 5
- 229930195729 fatty acid Natural products 0.000 claims description 5
- 239000000194 fatty acid Substances 0.000 claims description 5
- 150000004665 fatty acids Chemical class 0.000 claims description 5
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 5
- 229920002647 polyamide Polymers 0.000 claims description 5
- 229920000515 polycarbonate Polymers 0.000 claims description 5
- 239000004417 polycarbonate Substances 0.000 claims description 5
- 229920000728 polyester Polymers 0.000 claims description 5
- 150000003384 small molecules Chemical class 0.000 claims description 5
- 150000003871 sulfonates Chemical class 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- 108090001008 Avidin Proteins 0.000 claims description 4
- 238000001712 DNA sequencing Methods 0.000 claims description 4
- 239000004677 Nylon Substances 0.000 claims description 4
- 108010090804 Streptavidin Proteins 0.000 claims description 4
- 229960002685 biotin Drugs 0.000 claims description 4
- 235000020958 biotin Nutrition 0.000 claims description 4
- 239000011616 biotin Substances 0.000 claims description 4
- 229920006317 cationic polymer Polymers 0.000 claims description 4
- 239000004053 dental implant Substances 0.000 claims description 4
- 229910001092 metal group alloy Inorganic materials 0.000 claims description 4
- 229920001778 nylon Polymers 0.000 claims description 4
- 229920001059 synthetic polymer Polymers 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical class CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 3
- 239000003125 aqueous solvent Substances 0.000 claims description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 3
- 229940113088 dimethylacetamide Drugs 0.000 claims description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- 150000003738 xylenes Chemical class 0.000 claims description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 2
- 238000003559 RNA-seq method Methods 0.000 claims description 2
- 210000003463 organelle Anatomy 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- 150000001299 aldehydes Chemical class 0.000 claims 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 229920002939 poly(N,N-dimethylacrylamides) Polymers 0.000 claims 1
- 238000007306 functionalization reaction Methods 0.000 abstract description 16
- 230000002265 prevention Effects 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 description 62
- 125000004432 carbon atom Chemical group C* 0.000 description 54
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 29
- 125000000217 alkyl group Chemical group 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 23
- 239000000243 solution Substances 0.000 description 21
- 238000001878 scanning electron micrograph Methods 0.000 description 20
- 239000000758 substrate Substances 0.000 description 20
- 150000003254 radicals Chemical group 0.000 description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- 125000005842 heteroatom Chemical group 0.000 description 18
- 125000003118 aryl group Chemical group 0.000 description 17
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 14
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 11
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- 125000000753 cycloalkyl group Chemical group 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- 125000002950 monocyclic group Chemical group 0.000 description 9
- 229940070721 polyacrylate Drugs 0.000 description 9
- 238000006116 polymerization reaction Methods 0.000 description 9
- 0 CC(C)CC(C)(*(C)C)N Chemical compound CC(C)CC(C)(*(C)C)N 0.000 description 8
- 239000011230 binding agent Substances 0.000 description 8
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 8
- 125000001183 hydrocarbyl group Chemical group 0.000 description 8
- 238000006557 surface reaction Methods 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 239000003989 dielectric material Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 150000003007 phosphonic acid derivatives Chemical class 0.000 description 7
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 6
- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000007943 implant Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 150000002739 metals Chemical class 0.000 description 6
- 229940058401 polytetrafluoroethylene Drugs 0.000 description 6
- 229910000640 Fe alloy Inorganic materials 0.000 description 5
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 229910052796 boron Inorganic materials 0.000 description 5
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 229910052707 ruthenium Inorganic materials 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 125000004434 sulfur atom Chemical group 0.000 description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 5
- 229910000838 Al alloy Inorganic materials 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 229910001020 Au alloy Inorganic materials 0.000 description 4
- 229910000575 Ir alloy Inorganic materials 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 229910001252 Pd alloy Inorganic materials 0.000 description 4
- 229910001260 Pt alloy Inorganic materials 0.000 description 4
- 229910000629 Rh alloy Inorganic materials 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 229910001069 Ti alloy Inorganic materials 0.000 description 4
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 238000010560 atom transfer radical polymerization reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 238000010195 expression analysis Methods 0.000 description 4
- 239000003353 gold alloy Substances 0.000 description 4
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 150000002894 organic compounds Chemical class 0.000 description 4
- 229910052762 osmium Inorganic materials 0.000 description 4
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 4
- 125000003367 polycyclic group Chemical group 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 229910052718 tin Inorganic materials 0.000 description 4
- 125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- 108091023037 Aptamer Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 229910001297 Zn alloy Inorganic materials 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910052750 molybdenum Inorganic materials 0.000 description 3
- 239000011733 molybdenum Substances 0.000 description 3
- 229910052758 niobium Inorganic materials 0.000 description 3
- 239000010955 niobium Substances 0.000 description 3
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 239000011574 phosphorus Chemical group 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 230000003746 surface roughness Effects 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 125000000464 thioxo group Chemical group S=* 0.000 description 3
- 239000011135 tin Substances 0.000 description 3
- 229910052720 vanadium Inorganic materials 0.000 description 3
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 3
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 description 2
- IEVADDDOVGMCSI-UHFFFAOYSA-N 2-hydroxybutyl 2-methylprop-2-enoate Chemical compound CCC(O)COC(=O)C(C)=C IEVADDDOVGMCSI-UHFFFAOYSA-N 0.000 description 2
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 2
- GNSFRPWPOGYVLO-UHFFFAOYSA-N 3-hydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCO GNSFRPWPOGYVLO-UHFFFAOYSA-N 0.000 description 2
- YGTVWCBFJAVSMS-UHFFFAOYSA-N 5-hydroxypentyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCO YGTVWCBFJAVSMS-UHFFFAOYSA-N 0.000 description 2
- XFOFBPRPOAWWPA-UHFFFAOYSA-N 6-hydroxyhexyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCO XFOFBPRPOAWWPA-UHFFFAOYSA-N 0.000 description 2
- CPDZIKHNXVPGST-UHFFFAOYSA-N 7-hydroxyheptyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCCO CPDZIKHNXVPGST-UHFFFAOYSA-N 0.000 description 2
- YPMOAQISONSSNL-UHFFFAOYSA-N 8-hydroxyoctyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCCCO YPMOAQISONSSNL-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241001082241 Lythrum hyssopifolia Species 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 150000003926 acrylamides Chemical class 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 230000000739 chaotic effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000005518 electrochemistry Effects 0.000 description 2
- 238000005868 electrolysis reaction Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 125000000262 haloalkenyl group Chemical group 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000000232 haloalkynyl group Chemical group 0.000 description 2
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- UACSZOWTRIJIFU-UHFFFAOYSA-N hydroxymethyl 2-methylprop-2-enoate Chemical group CC(=C)C(=O)OCO UACSZOWTRIJIFU-UHFFFAOYSA-N 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 150000003057 platinum Chemical class 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 238000010526 radical polymerization reaction Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000004439 roughness measurement Methods 0.000 description 2
- 238000004626 scanning electron microscopy Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229910052715 tantalum Inorganic materials 0.000 description 2
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- 125000006732 (C1-C15) alkyl group Chemical group 0.000 description 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- 125000006833 (C1-C5) alkylene group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 description 1
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 description 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- OQJVXNHMUWQQEW-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrazine Chemical compound C1CNC=CN1 OQJVXNHMUWQQEW-UHFFFAOYSA-N 0.000 description 1
- JQIZHNLEFQMDCQ-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridazine Chemical compound C1CC=CNN1 JQIZHNLEFQMDCQ-UHFFFAOYSA-N 0.000 description 1
- OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
- QYMGRIFMUQCAJW-UHFFFAOYSA-N 1,2-dihydropyrazine Chemical compound C1NC=CN=C1 QYMGRIFMUQCAJW-UHFFFAOYSA-N 0.000 description 1
- BKWQKVJYXODDAC-UHFFFAOYSA-N 1,2-dihydropyridazine Chemical compound N1NC=CC=C1 BKWQKVJYXODDAC-UHFFFAOYSA-N 0.000 description 1
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 1
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000005987 1-oxo-thiomorpholinyl group Chemical group 0.000 description 1
- SBFNQWAMVLRANY-UHFFFAOYSA-N 11-(2-bromo-2-methylpropanoyl)oxyundecylphosphonic acid Chemical compound CC(C)(Br)C(=O)OCCCCCCCCCCCP(O)(O)=O SBFNQWAMVLRANY-UHFFFAOYSA-N 0.000 description 1
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 1
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
- FJRPOHLDJUJARI-UHFFFAOYSA-N 2,3-dihydro-1,2-oxazole Chemical compound C1NOC=C1 FJRPOHLDJUJARI-UHFFFAOYSA-N 0.000 description 1
- YTQQIHUQLOZOJI-UHFFFAOYSA-N 2,3-dihydro-1,2-thiazole Chemical compound C1NSC=C1 YTQQIHUQLOZOJI-UHFFFAOYSA-N 0.000 description 1
- RZQQXRVPPOOCQR-UHFFFAOYSA-N 2,3-dihydro-1,3,4-oxadiazole Chemical compound C1NN=CO1 RZQQXRVPPOOCQR-UHFFFAOYSA-N 0.000 description 1
- ZABMHLDQFJHDSC-UHFFFAOYSA-N 2,3-dihydro-1,3-oxazole Chemical compound C1NC=CO1 ZABMHLDQFJHDSC-UHFFFAOYSA-N 0.000 description 1
- OYJGEOAXBALSMM-UHFFFAOYSA-N 2,3-dihydro-1,3-thiazole Chemical compound C1NC=CS1 OYJGEOAXBALSMM-UHFFFAOYSA-N 0.000 description 1
- LWTIGYSPAXKMDG-UHFFFAOYSA-N 2,3-dihydro-1h-imidazole Chemical compound C1NC=CN1 LWTIGYSPAXKMDG-UHFFFAOYSA-N 0.000 description 1
- KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical compound C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 description 1
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-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
- BOLMDIXLULGTBD-UHFFFAOYSA-N 3,4-dihydro-2h-oxazine Chemical compound C1CC=CON1 BOLMDIXLULGTBD-UHFFFAOYSA-N 0.000 description 1
- NWWJFMCCTZLKNT-UHFFFAOYSA-N 3,4-dihydro-2h-thiazine Chemical compound C1CC=CSN1 NWWJFMCCTZLKNT-UHFFFAOYSA-N 0.000 description 1
- ATVJJNGVPSKBGO-UHFFFAOYSA-N 3,4-dihydro-2h-thiopyran Chemical compound C1CSC=CC1 ATVJJNGVPSKBGO-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- XDLMVUHYZWKMMD-UHFFFAOYSA-N 3-trimethoxysilylpropyl 2-methylprop-2-enoate Chemical compound CO[Si](OC)(OC)CCCOC(=O)C(C)=C XDLMVUHYZWKMMD-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 1
- WEDKTMOIKOKBSH-UHFFFAOYSA-N 4,5-dihydrothiadiazole Chemical compound C1CN=NS1 WEDKTMOIKOKBSH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- OSDLLIBGSJNGJE-UHFFFAOYSA-N 4-chloro-3,5-dimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1Cl OSDLLIBGSJNGJE-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- 108700042778 Antimicrobial Peptides Proteins 0.000 description 1
- 102000044503 Antimicrobial Peptides Human genes 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 1
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 229920000144 PEDOT:PSS Polymers 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005870 benzindolyl group Chemical group 0.000 description 1
- 125000005873 benzo[d]thiazolyl group Chemical group 0.000 description 1
- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000005878 benzonaphthofuranyl group Chemical group 0.000 description 1
- 125000005872 benzooxazolyl group Chemical group 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229960005443 chloroxylenol Drugs 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229920001940 conductive polymer Polymers 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- ZPWOOKQUDFIEIX-UHFFFAOYSA-N cyclooctyne Chemical compound C1CCCC#CCC1 ZPWOOKQUDFIEIX-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000005509 dibenzothiophenyl group Chemical group 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 229940042400 direct acting antivirals phosphonic acid derivative Drugs 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical group C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical group FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 229920002313 fluoropolymer Polymers 0.000 description 1
- 239000004811 fluoropolymer Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000003844 furanonyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- KFZAUHNPPZCSCR-UHFFFAOYSA-N iron zinc Chemical compound [Fe].[Zn] KFZAUHNPPZCSCR-UHFFFAOYSA-N 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000011133 lead Substances 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- AWIJRPNMLHPLNC-UHFFFAOYSA-N methanethioic s-acid Chemical compound SC=O AWIJRPNMLHPLNC-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Chemical group C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 238000001020 plasma etching Methods 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000075 poly(4-vinylpyridine) Polymers 0.000 description 1
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 1
- 229920001977 poly(N,N-diethylacrylamides) Polymers 0.000 description 1
- 229920001584 poly(acrylomorpholines) Polymers 0.000 description 1
- 229920000548 poly(silane) polymer Polymers 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 229910052706 scandium Inorganic materials 0.000 description 1
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 description 1
- 229920005573 silicon-containing polymer Polymers 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- 238000010301 surface-oxidation reaction Methods 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- DNYWZCXLKNTFFI-UHFFFAOYSA-N uranium Chemical compound [U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U] DNYWZCXLKNTFFI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C22/00—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals
- C23C22/02—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using non-aqueous solutions
- C23C22/03—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using non-aqueous solutions containing phosphorus compounds
Definitions
- Surface modification of a material may be used to achieve different interfacial properties of the material.
- antibacterial layers, corrosion resistant layers, or anti -biofouling layers may be incorporated onto the surface of medical devices designed to be implanted in the body.
- reagents, methods, and compositions which fulfill a need for new and improved methods of functionalizing metallic surfaces, including platinum and gold surfaces.
- the metallic surface is a platinum-group metal.
- the reagents, methods, and compositions can be used to functionalize palladium, iridium, or rhodium surfaces.
- the reagents, methods and compositions can be used to add various functionalities onto metallic surfaces through the formation of a metallic phosphonate bond between a phosphonic acid or phosphonate ester and the metallic surface.
- the phosphonic acid or phosphonate comprises a reactive group or capture moiety that enable the addition of further materials to the metallic surface, such as additional surface modification groups (e.g. hydrogels) or other functional moieties (e.g. binding agents such as peptides or oligonucleotides).
- the phosphonic acid or phosphonate comprises the desired surface modification group (e.g. without the need for conducting another reaction to add the desired group).
- the metallic surface is a platinum surface, or an oxide thereof.
- the metallic surface is a gold surface, or an oxide thereof.
- the metallic surface is a palladium surface, or an oxide thereof.
- the metallic surface is an iridium surface, or an oxide thereof.
- the metal surface is a rhodium surface, or an oxide thereof.
- the reagents, methods and compositions of the present disclosure are especially suited to allow for precise control of the addition of various functionalities onto metallic surfaces, including platinum, gold, palladium, iridium, rhodium, or an oxide thereof.
- the materials provided herein allow for facile functionalization of the surfaces with a controlled amount of reagent that forms a stable bond with the metallic surface.
- the ease of synthesis, robustness of protocols for synthesis, and stability of metal phosphonate bonds allow for easy and controlled further functionalization of the surface. In some embodiments, this allows for robust protocols to be developed for addition of further surface functionalization groups in a manner that allows for control of fine characteristics.
- hydrogels with finely tunable characteristics can be allowed to polymerize upon a metallic surface functionalized with the reagents provided herein.
- the reagents and protocols provided herein yield predictable results, fine tuning of the hydrogel characteristics, such as density, thickness, cross-linking density, grafting density, functional groups, or conductivity, can be performed. Similar processes can be used to develop robust protocols for functionalization with any other surface modification group.
- hydrogel materials suitable for grafting on to metallic surfaces in order to prevent biofouling on the surface.
- Such hydrogels are particularly useful when deployed on electrodes and other electrokinetic devices that produce electric fields in proximity to biological samples, as the presence of a hydrogel layer can prevent destruction of the sample and accumulation of degraded sample on the electrode surface.
- certain fine characteristics for example, density, thickness, and conductivity
- these hydrogels may also be linked to other metal surfaces capable of forming bonds with phosphonates, including without limitation silicon, aluminum, titanium, iron, zinc, zirconium, nickel, silver, copper, cobalt, or chromium.
- a functionalized metallic surface comprising a metallic surface bound to a molecule having the structure: wherein
- R is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; and wherein the metallic surface comprises at least one metal selected from platinum, gold, palladium, iridium, and rhodium, an oxide thereof, or any combination thereof.
- R has the structure X-L-, wherein L is a linking moiety and X is a reactive handle or capture moiety, or R has the structure Y-L-, wherein L is a linking moiety and Y is a surface modification group.
- L is an optionally substituted alkylene chain or optionally substituted heteroalkylene chain.
