WO1998035053A2 - Electrochemical analyte sensors using thermostable soybean peroxidase - Google Patents
Electrochemical analyte sensors using thermostable soybean peroxidase Download PDFInfo
- Publication number
- WO1998035053A2 WO1998035053A2 PCT/US1998/002403 US9802403W WO9835053A2 WO 1998035053 A2 WO1998035053 A2 WO 1998035053A2 US 9802403 W US9802403 W US 9802403W WO 9835053 A2 WO9835053 A2 WO 9835053A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- enzyme
- sensor
- electrode
- layer
- polymer
- Prior art date
Links
- 239000012491 analyte Substances 0.000 title claims abstract description 50
- 102000003992 Peroxidases Human genes 0.000 title claims abstract description 49
- 108040007629 peroxidase activity proteins Proteins 0.000 title claims description 47
- 244000068988 Glycine max Species 0.000 title claims description 15
- 235000010469 Glycine max Nutrition 0.000 title claims description 15
- 102000004190 Enzymes Human genes 0.000 claims abstract description 163
- 108090000790 Enzymes Proteins 0.000 claims abstract description 163
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 104
- 229920000642 polymer Polymers 0.000 claims abstract description 71
- 239000011159 matrix material Substances 0.000 claims abstract description 30
- 238000005259 measurement Methods 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 6
- 230000003100 immobilizing effect Effects 0.000 claims abstract description 4
- -1 osmium cation Chemical class 0.000 claims description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- 229920002301 cellulose acetate Polymers 0.000 claims description 32
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 28
- 239000001301 oxygen Substances 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 21
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 20
- 229920001296 polysiloxane Polymers 0.000 claims description 18
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 16
- 102000004316 Oxidoreductases Human genes 0.000 claims description 16
- 108090000854 Oxidoreductases Proteins 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 16
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000012528 membrane Substances 0.000 claims description 14
- 230000035945 sensitivity Effects 0.000 claims description 14
- 229910052710 silicon Inorganic materials 0.000 claims description 14
- 239000010703 silicon Substances 0.000 claims description 13
- 230000035699 permeability Effects 0.000 claims description 12
- 229940072107 ascorbate Drugs 0.000 claims description 10
- 235000010323 ascorbic acid Nutrition 0.000 claims description 10
- 239000011668 ascorbic acid Substances 0.000 claims description 10
- 229910052762 osmium Inorganic materials 0.000 claims description 10
- 239000012633 leachable Substances 0.000 claims description 8
- 229960005489 paracetamol Drugs 0.000 claims description 8
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 7
- 108090000623 proteins and genes Proteins 0.000 claims description 7
- 210000001124 body fluid Anatomy 0.000 claims description 6
- 239000010839 body fluid Substances 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 229920000447 polyanionic polymer Polymers 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229920000620 organic polymer Polymers 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- 229910001882 dioxygen Inorganic materials 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 238000000840 electrochemical analysis Methods 0.000 claims 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 85
- 239000000499 gel Substances 0.000 abstract description 28
- 239000000377 silicon dioxide Substances 0.000 abstract description 13
- 239000000017 hydrogel Substances 0.000 abstract description 9
- 230000004044 response Effects 0.000 abstract description 7
- 238000006116 polymerization reaction Methods 0.000 abstract description 4
- 230000006641 stabilisation Effects 0.000 abstract description 3
- 238000011105 stabilization Methods 0.000 abstract description 3
- 238000001514 detection method Methods 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 137
- 229940088598 enzyme Drugs 0.000 description 132
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 72
- 239000008103 glucose Substances 0.000 description 72
- 239000000243 solution Substances 0.000 description 65
- 239000000741 silica gel Substances 0.000 description 59
- 229910002027 silica gel Inorganic materials 0.000 description 59
- 229960001866 silicon dioxide Drugs 0.000 description 55
- 108010015776 Glucose oxidase Proteins 0.000 description 54
- 239000004366 Glucose oxidase Substances 0.000 description 53
- 229940116332 glucose oxidase Drugs 0.000 description 53
- 235000019420 glucose oxidase Nutrition 0.000 description 53
- 108010073450 Lactate 2-monooxygenase Proteins 0.000 description 48
- 239000000843 powder Substances 0.000 description 47
- 230000000694 effects Effects 0.000 description 46
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 43
- 238000012360 testing method Methods 0.000 description 22
- 239000000758 substrate Substances 0.000 description 21
- 238000011068 loading method Methods 0.000 description 18
- 229920002006 poly(N-vinylimidazole) polymer Polymers 0.000 description 18
- 102100038837 2-Hydroxyacid oxidase 1 Human genes 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 14
- 108010062584 glycollate oxidase Proteins 0.000 description 14
- 230000004907 flux Effects 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 10
- 229920002873 Polyethylenimine Polymers 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 8
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- LRCFXGAMWKDGLA-UHFFFAOYSA-N dioxosilane;hydrate Chemical compound O.O=[Si]=O LRCFXGAMWKDGLA-UHFFFAOYSA-N 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 229960004029 silicic acid Drugs 0.000 description 7
- 241000894007 species Species 0.000 description 7
- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 description 7
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000004971 Cross linker Substances 0.000 description 5
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 5
- 229940061720 alpha hydroxy acid Drugs 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000004132 cross linking Methods 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 230000000977 initiatory effect Effects 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 239000000693 micelle Substances 0.000 description 5
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 150000002978 peroxides Chemical class 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 239000008055 phosphate buffer solution Substances 0.000 description 5
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 229940013640 flavin mononucleotide Drugs 0.000 description 4
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 4
- FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 4
- 239000011768 flavin mononucleotide Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000004570 mortar (masonry) Substances 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 229920002379 silicone rubber Polymers 0.000 description 4
- 238000003980 solgel method Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241000228245 Aspergillus niger Species 0.000 description 3
- 208000013016 Hypoglycemia Diseases 0.000 description 3
- 239000004642 Polyimide Substances 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 239000008119 colloidal silica Substances 0.000 description 3
- 230000000536 complexating effect Effects 0.000 description 3
- 238000002484 cyclic voltammetry Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- GYZLOYUZLJXAJU-UHFFFAOYSA-N diglycidyl ether Chemical compound C1OC1COCC1CO1 GYZLOYUZLJXAJU-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 230000002218 hypoglycaemic effect Effects 0.000 description 3
- 239000012212 insulator Substances 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 229920001721 polyimide Polymers 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000008279 sol Substances 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- IZQAUUVBKYXMET-UHFFFAOYSA-N 2-bromoethanamine Chemical compound NCCBr IZQAUUVBKYXMET-UHFFFAOYSA-N 0.000 description 2