- L has the structure of formula:
- each R 1 and R 2 is independently H or optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl, or R 1 and R 2 on the same atom are taken together to form an oxo, or R 1 s on adjacent atoms are taken together to form a double bond, or R 1 s and R 2 s on adjacent atoms are taken together to from a triple bond; each Z is independently absent, -O-, -NR 3 -, -S-, -SS-, -S(O)-, -S(O) 2 -, -C(O)-, -C(O)O-, - C(O)NR 3 , -OC(O)O-, -NR 3 C(O)NR 3 -, -OC(O)NR 3 -, -OC(O)NR 3 -, -OC(O)NR
- L comprises one or more subunits selected from wherein each n is independently an integer from 1-30.
- L comprises the structure: wherein each n is independently an integer from 1-30; and each p is independently an integer from
- L comprises a polymer.
- the polymer comprises a polyethylene, a polypropylene, a polyvinyl halide, a polystyrene, a nylon, a polyamide, a polyester, a polyaramide, a polyacrylate, a poly methacrylate, a poly tetrafluoroethylene, a polysaccharide, a poly(alkylene oxide), a poly(vinyl pyrrolidone), a poly(vinyl alcohol), a polyoxazoline, a poly(acryloylmorpholine), or any combination or derivative thereof.
- R has the structure X-L-.
- X comprises a reactive functional group selected from an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, acid, activated ester, alkene, alcohol, halide, acyl halide, sulfonic acid, sulfmic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, oxime, isocyanate, isothiocyanate, hydrazine, and hydrazide, or any combination thereof.
- X has the structure:
- Z x is a bond, -O-, -NR 4 -, -S-, -SS-, -S(O)-, S(O) 2 -, -C(O)-, -C(O)O-, -C(O)NR 4 , - OC(O)O-, -NR 4 C(O)NR 4 -, -OC(O)NR 4 -, -S(O) 2 O-, -S(O) 2 NR 4 ., -OS(O) 2 O-, - NR 4 S(O) 2 NR 4 -, or -OS(O) 2 NR 4 -;
- L x is absent, optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted arylalkylene, optionally substituted heteroarylalkylene, optionally substituted arylheteroalkylene, or optionally substituted heteroarylheteroalkylene;
- X 1 comprises an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, carboxylic acid, activated ester, alkene, alcohol, acyl halide, sulfonic acid, sulfmic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, oxime, isocyanate, isothiocyanate, hydrazine, or hydrazide; and each R 4 is independently H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl.
- L x has the structure -(CR 5 R 6 ) r -, wherein each R 5 and R 6 is independently H, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl, or R 5 and R 6 on the same atom are taken together to form an oxo, or R 5 s on adjacent atoms are taken together to form a double bond, or R 5 s and R 6 s on adjacent atoms are taken together to from a triple bond; and r is an integer from 0-30.
- X 1 comprises an amine, carboxylic acid, maleimide, azide
- X is wherein
- R 5 and R 6 are each independently H or C 1 -C 3 alkyl; r is 0 or 1; and
- X 1 is azide, alkyne, halide, alkene, or sulfhydryl.
- X is In some embodiments, X comprises a capture moiety selected from biotin, avidin, streptavidin, a nucleic acid, a peptide, and a protein, or any combination thereof.
- kits comprising a functionalized metallic surface provided herein and instructions for use.
- R has the structure Y-L-.
- Y comprises a surface modification group selected from hydrophobic residues, hydrophilic residues, charged residues, cationic residues, anionic residues, polysaccharides, hydrophobic polymers, hydrophilic polymers, antimicrobial agents, biological materials, biocompatibility materials, anti-fouling materials, conductivity materials, semi-conductive materials, heat resistant materials, anti-corrosive material, catalysts, and magnetic materials, or any combination thereof.
- Y has the structure Y 4 -L Y -Z y -, wherein Z Y is a bond, -O-, -NR 4 -, -S-, -SS-, -S(O)-, S(O) 2 -, -C(O)-, -C(O)O-, -C(O)NR 4 , - OC(O)O-, -NR 4 C(O)NR 4 -, -OC(O)NR 4 -, -S(O) 2 O-, -S(O) 2 NR 4 ., -OS(O) 2 O-, -NR 4 S(O) 2 NR 4 - , -OS(O) 2 NR 4 -, or reaction product formed by a covalent bond forming reaction between an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine,
- L Y is absent, optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted arylalkylene, optionally substituted heteroarylalkylene, optionally substituted arylheteroalkylene, or optionally substituted heteroarylheteroalkylene;
- Y 1 comprises at least one surface modification residue; and each R 4 is independently H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl.
- Z Y is a bond, -O-, -NR 4 -, -S-, -SS-, -S(O)-, S(O) 2 -, -C(O)-, - C(O)O-, -C(O)NR 4 -, -OC(O)O-, -NR 4 C(O)NR 4 -, -OC(O)NR 4 -, -S(O) 2 O-, -S(O) 2 NR 4 -, -OS(O) 2 O-, -
- L Y is absent. In some embodiments,
- Y 1 comprises hydrophobic residues.
- the hydrophobic residues comprise a hydrophobic polymer.
- the hydrophobic polymer comprises polyethylene, polypropylene, polystyrene, polyvinylhalide, polytetrafluoroethylene, polymethylmethacrylate, polycarbonate, polyether-urethane, polydimethylsiloxane, or any combination or derivative thereof.
- the hydrophobic residues comprise fatty acids or derivatives thereof.
- Y 1 comprises hydrophilic residues.
- the hydrophilic residues comprise a hydrophilic polymer.
- the hydrophilic polymer comprises a polyacrylamide, a polyacrylate, a poly methacrylate, a poly(alkylene oxide), a poly(vinyl pyrrolidone), a poly(vinyl alcohol), a polyoxazoline, a poly(N-acryloyl morpholine), or any combination of derivative thereof.
- the hydrophilic polymer comprises polyacrylamide, poly(diethyl acrylamide), poly(dimethyl acrylamide), poly(N-isopropylacrylamide), poly(acrylic acid), poly(methacrylic acid) poly(methyl acrylate), poly(ethyl acrylate), poly(2- hydroxyethyl acrylate), poly(propyl acrylate), poly(butyl acrylate), poly(methyl methacrylate), poly(2-hydroxyethyl methacrylate), poly(tetrahydrofurfuryl methacrylate), poly(ethylene oxide), poly(propylene oxide), poly(vinyl pyrrolidone), polyoxazoline, poly(2-ethyloxazoline), or poly(N- acryloyl morpholine).
- Y comprises the structure: wherein each R 7 is independently H, optionally substituted C 1 -C 3 alkyl or optionally substituted C 1 -C 3 hydroxy alkyl; each R 8 is independently H or C 1 -C 3 alkyl; each X 7 is independently absent, -O-, -S-, or -NR 9 ; each R 9 is independently H or C 1 -C 6 alkyl; and s is an integer from 1 to 10000.
- Y 1 comprises cationic residues. In some embodiments, Y 1 comprises a cationic polymer. In some embodiments, the cationic residues comprise protonated amine groups, protonated substituted amine groups, quaternary amine groups, or any combination thereof. In some embodiments, Y 1 comprises anionic residues. In some embodiments, Y 1 comprises an anionic polymer. In some embodiments, the anionic residues comprise carboxylates, sulfonates, sulfmates, phosphates, phosphonates, or any combination thereof.
- the surface modification group comprises hydrophobic residues, hydrophilic residues, charged residues, cationic residues, anionic residues, polysaccharides, hydrophobic polymers, hydrophilic polymers, antimicrobial agents, biological materials, biocompatibility materials, anti-fouling materials, conductivity materials, semi-conductive materials, heat resistant materials, anti-corrosive material, catalysts, magnetic materials, or any combination thereof.
- the surface modification group comprises a hydrogel.
- the hydrogel comprises an acrylate, a methacrylate, an acrylamide, or a methacrylamide, or any combination thereof.
- the hydrogel has a thickness from about 0.001 micron to about 10 microns. In some embodiments, wherein the hydrogel has a conductivity from about 0.1 S/m to about 10 S/m.
- At least about 1%, at least about 2%, at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% of the metallic surface is functionalized.
- the metallic surface is at least partially oxidized.
- at least about 1%, at least about 2%, at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% of the metallic surface is oxidized.
- the metallic surface comprises a metal alloy.
- the metal alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% of the metal by weight.
- the metallic surface comprises the metal and an additional material.
- the metal surface comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% of the metal or any oxide of the metal by weight.
- the metal surface is configured to be placed inside the body of a mammal.
- the metal surface is a surgical or dental implant.
- the metal surface is an electrode, a microchip, a bead, a microparticle, or a nanoparticle.
- the metal is platinum or gold, or an oxide thereof. In some embodiments, the metal is palladium, iridium, or rhodium, or an oxide thereof.
- a method of functionalizing a metallic surface comprising (a) depositing a phosphonic acid or phosphonate ester reagent on a metallic surface; and (b) heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metal surface; wherein the metallic surface comprises platinum, gold, palladium, iridium, or rhodium, an oxide thereof, or any combination thereof.
- depositing the phosphonic acid or phosphonate ester reagent comprises contacting the metallic surface with a solution comprising the phosphonic acid reagent and a solvent.
- the solvent comprises an organic solvent, an aqueous solvent, or any combination or mixture thereof.
- the organic solvent comprises acetic acid, acetone, acetonitrile, benzene, tert-butyl alcohol, tert-butyl methyl ether, carbon tetrachloride, chloroform, cyclohexane, 1,2-dichloroethane, di chi orom ethane, diethyl ether, diglyme, 1,2,- dimethoxyethane, dimethyl acetamide, dimethylformamide, dimethyl sulfoxide, dioxane, ethanol, ethyl acetate, ethyl methyl ketone, ethylene glycol, hexanes, hexamethylphosphoramide, methanol, nitromethane, pentanes, 2-proponal, pyridine, tetrahydrofuran, toluene, xylenes, or any combination thereof.
- the organic solvent comprises ethanol, tetrahydrofuran, or
- the phosphonic acid or phosphonate ester reagent is present in the solution at a concentration of up to about 1 ⁇ M, 10 ⁇ M, 100 ⁇ M, 1 mM, 10 mM, 100 mM, or 1 M.
- depositing the phosphonic acid or phosphonate ester reagent further comprises evaporating the solvent from the metallic surface.
- evaporating the solvent from the metallic surface comprises heating the metallic surface.
- the metallic surface is heated at a temperature of at least 30°C, at least 40°C, at least 50°C, at least 60°C, at least 70°C, at least 80°C, or at least 90°C.
- heating the metallic surface to bind the phosphonic acid reagent with the metallic surface occurs in an oven, a vacuum oven, or a microwave reactor. In some embodiments, heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metallic surface comprises heating the metallic surface to a temperature of at least 30°C, at least 50°C, at least 70°C, at least 80°C, at least 100°C, at least 120°C, at least 140°C, at least 160°C, or at least 180°C. [0030] In some embodiments, the metallic surface is an oxidized metallic surface.
- the oxidized metallic surface is oxidized by air oxidation, plasma treatment, ultraviolet-ozone oxidation, or chemical oxidation.
- the method further comprises the step of oxidizing the metallic surface.
- oxidizing the metallic surface comprises plasma treatment, ultraviolet-ozone oxidation, or chemical oxidation.
- the phosphonic acid or phosphonate ester reagent has the structure: wherein
- R is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; and each R E is independently H or optionally substituted alkyl.
- the metallic surface comprises platinum or gold, or an oxide thereof. In some embodiments, the metallic surface comprises palladium, iridium, or rhodium, or an oxide thereof.
- a metallic surface microarray comprising a probe moiety bound to the metallic surface through a phosphonate residue, wherein the metallic surface comprises platinum, gold, palladium, iridium, or rhodium, or an oxide thereof, or any combination thereof.
- the bound phosphonate residue has the structure: wherein R comprises the probe moiety and each indicates a point of attachment to the surface.
- the probe moiety comprises a nucleic acid, a peptide, a protein, an antibody, a small molecule, a glycan, or any combination thereof.
- the probe moiety comprises a nucleic acid.
- the nucleic acid comprises DNA or RNA.
- the microarray is configured for DNA or RNA sequencing.
- the probe moiety binds a biological agent.
- the biological agent is a nucleic acid, a protein, a cell, or an organelle.
- the probe moiety is specific for a biological agent.
- the microarray comprises at least 10, at least 100, at least 1000, at least 10000, or at least 100000 unique probe features.
- the metallic surface microarray comprises platinum or gold, or an oxide thereof.
- the metallic surface microarray comprises palladium, iridium, or rhodium, an oxide thereof, or any combination thereof.
- a drug delivery device comprising a drug moiety linked to a surface of the device through a phosphonate residue, wherein the surface comprises platinum, gold, palladium, iridium, or rhodium, an oxide thereof, or a combination thereof.
- the phosphonate residue has the structure: wherein R comprises the drug moiety and each indicates a point of attachment to the surface.
- the drug moiety is linked to the phosphonate residue through a linker.
- the linker is a cleavable linker.
- the linker is configured to release the drug moiety.
- the drug delivery device further comprises a targeting moiety.
- the targeting moiety comprises an antibody or antibody fragment, a peptide, or a nucleic acid.
- the drug delivery device is a nanoparticle, a microparticle, or a bead.
- the surface comprises platinum or gold, an oxide thereof, or a combination thereof.
- the surface comprises palladium, iridium, or rhodium, an oxide thereof, or a combination thereof.
- a functionalized metallic surface comprising a metallic surface bound to a molecule having the structure: wherein R comprise a hydrogel.
- the metallic surface comprises platinum, gold, palladium, iridium, rhodium, silicon, aluminum, titanium, iron, zinc, zirconium, nickel, silver, copper, cobalt, or chromium, or an oxide thereof, or any combination thereof.
- the hydrogel has a conductivity from about 0.001 S/m to about 10 S/m. In some embodiments, the hydrogel has a thickness from about 0.001 microns to about 10 microns. In some embodiments, the hydrogel comprises a synthetic polymer. In some embodiments, the hydrogel comprises an acrylamide polymer. In some embodiments, the acrylamide polymer comprises an N-substituted acrylamides, an N-substituted methacrylamides, or a methacrylamide, or any combination thereof.
- the hydrogel comprises polyacrylamide, poly(diethyl acrylamide), poly(dimethylacrylamide), poly(N-isopropylacrylamide), poly(acrylic acid), poly(methacrylic acid), poly(methyl acrylate), poly(ethyl acrylate), poly(2-hydroxyethyl acrylate), poly(propyl acrylate), poly(butyl acrylate), poly(methyl methacrylate), poly(2- hydroxyethyl methacrylate), poly(tetrahydrofurfuryl methacrylate), poly(ethylene oxide), poly(propylene oxide), poly(vinyl pyrrolidone), polyoxazoline, poly(2-ethyloxazoline), or poly(N- acryloyl morpholine).
- the metallic surface is an electrode. In some embodiments, the metallic surface is positions on an exterior surface of an electrode.
- FIG. 1A shows an example reaction of a phosphonic acid reagent with a metallic surface.
- FIG. 1B shows two exemplary binding modes of phosphonate modified metallic surfaces.
- FIG. 2 shows an example workflow for modifying metallic surfaces.
- FIG. 3A shows X-ray photoelectron spectroscopy measurements of oxidized and untreated platinum chips.
- FIG. 3B shows oxidation states of oxidized and untreated platinum chips measured by X- ray photoelectron spectroscopy.
- FIG. 4 shows optical profilometer measurements of a bare platinum electrode without functionalization.
- FIG. 5 shows optical profilometer measurements of a platinum electrode functionalized with a phosphonic acid reagent.
- FIG. 6A shows a scanning electron microscopy (SEM) image of a platinum electrode surrounded by dielectric material at a tilt angle of 45°.
- FIG. 6B shows an SEM image of a functionalized platinum electrode followed by a polymerization reaction.
- FIG. 7 shows an SEM image of a polymer functionalized platinum electrode at a tilt angle of 0°.
- FIG. 8 shows an SEM image of a polymer functionalized platinum electrode at a tilt angle of 14°.
- FIG. 9 shows an SEM image of a polymer functionalized platinum electrode at a tilt angle of 14°.
- FIG. 10 shows an SEM image of a polymer functionalized platinum electrode at a tilt angle of 14°.
- FIG. 11 shows an SEM image of non-functionalized platinum surface at a tilt angle of 1°.
- FIG. 12 shows an SEM image of non-functionalized platinum surface at a tilt angle of 45°.
- FIG. 13 shows an SEM image of non-functionalized platinum surface at a tilt angle of 4°.
- FIG. 14 shows an SEM image of non-functionalized platinum surface at a tilt angle of 45°.
- the reagents comprise phosphonic acids or phosphonic acid derivatives (e.g. phosphonate esters).
- the metallic surfaces include platinum and gold surfaces, or oxides thereof.
- the metallic surface is platinum surface or an oxide thereof.
- the metallic surface is a gold surface or an oxide thereof.
- the metallic surface is palladium, iridium, or rhodium surface, or an oxide thereof.
- the metallic surface is a palladium surface or an oxide thereof.
- the metallic surface is an iridium surface or an oxide thereof.
- the metallic surface is a rhodium surface or an oxide thereof.
- the phosphonic acid or derivative thereof comprises the desired surface modification group.
- the phosphonic acid or derivative thereof comprises a reactive handle for adding on the desired surface modification group after modification with the phosphonic acid or derivative thereof.
- the phosphonic acid or derivative thereof comprises a capture moiety for attaching another group, such as a biological binding moiety (e.g. a peptide or oligonucleotide).
- FIG. 1A An example of a metallic surface modified according to the present invention in shown in FIG. 1A, which shows an example reactant and the corresponding product bound to the metallic surface (e.g. a platinum surface).
- the phosphonic acid reagent forms a metal phosphonate bond with the metallic surface and has one of the binding modes shown in FIG. 1B.
- the modified metallic surfaces are useful as anti-fouling surfaces for electrodes in electrophoresis-based assays. In some embodiments, these anti-fouling surfaces employ hydrogel layers. In some embodiments, the modified metallic surfaces are useful for implantation into living bodies. In some embodiments, the modified metallic surfaces have anti-corrosive properties compared to unmodified metallic surfaces. In some embodiments, the modified metallic surfaces are useful for the creation of active surfaces capable of binding analytes (e.g. in biological capture assays).
- a functionalized metallic surface is oxidized.
- the metallic surface comprises platinum or gold, or an oxide thereof, or a combination thereof.
- the metallic surface comprises platinum, or an oxide thereof.
- the metallic surface comprises gold, or an oxide thereof.
- the metallic surface comprises palladium, iridium, or rhodium, or an oxide thereof.
- the metallic surface comprises palladium, or an oxide thereof.
- the metallic surface comprises iridium, or an oxide thereof.
- the metallic surface comprises rhodium, or an oxide thereof.
- the metallic surface is a platinum or gold surface, or an oxide thereof. In some embodiments, the metallic surface is a platinum surface, or an oxide thereof. In some embodiments, the metallic surface is a gold surface, or an oxide thereof. In some embodiments, the metallic surface is a palladium, iridium, or rhodium, or an oxide thereof. In some embodiments, the metallic surface is a palladium surface, or an oxide thereof. In some embodiments, the metallic surface is an iridium surface, or an oxide thereof. In some embodiments, the metallic surface is a rhodium surface, or an oxide thereof. In some embodiments, the modified metallic surface is bound to a phosphonate moiety.
- the phosphonate moiety is directly bound to the metallic surface. In some embodiments, the phosphonate moiety forms a bond with the metallic surface. In some embodiments, the phosphonate moiety forms a covalent bond with the metallic surface.
- the metallic surface is bound to a phosphonate moiety.
- the phosphonate moiety is a metal phosphonate.
- the surface bound phosphonate moiety is prepared from a phosphonic acid reagent or a phosphonic acid derivative.
- the phosphonic acid derivative is a phosphonate ester.
- the phosphonate ester is a C 1 -C 6 alkyl phosphonate ester.
- the phosphonate ester is a methyl or ethyl phosphonate ester.
- the phosphonic acid or phosphonate ester reagent is a bisphosphonic acid or bisphosphonate (e.g. a 1,1 bisphosphonic acid).
- a functionalized metallic surface comprising a metallic surface bound to a molecule having the structure:
- the functionalized metallic surface comprises a metallic surface bound to a molecule as shown in FIG. 1B.
- each indicates a point of attachment to the metallic surface.
- one or more is a point of attachment to the metallic surface.
- each is a point of attachment to the metallic surface.
- described herein is an R moiety bound to a metallic surface through a phosphonate residue.
- the metallic surface comprises platinum or an oxide thereof.
- the metallic surface comprises gold or an oxide thereof.
- the metallic surface comprises palladium or an oxide thereof.
- the metallic surface comprises iridium or an oxide thereof.
- the metallic surface comprises rhodium or an oxide thereof.
- the metallic surface is oxidized.
- R of the formula shown above can be any group.
- R is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, or optionally substituted heteroaryl.
- R is optionally substituted alkyl or optionally substituted heteroalkyl.
- R directly comprises the desired surface modification.
- R comprises hydrophobic residues, hydrophilic residues, charged residues, cationic residues, anionic residues, polysaccharides, hydrophobic polymers, hydrophilic polymers, antimicrobial agents, biological materials, biocompatibility materials, anti-fouling materials, conductivity materials, semi-conductive materials, heat resistant materials, anti-corrosive material, catalysts, or magnetic materials, or any combination thereof.
- R comprises an oligonucleotide or a polypeptide.
- R comprises a hydrogel.
- the surface modification group is tethered to the phosphonate group through a linking moiety.
- the linking moiety can be any suitable group capable of providing an attachment of the surface modification group to the phosphonate moiety.
- the linking moiety has the structure -L-, wherein L comprises an optionally substituted alkylene chain or an optionally substituted heteroalkylene chain. In some embodiments, the linking moiety comprises an optionally substituted alkylene chain. In some embodiments, the linking moiety comprises an unsubstituted alkylene chain. In some embodiments, the linking moiety comprises an optionally substituted heteroalkylene chain. In some embodiments, the linking moiety comprises an unsubstituted heteroalkylene chain. In some embodiments, the linking moiety comprises a chain of one to one hundred atoms. In some embodiments, the linking moiety comprises a chain of one to fifty atoms.
- the linking moiety comprises a chain of one to forty atoms. In some embodiments, the linking moiety comprises a chain of one to twenty atoms. In some embodiments, the linking moiety comprises a chain of five to one hundred atoms. In some embodiments, the linking moiety comprises a chain of five to fifty atoms. In some embodiments, the linking moiety comprises a chain of five to forty atoms. In some embodiments, the linking moiety comprises a chain of five to twenty atoms. In some embodiments, the linking moiety comprises a chain of ten to one hundred atoms. In some embodiments, the linking moiety comprises a chain of ten to fifty atoms. In some embodiments, the linking moiety comprises a chain of ten to forty atoms. In some embodiments, the linking moiety comprises a chain of ten to twenty atoms.
- each atom in the chain is independently selected from C, N, O, S, Si, and P. In some embodiments, each atom in the chain is independently selected from C, N, O, and S. In some embodiments, each atom in the chain is independently selected from C, N, and O. In some embodiments, the first atom in the chain is C.
- L has the structure of formula:
- each R 1 and R 2 is independently H or optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl, or R 1 and R 2 on the same atom are taken together to form an oxo, or R 1 s on adjacent atoms are taken together to form a double bond, or R 1 s and R 2 s on adjacent atoms are taken together to from a triple bond; each Z is independently absent, -O-, -NR 3 -, -S-, -SS-, -S(O)-, -S(O) 2 -, -C(O)-, -C(O)O-, - C(O)NR 3 , -OC(O)O-, -NR 3 C(O)NR 3 -, -OC(O)NR 3 -, -OC(O)NR 3 -, -OC(O)NR
- each R 1 and R 2 is independently H, optionally substituted alkyl, optionally substituted heteroalkyl, or R 1 and R 2 on the same atom are taken together to form an oxo, or R 3 S on adjacent atoms are taken together to form a double bond, or R's and R 2 s on adjacent atoms are taken together to from a triple bond.
- each R 1 and R 2 is independently H, optionally substituted alkyl, R 1 and R 2 on the same atom are taken together to form an oxo, or R 1 s on adjacent atoms are taken together to form a double bond.
- each R 1 and R 2 is independently H, optionally substituted alkyl, R 1 and R 2 on the same atom are taken together to form an oxo, or R 1 s on adjacent atoms are taken together to form a double bond.
- each R 1 and R 2 is independently H, optionally substituted alkyl, or R 1 and R 2 on the same atom are taken together to form an oxo.
- each R 1 and R 2 is independently H, optionally substituted C 1 -C 10 alkyl, or R 1 and R 2 on the same atom are taken together to form an oxo.
- each R 1 and R 2 is independently H, optionally substituted alkyl, or R 1 and R 2 on the same atom are taken together to form an oxo. In some embodiments, each R 1 and R 2 is independently H, Ci-Cio alkyl optionally substituted with hydroxy or alkoxy, or R 1 and R 2 on the same atom are taken together to form an oxo. In some embodiments, each R 1 and R 2 is independently H or R 1 and R 2 on the same atom are taken together to form an oxo. In some embodiments, each R 1 and R 2 is H.
- each Z is independently absent, -O-, -NR 3 -, -S-, -C(O)-, -C(O)O-, -C(O)NR 3 , -OC(O)O-, -NR 3 C(O)NR 3 -, or -OC(O)NR 3 -.
- each Z is independently.
- each Z is independently absent, -O-, -NR 3 -, -C(O)O-, or - C(O)NR 3 .
- each Z is independently absent, -O-, -C(O)O-, or -C(O)NR 3 .
- each Z is independently -O-, -C(O)O-, or -C(O)NR 3 . In some embodiments, each Z is -O-. In some embodiments, each Z is -C(O)O-, or -C(O)NR 3 . In some embodiments, each Z is - C(O)NR 3 .
- each R 3 is independently H, optionally substituted alkyl, or optionally substituted cycloalkyl. In some embodiments, each R 3 is independently H or optionally substituted alkyl. In some embodiments each R 3 is independently H or C 1 -C 6 alkyl optionally substituted with hydroxy or alkoxy. In some embodiments, each R 3 is independently H or methyl.
- each n is independently an integer from 1 to 20 In some embodiments, each n is independently an integer from 1 to 15 In some embodiments, each n is independently an integer from 1 to 10 In some embodiments, each n is independently an integer from 2 to 30 In some embodiments, each n is independently an integer from 2 to 20 In some embodiments, each n is independently an integer from 2 to 15 In some embodiments, each n is independently an integer from 2 to 10.
- m is an integer from 1 to 25 In some embodiments, m is an integer from 1 to 20 In some embodiments, m is an integer from 1 to 15 In some embodiments, m is an integer from 1 to 10 In some embodiments, m is an integer from 1 to 5 In some embodiments, m is an integer from 2 to 30 In some embodiments, m is an integer from 2 to 25 In some embodiments, m is an integer from 2 to 20 In some embodiments, m is an integer from 2 to 15 In some embodiments, m is an integer from 2 to 10 In some embodiments, m is an integer from 2 to 5
- L may comprise one or more subunit building blocks. In some embodiments, L comprises one or more subunits selected from and wherein each n is independently an integer from 1-30. In some embodiments, L comprises one or more subunits selected from and In some embodiments, L comprises one or more subunits selected from and In some embodiments, L comprises one or more subunits selected from and
- L comprises the structure or wherein each n is independently an integer from 1-30; and each p is independently an integer from 1-30. In some embodiments, L has the structure or wherein each n is independently an integer from 1-30; and each p is independently an integer from 1-30. In some embodiments, L has the structure or O
- L has the structure
- p is an integer from 1 to 20 In some embodiments, p is an integer from 1 to 15 In some embodiments, p is an integer from 1 to 10 In some embodiments, p is an integer from 1 to 5 In some embodiments, p is an integer from 2 to 30 In some embodiments, p is an integer from 2 to 20 In some embodiments, p is an integer from 2 to 15 In some embodiments, p is an integer from 2 to 10 In some embodiments, p is an integer from 2 to 5
- L comprises a polymer. Any polymer may be used for the linking moiety L.
- the polymer may be branched or linear.
- the polymer comprises a polyethylene, a polypropylene, a polyvinyl halide, a polystyrene, a nylon, a polyamide, a polyester, a polyaramide, a polyacrylate, a poly methacrylate, a poly tetrafluoroethylene, a polysaccharide, a poly(alkylene oxide), a poly(vinyl pyrrolidone), a poly(vinyl alcohol), a polyoxazoline, a poly(N- acryloyl morpholine), or any combination or derivative thereof.
- the polymer comprises a polyethylene, a nylon, a polyamide, a polyester, a polyacrylate, a poly methacrylate, a poly(alkylene oxide), a poly(vinyl pyrrolidone), a poly(vinyl alcohol), or any combination or derivative thereof.
- the polymer comprises a polyamide, a polyester, a polyacrylate, a poly methacrylate, a poly(alkylene oxide), or any combination or derivative thereof.
- the polymer comprises a poly(alkylene oxide).
- the polymer comprises polyethylene glycol.
- the polymer comprises a poly methacrylate.
- the poly methacrylate is a hydroxyalkyl methacrylate. In some embodiments, the poly methacrylate is a C 1 -C20 hydroxyalkyl methacrylate. In some embodiments, the poly methacrylate is hydroxymethyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, hydroxypentyl methacrylate, hydroxyhexyl methacrylate, hydroxyheptyl methacrylate, or hydroxyoctyl methacrylate.
- L comprises a cleavable linker.
- the linking moiety comprises a cleavable linker. Any cleavable linker may be used with the present invention.
- the cleavable linker is a photocleavable linker, a chemically cleavable linker, or an enzyme cleavable linker.
- the linking moiety may be used to link the phosphonate moiety to a reactive handle.
- the reactive handle is configured to allow the additional of additional surface functionalization reagents.
- CLICK chemistry reagents are one example of compatible reactive handles. Any suitable reactive group may be used.
- the reactive handle is represented by X.
- R has the structure X-L-, wherein L is any of the linking moieties provided herein.
- X comprises a reactive functional group. Any suitable functional group may be employed for this purpose.
- X comprises a reactive functional group selected from an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, acid, activated ester, alkene, alcohol, halide, acyl halide, sulfonic acid, sulfmic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, oxime, isocyanate, isothiocyanate, hydrazine, and hydrazide, or any combination thereof.
- X comprises a reactive functional group selected from an azide, alkyne, sulfhydryl, maleimide, activated ester, halide, acyl halide, epoxide, aldehyde, and ketone, or any combination thereof.
- X comprises a reactive functional group selected from an azide, alkyne, sulfhydryl, maleimide, halide, and epoxide, or any combination thereof.
- X comprises an azide.
- X comprises an alkyne.
- X comprises a cyclooctyne.
- X comprises a dibenzolcyclooctyne. In some embodiments, X comprises a maleimide. In some embodiments, X comprises a halide. In some embodiments, X comprises an epoxide. In some embodiments, X comprises a sulfhydryl. In some embodiments, X comprises a carboxylic acid. In some embodiments,
- X comprises an amine. In some embodiments, X comprises an alkene. In some embodiments, X comprises a CLICK chemistry reagent.
- X has the structure X 1 -L x -ZX x - , wherein
- Z x is a bond, -O-, -NR 4 -, -S-, -SS-, -S(O)-, S(O) 2 -, -C(O)-, -C(O)O-, -C(O)NR 4 , -OC(O)O-, - NR 4 C(O)NR 4 -, -OC(O)NR 4 -, -S(O) 2 O-, -S(O) 2 NR 4 ., -OS(O) 2 O-, -NR 4 S(O) 2 NR 4 -, or - 0S(O) 2 NR 4 -;
- L x is absent, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted arylheteroalkyl, or optionally substituted heteroarylheteroalkyl;
- X 1 comprises an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, carboxylic acid, activated ester, alkene, alcohol, acyl halide, sulfonic acid, sulfmic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, oxime, isocyanate, isothiocyanate, hydrazine, or hydrazide; and each R 4 is independently H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl.
- Z x serves as a point of attachment of linking the reactive handle to the linking moiety L. Any group allowing the attachment of the reactive moiety to the linking moiety may be employed.
- Z x is a bond, -O-, -NR 4 -, -S-, -SS-, -C(O)-, -C(O)O- , -C(O)NR 4 , -OC(O)O-, -NR 4 C(O)NR 4 -, or -OC(O)NR 4 -.
- Z x is a bond, -O-, - NR 4 -, -C(O)-, -C(O)O-, or -C(O)NR 4 -. In some embodiments, Z x is a bond. In some embodiments, Z x is -O-. In some embodiments, Z x is -NR 4 -. In some embodiments, Z x is -C(O)-. In some embodiments, Z x is -C(O)O-. In some embodiments, Z x is -C(O)NR 4 -.
- L x' serves as a secondary linking moiety between the point of attachment to the linking moiety L and the reactive functional group of X. Any suitable linker may be employed.
- L x is absent, optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted arylalkylene, optionally substituted heteroarylalkylene, optionally substituted arylheteroalkylene, or optionally substituted heteroarylheteroalkylene.
- L x is optionally substituted alkylene or optionally substituted heteroalkylene.
- L x is optionally substituted alkylene. In some embodiments, L x is alkylene. In some embodiments, L x is optionally substituted heteroalkylene. In some embodiments, L x is heteroalkylene. In some embodiments, L x comprises a cleavable linker group.