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N 4-aminoantipyrine Chemical compound CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- 241000193792 Aerococcus viridans Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 108090000841 L-Lactate Dehydrogenase (Cytochrome) Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 241000656145 Thyrsites atun Species 0.000 description 2
- 150000001280 alpha hydroxy acids Chemical class 0.000 description 2
- 235000009697 arginine Nutrition 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- ZOMNIUBKTOKEHS-UHFFFAOYSA-L dimercury dichloride Chemical compound Cl[Hg][Hg]Cl ZOMNIUBKTOKEHS-UHFFFAOYSA-L 0.000 description 2
- 239000000806 elastomer Substances 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 238000006056 electrooxidation reaction Methods 0.000 description 2
- 229910021397 glassy carbon Inorganic materials 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000075 poly(4-vinylpyridine) Polymers 0.000 description 2
- 239000013047 polymeric layer Substances 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical group OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 2
- 230000027756 respiratory electron transport chain Effects 0.000 description 2
- WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 2
- 239000004945 silicone rubber Substances 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- RGEMJCLUPGZKTQ-WAUHAFJUSA-N (3s,8r,9s,10r,13s,14s)-3-[2-(dimethylamino)ethoxy]-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one Chemical compound C([C@@H]12)C[C@]3(C)C(=O)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OCCN(C)C)C1 RGEMJCLUPGZKTQ-WAUHAFJUSA-N 0.000 description 1
- 108030001056 (S)-2-hydroxy-acid oxidases Proteins 0.000 description 1
- 102100038838 2-Hydroxyacid oxidase 2 Human genes 0.000 description 1
- DUHQIGLHYXLKAE-UHFFFAOYSA-N 3,3-dimethylglutaric acid Chemical compound OC(=O)CC(C)(C)CC(O)=O DUHQIGLHYXLKAE-UHFFFAOYSA-N 0.000 description 1
- IMEVSAIFJKKDAP-UHFFFAOYSA-N 4-methoxy-2-(4-methoxypyridin-2-yl)pyridine Chemical compound COC1=CC=NC(C=2N=CC=C(OC)C=2)=C1 IMEVSAIFJKKDAP-UHFFFAOYSA-N 0.000 description 1
- NBPGPQJFYXNFKN-UHFFFAOYSA-N 4-methyl-2-(4-methylpyridin-2-yl)pyridine Chemical compound CC1=CC=NC(C=2N=CC=C(C)C=2)=C1 NBPGPQJFYXNFKN-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102000036112 FAD binding proteins Human genes 0.000 description 1
- 108091000329 FAD binding proteins Proteins 0.000 description 1
- 206010053172 Fatal outcomes Diseases 0.000 description 1
- 102000003983 Flavoproteins Human genes 0.000 description 1
- 108010057573 Flavoproteins Proteins 0.000 description 1
- 108010050375 Glucose 1-Dehydrogenase Proteins 0.000 description 1
- 244000286779 Hansenula anomala Species 0.000 description 1
- 235000014683 Hansenula anomala Nutrition 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 108010022399 L-2-hydroxyacid oxidase Proteins 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 108700020962 Peroxidase Proteins 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 244000300264 Spinacia oleracea Species 0.000 description 1
- 235000009337 Spinacia oleracea Nutrition 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000008364 bulk solution Substances 0.000 description 1
- 229940075397 calomel Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000010292 electrical insulation Methods 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- FDQKSGOYXZLUKK-UHFFFAOYSA-N ethanamine;pyridine Chemical group CCN.C1=CC=NC=C1 FDQKSGOYXZLUKK-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 150000003893 lactate salts Chemical group 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- 229910052745 lead Inorganic materials 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 150000002669 lysines Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- GUAWMXYQZKVRCW-UHFFFAOYSA-N n,2-dimethylaniline Chemical compound CNC1=CC=CC=C1C GUAWMXYQZKVRCW-UHFFFAOYSA-N 0.000 description 1
- ZBJVLWIYKOAYQH-UHFFFAOYSA-N naphthalen-2-yl 2-hydroxybenzoate Chemical compound OC1=CC=CC=C1C(=O)OC1=CC=C(C=CC=C2)C2=C1 ZBJVLWIYKOAYQH-UHFFFAOYSA-N 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000001453 nonthrombogenic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940079877 pyrogallol Drugs 0.000 description 1
- 239000001008 quinone-imine dye Substances 0.000 description 1
- 150000004053 quinones Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010405 reoxidation reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HFQQZARZPUDIFP-UHFFFAOYSA-M sodium;2-dodecylbenzenesulfonate Chemical compound [Na+].CCCCCCCCCCCCC1=CC=CC=C1S([O-])(=O)=O HFQQZARZPUDIFP-UHFFFAOYSA-M 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/6825—Nucleic acid detection involving sensors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/001—Enzyme electrodes
- C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/817—Enzyme or microbe electrode
Definitions
- thermostable analyte sensors More particularly, the invention relates to electrochemical sensors for the measurement of bioanalytes such as glucose and lactate.
- the inventive sensors include a thermostable peroxidase, such as soybean peroxidase, disposed on an electrode in a redox-compound-containing film.
- the sensor further includes a hydrogen peroxide- producing enzyme.
- the inventive sensors for example in the measurement of blood glucose or lactate, operate for five days or more at 37° C, losing less than 10% of their sensitivity during continuous or intermittent operation.
- the assay of biochemicals is important in medicine, biotechnology, and food processing (dairy and wine).
- Monitoring of glucose concentrations in fluids of the human body is of particular relevance to diabetes management.
- Monitoring of lactate in fluids of the human body is of relevance to diagnosis of trauma, of myocardial infarction, congestive heart failure, pulmonary edema, septicemia, hemorrhage, and others.
- Blood lactate levels above 7-8mM are indicative of a fatal outcome.
- Bedside analyzers of lactate are useful in determining the response of patients to treatment, while in accidents and battle, they are useful in triage.
- Glucose assays are common in clinical practice and are applied in the diagnosis of Diabetes Mellitus and its management.
- Continuously or intermittently operating glucose sensors are sought for the management of Type I diabetes, for example, for warning of imminent or actual hypoglycemia and its avoidance.
- Hypoglycemia can be fatal.
- For maintenance of diabetic patients at or near normal blood glucose levels frequent or continuous monitoring of glucose is needed.
- the present invention discloses material, structures, and methods enabling continuous operation of electrochemical sensors, for example, measuring glucose for more than one week or measuring lactate for more than 100 hours, with less than 10% loss in sensitivity.
- Novel electrochemical sensors are presented, some of which are capable of operating at 37°C continuously or intermittently, measuring biochemicals in body fluids with less than 10% loss of sensitivity in more than 100 hours of operation are described herein.
- the inventive sensors are relatively insensitive to electrooxidizable interferants, including ascorbate and acetaminophen.
- the sensors of the invention include at least two enzymes, a thermostable peroxidase, such as soybean peroxidase, and a peroxidase-generating enzyme.
- a thermostable peroxidase such as soybean peroxidase
- a peroxidase-generating enzyme e.g., a peroxidase-generating enzyme.
- redox centers of a thermostable peroxidase are electroreduced by electrons transported from a working electrode through a redox hydrogel in which the thermostable peroxidase is immobilized, preferably at a potential negative of 0.4 V versus the standard calomel electrode (SCE) and positive of -0.15 V (vs SCE).