- L x has the structure:
- each R 5 and R 6 is independently H, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl, or R 5 and R 6 on the same atom are taken together to form an oxo, or R 5 s on adjacent atoms are taken together to form a double bond, or R 5 S and R 6 s on adjacent atoms are taken together to from a triple bond; and r is an integer from 0-30.
- each R 5 and R 6 is independently H, optionally substituted alkyl, or optionally substituted heteroalkyl; or R 5 and R 6 on the same atom are taken together to form an oxo; or R 5 S on adjacent atoms are taken together to form a double bond.
- each R 5 and R 6 is independently H, optionally substituted alkyl, or optionally substituted heteroalkyl.
- each R 5 and R 6 is independently H, optionally substituted alkyl.
- each R 5 and R 6 is independently H or optionally substituted C 1 -C 6 alkyl.
- each R 5 and R 6 is independently H or C 1 -C 6 alkyl.
- each R 5 and R 6 is independently H or C 1 -C 3 alkyl.
- r is an integer from 0 to 30. In some embodiments, r is an integer from 0 to 20. In some embodiments, r is an integer from 0 to 10. In some embodiments, r is an integer from 0 to 5. In some embodiments, r is 0 or 1.
- X 1 comprises an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, carboxylic acid, activated ester, alkene, alcohol, acyl halide, sulfonic acid, sulfmic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, oxime, isocyanate, isothiocyanate, hydrazine, or hydrazide.
- X 1 is azide, alkyne, halide, sulfhydryl, maleimide, amine, carboxylic acid, alkene, alcohol, epoxide, aldehyde, ketone, imine, or hydrazine. In some embodiments, X 1 is an amine, carboxylic acid, azide, alkyne, halide, alkene, or sulfhydryl.
- X has the structure some embodiments, X has the structure . In some embodiments, X has the structure . In some embodiments, X has the structure
- X is some
- X may also comprise a capture moiety.
- the capture moiety may be any type of molecule capable of selectively capturing a desired material.
- the capture moiety comprises biotin, avidin, streptavidin, a nucleic acid, a peptide, a protein, or any combination thereof.
- the capture moiety comprises biotin.
- the capture moiety comprises avidin.
- the capture moiety comprises streptavidin.
- the capture moiety comprises a nucleic acid.
- the nucleic acid is an aptamer.
- the nucleic acid is a capture probe.
- the capture moiety is a peptide.
- the capture moiety is a protein.
- any of the modified metallic surfaces provided herein may be manufactured or distributed as a kit.
- the kit comprises the modified metallic surface and instructions for use.
- the modified metallic surface comprises a reactive handle or capture moiety linked to the metallic surface.
- the instructions for use provide a protocol for linking of additional moieties to the metallic surface via the reactive handle or capture moiety.
- the surface modification is attached to the phosphonate moiety by a linking moiety. In some embodiments, the surface modification is directly connected to the phosphonate moiety. In some embodiments, the surface modification group is attached to the phosphonate moiety through a reaction product of any of the reactive handles or capture moieties X described above.
- any desired surface modification group can be applied to the metallic surface by the metal phosphonate bonds described herein.
- the surface modification group selected from hydrophobic residues, hydrophilic residues, charged residues, cationic residues, anionic residues, polysaccharides, hydrophobic polymers, hydrophilic polymers, antimicrobial agents, biological materials, biocompatibility materials, anti-fouling materials, conductivity materials, semi- conductive materials, heat resistant materials, anti-corrosive material, catalysts, and magnetic materials, or any combination thereof.
- the surface modification group is a hydrogel.
- the surface modification is represented by Y.
- R has the structure Y-L-, wherein L is any of the linking moieties provided herein.
- Y has the structure Y 1 -L Y -Z y -.
- Y 1 represents the surface modification group.
- L Y serves as a secondary linking moiety between the point of attachment to the linking moiety L and the surface modification group of Y.
- Z Y serves as a point of attachment of linking the surface modification group to the linking moiety L.
- Z Y is a bond, -O-, -NR 4 -, -S-, -SS-, -S(O)-, S(O) 2 -, -C(O)-, - C(O)O-, -C(O)NR 4 , -OC(O)O-, -NR 4 C(O)NR 4 -, -OC(O)NR 4 -, -S(O) 2 O-, -S(O) 2 NR 4 ., -OS(O) 2 O-, - NR 4 S(O) 2 NR 4 -, -OS(O) 2 NR 4 -, or reaction product formed by a covalent bond forming reaction between an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, carboxylic acid, activated ester, alkene, alcohol, acyl halide,
- Z Y is a reaction product formed by a covalent bond forming reaction between an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, carboxylic acid, activated ester, alkene, alcohol, acyl halide, sulfonic acid, sulfmic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, hydrazine, or hydrazide and a suitable complementary reactive group.
- Z Y is a reaction product formed by a covalent bond forming reaction between an azide, alkyne, halide, sulfhydryl, maleimide, alkene, or epoxide and a suitable complementary reactive group.
- Z Y is a bond, -O-, -NR 4 -, -S-, - SS-, -S(O)-, S(O) 2 -, -C(O)-, -C(O)O-, -C(O)NR 4 , -OC(O)O-, -NR 4 C(O)NR 4 -, -OC(O)NR 4 -, - S(O) 2 O-, -S(O) 2 NR 4 ., -OS(O) 2 O-, -NR 4 S(O) 2 NR 4 -, -OS(O) 2 NR 4 -.
- Z Y is a bond, -O-, -NR 4 -, -S-, -SS-, -C(O)-, -C(O)O-, or -C(O)NR 4 . In some embodiments, Z Y is -SS-, -C(O)- , -C(O)O-, or -C(O)NR 4 .
- Z Y is a bond, -O-, -NR 4 -, -S-, -SS-, -S(O)-, S(O) 2 -, -C(O)-, -C(O)O-, -C(O)NR 4 -, -OC(O)O-, -NR 4 C(O)NR 4 -, -OC(O)NR 4 -, -S(O) 2 O-, -S(O) 2 NR 4 -, -
- Z Y is a bond, -O-, -NR 4 -, -S-, -SS-, -S(O)-, S(O) 2 -, -C(O)-, - C(O)O-, -C(O)NR 4 -, -OC(O)O-, -NR 4 C(O)NR 4 -, -OC(O)NR 4 -, -S(O) 2 O-, -S(O) 2 NR 4 -, -OS(O) 2 O-, - NR 4 S(O) 2 NR 4 -, -OS(O) 2 NR 4 -.
- L Y is absent, optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted arylalkylene, optionally substituted heteroarylalkylene, optionally substituted arylheteroalkylene, or optionally substituted heteroarylheteroalkylene.
- L Y is absent, optionally substituted alkylene, or optionally substituted heteroalkylene.
- L Y is alkylene.
- L Y is heteroalkylene.
- L Y is absent.
- L Y comprises a cleavable linker group.
- each R 4 is independently H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl. In some embodiments, each R 4 is independently H, optionally substituted alkyl, or optionally substituted heteroalkyl. In some embodiments, each R 4 is independently H or C 1 -C 6 alkyl. In some embodiments, each R 4 is independently H or methyl. [0101] In some embodiments, Y 1 comprises at least one surface modification residue. Any suitable surface modification residue may be employed.
- Y 1 comprises hydrophobic residues.
- the hydrophobic residue is a fatty acid or a fatty acid derivative.
- the hydrophobic residue is a fluorinated fatty acid.
- the hydrophobic residues comprise a hydrophobic polymer.
- the hydrophobic polymer comprises a polyethylene, a polypropylene, a polystyrene, a polyvinylhalide, a polytetrafluoroethylene, a polymethylmethacrylate, a polycarbonate, a polyether-urethane, a polydimethylsiloxane, or any combination or derivative thereof.
- the hydrophobic polymer comprises a polyethylene.
- the hydrophobic polymer comprises a polypropylene.
- the hydrophobic polymer comprises a polystyrene.
- the hydrophobic polymer comprises a polyvinylhalide. In some embodiments, the hydrophobic polymer comprises a polytetrafluoroethylene. In some embodiments, the hydrophobic polymer comprises a polymethylmethacrylate. In some embodiments, the hydrophobic polymer comprises a polycarbonate. In some embodiments, the hydrophobic polymer comprises a polyether-urethane. In some embodiments, the hydrophobic polymer comprises a polydimethylsiloxane. In some embodiments, the hydrophobic polymer comprises a polysilane. In some embodiments, the hydrophobic polymer comprises a fluoropolymer.
- Y 1 comprises hydrophilic residues. Any suitable hydrophilic residues may be used.
- the hydrophilic residues comprise a monosaccharide or a polysaccharide.
- the hydrophilic residues comprise a hydrophilic polymer.
- the hydrophilic polymer comprises a polyacrylamide, a polyacrylate, a poly methacrylate, a poly(alkylene oxide), a poly(vinyl pyrrolidone), a poly(vinyl alcohol), a polyoxazoline, a poly(N-acryloyl morpholine), or any combination of derivative thereof.
- the hydrophilic polymer comprises a polyacrylamide.
- the hydrophilic polymer comprises a polyacrylate. In some embodiments, the hydrophilic polymer comprises a poly methacrylate. In some embodiments, the hydrophilic polymer comprises a poly(alkylene oxide). In some embodiments, the hydrophilic polymer comprises a poly(vinyl pyrrolidone). In some embodiments, the hydrophilic polymer comprises a poly(vinyl alcohol). In some embodiments, the hydrophilic polymer comprises a polyoxazoline. In some embodiments, the hydrophilic polymer comprises a poly(N-acryloyl morpholine).
- the hydrophilic polymer comprises polyacrylamide, poly(diethyl acrylamide), poly(dimethylacrylamide), poly(N-isopropylacrylamide), poly(acrylic acid), poly(methacrylic acid), poly(methyl acrylate), poly(ethyl acrylate), poly(2-hydroxyethyl acrylate), poly(propyl acrylate), poly(butyl acrylate), poly(methyl methacrylate), poly(2-hydroxyethyl methacrylate), poly(tetrahydrofurfuryl methacrylate), poly(ethylene oxide), poly(propylene oxide), poly(vinyl pyrrolidone), polyoxazoline, poly(2-ethyloxazoline), or poly(N-acryloyl morpholine).
- the hydrophilic polymer comprises polyacrylamide. In some embodiments, the hydrophilic polymer comprises poly(N,N-diethyl acrylamide). In some embodiments, the hydrophilic polymer comprises poly(dimethylacrylamide). In some embodiments, the hydrophilic polymer comprises poly(N-isopropylacrylamide). In some embodiments, the hydrophilic polymer comprises poly(acrylic acid). In some embodiments, the hydrophilic polymer comprises poly(methacrylic acid). In some embodiments, the hydrophilic polymer comprises poly(methyl acrylate). In some embodiments, the hydrophilic polymer comprises poly(ethyl acrylate). In some embodiments, the hydrophilic polymer comprises poly(2-hydroxyethyl acrylate).
- the hydrophilic polymer comprises poly(propyl acrylate). In some embodiments, the hydrophilic polymer comprises poly(butyl acrylate). In some embodiments, the hydrophilic polymer comprises poly(methyl methacrylate). In some embodiments, the hydrophilic polymer comprises a poly methacrylate. In some embodiments, the poly methacrylate is a hydroxyalkyl methacrylate. In some embodiments, the poly methacrylate is a C 1 -C 20 hydroxyalkyl methacrylate.
- the poly methacrylate is hydroxymethyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, hydroxypentyl methacrylate, hydroxyhexyl methacrylate, hydroxyheptyl methacrylate, or hydroxyoctyl methacrylate.
- the hydrophilic polymer comprises poly(2-hydroxyethyl methacrylate).
- the hydrophilic polymer comprises poly(tetrahydrofurfuryl methacrylate).
- the hydrophilic polymer comprises poly(ethylene oxide).
- the hydrophilic polymer comprises poly(propylene oxide).
- the hydrophilic polymer comprises poly(vinyl pyrrolidone). In some embodiments, the hydrophilic polymer comprises polyoxazoline. In some embodiments, the hydrophilic polymer comprises poly(2-ethyloxazoline). In some embodiments, the hydrophilic polymer comprises poly(N-acryloyl morpholine).
- the surface modification group of Y comprises the structure wherein each R 7 is independently optionally substituted C 1 -C 3 alkyl or optionally substituted C 1 -C 3 hydroxyalkyl; each R 8 is independently H or C 1 -C 3 alkyl; each X 7 is independently absent, -O-, -S-, or NR 9 ; each R 9 is independently H or optionally substituted C 1 -C 6 alkyl; and s is an integer from 1 to 1000000.
- the structure linked to the linking moiety is linked to
- each R 7 is independently H, C 1 -C 3 alkyl or C 1 -C 3 hydroxyalkyl. In some embodiments, each R 7 is independently H, methyl, ethyl, propyl, isopropyl, 2-hydroxyethyl, 3- hydroxypropyl, or 2-hydroxypropyl.
- each R 8 is independently H, ethyl, methyl, or propyl. In some embodiments, each R 8 is independently H or methyl. In some embodiments, each R 8 is H. In some embodiments, each R 8 is methyl.
- each X 7 is independently absent, -O-, -S-, or NR 9 . In some embodiments, each X 7 is independently -O- or -NR 9 . In some embodiments, each X 7 is -O-. In some embodiments, each X 7 is independently -NR 9 . In some embodiments, each X 7 is absent.
- each R 9 is independently H or C 1 -C 3 alkyl optionally substituted with hydroxy or alkoxy. In some embodiments, each R 9 is independently H or C 1 -C 3 alkyl. In some embodiments, each R 9 is independently H or methyl. In some embodiments, each R 9 is H.
- s is an integer from 1 to 1000000. In some embodiments, s is an integer from 1 to 100000. In some embodiments, s is an integer from 1 to 10000. In some embodiments, s is an integer from 1 to 1000. In some embodiments, s is an integer from 1 to 100. In some embodiments, s is an integer from 10 to 1000000. In some embodiments, s is an integer from 10 to 100000. In some embodiments, s is an integer from 10 to 10000. In some embodiments, s is an integer from 10 to 1000. In some embodiments, s is an integer from 10 to 100. In some embodiments, s is an integer from 1 to 100. In some embodiments, s is an integer from 100 to 1000000.
- the surface modification group comprises cationic residues.
- Y 1 comprises cationic residues.
- the cationic residues comprise amine groups, substituted amine groups, quaternary amine groups, or any combination thereof.
- the cationic residues are amine groups.
- the cationic residues are substituted amine groups.
- the cationic residues comprise protonated amine groups, protonated substituted amine groups, or quaternary amine groups, or any combination thereof.
- the Y 1 comprises a cationic polymer. Any polymerizable monomer comprising a cationic group may be used.
- the cationic polymer comprises a poly(ethyleneimine) (PEI), a poly amino acid (e.g. polylysine, polyarginine), a polypyridinium, a polyammonium, a polyacrylate comprising an amino group, a polyacrylamide comprising an amino group, or a chitosan.
- the surface modification group comprises anionic residues.
- Y 1 comprises anionic residues. Any anionic residue may be used.
- the anionic residues comprise carboxylates, sulfonates, sulfmates, phosphates, phosphonates, or any combination thereof.
- the anionic residues are carboxylates.
- the anionic residues are sulfonates.
- the anionic residues are sulfmates.
- the anionic residues are phosphates.
- the anionic residues are phosphonates.
- the surface modification group comprises an anionic polymer.
- Y 1 comprises an anionic polymer.
- the anionic polymer comprises anionic groups selected from carboxylates, sulfonates, sulfmates, phosphates, and phosphonates, or any combination thereof.
- the anionic polymer comprises a poly amino acid (e.g. poly glutamic acid, poly aspartic acid), a poly acrylate, a poly methacrylate, a polysulfonate, or a polyacid.
- the surface modification group is a zwitterionic group.
- Y 1 comprises a zwitterionic group.
- Y comprises a zwitterionic group. Any combination of the listed cationic or anionic groups listed herein may be employed.
- the surface modification group comprises a hydrogel.
- Y comprises a hydrogel.
- Y 1 comprises a hydrogel.
- R comprises a hydrogel. Any hydrogel may be linked with the phosphonic acid reagents herein.
- the properties of the hydrogel can be modified for any desired purpose of the functionalized metallic surfaces provide herein.
- the properties of the hydrogel are optimized for use with metal electrodes. Further description of hydrogels which may be attached to the metal surfaces can be found below in the “ Hydrogel Surface Modifications” section.
- the surface modification group comprises a probe moiety.
- Y comprises a probe moiety.
- Y 1 comprises a probe moiety.
- R comprises a probe moiety. Any type of probe moiety may be employed.
- the probe moiety comprises a binding agent specific for an analyte or target.
- the probe moiety comprises a nucleic acid, a peptide, a protein, an antibody, a small molecule, a glycan, or any combination thereof.
- the probe moiety comprises a nucleic acid.
- the nucleic acid comprises DNA or RNA.
- the nucleic acid is configured to hybridize with a target moiety or analyte.
- the nucleic acid comprises an aptamer.
- the nucleic acid comprises unnatural oligonucleotides.
- the probe moiety comprises a peptide. In some embodiments, the probe moiety comprises a protein. In some, the probe moiety comprises a protein fragment. In some embodiments, the probe moiety comprises an antibody. In some embodiments, the probe moiety comprises an antibody fragment. In some embodiments, the probe moiety comprises a small molecule. In some embodiments, the probe moiety comprises a glycan.
- the surface modification group comprises a drug moiety.
- the drug moiety may be linked to the phosphonate moiety by any linking moiety.
- the drug moiety is linked to the surface through a cleavable linker.
- the linker is configured to release the drug moiety.
- the surface modification group comprises a targeting moiety.
- the targeting moiety is specific for a particular biomarker.
- the targeting moiety may be any suitable group.
- the targeting moiety comprises an antibody or antibody fragment, a peptide, or a nucleic acid.
- a targeting moiety and a drug moiety are attached to the same surface.
- hydrogels which may be linked to metallic surfaces through bonds between a phosphonate group and the metallic surface.
- these hydrogels may also be linked to other metal surfaces capable of forming bonds with phosphonates, including without limitation silicon, aluminum, titanium, iron, zinc, zirconium, nickel, silver, copper, cobalt, or chromium, or an oxide thereof, or any combination thereof.
- the hydrogel is linked a metallic surface comprising platinum.
- the hydrogel is linked a metallic surface comprising gold.
- the hydrogel is linked a metallic surface comprising palladium.
- the hydrogel is linked a metallic surface comprising iridium. In some embodiments, the hydrogel is linked a metallic surface comprising rhodium. In some embodiments, the hydrogel is linked a metallic surface comprising silicon. In some embodiments, the hydrogel is linked a metallic surface comprising aluminum. In some embodiments, the hydrogel is linked a metallic surface comprising titanium. In some embodiments, the hydrogel is linked a metallic surface comprising iron. In some embodiments, the hydrogel is linked a metallic surface comprising zinc.
- hydrogels provided herein may be linked to the metallic surface through any of the linking moieties provided herein, including the linking moieties provided in the "Linking Moieties” section, or linked through a bond formed through a reaction of any of the reactive handles provided therein.
- the surface modification group comprises a hydrogel.
- Y comprises a hydrogel.
- Y 1 comprises a hydrogel.
- R comprises a hydrogel. Any hydrogel may be linked with the phosphonic acid reagents herein.
- the properties of the hydrogel can be modified for any desired purpose of the functionalized metallic surfaces provide herein. In some embodiments, the properties of the hydrogel are optimized for use with metal electrodes.
- hydrogels are employed on electrodes configured for electrophoretic analysis of biological samples.
- the metallic surface comprises an electrode
- overlaying electrode structures with one or more layers of materials can reduce the deleterious electrochemistry effects, including but not limited to electrolysis reactions, heating, and chaotic fluid movement that may occur on or near the electrodes, and still allow the effective separation of cells, bacteria, virus, nanoparticles, DNA, and other biomolecules to be carried out.
- the hydrogel layered over the electrode structures may comprise one or more porous layers.
- the hydrogel has sufficient mechanical strength and is relatively chemically inert such that it will be able to endure the electrochemical effects at the electrode surface without disconfiguration or decomposition.
- the hydrogel is sufficiently permeable to small aqueous ions, but keeps biomolecules away from the electrode surface.
- the hydrogel comprises a gradient of porosity, wherein the bottom of the hydrogel layer has greater porosity than the top of the hydrogel layer.
- Y comprises a hydrogel. In some embodiments, Y 1 comprises a hydrogel. [0130] In some embodiments, the hydrogel has a conductivity from about 0.001 S/m to about 10 S/m. In some embodiments, the hydrogel has a conductivity from about 0.01 S/m to about 10 S/m. In some embodiments, the hydrogel has a conductivity from about 0.1 S/m to about 10 S/m. In some embodiments, the hydrogel has a conductivity from about 1.0 S/m to about 10 S/m. In some embodiments, the hydrogel has a conductivity from about 0.01 S/m to about 5 S/m.
- the hydrogel has a conductivity from about 0.01 S/m to about 4 S/m. In some embodiments, the hydrogel has a conductivity from about 0.01 S/m to about 3 S/m. In some embodiments, the hydrogel has a conductivity from about 0.01 S/m to about 2 S/m. In some embodiments, the hydrogel has a conductivity from about 0.1 S/m to about 5 S/m. In some embodiments, the hydrogel has a conductivity from about 0.1 S/m to about 4 S/m. In some embodiments, the hydrogel has a conductivity from about 0.1 S/m to about 3 S/m. In some embodiments, the hydrogel has a conductivity from about 0.1 S/m to about 2 S/m. In some embodiments, the hydrogel has a conductivity from about 0.1 S/m to about 1.5 S/m. In some embodiments, the hydrogel has a conductivity from about 0.1 S/m to about 1.0 S/m.
- the hydrogel has a conductivity of about 0.1 S/m. In some embodiments, the hydrogel has a conductivity of about 0.2 S/m. In some embodiments, the hydrogel has a conductivity of about 0.3 S/m. In some embodiments, the hydrogel has a conductivity of about 0.4 S/m. In some embodiments, the hydrogel has a conductivity of about 0.5 S/m. In some embodiments, the hydrogel has a conductivity of about 0.6 S/m. In some embodiments, the hydrogel has a conductivity of about 0.7 S/m. In some embodiments, the hydrogel has a conductivity of about 0.8 S/m. In some embodiments, the hydrogel has a conductivity of about 0.9 S/m. In some embodiments, the hydrogel has a conductivity of about 1.0 S/m.
- the hydrogel has a thickness from about 0.001 microns to about 10 microns. In some embodiments, the hydrogel has a thickness from about 0.001 microns to about 5 microns. In some embodiments, the hydrogel has a thickness from about 0.001 microns to about 1 microns. In some embodiments, the hydrogel has a thickness from about 0.001 microns to about 0.5 microns. In some embodiments, the hydrogel has a thickness from about 0.01 microns to about 10 microns. In some embodiments, the hydrogel has a thickness from about 0.01 microns to about 5 microns. In some embodiments, the hydrogel has a thickness from about 0.01 to about 1 microns.
- the hydrogel has a thickness from about 0.1 microns to about 10 microns. In some embodiments, the hydrogel has a thickness from about 0.1 microns to about 5 microns. In some embodiments, the hydrogel has a thickness from about 0.1 microns to about 4 microns. In some embodiments, the hydrogel has a thickness from about 0.1 microns to about 3 microns. In some embodiments, the hydrogel has a thickness from about 0.1 microns to about 2 microns. In some embodiments, the hydrogel has a thickness from about 1 micron to about 5 microns. In some embodiments, the hydrogel has a thickness from about 1 micron to about 4 microns.
- the hydrogel has a thickness from about 1 micron to about 3 microns. In some embodiments, the hydrogel has a thickness from about 1 micron to about 2 microns. In some embodiments, the hydrogel has a thickness from about 0.5 microns to about 1 micron.
- the hydrogel comprises any suitable synthetic polymer forming a hydrogel.
- any sufficiently hydrophilic and polymerizable molecule may be utilized in the production of a synthetic polymer hydrogel for use as disclosed herein.
- Polymerizable moieties in the monomers may include alkenyl moieties including but not limited to substituted or unsubstituted a,b, unsaturated carbonyls wherein the double bond is directly attached to a carbon which is double bonded to an oxygen and single bonded to another oxygen, nitrogen, sulfur, halogen, or carbon; vinyl, wherein the double bond is singly bonded to an oxygen, nitrogen, halogen, phosphorus or sulfur; allyl, wherein the double bond is singly bonded to a carbon which is bonded to an oxygen, nitrogen, halogen, phosphorus or sulfur; homoallyl, wherein the double bond is singly bonded to a carbon which is singly bonded to another carbon which is then singly bonded to an oxygen, nitrogen, halogen
- acryloyl or acrylamido monomers such as acrylates, methacrylates, acrylamides, methacrylamides, etc., are useful for formation of hydrogels as disclosed herein. More preferred acrylamido monomers include acrylamides, N-substituted acrylamides, N-substituted methacrylamides, and methacrylamide.
- a hydrogel comprises polymers such as epoxide-based polymers, vinyl-based polymers, allyl-based polymers, homoallyl-based polymers, cyclic anhydride-based polymers, ester-based polymers, ether-based polymers, alkylene-glycol based polymers (e.g., polypropylene glycol), and the like.
- the hydrogel comprises poly(2-hydroxyethyl methacrylate) (pHEMA), cellulose acetate, cellulose acetate phthalate, cellulose acetate butyrate, or any appropriate acrylamide or vinyl-based polymer, or a derivative thereof.
- pHEMA poly(2-hydroxyethyl methacrylate)
- the hydrogel is polymerized via atom-transfer radical- polymerization via (ATRP). In some embodiments, the hydrogel is polymerized via reversible addition-fragmentation chain-transfer (RAFT) polymerization. In some embodiments, the hydrogel is polymerized onto the metallic surface through a reactive group linked to the phosphonate bound to the metallic surface, wherein the reactive group comprises halide in an alpha position to a carbonyl. In some embodiments, the alpha position to a carbonyl is a tertiary carbon. In some embodiments, the reactive group has the structure (CH 3 ) 2 BrC-C(O)-.
- additives are added to a hydrogel to increase conductivity of the gel.
- hydrogel additives are conductive polymers (e.g., PEDOT: PSS), salts (e.g., copper chloride), metals (e.g., gold), plasticizers (e.g., PEG200, PEG 400, or PEG 600), or cosolvents.
- the hydrogel also comprises compounds or materials which help maintain the stability of the DNA hybrids, including, but not limited to histidine, histidine peptides, polyhistidine, lysine, lysine peptides, and other cationic compounds or substances.
- any suitable metallic surface may be modified with the compositions and systems according to the present disclosure.
- the metallic surface is oxidized.
- the metallic surfaces modified according to the present disclosure may be of any shape, so long as there exists a metallic surface available to react with the phosphonic acid or phosphonate ester reagents described herein.
- the metallic surface comprises platinum or an oxide thereof.
- the metallic surface comprises gold or an oxide thereof.
- the metallic surface comprises palladium or an oxide thereof.
- the metallic comprises iridium or an oxide thereof.
- the metallic surface comprises rhodium surface or an oxide thereof.
- the metallic surface is a platinum surface, or an oxide thereof.
- the metallic surface is a gold surface, or an oxide thereof. In some embodiments, the metallic surface is a palladium surface, or an oxide thereof. In some embodiments, the metallic surface is an iridium surface, or an oxide thereof. In some embodiments, the metallic surface is a rhodium surface, or an oxide thereof. In some embodiments, the metallic surface comprises silicon, aluminum, titanium, iron, zinc, zirconium, nickel, silver, copper, cobalt, or chromium. In some embodiments, the metallic surface is oxidized.
- the metallic surface is a planar metallic surface. In some embodiments, the metallic surface is a curved metallic surface. In some embodiments, the metallic surface has a 3D geometry. In some embodiments, the metallic surface is an electrode, a microchip, a bead, a microparticle, or a nanoparticle. In some embodiments, the metallic surface is an electrode. In some embodiments, the metallic surface is a microchip. In some embodiments, the metallic surface is a bead. In some embodiments, the metallic surface is a microparticle. In some embodiments, the metallic surface is a nanoparticle.
- any portion of the metallic surface may be modified with the surface modification provided herein.
- at least about 1%, at least about 2%, at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% of the metallic surface is functionalized.
- at most about 1%, at most about 2%, at most about 5%, at most about 10%, at most about 20%, at most about 30%, at most about 40%, at most about 50%, at most about 60%, at most about 70%, at most about 80%, or at most about 90% of the metallic surface is functionalized.
- the degree of surface functionalization is measured by the degree of coverage of the surface modification material over the surface. In some embodiments, the degree of surface functionalization is measured by the amount of phosphonate residues bound to the surface.
- the metallic surface is modified with the phosphonate at a concentration of about 0.0001 nmol/cm 2 to about 5 nmol/cm 2 . In some embodiments, the metallic surface is modified with the phosphonate at a concentration of about 0.0001 nmol/cm 2 to about 0.001 nmol/cm 2 , about 0.0001 nmol/cm 2 to about 0.01 nmol/cm 2 , about 0.0001 nmol/cm 2 to about 0.05 nmol/cm 2 , about 0.0001 nmol/cm 2 to about 0.1 nmol/cm 2 , about 0.0001 nmol/cm 2 to about 0.5 nmol/cm 2 , about 0.0001 nmol/cm 2 to about 1 nmol/cm 2 , about 0.0001 nmol/cm 2 to about 1.5 nmol/cm 2 , about 0.0001 nmol/cm 2 to about 2 nmol/cm 2 ,
- the metallic surface is modified with the phosphonate at a concentration of about 0.0001 nmol/cm 2 , about 0.001 nmol/cm 2 , about 0.01 nmol/cm 2 , about 0.05 nmol/cm 2 , about 0.1 nmol/cm 2 , about 0.5 nmol/cm 2 , about 1 nmol/cm 2 , about 1.5 nmol/cm 2 , about 2 nmol/cm 2 , or about 5 nmol/cm 2 .
- the metallic surface is modified with the phosphonate at a concentration of at least about 0.0001 nmol/cm 2 , about 0.001 nmol/cm 2 , about 0.01 nmol/cm 2 , about 0.05 nmol/cm 2 , about 0.1 nmol/cm 2 , about 0.5 nmol/cm 2 , about 1 nmol/cm 2 , about 1.5 nmol/cm 2 , or about 2 nmol/cm 2 .
- the metallic surface is modified with the phosphonate at a concentration of at most about 0.001 nmol/cm 2 , about 0.01 nmol/cm 2 , about 0.05 nmol/cm 2 , about 0.1 nmol/cm 2 , about 0.5 nmol/cm 2 , about 1 nmol/cm 2 , about 1.5 nmol/cm 2 , about 2 nmol/cm 2 , or about 5 nmol/cm 2 . In some embodiments, the metallic surface is modified with the phosphonate at concentration of about 0.01 nmol/cm 2 to about 2 nmol/cm 2 .
- the metallic surface is oxidized. In some embodiments, the metallic surface is oxidized to allow attachment of the phosphonate moiety of the surface modification provided herein. In some embodiments, the metallic surface is partially oxidized. In some embodiments, the metallic surface is fully oxidized. In some embodiments, a portion of the metallic surface is oxidized.
- At least about 1%, at least about 2%, at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% of the metallic surface is oxidized.
- at most about 1%, at most about 2%, at most about 5%, at most about 10%, at most about 20%, at most about 30%, at most about 40%, at most about 50%, at most about 60%, at most about 70%, at most about 80%, or at most about 90% of the metallic surface is oxidized.
- the degree of oxidation of the metallic surface is measured by a percentage of the metal atoms on the metallic surface having an oxidation state greater than 0. In some embodiments, the degree of oxidation of the metallic surface is measured by the percentage of oxygen atoms covering the metallic surface.
- the metallic surface is an oxidized metal layer positioned on an exterior of a substrate.
- the substrate is a metallic substrate.
- the metallic substrate is an unoxidized metal.
- the metallic substrate is the same metal as the oxidized metal layer.
- the metallic substrate is the non-oxidized version of the oxidized metal layer.
- the substrate is a different metal than the metallic surface.
- the oxidized metal layer has a thickness of about 0.1 nm to about 10 nm.
- the oxidized metal layer has a thickness of about 0.1 nm to about 0.2 nm, about 0.1 nm to about 0.5 nm, about 0.1 nm to about 1 nm, about 0.1 nm to about 5 nm, about 0.1 nm to about 10 nm, about 0.2 nm to about 0.5 nm, about 0.2 nm to about 1 nm, about 0.2 nm to about 5 nm, about 0.2 nm to about 10 nm, about 0.5 nm to about 1 nm, about 0.5 nm to about 5 nm, about 0.5 nm to about 10 nm, about 1 nm to about 5 nm, about 1 nm to about 10 nm, or about 5 nm to about 10 nm.
- the oxidized metal layer has a thickness of about 0.1 nm, about 0.2 nm, about 0.5 nm, about 1 nm, about 5 nm, or about 10 nm. In some embodiments, the oxidized metal layer has a thickness of at least about 0.1 nm, about 0.2 nm, about 0.5 nm, about 1 nm, or about 5 nm. In some embodiments, the oxidized metal layer has a thickness of at most about 0.2 nm, about 0.5 nm, about 1 nm, about 5 nm, or about 10 nm. In some embodiments, the oxidized metal layer has a thickness of about 0.1 nm to about 1,000 nm.