- SCE standard calomel electrode
- vs SCE positive of -0.15 V
- the thermostable peroxidase is coated on the electrode at a potential near 0.0V (vs SCE).
- the preferred redox hydrogel comprises at least 20% by weight of water when in contact with a fluid to be assayed, and its redox centers are not leached by the assay fluid at 37°C.
- Non-leachable redox centers are bound to a polymer that forms the hydrogel upon water uptake.
- the binding to the polymer is through covalent, electrostatic/ionic, or coordination bonds.
- the redox centers of the peroxide-generating enzyme are preferably electrically insulated from the electrode, from the redox centers of the thermostable peroxidase, and from the redox centers of the redox hydrogel.
- the electrically insulated, peroxide-generating enzyme catalyzes reaction of a biochemical analyte, e.g., glucose or lactate, or a product of the analyte, with molecular oxygen.
- a biochemical analyte e.g., glucose or lactate
- oxygen is reduced to hydrogen peroxide (H 2 O 2 ).
- the hydrogen peroxide-generating enzyme is preferably stabilized in a matrix.
- the preferred stabilizing matrices are macromolecular and inorganic.
- the most preferred matrices include silicon atoms, at least 50% of which are covalently linked to neighboring oxygen atoms, which are formed into a three-dimensional, crosslinked network. Such matrices can be made using a sol-gel polymerization process.
- the stabilizing matrix optionally includes a second polymer, which functions to further stabilize the insulated, peroxide-generating enzyme.
- the peroxide-generating enzyme is preferably positioned behind or immobilized in a polymer that is at least tenfold, and preferably at least 100-fold, more permeable to oxygen than is the biochemical analyte to be measured.
- polymers include silicone rubbers, produced by cross-linking a poly(dimethyl siloxane) derivative and cellulose acetate.
- Figure 1 is a graph showing the dependence of current density on the weight fraction of the thermostable peroxidase in the sensing layer at 60 ⁇ g cm "2 loading (16mM glucose, lOOOrpm, 37°C, pH7.3, in air, 0.00V (SCE));
- Figure 2 is a graph showing the dependence of the electroreduction current density on the GOx loading (16mM glucose, lOOOrpm, 37°C, pH7.3, in air, 0.00V (SCE));
- Figure 3 is a graph showing the dependence of the calibration curves on the thickness of the cellulose acetate layer between the sensing layer and the immobilized glucose oxidase film.
- Figure 4 is a graph showing the potential dependence of the current density for a glucose sensor according to Example 4 (5mM glucose, 1000 rpm, 37°C, pH7.3, in air, O.OOV (SCE));
- Figure 5 is a graph showing the dependence of the current density on the dissolved oxygen concentration, according to Example 5 (1000 rpm, 37°C, pH7.3, in air, O.OOV (SCE)), (A) 5mM glucose, (B) 5mM lactate);
- Figure 6 is a graph showing the dependence of current density on the concentration of NaCl (1000 rpm, 37°C, pH7.3, in air, O.OOV (SCE)), (A) 5mM glucose, (B) 5mM lactate);
- Figure 7A and Figure 7B are graphs showing the dependence of current density on pH
- Figure 7A shows data for 5mM glucose
- Figure 7B shows data for 5mM lactate (1000 rpm, 37°C, pH7.3, in air, O.OOV (SCE)
- Figure 8 is a graph showing the dependence of current density on the angular velocity (37°C, pH7.3, in air, O.OOV (SCE)), (A) 5mM glucose, (B) 5mM lactate);
- Figure 9A and Figure 9B are graphs showing the dependence of current density on temperature.
- Figure 9A shows data for 5mM glucose
- Figure 9B shows data for 5mM lactate (1000 rpm, pH7.3, in air, O.OOV (SCE));
- Figure 10 A and Figure 10B are graphs showing the stability of thermostable peroxidase-based glucose and lactate sensors at different oxidase loadings: Figure (a) 1.3 ⁇ g; (b) 13 ⁇ g; (c) 26 ⁇ g; (d) 52 ⁇ g of immobilized glucose oxidase (Figure 10 A); (a)20 ⁇ g; (b) 40 ⁇ g; (c) 96 ⁇ g; (d) 160 ⁇ g of immobilized lactate oxidase ( Figure 10 B) (1000 rpm, 37°C, pH7.3, in air, O.OOV (SCE));
- Figure 11 is a graph showing glucose calibration curves before and after 280 hours of operation at 37°C in the stability study of Example 8, (A) 26 ⁇ g
- FIG. 12 is a graph showing cyclic voltammograms of the glucose sensor before and after 280 hours of operation at 37°C; (A) after stability experiment; (B) before stability experiment;
- Figure 13 is a graph of the time dependence of lactate oxidase activity in solution at 63 °C;
- Figure 14A and Figure 14B are graphs showing time dependence of lactate oxidase-doped silica gel powder activity at 63°C;
- Figure 14A and 14B(a) PVI-lactate oxidase-doped silica gel
- Figure 14B(b) lactate oxidase-doped silica gel
- Figure 15 is a graph showing time dependence of the activity of lactate oxidase in different environments at 50°C, (A) PVI-LOx-doped silica gel; (B) Lox-doped silica gel; (C) PVI-LOx in solution; (D) LOx in solution;
- Figure 16 is a graph showing time dependence of the activity of glucose oxidase in different environments at 63°C (A), glucose oxidase in solution; (B) glucose oxidase-doped silica gel powder; the inset shows the short term behavior of (A);
- Figure 17 is a graph showing time dependence of PEI-lactate oxidase- doped silica gel powder activity at 63°C, inset shows the short term behavior;
- Figure 18A is a diagrammatic representation of an electrode;
- Figure 18B is a diagrammatic representation of an electrode with a sensing layer.
- Figure 19 is a diagrammatic representation of a sensing layer of a biosensor of the invention.
- Figure 20 is a diagrammatic representation of a two-layered sensing layer of a thermostable biosensor of the invention.
- Figure 21 is a diagrammatic representation of a three-layered sensing layer of a thermostable biosensors of the invention.
- the sensors of the invention typically include a non-corroding working electrode 1 which is substantially covered by an insulator 2 having a recess 4 to allow electrolytic contact between an analyte-containing fluid and the working electrode 1.
- a film 3, having a plurality of layers, is positioned within recess 4.
- Figures 19-21 show three embodiments of film 3.
- film 3 includes a sensing layer 11, 21 and a second enzyme layer 13, 24.
- Film 3 may also contain one or more optional layers, such as an electrically insulating layer 12 between the sensing layer 11 and second enzyme layer 13; an analyte-transport controlling layer
- the electrochemical sensors of the invention include at least two electrodes for contacting the electrolytic solution to be assayed.
- One of these electrodes is a working electrode 1 , which is made from non-corroding metal or carbon.
- a carbon working electrode may be vitreous or graphitic and can be made from a solid or a paste.
- a metallic working electrode may be made from platinum group metals, including palladium or gold, or a non-corroding metalically conducting oxide, such as ruthenium dioxide.
- the working electrode may be a wire or a thin conducting film applied to a substrate, for example, by coating or printing. Typically, only a portion of the surface of the metallic or carbon conductor is in electrolytic contact with the analyte-containing solution. This portion is called the working surface of the electrode.
- the sensors of the invention also include a reference electrode or a combined reference and counter electrode (also termed a quasi-reference electrode or a counter/reference electrode).
- the reference or counter/reference electrode may be, for example, a silver/silver chloride electrode. If the sensor does not have a counter/reference electrode then it will include a separate counter electrode, which may be made from the same materials as the working electrode.
- Sensors of the present invention have one or more working electrodes and one or more counter, reference, and/or counter/reference electrodes.
- One embodiment of the sensor of the present invention has two or more working electrodes. These working electrodes may be integrally connected or they may be kept separate.
- the working electrodes of the present invention are implanted subcutaneously in the skin of a patient for direct contact with the body fluids of the patient, such as blood.
- the working electrodes may be implanted together or at different positions in the body.
- the counter, reference, and/or counter/reference electrodes may also be implanted either proximate to the working electrodes or at other positions within the body of the patient.
- the counter, reference, and/or counter/reference electrodes may be placed on the skin of the patient.
- sensing layer 3 The portion of the working electrode that is not insulated is coated with a sensing layer 3.
- the typical sensing layer 3 of the sensors of the present invention includes a redox polymer which is capable of swelling in water to form a redox hydrogel.
- Sensing layer 3 also typically includes an enzyme which is capable of catalyzing a reaction of the analyte or an analyte-generated compound.
- the senor contains a peroxidase which is preferably a thermostable peroxidase such as soybean peroxidase.
- the peroxidase-containing hydrogel forms a sensing layer that transduces a flux of H 2 O 2 into an electrical signal.
- the redox polymer contains redox centers that are bound to the polymer by covalent, coordinative, or electrostatic bonds; the latter resulting preferably from interactions of charged sites of the polymer with an oppositely charged redox species.
- the redox mediator is covalentiy or coordinatively bound to the redox polymer, although it may also be immobilized by entrapment or by electrostatic bonding.
- the redox centers are preferably non-leachable.
- the absence of leaching generally requires that the charged redox species has, at the pH of the analyte solution, a charge of at least two, and preferably three or more.
- the redox species is a cation, it preferably has at least a +2 charge, and is preferably +3 or better. The greater the charge of the redox species, the slower the leaching.
- the redox species is an anion and the binding to the polymer is electrostatic, then it should have a -2 charge and is preferably -3 or better.
- most of the redox centers (at least about 90%>) remain electrode-bound for at least 14 days at 37°C.
- the redox polymer is designed to swell in water and dilute aqueous solutions.
- the water uptake should add at least 10 weight percent, and preferably 20 weight percent, to the weight of the dry polymer.
- the thermostable peroxidase in the redox polymer layer is not substantially leached by water or by a physiological buffer solution at 37°C.
- the redox polymer layer containing the thermostable peroxidase can be conveniently made, for example, as described by Gregg and Hd ⁇ er, J. Phys. Chem. 95:5970 (1991), in US Patent 5,262,035, and in copending U.S. Patent Application Serial No: 08/540,789, filed October 11, 1995.
- the redox polymer contains redox centers that are stable and have a redox potential between about -0.1V (vs SCE) and about + 0.6V (vs SCE).
- the preferred range is between about -0.1V (vs SCE) and about +0.4V (vs SCE). Poising the electrode at a potential where O 2 is not electroreduced is desirable; otherwise the measured signal resulting from the electroreduction of H 2 O 2 to water must be corrected for the background caused by electroreduction of dissolved O 2 .
- redox mediators are metal complexes, particularly of osmium, ruthenium, iron and cobalt, or organic redox compounds, such as quinones and other compounds having a quinoid structure.
- the preferred redox centers exchange electrons rapidly with each other.
- One example of the preferred redox centers are osmium transition metal complexes with one or more ligands having a nitrogen-containing heterocycle such as 2,2'- bipyridine, 1,10-phenanthroline or derivatives thereof.
- ligands having a nitrogen-containing heterocycle such as 2,2'- bipyridine, 1,10-phenanthroline or derivatives thereof.
- Preferred derivatives of 2,2'-bipyridine for complex formation with the osmium cation are 4,4'-dimethyl-2,2'-bipyridine and mono-, di-, and polyalkoxy-2,2'-bipyridines, such as 4,4'-dimethoxy-2,2'-bipyridine, where the carbon to oxygen ratio of the alkoxy groups is sufficient to retain solubility of the transition metal complex in water.
- One useful group of redox polymers is derived from poly(4-vinyl pyridine) and is made by complexing between one third and one fifteenth of the pyridine rings with [Os(bpy) 2 Cl] +/2+ where bpy is 2,2'-bipyridine, or with
- a hydrogen peroxide sensing layer containing a thermostable peroxidase
- a hydrogen peroxide sensing layer is prepared by the dropwise mixing of solutions of the peroxidase, the redox polymer, and a crosslinker on a clean electrode surface. These solutions are allowed to dry and cure. The solutions may also be premixed, and a droplet of the premixed solution may be placed on the electrode.
- An example of a useful crosslinker is poly(ethylene glycol) diglycidyl ether with a molecular weight between 300 and 600, preferably 400 and 600.
- Another useful crosslinker is the bis N-hydroxysuccinimide ester of poly(ethylene glycol) - ⁇ , ⁇ - dicarboxylic acid.
- a second enzyme layer 13 on the working electrode catalyzes the reaction of O 2 with a substrate whereby H 2 O 2 is produced.
- the substrate is generally the analyte to be assayed by the sensor.
- the substrate is a reaction product of the analyte to be assayed, for example the product of hydrolysis of the analyte.
- the second enzyme used in layer 13 is also termed herein the peroxide-generating enzyme.
- the redox centers of the peroxide-generating enzyme are prevented from being reduced or oxidized directly by electron exchange with the redox polymer of the sensing layer. Prevention of such oxidation or reduction is accomplished by methods discussed hereinbelow.
- the second enzyme may include a sufficiently thick, natural, electrically insulating protein or glycoprotein layer over its reaction center or centers. Such a layer prevents electron transfer to or from the redox polymer. In this case, no further means for preventing reduction or oxidation of the second enzyme by the redox polymer is required.
- the H 2 O 2 -generating (second) enzyme is immobilized in a non-conducting inorganic or organic polymeric matrix to prevent electron exchange between its redox centers and the redox polymer.
- the immobilizing matrix is preferably highly permeable to O 2 and usually is more permeable to O 2 than to the analyte or to its precursor.
- the preferred immobilizing matrices are those in which the second enzyme is stabilized, becoming itself thermostable through immobilization, as discussed more fully below.
- the sol-gel polymerization process provides a method for the preparation of an inorganic polymeric matrix (e.g., glass) by the polymerization of suitable monomers at or near room-temperature.