- the oxidized metal layer has a thickness of about 0.1 nm to about 0.5 nm, about 0.1 nm to about 1 nm, about 0.1 nm to about 5 nm, about 0.1 nm to about 10 nm, about 0.1 nm to about 50 nm, about 0.1 nm to about 100 nm, about 0.1 nm to about 500 nm, about 0.1 nm to about 1,000 nm, about 0.5 nm to about 1 nm, about 0.5 nm to about 5 nm, about 0.5 nm to about 10 nm, about 0.5 nm to about 50 nm, about 0.5 nm to about 100 nm, about 0.5 nm to about 500 nm, about 0.5 nm to about 1,000 nm, about 1 nm to about 5 nm, about 1 nm to about 10 nm, about 1 nm to about 50 nm, about 1 nm to about 100 nm
- the oxidized metal layer has a thickness of about 0.1 nm, about 0.5 nm, about 1 nm, about 5 nm, about 10 nm, about 50 nm, about 100 nm, about 500 nm, or about 1,000 nm. In some embodiments, the oxidized metal layer has a thickness of at least about 0.1 nm, about 0.5 nm, about 1 nm, about 5 nm, about 10 nm, about 50 nm, about 100 nm, or about 500 nm.
- the oxidized metal layer has a thickness of at most about 0.5 nm, about 1 nm, about 5 nm, about 10 nm, about 50 nm, about 100 nm, about 500 nm, or about 1,000 nm.
- the metallic surface comprises a mixture of metals. In some embodiments, the metallic surface comprises at least two metals selected from platinum, gold, palladium, titanium, and rhodium, or an oxide thereof. In some embodiments, the metallic surface comprises at least three metals selected from platinum, gold, palladium, titanium, and rhodium, or an oxide thereof.
- the metallic surface comprises at least one metal selected from platinum, gold, palladium, titanium, and rhodium, or an oxide thereof, and an additional material.
- the additional material comprises an additional metal.
- the additional material comprises an additional element.
- the metallic surface comprises platinum, or an oxide thereof, and an additional material.
- the additional material comprises an additional metal.
- the additional material comprises an additional element.
- the metallic surface comprises platinum and the additional material comprises silicon, zirconium, gold, aluminum, titanium, iron, or zinc, or an oxide thereof, or any combination thereof.
- the metallic surface comprises platinum and the additional material comprises silicon or zirconium.
- the metallic surface comprises gold, or an oxide thereof, and an additional material.
- the additional material comprises an additional metal.
- the additional material comprises an additional element.
- the metallic surface comprises gold and the additional material comprises silicon, zirconium, platinum, aluminum, titanium, iron, or zinc, or an oxide thereof, or any combination thereof.
- the metallic surface comprises gold and the additional material comprises silicon or zirconium.
- the metallic surface comprises palladium, or an oxide thereof, and an additional material.
- the additional material comprises an additional metal.
- the additional material comprises an additional element.
- the metallic surface comprises palladium and the additional material comprises silicon, zirconium, gold, platinum, titanium, iron, or zinc, or an oxide thereof, or any combination thereof.
- the metallic surface comprises palladium and the additional material comprises silicon or zirconium.
- the metallic surface comprises iridium, or an oxide thereof, and an additional material.
- the additional material comprises an additional metal.
- the additional material comprises an additional element.
- the metallic surface comprises iridium and the additional material comprises silicon, zirconium, gold, aluminum, platinum, iron, or zinc, or an oxide thereof, or any combination thereof.
- the metallic surface comprises iridium and the additional material comprises silicon or zirconium.
- the metallic surface comprises rhodium, or an oxide thereof, and an additional material.
- the additional material comprises an additional metal.
- the additional material comprises an additional element.
- the metallic surface comprises rhodium and the additional material comprises silicon, zirconium, gold, aluminum, platinum, titanium, or zinc, or an oxide thereof, or any combination thereof.
- the metallic surface comprises rhodium and the additional material comprises silicon or zirconium.
- the metallic surface comprises at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 98% of the metal by weight. In some embodiments, the metallic surface comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% of the metal by weight. In some embodiments, the metallic surface comprises at most about 50%, at most about 60%, at most about 70%, at most about 80%, at most about 90%, at most about 95%, or at most about 98% of the metal by weight.
- the metallic surface comprises at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 98% of the metal or any oxide thereof by weight. In some embodiments, the metallic surface comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% of the metal or any oxide thereof by weight. In some embodiments, the metallic surface comprises at most about 50%, at most about 60%, at most about 70%, at most about 80%, at most about 90%, at most about 95%, or at most about 98% of the metal or any oxide thereof by weight.
- the metallic surfaces used herein may be substantially pure metals or alloys of different materials.
- the metallic surface comprises a platinum alloy.
- the platinum may be alloyed with any other metal.
- the platinum alloy comprises platinum alloyed with another metal, such as iron, nickel, copper, palladium, chromium, iridium, osmium, aluminum, tin, molybdenum, vanadium, niobium, tantalum, zirconium, manganese, ruthenium, gold, or cobalt.
- the platinum alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% platinum by weight.
- the platinum alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% platinum by weight.
- the metallic surface comprises a gold alloy.
- the gold may be alloyed with any other metal.
- the gold alloy comprises gold alloyed with another metal, such as nickel, silver, palladium, platinum, rhodium, mercury, copper, zinc, aluminum, cadmium, manganese, gallium, indium, chromium, cobalt, iron, or ruthenium.
- the gold alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% gold by weight.
- the gold alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% gold by weight.
- the metallic surface comprises a palladium alloy.
- the palladium may be alloyed with any other metal.
- the palladium alloy comprises palladium alloyed with gold, platinum, iridium, rhodium, ruthenium, osmium, silver, nickel, copper, or manganese.
- the palladium alloy comprises least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% palladium by weight.
- the palladium alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% palladium by weight.
- the metallic surface comprises an iridium alloy.
- the iridium may be alloyed with any other metal.
- the iridium alloy comprises iridium alloyed with platinum, ruthenium, osmium, nickel, cobalt, copper, titanium, or zirconium.
- the iridium alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% iridium by weight.
- the iridium alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% iridium by weight.
- the metallic surface comprises a rhodium alloy.
- the rhodium may be alloyed with any other metal.
- the rhodium alloy comprises rhodium alloyed with platinum, molybdenum, iridium, ruthenium, palladium, osmium, titanium, rhenium, gold, or nickel.
- the rhodium alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% rhodium by weight.
- the rhodium alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% rhodium by weight.
- the metallic surface comprises an aluminum alloy.
- the aluminum may be alloyed with any other metal.
- the aluminum alloy comprises aluminum alloyed with another metal, such as copper, magnesium, manganese, silicon, tin, zinc, iron, scandium, or zirconium.
- the aluminum alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% aluminum by weight.
- the aluminum alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% aluminum by weight.
- the metallic surface comprises a titanium alloy.
- the titanium may be alloyed with any other metal.
- the titanium alloy comprises titanium alloyed with another metal, such as aluminum, vanadium, tin, niobium, iron, tantalum, zirconium, molybdenum, silicon, manganese, chromium, cobalt, nickel, or copper.
- the titanium alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% titanium by weight.
- the titanium alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% titanium by weight.
- the metallic surface comprises an iron alloy.
- the iron may be alloyed with any other metal or other element.
- the iron is alloyed with another material, such as carbon, vanadium, chromium, niobium, titanium, nickel, cobalt, aluminum, manganese, uranium, silicon, or copper.
- the iron alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% iron by weight.
- the iron alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% iron by weight.
- the iron alloy is steel.
- the metallic surface comprises a zinc alloy.
- the zinc may be alloyed with any other metal.
- the zinc alloy comprises zinc alloyed with another metal, such as copper, tin, nickel, silver, mercury, magnesium, silicon, iron, lead, or aluminum.
- the zinc iron alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% zinc by weight.
- the zinc alloy comprises about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98% zinc by weight.
- the metallic surface may be functionalized with any number or combination of the surface modification, reactive groups, or capture moieties provided herein.
- the metallic surface is functionalized with a single type of surface modification group, reactive group, or capture moiety.
- the metallic surface is functionalized with a plurality of different surface modification groups, reactive groups, or capture moieties.
- the metallic surface is modified by multiple copies of the same surface modification group, reactive group, or capture moiety.
- the metallic surfaces modified as provided herein may be used for any suitable purpose or configured to have any desired properties. Because of the wide range of moieties that can be bound to the metallic surfaces using the methods and reagents described herein, there is no limit to the application of such surfaces. Provided herein are non-limiting examples of potential uses of the modified metallic surfaces described herein.
- metals such as gold and platinum are frequently used in electrodes, amongst other uses.
- Gold and platinum electrodes may be used in electrokinetic assays.
- materials can be linked to metal electrode surfaces using the phosphonate bonds provided herein that can mitigate these effects, yet still allow the effective separation of cells, bacteria, virus, nanoparticles, DNA, and other biomolecules to be carried out.
- a hydrogel is linked to the metal surface of the electrode in order prevent biological material from depositing on the electrode surface during an electrokinetic assay.
- a hydrogel is linked to the metal surface of the electrode in order prevent biological material from becoming damaged or degraded during an electrokinetic assay.
- the hydrogel should have sufficient mechanical strength and be relatively chemically inert such that it will be able to endure the electrochemical effects at the electrode surface without disconfiguration or decomposition.
- the hydrogel is sufficiently permeable to small aqueous ions, but keeps biomolecules away from the electrode surface.
- the metallic surface is configured to come into contact with a biological material.
- the metallic surface is configured to come into contact with biological fluids (e.g. blood).
- biological fluids e.g. blood
- the metallic surface is modified with a phosphonate moiety provided herein in order to imbibe the metallic surface with anti-biofouling properties.
- the metallic surfaces configured to come into contact with biological material comprise anti-biofouling coatings, such as hydrogels, hydrophilic polymers, or hydrophobic polymers.
- the metallic surfaces modified herein may be configured to be placed inside the body of an animal. In some embodiments, the metallic surface is configured to be placed inside the body of a mammal. In some embodiments, the metallic surface is configured to be placed inside the body of a human. In some embodiments, the metallic surface is part of a medical implant. In some embodiments, the metallic surface is part of a surgical or dental implant. In some embodiments, the metallic surface is a surgical or dental implant. Such an implant may be modified with a phosphonate provided herein in order to prevent corrosion of the implant, prevent biofouling on the implant, prevent bacterial or other cell growth on the implant, or to alter any other desired surface property of the implant.
- the metallic surface comprises a material linked through the phosphonate moiety to prevent cell adhesion to the metallic surface.
- the material is configured to prevent bacterial cell adhesion to the metallic surface.
- the material comprises a polymer.
- the polymer is grafted onto the metallic surface.
- the polymer comprises quaternary ammonium ion- containing polymers (e.g. poly 2-dimethylaminoethyl methacrylate).
- the polymer is poly 2-dimethylaminoethyl methacrylate.
- the polymer is poly 4- vinyl pyridine.
- the polymer is poly (3-(trimethoxysilyl)propyl methacrylate). In some embodiments, the polymer is a fluorocarbon of perfluorocarbon polymer. In some embodiments, the material comprises an antimicrobial peptide. In some embodiments, the material comprises a biocide chemically attached to the phosphonate. In some embodiments, the material linked through the phosphonate is used in conjunction with an additional anti-microbial treatment (e.g. surface treatment with an antiseptic such as chlorhexidine and/or chloroxylenol).
- an additional anti-microbial treatment e.g. surface treatment with an antiseptic such as chlorhexidine and/or chloroxylenol.
- the metallic surface comprises a material linked through the phosphonate moiety to prevent marine biofouling.
- the material comprises a hydrophobic polymer.
- the material comprises a silicone elastomer (e.g. polydimethylsiloxane).
- the material comprises a mixture of silicone polymers.
- the material comprises a hydrophobic polymer.
- the hydrophobic polymer comprises polyethylene, polypropylene, polystyrene, polyvinylhalide, polytetrafluoroethylene, poly(methyl methacrylate), polycarbonate, polyether-urethane, polydimethylsiloxane, or any combination or derivative thereof.
- the material comprises a fouling release coating.
- the metal phosphonate bonds provided herein may be used to immobilize drug moieties onto delivery devices with metallic surfaces.
- the delivery devices are nanoparticles, microparticles, beads, or similar moieties having metallic surfaces.
- a drug delivery device comprising a drug moiety covalently linked to a surface of the device through a phosphonate residue, wherein the surface is platinum or gold.
- the surface is platinum.
- the surface is gold.
- the surface is palladium, iridium, or rhodium.
- the drug moiety is linked to the phosphonate residue through a linker.
- the metal phosphonate provided herein may be used to prepare metallic surfaces useful in the purification of biological media.
- the phosphonate bonds to metallic surfaces may be used to link a plurality of binding agents to the surface.
- the binding agents may bind a material of interest to the surface.
- the biological media is washed over the surface, and materials of interest are bound to the surface. The biological media may then be removed from the surface.
- the metallic surface is then washed to remove non-specifically bound materials from the surface.
- the material of interest may then be released from the metallic surface and recovered (e.g., by cleaving a linker between the binding agent and the surface or altering the properties of the binding agent, for example by denaturation).
- the binding agents may be configured to bind material that is not of interest in order to remove it from the biological media.
- the binding agents may be deployed on a metallic surface that can be easily removed from the media, such as a bead or microparticle. Such particles can be collected by a variety of methods (e.g. magnetic field or centrifugation). Collection of the particles with the undesired material bond can clarify a complex biological sample to leave behind only the material of interest.
- the metal phosphonate bonds provided herein may be used in the preparation of microarrays.
- the microarrays can be used for any purpose.
- the microarrays can be used for DNA sequencing, protein expression analysis, protein-protein interaction screens, or any other biological assay capable of being performed in an array format.
- the array comprises a plurality of features bound to a metallic surface through a phosphonate residue.
- the features comprise probe moieties.
- each feature comprises a unique probe moiety.
- the probe moiety comprises a nucleic acid, a peptide, a protein, an antibody, a small molecule, a glycan, or any combination thereof.
- the probe moieties comprise nucleic acids.
- the nucleic acids comprise DNA or RNA.
- the nucleic acids are single-stranded.
- the nucleic acids comprise aptamers.
- the microarray is configured for DNA sequencing.
- the microarray is configured for expression analysis.
- the expression analysis is protein expression analysis.
- the probe moieties are configured to capture mRNA.
- the probe moieties comprise peptides are proteins.
- microarrays are configured for protein-protein interaction screens. The microarrays may have any number of features.
- the microarray comprises at least 10, at least 100, at least 1000, at least 10000, or at least 100000 unique probe features.
- metallic surfaces are able to be modified in a robust, reproducible fashion using a simple procedure.
- the simplicity of the methods provided herein allow for metallic surfaces to be modified with a high degree of control, which can be used to further functionalize the metallic surfaces in a reliable and consistent manner across batches.
- a method of functionalizing a metallic surface comprises depositing a phosphonic acid or phosphonate ester reagent on a metallic surface. In some embodiments, the method further comprises heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metallic surface.
- the metallic surface is a platinum surface, or an oxide thereof. In some embodiments, the metallic surface is a gold surface, or an oxide thereof. In some embodiments, the metallic surface is a palladium, titanium, or rhodium, or an oxide thereof. In some embodiments, the metallic surface is oxidized.
- the phosphonic acid reagent comprises a phosphonic acid moiety. In some embodiments, the phosphonic acid reagent comprises a phosphonic acid derivative. In some embodiments, the phosphonic acid derivative is a phosphonate ester. In some embodiments, the phosphonate ester is an alkyl phosphonate ester. In some embodiments, the phosphonate ester is a methyl or ethyl ester. In some embodiments wherein the phosphonic acid reagent is a phosphonic acid derivative, the method further comprises adding an acid to the reaction mixture. In some embodiments, the acid is an organic acid (e.g. acetic acid, formic acid, and the like). In some embodiments, the acid is an inorganic acid (e.g. HC 1 , HBr, H 2 SO 4 , and the like). In some embodiments, the acid is a strong acid. In some embodiments, the acid is a weak acid.
- the acid is an organic acid (e.g. acetic
- depositing the phosphonic acid or phosphonate ester reagent comprises contacting the metallic surface with a solution comprising the phosphonic acid reagent. In some embodiments, depositing the phosphonic acid reagent comprises contacting the platinum surface with a solution comprising the phosphonic acid reagent and a solvent. Any solvent capable of dissolving the phosphonic acid reagent may be used. In some embodiments, the solvent comprises an organic solvent, an aqueous solvent, or any combination or mixture thereof. In some embodiments, the solvent is an organic solvent.