- suitable monomers include alkoxides and esters of metal and semiconducting elements, with preferred metals and semiconductors comprising Si, Al, Ti, and Pb.
- the most preferred monomers include silicon and have a silicon to oxygen ratio of between about 1 :2 and about 1:4.
- Enzymes can be immobilized in silica and other inorganic polymeric matrices made by sol-gel processes, involving, for example, the hydrolysis of tetramethoxysilane or another polyalkoxysilane that may contain one or more silicon atoms. Condensation of the resulting silanol in the presence of the enzyme results in entrapment of e enzyme. This process has been referred to as sol-gel immobilization.
- Enzymes can be immobilized in inorganic polymeric matrices to prevent electrical contact between the immobilized second enzyme and the redox polymer and/or electrode. Furthermore, binding of enzymes in silica or other inorganic polymeric matrices formed from sol-gels can stabilize the enzyme. Entrapment of glucose oxidase, a glycoprotein, in silica sol-gel greatly improves the stability of the enzyme, which retains activity when heated in water to 98°C for 10 minutes.
- lactate oxidase which is not a glycoprotein
- the enzyme was not particularly thermostable.
- lactate oxidase is dissolved in an aqueous buffer solution in which poly(N-vinyl imidazole) is co-dissolved, and the lactate oxidase- poly(N-vinyl imidazole) mixture is immobilized in the silica by the sol-gel process, a uniquely stable, immobilized lactate oxidase is obtained.
- the stabilized lactate oxidase can be heated in water to 90°C for 10 minutes and still retain enzymatic activity.
- enzymes such as lactate oxidase, that are polyanions at pH 7.
- lactate oxidase addition of polyethyleneimine, also a polybasic polymer and also multiply protonated at pH 7, in place of poly(N-vinyl imidazole) improved stability of the enzyme, although not as much as the addition of the preferred polymer, poly(N-vinyl imidazole).
- a polymeric polyanion or polycation can be coimmobilized in an inorganic polymeric matrix formed from a sol-gel to stabilize the enzyme.
- the stabilized enzyme can then be used at higher temperatures and or for longer durations than would be possible if the enzyme were immobilized alone in the sol- gel.
- the silicas, in which the peroxide-generating, now thermostable, second enzyme is immobilized are hard materials that can be ground into fine powders. These powders are then dispersed in highly O 2 -permeable polymers, further discussed hereinbelow, to form a peroxide-generating second layer 13 of the inventive sensors.
- the peroxide-generating layer 13 preferably has the following desired properties: thermostability; absence of electron transfer between the redox polymer of the sensing layer and the redox centers of the enzyme of the second enzyme containing H 2 O 2 -generating layer, i.e. absence of oxidation or reduction of the redox polymer by redox centers of the second enzyme; and high O 2 permeability.
- the sensing layer includes the redox polymer, electrically connecting the thermostable peroxidase (first enzyme) to the electrode, and also includes the peroxide-generating enzyme (second enzyme), the redox centers of which are not electrically connected to the redox polymer or to the electrode.
- the peroxide-generating enzyme layer 24 can be formed directly over the sensing layer 21 (see Figures 20 and 21), but only when the peroxide-generating enzyme is intrinsically insulated or immobilized in an electrically insulating matrix. If the H 2 O 2 -generating enzyme is neither intrinsically insulating nor immobilized in an insulating matrix, an H 2 O 2 -permeable, electrically insulating layer 12 can be placed between the sensing layer 11 and the peroxide- generating (second) enzyme layer 13 to achieve the desired insulation.
- the peroxide-generating (second) enzyme layer is formed by any of the following methods. Particles, such as silica-containing particles in which the second enzyme is stabilized, can be dispersed in a polymer, such as a silicone rubber solution or silicone rubber precursor solution. A droplet of this mixture is then applied to the working electrode. Alternatively, the peroxide-generating layer is formed by adding a cross-linking agent to the second enzyme and applying a droplet containing the second enzyme and its crosslinker to the working electrode.
- Useful cross-linking agents include, for example, poly(ethylene glycol) diglycidyl ether
- PEGDGE For cross-linking of glycoproteins such as glucose oxidase, the enzyme is oxidized with NaIO 4 , forming reactive aldehyde functions condensing with surface amines, such as those of enzyme lysines.
- the second enzyme may also be immobilized with glutaraldehyde or glutaraldehyde and a protein such as albumin.
- An enzyme stabilized by the silica sol gel matrix can be ground to a find powder and dispersed in a silicone, preferably in an elastomeric silicone, and most preferably in a water-based elastomeric silicone precursor. This dispersion is then applied to the thermostable peroxidase layer to form a hydrogen peroxide- generating layer. Silicone is a preferred binder in this layer due to its oxygen permeability.
- Another means for preventing oxidation/reduction of the peroxide- generating (second) enzyme is the addition of an electrically insulating membrane 12 that is permeable to H 2 O 2 between sensing layer 11 and second enzyme layer 13.
- the insulating membrane can be inorganic or organic, but preferably is an organic polymer such as cellulose acetate.
- the second enzyme may be immobilized in a layer 13 over the polymeric membrane.
- the insulating membrane 12 is permeable to the small H 2 O 2 molecule but is not permeable to the larger, readily oxidizable, potentially interfering ascorbate, acetaminophen or urate species.
- the ratio of the permeability of layer 12 to H 2 O 2 and one or more of ascorbate, acetaminophen, and urate is greater than 2: 1.
- Useful, selectively H 2 O 2 permeating polymer films include dense cellulose acetate, cured NafionTM, and nylon.
- an analyte-transport controlling layer 14 is placed between the solution that is being analyzed and second enzyme layer 13 of the sensor.
- This analyte-transport controlling layer 13 functions to contain the second enzyme and thereby avoid its loss, and/or to limit the flux of the analyte or second enzyme substrate to the second enzyme layer.
- this second membrane be permeable to O 2 , the co- reactant in the enzyme-catalyzed generation of H 2 O 2 in the presence of the substrate. It is also of essence that the ratio of permeabilities of O 2 and of the substrate or its precursor through this second membrane be large enough for oxidation or dehydrogenation of the substrate in the reaction catalyzed by the second enzyme with the concurrent formation of water, a reaction whereby O 2 is consumed. Because the concentration of O 2 in saturated aqueous solutions is well below the usual concentrations of analytes such as glucose or lactate in biological fluids, including fluids in the body of animals, analyte-transport controlling layers 14 that are much more permeable to O 2 than to the substrate or its precursor are preferred.
- membranes or polymers for which the permeability coefficient of molecular oxygen is greater than 10 "8 cm 3 (STP) cm cm “2 s “1 (cm Hg) "1 at 25°C are preferred.
- STP cm 3
- Polymers for use in the analyte- transport controlling layer 14 are those that are highly permeable to O 2 , preferably those in which the ratio of O 2 and substrate (or substrate precursor) permeabilities is greater than 10:1, and more preferably greater than 100:1.
- silicones for example in silicone rubbers, formed by cross- linking poly(dimethyl siloxanes), are particularly high.
- silicones are useful polymers for this layer.
- Another useful material is cellulose acetate.
- the sensor is preferably coated with a biocompatible film 15 that is permeable to the substrate converted in the reaction catalyzed by the second enzyme.
- This biocompatible film is placed on the solution side of the sensor.
- the preferred biocompatible layer 15 is formed of a hydrogel, e.g., a polymeric composition which contains more than 20% by weight of water when in equilibrium with a physiological environment such as living tissue or blood.
- a hydrogel e.g., a polymeric composition which contains more than 20% by weight of water when in equilibrium with a physiological environment such as living tissue or blood.
- An example is a cross-linked derivative of polyethylene oxide, e.g., a tetraacrylated derivative of polyethylene oxide.
- the polymeric compositions are non-toxic, non- immunogenic, non-thrombogenic, and otherwise compatible with living tissue of animals.
- a biocompatible layer 15 is not necessary if the analyte-transport controlling layer 14 or the second enzyme layer 13 are biocompatible.
- many solid silicones are biocompatible and therefore require no additional biocompatible layer (see Figure 20, in contrast the embodiment of the invention shown in Figure 21 includes a biocompatible layer 25).
- An important performance criterion of the inventive sensor is the rate of loss of sensitivity. This rate depends on the concentration of the analyte, because loss in sensitivity is usually first noticed at high analyte concentrations. At higher analyte concentrations, where complete conversion of the incoming analyte flux to H 2 O 2 requires the presence of more of the active second enzyme, the system is very sensitive to inadequate substrate conversion in the second enzyme layer.
- the rate of loss of sensitivity can be reduced, even when the second enzyme is not particularly thermostable, by limiting the flux of analyte to the second enzyme layer 13 by using an analyte-transport controlling layer 14 and limiting thereby the analyte concentration.
- Loss of sensitivity can also be limited and even avoided for a period of days or weeks, by incorporating in the second enzyme layer a large amount of enzyme that even if part of it becomes inactive, all of the analyte flux is still transduced by the remaining second enzyme into an H 2 O 2 flux.
- a thermostable second enzyme such as an enzyme entrapped in an inorganic polymeric matrix, is used to form the second enzyme layer 13
- sensors of unprecedentedly good stability and long life can be built and can be further improved either by incorporating a large excess of the thermostable second enzyme, much more than needed to convert the analyte flux into an H 2 O 2 flux , or by limiting the analyte flux , or by using both techniques cooperatively.
- the preferred sensors are also stable for long periods of time at temperatures of 37°C or greater.
- the sensor is stable for 100 hours or more at this temperature with a drop in the sensor's output of 10% or less.
- the sensor and the enzymes within the sensor are stable at 30°C, more preferably at 40°C, and most preferably at 50°C or 60°C or higher.
- the immobilization of a second enzyme in an inorganic polymeric matrix formed using the sol-gel process can be used effectively in the enzyme sensor described in U.S. Patent No. 5,593,852, herein incorporated by reference.
- a layered structure similar to that depicted in Figures 19-21 is used.
- an analyte-sensitive enzyme is used rather than a peroxidase.
- glucose oxidase or glucose dehydrogenase is present in the sensing layer if the analyte is glucose or lactate oxidase is used if the analyte is lactate.
- This layer contains one or more enzymes which catalyze reactions of interferents, such as ascorbate, urate, acetaminophen.
- Enzymes for use in this layer include peroxidases and lactate oxidase (when glucose is the analyte) or glucose oxidase (when lactate is the analyte).
- These enzymes can be immobilized in an inorganic polymeric matrix as described hereinabove and used to form a second enzyme layer. Furthermore, these enzymes may be stabilized by immobilization in the inorganic polymeric matrix either alone or in conjunction with a polyelectrolytic polymer as described hereinabove.
- Soybean peroxidase was obtained from Harlan Bioproducts for Science. Indianapolis, IN, High grade, 130 pyrogallol units/mg (Cat. No: SP04 Lot No: SPLO515).
- the lactate oxidase (LOx) was obtained from Genzyme, Boston, MA, Lot # D50293, Cat. # 70-1381-01, EC 1.1.2.3 from Acerococcus viridans, 37.0 units/mg of powder.
- Poly(ethylene glycol) diglycidyl ether (PEGDGE) was obtained from Polysciences, Inc., Warrington, PA. A 30% hydrogen peroxide solution was obtained from Aldrich, and diluted solutions were prepared daily.
- the four-layered sensors were prepared as follows:
- a redox polymer PVP-bpy-Os (or POs-EA.), was synthesized by partially complexing the pyridine nitrogens of poly-(4-vinylpyridine) with Os(bpy) 2 Cl + +2 , and then partially quaternizing the resulting polymer with 2- bromoethylamine, by the method described in Gregg and Heller, 1991, J. Phys. Chem. 95:5970.
- the osmium-containing redox centers allow for electrical communication between the carbon surface and the peroxidase heme centers, and the pyridinium-N-ethylamine functions enhance hydration and provide primary amines for cross-linking.
- the ratio of unmodified pyridines to osmium-complexed pyridines to ethylamine quarternized pyridines was 3.3:1.0:0.8.
- the first layer, the hydrogen peroxide sensing layer was prepared by placing droplets of 2 ⁇ l PVP-bpy-Os (5mg/ml), 2 ⁇ l soybean peroxidase (5 mg/ml), and 1 ⁇ l of the crosslinker PEGDGE (2.5 mg/ml) on the carbon surface. The droplets were mixed on the surface of the electrode with the tip of a syringe. The electrode was then allowed to dry for 16 hours at room temperature. The resulting dark purple film appeared to be well spread and uniform. The dried electrode was washed in PBS for 20 minutes at 1000 rpm, rinsed with water, and permitted to dry at room temperature.
- GOx glucose oxidase
- Glucose oxidase (GOx) was obtained from Sigma, ED 1.1.3.4 from Aspergillus niger type X-S, 198 units/mg solid, 75% protein.
- 50 ⁇ l of 12 mg/ml NaIO 4 in water the enzyme-periodate solution was incubated at room temperature and in the dark for two hours, following the procedure described in Vreeke etal., 1995, Anal. Chem. 67:4247.
- a volume of 4 ⁇ l of the incubated mixture was placed atop the cellulose acetate film to form an immobilized GOx analyte sensing layer, which was permitted to dry overnight.
- a mixture of lO ⁇ l of 20 mg/ml LOx, 20 ⁇ l of 10 mg/ml PVI, and lO ⁇ l of 5 mg/ml PEGDGE in water was prepared.
- a volume of 4 ⁇ l of the LOx mixture was placed atop the cellulose acetate film to form an immobilized LOx analyte sensing layer, which was permitted to dry overnight.