- the organic solvent comprises acetic acid, acetone, acetonitrile, benzene, tert-butyl alcohol, tert- butyl methyl ether, carbon tetrachloride, chloroform, cyclohexane, 1,2-dichloroethane, di chi orom ethane, diethyl ether, diglyme, 1,2,- dimethoxyethane, dimethyl acetamide, dimethylformamide, dimethyl sulfoxide, dioxane, ethanol, ethyl acetate, ethyl methyl ketone, ethylene glycol, hexanes, hexamethylphosphoramide, methanol, nitromethane, pentanes, 2-proponal, pyridine, tetrahydrofuran, toluene, xylenes, or any combination thereof.
- the organic solvent comprises ethanol, tetrahydrofuran, or toluene, or any combination thereof. In some embodiments, the organic solvent comprises ethanol, tetrahydrofuran, or toluene. In some embodiments, the organic solvent comprises ethanol. In some embodiments, the organic solvent comprises tetrahydrofuran. In some embodiments, the organic solvent comprises toluene.
- the phosphonic acid or phosphonate ester reagent can be present in the solution at any concentration.
- the reagent is present in the solution at a concentration of up to about 1 ⁇ M, 10 ⁇ M, 100 ⁇ M, 1 mM, 10 mM, 100 mM, or 1M.
- the reagent is present in the solution at a concentration of about 1 ⁇ M, 10 ⁇ M, 100 ⁇ M, 1 mM, 10 mM, 100 mM, or 1 M.
- the reagent is present in the solution at a concentration of at least about 1 ⁇ M, 10 ⁇ M, 100 ⁇ M, 1 mM, 10 mM, 100 mM, or 1 M. In some embodiments, the reagent is present in the solution at a concentration of about 1 mM. In some embodiments, the reagent is present in the solution at a concentration from about 1 ⁇ M, 10 ⁇ M, 100 ⁇ M, 1 mM, or 10 mM to about 10 ⁇ M, 100 ⁇ M, 1 mM, 10 mM, 100 mM, or 1 M. In some embodiments, the reagent is present in the solution at a concentration from about 1 ⁇ M to about 1 M.
- the depositing the reagent on the metallic surface comprises evaporating the solvent from the metallic surface. Any suitable method can be used to evaporate the solvent. In some embodiments, the solvent is allowed to evaporate under atmospheric pressure. In some embodiments, the solvent is evaporated using a vacuum source. In some embodiments, evaporating the solvent comprises heating the metallic surface. In some embodiments, the metallic surface is heated at a temperature of least 30°C, at least 40°C, at least 50°C, at least 60°C, at least 70°C, at least 80°C, or at least 90°C. In some embodiments, the metallic surface is heated at a temperature of about 30°C, about 40°C, about 50°C, about 60°C, about 70°C, about 80°C, or about 90°C.
- the metallic surface is heated to bind the phosphonic acid or phosphonate ester reagent with the metallic surface. Any method to heat the surface may be employed. In some embodiments, heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metallic surface occurs in an oven, a vacuum oven, or a microwave reactor. In some embodiments, heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metallic surface occurs in an oven. In some embodiments, heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metallic surface occurs in a vacuum oven. In some embodiments, heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metallic surface occurs in a microwave reactor.
- heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metallic surface comprises heating the metallic surface at a temperature of at least 30°C, at least 50°C, at least 70°C, at least 80°C, at least 100°C, at least 120°C, at least 140°C, at least 160°C, or at least 180°C.
- heating the metallic surface to bind the reagent with the metallic surface comprises heating the metallic surface at a temperature of about 30°C, about 50°C, about 70°C, about 80°C, about 100°C, about 120°C, about 140°C, about 160°C, or about 180°C.
- heating the metallic surface to bind the reagent with the metallic surface comprises heating the metallic surface at a temperature of at most 50°C, at most 70°C, at most 80°C, at most 100°C, at most 120°C, at most 140°C, at most 160°C, or at most 180°C.
- the metallic surface is oxidized. In some embodiments, the metallic surface is an oxidized metallic surface. In some embodiments, the metallic surface is partially oxidized. In some embodiments, the metallic surface is at least partially oxidized. In some embodiments, the metallic surface is fully oxidized.
- the method further comprises the step of oxidizing the metallic surface.
- Oxidizing the metallic surface may be accomplished using any method.
- the metallic surface is oxidized by air oxidation, plasma treatment, ultraviolet-ozone oxidation, or chemical oxidation.
- the metallic surface is oxidized by air oxidation.
- the metallic surface is oxidized by ultraviolet-ozone oxidation.
- the metallic surface is oxidized by plasma treatment.
- the metallic surface is oxidized by chemical oxidation.
- the phosphonic acid or phosphonate ester reagent may have any structure.
- the phosphonic acid or phosphonate ester reagent has the structure wherein each R E is independently H or optionally substituted alkyl; and R is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, or optionally substituted heteroaryl.
- each R E is independently H or optionally substituted C 1 -C 6 alkyl. In some embodiments, each R E is independently H or C 1 -C 6 alkyl. In some embodiments, each R E is independently H, methyl, ethyl, or propyl. In some embodiments, each R E is H. In some embodiments, each R E is independently methyl, ethyl, or propyl.
- the R group of the phosphonic acid or phosphonate ester reagent can be any group.
- R is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, or optionally substituted heteroaryl.
- R is any of the groups R as described in the "Modified Metallic Surfaces” section.
- the phosphonic acid reagent is a phosphonate ester comprising any of the R groups as described in the "Modified Metallic Surfaces” section.
- the phosphonate ester is an alkyl phosphonate ester. In some embodiments, the phosphonate ester is a C 1 -C 6 alkyl phosphonate ester. In some embodiments, the phosphonate ester is a methyl, ethyl, or propyl phosphonate ester.
- the method further comprises adding a second group to the reagent by performing a further reaction.
- further groups are added after attachment of the phosphonic acid or phosphonate ester reagent to the metallic surface. Any suitable reaction conditions that allows for the reaction of the reactive tag or capture moiety may be employed.
- further groups are added by CLICK chemistry.
- further groups are added by nucleophilic addition.
- further groups are added by a polymerization reaction.
- the polymerization reaction is atom-transfer radical- polymerization via (ATRP). In some embodiments, the polymerization reaction is reversible addition-fragmentation chain-transfer (RAFT) polymerization. In some embodiments, further groups are added by a cycloaddition reaction. In some embodiments, further groups are added by a conjugation reaction. In some embodiments, further groups are added by a bioconjugation reaction. The reactions used to add further groups may be employed in any solvent or solutions, such as an organic solvent, aqueous solution, or suitable buffer.
- determining means determining if an element is present or not (for example, detection). These terms can include quantitative, qualitative or quantitative and qualitative determinations. Assessing can be relative or absolute. "Detecting the presence of’ can include determining the amount of something present in addition to determining whether it is present or absent depending on the context.
- a “ subject” can be a biological entity containing expressed genetic materials.
- the biological entity can be a plant, animal, or microorganism, including, for example, bacteria, viruses, fungi, and protozoa.
- the subject can be tissues, cells and their progeny of a biological entity obtained in vivo or cultured in vitro.
- the subject can be a mammal.
- the mammal can be a human.
- the subject may be diagnosed or suspected of being at high risk for a disease. In some cases, the subject is not necessarily diagnosed or suspected of being at high risk for the disease.
- the term "about” a number refers to that number plus or minus 10% of that number.
- the term “about” a range refers to that range minus 10% of its lowest value and plus 10% of its greatest value.
- Alkyl refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, which may optionally be unsaturated with one or more double or triple bonds. The alkyl is attached to the rest of the molecule by a single bond. Unless otherwise specified, the term “alkyl” and its equivalents encompass linear or branched alkyl groups. When an alkyl group is described as “linear,” the referenced alkyl group is not substituted with additional alkyl groups and is unbranched. When an alkyl group is described as " saturated,” the referenced alkyl group does not contain any double or triple carbon-carbon bonds (e.g. alkene or alkyne).
- the alkyl groups may be of any length, including, for example, one to fifteen carbon atoms (i.e., C 1 -C 15 alkyl), one to thirteen carbon atoms (i.e., C 1 -C 13 alkyl), one to eight carbon atoms (i.e., C 1 -C 8 alkyl), one to five carbon atoms (i.e., C 1 -C 5 alkyl), one to three carbon atoms (i.e., C 1 -C 3 alkyl), or one carbon atom (i.e., C 1 alkyl). Additional lengths are also possible, such as up to twenty carbon atoms, up to thirty carbon atoms, up to fifty carbon atoms, or up to one hundred carbon atoms.
- the alkyl group is selected from methyl, ethyl, 1 -propyl ( «-propyl), 1 -methyl ethyl (iso-propyl), 1 -butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1 -dimethyl ethyl (tert-butyl), 1 -pentyl (n-pentyl).
- Alkenyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms (i.e., C 2 -C 12 alkenyl).
- an alkenyl comprises two to ten carbon atoms (i.e., C 2 -C 10 alkenyl).
- an alkenyl comprises two to eight carbon atoms (i.e., C 2 -C 8 alkenyl).
- an alkenyl comprises two to six carbon atoms (i.e., C 2 -C 6 alkenyl).
- the alkenyl may be attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like.
- ethenyl i.e., vinyl
- prop-1-enyl i.e., allyl
- but-1-enyl i.e., pent-1-enyl, penta-1,4-dienyl, and the like.
- Alkynyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms (i.e., C 2 -C 12 alkynyl).
- an alkynyl comprises two to eight carbon atoms (i.e., C 2 -C 8 alkynyl).
- an alkynyl comprises two to six carbon atoms (i.e., C 2 -C 6 alkynyl).
- an alkynyl comprises two to four carbon atoms (i.e., C 2 -C 4 alkynyl).
- the alkynyl may be attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.
- Alkylene refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, which may optionally by unsaturated with one or more double or triple carbon-carbon bonds, and preferably having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like.
- the alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain.
- an alkylene comprises one to ten carbon atoms (i.e., C 1 -C 8 alkylene). In certain embodiments, an alkylene comprises one to eight carbon atoms (i.e., C 1 -C 8 alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (i.e., C 1 -C 5 alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (i.e., C 1 -C 4 alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (i.e., C 1 -C 3 alkylene).
- an alkylene comprises one to two carbon atoms (i.e., C 1 -C 2 alkylene). In other embodiments, an alkylene comprises one carbon atom (i.e., Ci alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (i.e., C 5 -C 8 alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (i.e., C 2 -C 5 alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (i.e., C 3 -C 5 alkylene).
- Alkenylene or "alkenyl ene chain” refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms.
- the alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond.
- the points of attachment of the alkenylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain.
- an alkenylene comprises two to ten carbon atoms (i.e., C 2 -C 10 alkenylene).
- an alkenylene comprises two to eight carbon atoms (i.e., C 2 -C 8 alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (i.e., C 2 -C 5 alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (i.e., C 2 -C 4 alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (i.e., C 2 -C 3 alkenylene). In other embodiments, an alkenylene comprises two carbon atoms (i.e., C 2 alkenylene).
- an alkenylene comprises five to eight carbon atoms (i.e., C 5 -C 8 alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (i.e., C 3 -C 5 alkenylene).
- Alkynylene or "alkynylene chain” refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms.
- the alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond.
- the points of attachment of the alkynylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain.
- an alkynylene comprises two to ten carbon atoms (i.e., C 2 -C 10 alkynylene).
- an alkynylene comprises two to eight carbon atoms (i.e., C 2 -C 8 alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (i.e., C 2 -C 5 alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (i.e., C 2 -C 4 alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (i.e., C 2 -C 3 alkynylene). In other embodiments, an alkynylene comprises two carbon atoms (i.e., C 2 alkynylene).
- an alkynylene comprises five to eight carbon atoms (i.e., C 5 -C 8 alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (i.e., C 3 -C 5 alkynylene).
- Aryl refers to an aromatic monocyclic or aromatic multicyclic hydrocarbon ring system.
- the aromatic monocyclic or aromatic multicyclic hydrocarbon ring system contains only hydrogen and carbon and from five to eighteen carbon atoms, where at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) ⁇ -electron system in accordance with the Hiickel theory.
- the ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene.
- alkyl refers to a radical of the formula -R c -aryl where R c is an alkylene chain as defined above, for example, methylene, ethylene, and the like.
- R c is an alkylene chain as defined above, for example, methylene, ethylene, and the like.
- the alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain.
- alkenyl refers to a radical of the formula -R d -aryl where R d is an alkenylene chain as defined above.
- R d is an alkenylene chain as defined above.
- the aryl part of the aralkenyl radical is optionally substituted as described above for an aryl group.
- Alkynyl refers to a radical of the formula -R e -aryl, where R e is an alkynylene chain as defined above.
- the aryl part of the aralkynyl radical is optionally substituted as described above for an aryl group.
- C x.y or "C x -C y ” when used in conjunction with a chemical moiety, such as alkyl, alkenyl, or alkynyl is meant to include groups that contain from x to y carbons in the chain.
- C x.y alkyl refers to saturated or unsaturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups that contain from x to y carbons in the chain.
- C x.y alkenyl and C x.y alkynyl refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.
- Cycloalkyl refers to a saturated ring in which each atom of the ring is carbon. Cycloalkyl may include monocyclic and polycyclic rings such as 3- to 10-membered monocyclic rings, 6- to 12- membered fused bicyclic rings, 6- to 12-membered spirocyclic rings, and 6- to 12-membered bridged rings. In certain embodiments, a cycloalkyl comprises three to ten carbon atoms. In other embodiments, a cycloalkyl comprises five to seven carbon atoms. The cycloalkyl may be attached to the rest of the molecule by a single bond.
- Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.
- Polycyclic cycloalkyl radicals include, for example, adamantyl, norbomyl (z ' .e., bicyclo[2.2.1]heptanyl), norbomenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like.
- a cycloalkyl group as described herein may contain one or more carbon-carbon double or triple bonds.
- Heteroalkyl refers to a straight or branched hydrocarbon chain radical containing one or more heteroatoms.
- the heteroalkyl group may optionally be unsaturated with one or more double or triple bonds, either between adjacent carbon atoms, a carbon atom and a hetero atom, or between two heteroatoms.
- the heteroalkyl is attached to the rest of the molecule by a single bond.
- the term “heteroalkyl” and its equivalents encompass linear or branched alkyl groups. When a heteroalkyl group is described as "linear,” the referenced heteroalkyl group is not substituted with additional alkyl or heteroalkyl groups and is unbranched.
- heteroalkyl group When an heteroalkyl group is described as " saturated,” the referenced alkyl group does not contain any double or triple bonds (e.g. alkene or alkyne).
- the heteroalkyl groups may be of any length, including, for example, one to fifteen atom, one to thirteen atoms, one to eight atoms, one to five atoms, one to three atoms, or one to two atoms. Longer lengths are also possible, such as up to twenty atoms, up to thirty atoms, up to fifty atoms, or up to one hundred atoms.
- Heteroalkylene refers to a straight or branched divalent chain linking the rest of the molecule to a radical group, consisting of carbon , hydrogen, and one or more heteroatoms which may optionally by unsaturated with one or more double or triple carbon-carbon or carbon-heteroatom bonds.
- exemplary heteroatoms include N, O, Si, P, B, and S atoms.
- the heteroalkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the heteroalkylene chain to the rest of the molecule and to the radical group may be through any two atoms within the chain.
- Heterocycle refers to a saturated, unsaturated or aromatic ring comprising carbon atoms and one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycle may be monocyclic or polycyclic and may include 3- to 10-membered monocyclic rings, 6- to 12-membered fused bicyclic rings, 6- to 12-membered spirocyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. In some embodiments, the heterocycle is a heteroaryl. In some embodiments, the heterocycle is a heterocycloalkyl.
- a heterocycle e.g., pyridyl
- a saturated or unsaturated ring e.g., cyclohexane, cyclopentane, or cyclohexene.
- Heterocycloalkyl refers to a saturated ring with carbon atoms and at least one heteroatom. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycloalkyl may include monocyclic and polycyclic rings such as 3- to 10-membered monocyclic rings, 6- to 12- membered fused bicyclic rings, 6- to 12-membered spirocyclic rings, and 6- to 12-membered bridged rings. The heteroatoms in the heterocycloalkyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized.
- heterocycloalkyl is attached to the rest of the molecule through any atom of the heterocycloalkyl, valence permitting, such as any carbon or nitrogen atoms of the heterocycloalkyl.
- heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl,
- Heterocycloalkenyl refers to a saturated ring with carbon atoms and at least one heteroatom and there is at least one double bond between two ring carbons.
- exemplary heteroatoms include N, O, Si, P, B, and S atoms.
- Heterocycloalkenyl may include monocyclic and polycyclic rings such as 3- to 10-membered monocyclic rings, 6- to 12-membered fused bicyclic rings, 6- to 12- membered spirocyclic rings, and 6- to 12-membered bridged rings.