- Analyte Transport-Limiting Layer The fourth polymeric layer, an analyte transport-limiting layer of cellulose acetate, was prepared and applied to the analyte sensing layer as described above for the hydrogen peroxide transport-limiting layer. A volume of 4 ⁇ l of 0.5%) cellulose acetate in cyclohexanone was placed atop the immobilized oxidase layer (analyte sensing layer), and permitted to dry for two hours. The four-layered electrode was then washed in PBS for 25 minutes and rinsed with water.
- Example 2 Varying amounts of Soybean Peroxidase
- the 4-layered electrodes were prepared as described for Example 1 , but varying the enzyme weight fraction of soybean peroxidase in the crosslinked redox polymer of the hydrogen peroxide sensing layer or by varying the total loading of SBP.
- Current measurements were collected using a Princeton Applied Research model 273 potentiostat/galvanostat in a 3-electrode cell. All measurements were performed using a 20 mM phosphate buffer (pH 7.3) containing 0.1M NaCl, except measurements in which pH dependence was studied. In experiments where pH was varied, 2M solutions of HCI or NaOH were added to the phosphate buffer solution.
- Glucose and lactate solutions were prepared by diluting a stock 2M solution in phosphate buffer. All experiments were run at 37°C under air in 100ml of phosphate buffer, unless otherwise indicated.
- the cell contained a rotating glassy carbon working electrode, a saturated calomel reference electrode (SCE), and a platinum counter electrode, isolated from the bulk solution by a Vycor TM frit.
- SCE saturated calomel reference electrode
- Vycor TM frit isolated from the bulk solution by a Vycor TM frit.
- the stability measurements were run in a stirred cell, the rotating disk experiments were performed using a Pine RDE4 potentiostat, with an MSRX speed controller, an X-Y- Y' plotter, and a VWR 1165 refrigerated constant temperature circulator. The rotating electrode experiments were performed at 1000 rpm, unless otherwise noted. Results:
- Figure 2 shows the dependence of current densities on the amount of glucose oxidase immobilized on the electrode.
- the current densities at 4mM glucose reached a plateau at GOx loadings of 375 ⁇ g/cm 2 .
- Electrodes made with LOx exhibited similar behavior with a current density plateau at a loading of 600 ⁇ g/cm 2 .
- the hydrogen peroxide transport-controlling layer functions to control the transport of hydrogen peroxide from the analyte sensing layer to the hydrogen peroxide sensing layer.
- This layer also serves to electrically isolate the POsEA of the hydrogen peroxide sensing layer from the immobilized oxidase layer, that is, to prevent "short-circuiting" of the sensor through “wiring" of the oxidase.
- a typical glucose electrode made without this insulating layer showed current suppression at concentrations higher than ImM glucose, and the current was suppressed to less than 50% of its maximum value at a concentration of 20mM.
- Membranes having a range of thickness, were obtained by using solutions of different cellulose acetate concentrations, and applying various volumes of these.
- the thinnest membranes were made by applying l ⁇ l of 0.25 weight % cellulose acetate.
- the thickest membranes were made by applying 4 ⁇ l of 0.5 weight
- the sensitivity of the electrodes dropped by about 50%.
- the sensitivity loss is attributed to less efficient collection of the H 2 O 2 generated by the oxidase-catalyzed reaction.
- An analyte transport-limiting layer forms a fourth polymeric layer.
- this layer was made of cellulose acetate, and provides substrate transport control, thereby defining the dynamic range of the sensor.
- Increasing the thickness of the outer cellulose acetate layer decreased the sensor's sensitivity, but increased the apparent K-,..
- Figure 3 shows the response of an electrode over-coated with varying amounts of cellulose acetate: (A) 4 ⁇ l; (B) 8 ⁇ l; (C) 28 ⁇ l of 0.25% cellulose acetate.
- Increasing the thickness of the outer cellulose acetate layer from 4 ⁇ l (A) of 0.25% cellulose acetate to 8 ⁇ l (B) decreased the sensitivity by 50%, but increased the apparent K,-, from 1 mM to 2 mM glucose.
- the response time (t 10/90 ) for electrodes with an outer cellulose acetate layer of 8 ⁇ l of 0.25%) was less than 2 minutes.
- the redox polymer of the electrodes of Example 1, POs-EA has a formal redox potential of +278 mV (vs. SCE).
- Figure 4 shows the dependence of current density on the applied potential for a glucose electrode of Example 1. Between 0.20 V and +0.35 V (vs. SCE), the current density was independent of applied potential. At applied potentials positive of +0.40 V, a reduction current was no longer observed. At applied potentials more negative than -0.20 V, oxygen reduction effects are observed.
- FIG. 5 shows the dependence of the current density on the partial pressure of the dissolved oxygen for the electrodes of Example 1.
- concentration of oxygen in an air-saturated aqueous solution is about 0.2mM (See, Hodgman IN: Handbook of Chemistry and Physics, 44th Ed, The Chemical Rubber Publishing Co., Cleveland, OH, 1963, page 1706).
- the current densities were lower only by about 20% than those in oxygen saturated solutions.
- Figure 6 shows the dependence of current density on the concentration of NaCl for both GOx (A) and LOx (B) electrodes of Example 1. Although the current densities were somewhat higher at low salt concentrations, the electrodes were virtually insensitive to salt concentrations up to IM NaCl. Increasing the salt concentration from 0.1M to IM decreased the current density by less than 10%).
- Figures 7 A and 7B show the dependence of the current density on pH for both GOx ( Figure 7A) and LOx ( Figure 7B) electrodes of Example 1.
- the current density was near its maximum between pH 4.5 and pH 6.5, the plateau matching the pH dependence of GOx activity in solution, which exhibits maximal activity near pH 5.5.
- the current density reached its maximum at pH 4.0, differing from the pH dependence of LOx activity in solution, which exhibits maximal activity at pH 6.5. Both glucose and lactate electrodes were irreversibly deactivated below pH 3.0.
- Example 7 Rotation Rate and Temperature Dependence Figure 8 shows the dependence of current density on the angular velocity of the rotating electrodes for both GOx (A) and LOx (B).
- the current density was practically independent of rotation rate. For example, in the case of the glucose electrode, increasing the rotation rate from 50 rpm to 1000 rpm increased the current density by less than 5%.
- Figures 9A and 9B show the dependence of the current density on temperature for both electrodes, Figure 9A shows data for 5 mM glucose; and Figure 9B shows data for 5 mM lactate.
- Interferents such as ascorbate, urate, and acetaminophen are oxidized at POsEA coated carbon electrodes. These interferents decrease the catalytic hydrogen peroxide electroreduction current. Nevertheless, no current change was observed with the electrodes of Example 1, upon the addition of urate up to 0.5 mM or acetaminophen up to 1.0 mM, both in the presence and absence of substrate. Ascorbate was electrooxidized only at a negligibly slow rate.
- an injection of 0.1 mM ascorbate caused a decrease of less than 1% in the current density
- injection of 0.1 mM ascorbate caused a decrease of less than 0.1 % in the current density.