- a heterocycloalkenyl comprises five to seven ring atoms. The heterocycloalkenyl may be attached to the rest of the molecule by a single bond.
- Examples of monocyclic cycloalkenyls include, e.g., pyrroline (dihydropyrrole), pyrazoline (dihydropyrazole), imidazoline (dihydroimidazole), triazoline (dihydrotriazole), dihydrofuran, dihydrothiophene, oxazoline (dihydrooxazole), isoxazoline (dihydroisoxazole), thiazoline (dihydrothiazole), isothiazoline (dihydroisothiazole), oxadiazoline (dihydrooxadiazole), thiadiazoline (dihydrothiadiazole), dihydropyridine, tetrahydropyridine, dihydropyridazine, tetrahydropyridazine, dihydropyrimidine, tetrahydropyrimidine, dihydropyrazine, tetrahydropyrazine,
- Heteroaryl refers to an aromatic ring comprising carbon atoms and one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridged ring systems rings wherein at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) p-electron system in accordance with the Hiickel theory.
- the heteroatom(s) in the heteroaryl radical may be optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized.
- heteroaryl may be attached to the rest of the molecule through any atom of the heteroaryl, valence permitting, such as a carbon or nitrogen atom of the heteroaryl.
- heteroaryls include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzooxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[Z>][l,4]dioxepinyl, benzo[b][l,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (
- substituted refers to moieties having substituents replacing a hydrogen on one or more carbons or heteroatoms of the structure. It will be understood that " substitution” or “ substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term " substituted” is contemplated to include all permissible substituents of organic compounds.
- the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds.
- the permissible substituents can be one or more and the same or different for appropriate organic compounds.
- the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms.
- a specified group is described as "optionally substituted,” it is intended that the group may or may not contain a substituent.
- the substituents described herein may themselves be further substituted with their own substituents, with each of these substituents being further optionally substituted.
- Substituents can include any substituents described herein, for example, a halogen, a hydroxyl, a carbonyl (such as a carboxyl, an alkoxycarbonyl, a formyl, or an acyl), a thiocarbonyl (such as a thioester, a thioacetate, or a thioformate), an alkoxyl, a phosphoryl, a phosphate, a phosphonate, a phosphinate, an amino, an amido, an amidine, an imine, a cyano, a nitro, an azido, a sulfhydryl, an alkylthio, a sulfate, a sulfonate, a sulfamoyl, a sulfonamido, a sulfonyl, an aralkyl, a carbocycle, a heterocycle, a
- any group bearing multiple points of attachment to a parent molecule or to two or more moieties can be oriented in any direction.
- B is it is intended that both and are encompassed.
- a variety of conditions for functionalizing a platinum surface were attempted in order to attach a phosphonic acid reagent to the platinum surface.
- the reagent 11-((2-BROMO-2- METHYLPROPANOYL)OXY)UNDECYL)PHOSPHONIC ACID (BMPOUA) was selected because it contains the 2-bromo-2-methylpropanoyl moiety to allow for further functionalization of the platinum surface after attachment of the phosphonic acid moiety directly to the surface.
- Plasma treated and untreated platinum chips were analyzed by X-ray photoelectron spectroscopy (XPS) in order to assess the oxidation state of the chips.
- Atomic composition and chemical state information was obtained on a PHI Quantum 2000 using the following parameters: X- ray source: Monochromated Alk ⁇ 1486.6eV; Acceptance Angle: ⁇ 23°; Take-off Angle: 45°; Analysis area: 600 ⁇ m diameter; Charge Correction: Cls 284.8eV (C-C, C-H).
- Chemical state assignments for a given element were made by consulting reference data from the literature. Non-linear least squares (NLLS) curve fitting was applied to assist in chemical state assignment.
- NLLS Non-linear least squares
- FIG. 3A and FIG. 3B XPS measurements of the oxidized and untreated platinum chips are shown in FIG. 3A and FIG. 3B.
- FIG. 3A shows a survey scan of the surfaces of three chips. Chips 1 and 2 were subjected to plasma treatment, and Chip 3 was untreated.
- FIG. 3B shows an XPS assessment of the various oxidation states of platinum on the chip. The data indicates that the platinum existed in various oxidation states on each chip. The relative proportion of platinum in each oxidation state (Pt 0 , Pt 2+ , Pt 4+ ) for the oxidized platinum and non-plasma treated chips is shown in Table 1 below. For the untreated chip, most of the platinum was in an unoxidized state. In contrast, the plasma treated platinum chips showed elevated levels of oxidized platinum.
- BMPOUA (Millipore Sigma) was dissolved in ethanol (Millipore Sigma) at a concentration of 1.2 mM. After mixing at room temperature for 5 minutes the solution was poured into a reaction vessel and the platinum metal substrate (plasma treated, untreated, or post-etch removal reagent treated) was submerged in the phosphonic acid solution without stirring. The reaction vessel was flushed with ultra-high purity argon gas (Airgas) for 5 minutes, and the platinum substrate remained submerged for 18 hours at room temperature.
- Airgas ultra-high purity argon gas
- the substrate was removed from the ethanol solution and placed directly into an oven (VWR Gravity Convection Oven) without washing at 140 C for 2 hours to allow the BMPOUA to anneal to the substrate.
- VWR Gravity Convection Oven VWR Gravity Convection Oven
- the materials were subject to a polymerization reaction with an acrylate reagent. If the platinum surface was successfully modified with BMPOUA, a polymer should "grow” on the platinum surface under the reaction conditions. The more BMPOUA that is bound to the surface of the platinum substrate, the more polymer will be present bound to the chip following the reaction.
- BMPOUA Millipore Sigma
- ethanol Millipore Sigma
- the reaction vessel was flushed with ultra-high purity argon gas (Airgas) for 5 minutes, and the platinum substrate remained submerged for 18 hours at room temperature.
- FIG. 4 shows an image of a bare platinum electrode before surface functionalization.
- the arithmetic mean height (Sa) before functionalization is 0.763 nm.
- FIG. 5 shows the same platinum electrode following functionalization with BMPOUA phosphonic acid reagent as described above. The Sa electrode after functionalization increased to 2.328 nm, consistent with successful attachment of the reagent.
- FIG. 6A shows an SEM image of a bare platinum electrode surrounded by dielectric at a tilt angle of 45°. Both the platinum metal surface and dielectric appear smooth.
- FIG. 6B shows a platinum electrode functionalized with BMPOUA followed by a polymerization reaction similarly surrounded by a dielectric material. After running electric current through the electrode in FIG. 6B, polymer "folding” is observed at the edge of the modified platinum surface near the interface of the dielectric material.
- FIGs 7-10 show additional SEM images of polymer functionalized platinum electrodes.
- FIG. 7 shows an SEM image taken from a 0° tilt angle. Folded polymer can be seen on the platinum surface.
- FIG. 8 shows an SEM image taken a 14° tilt angle. Polymer folding near the interface of the platinum surface and the dielectric layer can be clearly seen.
- FIG. 9 shows a similar SEM image at a tilt angle of 14°. The region captured is the same as FIG. 8, but with a broader view.
- FIG. 10 shows an additional SEM image at a tilt angle of 14° from a further zoomed out view.
- FIGs 11-14 show SEM images of unfunctionalized platinum electrodes surrounded by a dielectric material. Notably, all of the images show a smooth surface as compared to the functionalized platinum surfaces shown in FIGs 7-10.
- FIG. 11 shows an SEM image at a tilt angle of 1°. The left side of the image shows the platinum surface with a dielectric material at the right side.
- FIG. 12 shows a SEM image of the same electrode at a 45° tilt angle. The interface of the platinum surface and dielectric material appears smooth.
- FIG. 13 shows an SEM image at a 4° tilt angle in a zoomed-out view of the electrode.
- FIG. 14 shows a close-up image of the smooth platinum surface boundary with the dielectric material at an angle of 45°.
Landscapes
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Mechanical Engineering (AREA)
- Metallurgy (AREA)
- Organic Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Other Surface Treatments For Metallic Materials (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2021304354A AU2021304354A1 (en) | 2020-07-10 | 2021-07-09 | Modification of metallic surfaces with phosphonic acids |
US18/004,659 US20230250536A1 (en) | 2020-07-10 | 2021-07-09 | Modification of metallic surfaces with phosphonic acids |
EP21838455.0A EP4179133A4 (en) | 2020-07-10 | 2021-07-09 | Modification of metallic surfaces with phosphonic acids |
CN202180054777.4A CN116348638A (en) | 2020-07-10 | 2021-07-09 | Modification of metal surfaces by phosphonic acids |
JP2023501337A JP2023533742A (en) | 2020-07-10 | 2021-07-09 | Modification of metal surfaces with phosphonic acid |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063050228P | 2020-07-10 | 2020-07-10 | |
US63/050,228 | 2020-07-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022011313A1 true WO2022011313A1 (en) | 2022-01-13 |
Family
ID=79552716
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2021/041177 WO2022011313A1 (en) | 2020-07-10 | 2021-07-09 | Modification of metallic surfaces with phosphonic acids |
Country Status (6)
Country | Link |
---|---|
US (1) | US20230250536A1 (en) |
EP (1) | EP4179133A4 (en) |
JP (1) | JP2023533742A (en) |
CN (1) | CN116348638A (en) |
AU (1) | AU2021304354A1 (en) |
WO (1) | WO2022011313A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11534756B2 (en) | 2016-03-24 | 2022-12-27 | Biological Dynamics, Inc. | Compact device for detection of nanoscale analytes |
US11731132B2 (en) | 2017-12-19 | 2023-08-22 | Biological Dynamics, Inc. | Methods and devices for detection of multiple analytes from a biological sample |
US11883833B2 (en) | 2018-04-02 | 2024-01-30 | Biological Dynamics, Inc. | Dielectric materials |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100167072A1 (en) * | 2008-12-29 | 2010-07-01 | Basf Corporation | Electrocoat composition and process replacing phosphate pretreatment |
US20170292064A1 (en) * | 2013-09-20 | 2017-10-12 | Baker Hughes Incorporated | Method of pumping aqueous fluid containing surface modifying treatment agent into a well |
US20190017107A1 (en) * | 2013-03-14 | 2019-01-17 | Life Technologies Corporation | Matrix arrays and methods for making same |
WO2019200323A1 (en) * | 2018-04-13 | 2019-10-17 | Molecular Surface Technologies, Llc | Electrochemical attachment of phosphonic acids to metallic substrates and osteoconductive medical devices containing same |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060194008A1 (en) * | 1999-09-22 | 2006-08-31 | Princeton University | Devices with multiple surface functionality |
US20090123516A1 (en) * | 2005-08-08 | 2009-05-14 | The Board Of Regents Of The University Of Texas System | Drug delivery from implants using self-assembled monolayers-therapeutic sams |
US7883738B2 (en) * | 2007-04-18 | 2011-02-08 | Enthone Inc. | Metallic surface enhancement |
FR2990433A1 (en) * | 2012-05-10 | 2013-11-15 | Surfactis Technologies | CATANIONIC SURFACE RECOVERY COMPOSITIONS THROUGH PHOSPHONIC MOLECULES AND AMINES |
FR3026412B1 (en) * | 2014-09-26 | 2019-03-29 | Aperam | SURFACE TREATMENT OF METAL SUBSTRATES |
US11002730B2 (en) * | 2018-05-23 | 2021-05-11 | International Business Machines Corporation | Molecular design to suppress desorption of self-assembled monolayers |
-
2021
- 2021-07-09 WO PCT/US2021/041177 patent/WO2022011313A1/en unknown
- 2021-07-09 AU AU2021304354A patent/AU2021304354A1/en active Pending
- 2021-07-09 EP EP21838455.0A patent/EP4179133A4/en active Pending
- 2021-07-09 JP JP2023501337A patent/JP2023533742A/en active Pending
- 2021-07-09 US US18/004,659 patent/US20230250536A1/en active Pending
- 2021-07-09 CN CN202180054777.4A patent/CN116348638A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100167072A1 (en) * | 2008-12-29 | 2010-07-01 | Basf Corporation | Electrocoat composition and process replacing phosphate pretreatment |
US20190017107A1 (en) * | 2013-03-14 | 2019-01-17 | Life Technologies Corporation | Matrix arrays and methods for making same |
US20170292064A1 (en) * | 2013-09-20 | 2017-10-12 | Baker Hughes Incorporated | Method of pumping aqueous fluid containing surface modifying treatment agent into a well |
WO2019200323A1 (en) * | 2018-04-13 | 2019-10-17 | Molecular Surface Technologies, Llc | Electrochemical attachment of phosphonic acids to metallic substrates and osteoconductive medical devices containing same |
Non-Patent Citations (2)
Title |
---|
RYAN D. ROSS, RYAN K. ROEDER: "Binding affinity of surface functionalized gold nanoparticles to hydroxyapatite", JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, JOHN WILEY & SONS, vol. 99A, no. 1, 1 October 2011 (2011-10-01), pages 58 - 66, XP055059995, ISSN: 15493296, DOI: 10.1002/jbm.a.33165 * |
See also references of EP4179133A4 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11534756B2 (en) | 2016-03-24 | 2022-12-27 | Biological Dynamics, Inc. | Compact device for detection of nanoscale analytes |
US11731132B2 (en) | 2017-12-19 | 2023-08-22 | Biological Dynamics, Inc. | Methods and devices for detection of multiple analytes from a biological sample |
US11883833B2 (en) | 2018-04-02 | 2024-01-30 | Biological Dynamics, Inc. | Dielectric materials |
Also Published As
Publication number | Publication date |
---|---|
JP2023533742A (en) | 2023-08-04 |
CN116348638A (en) | 2023-06-27 |
EP4179133A1 (en) | 2023-05-17 |
US20230250536A1 (en) | 2023-08-10 |
EP4179133A4 (en) | 2024-03-20 |
AU2021304354A1 (en) | 2023-03-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20230250536A1 (en) | Modification of metallic surfaces with phosphonic acids | |
DE60027309T2 (en) | POLYMER BRANCHES FOR THE IMMOBILIZATION OF MOLECULES ON SURFACES OR SUBSTRATES WHERE THE POLYMERS HAVE WATER-SOLUBLE OR WATER-DISPERSIBLE SEGMENTS AND PROBES | |
EP3202799B1 (en) | Block copolymer | |
JP2011518907A (en) | Modified halogenated polymer surface | |
Gabriel et al. | Cathodic electrografting of acrylics: From fundamentals to functional coatings | |
US20220154177A1 (en) | Functionalized plasmonic nanostructures | |
Wu et al. | Accelerating the design of gold/polymers/silica-based imprinted nanocomposite for light-triggered recognition and separation of biomolecules | |
Baccar et al. | Development of an impedimetric DNA-biosensor based on layered double hydroxide for the detection of long ssDNA sequences | |
WO2019032265A9 (en) | Ultrathin, conductive and fouling-resistant zwitterionic polymer films | |
Laure et al. | Switching the wettability of titanium surfaces through diels–alder chemistry | |
ES2299431T3 (en) | PHOTOINJERTABLE ELECTROPOLIMEROS, ITS OBTAINING PROCEDURE AND ITS APPLICATIONS AS SUPPORTS OF SPECIFIC RECOGNITION PROBES IN ELECTRONIC BIOCEPTERS. | |
AU2013262429B2 (en) | Hydrogen cyanide-based polymer surface coatings and hydrogels | |
Flemming et al. | Multiresponsive transitions of PDMAEMA brushes for tunable surface patterning | |
Cimen et al. | Preparation of oligo‐N‐isopropylacrylamide brushes with OH and COOH end‐groups via surface‐initiated NMP | |
US20040191538A1 (en) | Nanometer-controlled polymeric thin films that resist adsorption of biological molecules and cells | |
Henry et al. | Electrochemical genosensor based on three-dimensional DNA polymer brushes monolayers | |
US10208225B2 (en) | Fluoro copolymers, immobilization of biomolecules, and microarrays | |
de León et al. | Straightforward functionalization of breath figures: simultaneous orthogonal host–guest and pH-responsive interfaces | |
WO2006128644A1 (en) | Polymer coating and functionalization of solid surfaces | |
Rodríguez-Hernández | Nano-microporous structured surfaces prepared by the breath figures approach and their biorelated applications | |
KR20200092691A (en) | Polymer Thin Films for Collecting and Immobilizing Gene and Method for Preparing the Same | |
TWI535750B (en) | Polymer composition on substrate and surface modification method | |
TWI663190B (en) | A zwitterionic hydrogel and application thereof | |
Arafeh | Micro-and nano-patterned gold structures for selective immobilization of proteins | |
Chen | Reactive Polymer Coatings: A Robust Platform Towards Sophisticated Surface Engineering for Biotechnology. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21838455 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2023501337 Country of ref document: JP Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2021838455 Country of ref document: EP Effective date: 20230210 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2021304354 Country of ref document: AU Date of ref document: 20210709 Kind code of ref document: A |