- TMOS tetramethylorthosilicate
- the vial was placed into an ice- bath, and stirred at approximately 600 rpm. 36 mL of 2.44 mM HCI was added and the solution was stirred for 10 min. A vacuum was then applied to the vial for an additional 10 minutes to eliminate the methanol produced in the sol process. The vacuum was released, and pH of the solution was adjusted to pH 5.1 by adding 20 mL of 20 mM phosphate buffer (pH 7.4).
- lactate oxidase from aerococcous viridens, 41 units/mg, Cat. #1381, Genzyme, Cambridge, Massachusetts
- lactate oxidase from aerococcous viridens, 41 units/mg, Cat. #1381, Genzyme, Cambridge, Massachusetts
- HEPES 4-(2-hydroxyethyl)-l-piperazineethane-sulfonic acid
- 20 mL of 20 mg/mL of aqueous poly(l- vinylimidazole) were mixed as described by Timothy J. Ohara, Ravi Rajagopalan and Adam Heller, Anal. Chem. 1994, 66, 2451-57.
- This solution was added to the TMOS-containing solution and was stirred for 1 minute.
- a lactate oxidase catalyzes the oxidation of lactate to pyruvate.
- hydrogen peroxide is formed stoichiometiically.
- the enzymatically formed hydrogen peroxide can be quantitatively measured using a peroxidase linked assay system, which causes the formation of a quinoneimine dye. This dye can be measured spectrophotometrically at 564 nm.
- Reaction mixture I was prepared by combining the following solutions:
- 1.0 mg of lactate oxidase-doped silica gel powder was weighed into a 3 mL cuvette. 100 ⁇ L of distilled water was used to wash the powder down from the inside walls to the bottom of the cuvette. The cuvette was then capped with parafilm and placed in a temperature bath set at 63 °C for the experimental period of time. After this period of time, the cuvette was removed from the bath, and 100 ⁇ L of enzyme diluent was added. The cuvette was then placed into a 37°C temperature bath for another five minutes.
- a solution with a 4: 1 ratio of reaction mixture I to 0.5% dimethylaniline was prepared and allowed to equilibrate at 37°C.
- One milliliter of this solution was added to the cuvette. This mixture was agitated and allowed to react for exactly 10 minutes at 37°C.
- 2.0 mL of the reaction stopper were added and the absorbance at 564 nm (As) was measured.
- the procedure was repeated, using 1.0 mg of enzyme-free silica gel powder in place of the lactate oxidase-doped silica gel powder. The same procedure was followed thereafter and the blank absorbance (Ab) was measured.
- Figure 13 shows the activity decrease of lactate oxidase in solution over time.
- the enzyme had a half-life of 6.8 minutes at 63°C , which was in agreement with the previously published value (H. Minagawa, N. Nakayama, and S. Nakamoto, 1995, Biotechnology Letters 17(9):975).
- Figures 14A and 14B show the comparison of the enzyme activity loss of PVI-lactate oxidase-doped silica gel powder with that of lactate oxidase- doped silica gel powder at 63°C.
- Figure 14A shows PVI-lactate oxidase-doped silica gel.
- Figure 14B compares PVI-lactate oxidase-doped silica gel (a) with lactate oxidase-doped silica gel (b). At 63°C, the LOx-doped silica gel powder (b) had the same half-life as that of LOx in solution. However, the PVI-LOx-doped silica gel powder Fig. 14B(a) and Fig. 14A maintained 60% of its initial activity after 900 minutes at 63°C.
- Figure 15 shows the time dependence of the activity loss for lactate oxidase in different environments at 50°C.
- the PVI-LOx-doped silica gel powder (A) maintained 85%) of its initial activity after 120 hours, whereas the LOx-doped silica gel powder (C) had a half-life of only 10 hours.
- Both the LOx in solution (D) and the PVI-LOx in solution (C) demonstrated a half-life of less than one hour at this temperature.
- the PVI-LOx-doped silica gel powder maintained 100% of its initial activity after 11 days of soaking in water at room temperature.
- TMOS tetramethylorthosilicate
- the powder was immobilized onto a glass slide according to the following procedure. 26 mg of Bermocoll ® EHM-100 ( Berol Nobel AB, Stenungsund, Sweden), 1 mL of cyclohexanone and 1 mL of water were mixed in a small vial. The vial was heated and agitated over a flame for 5 minutes. The solution was allowed to settle and the white micelle fraction was collected. 90 ⁇ L of the micelles and 10 mg of the glucose oxidase-doped silica gel powder were mixed and then stirred for 5 minutes. 10 ⁇ L of the mixture was applied to a glass slide and allowed to dry overnight.
- the glass slide was immersed in a temperature bath for 5 minutes at the experimental temperature. The slide was removed and allowed to dry. 10 ⁇ L of 2 M glucose was applied to the immobilized micelles. The active area of the peroxide testing strip was placed on top of the immobilized micelle area. The appearance of a blue color on the strip indicated the presence of glucose oxidase activity.
- the glucose oxidase-doped silica gel powder retained activity after immersion in water for 5 minutes at 40, 50, 60, 70, 84, and 92°C, while similarly immobilized glucose oxidase in DAEA Dextran, Heparin, Lactitol, Gafquats, and Dextran Sulfate showed no activity retention at temperatures higher than 70°C.
- the glucose oxidase-doped silica gel powder was then tested for activity at 92°C for longer time periods. Activity was retained for up to 20 minutes, after which, the micelles washed off of the slides. At 75 °C, activity was retained for over 60 minutes.
- Figure 16 shows the comparison of the enzyme activity loss of glucose oxidase-doped silica gel powder (B) with that of glucose oxidase in solution (A) at 63 °C. At this temperature, the GOx-doped silica gel powder (B) maintained 60% of its initial activity after 1200 minutes, while the half-life of GOx in solution (A) was 6.5 minutes, as shown in the figure inset.
- PEI-LOx-doped Silica Gel Polyethyleneimine is chemically similar to PVI and has been shown to stabilize enzymes.
- PEI-LOx-doped silica gel powder was prepared according to the same procedure as that for PVI-LOx-doped silica gel powder.
- Figure 17 shows the activity loss over time of PEI-LOx-doped silica gel powder at 63°C. After 900 minutes, the PEI-LOx-doped silica gel powder maintained 18% of its initial activity.
- Example 13 Preparation and Activity Test of PVI-LOx Adsorbed onto Colloidal Silica PVI-LOx was also adsorbed onto colloidal silica according to the following procedure. 1.69 mg of LOx was dissolved in 23 ⁇ L of 20 mg/mL of PVI. This solution was mixed with 33 ⁇ L of colloidal silica (34 wt. % suspension in water, Aldrich, Milwaukee, WI). The resulting solution was allowed to dry. The solid was first collected and then ground to a powder in a mortar and pestle. The
- PVI-LOx adsorbed silica had the same half-life as LOx in solution at 63°C.
- a 0.29 mm polyimide insulated gold wire (polyimide insulation thickness 0.02mm, gold wire OD 0.25 mm) was etched galvanostatically in a KCN solution as described by E. Cs ⁇ regi etal., Anaytical. Chemistry 66:3131-3138, 1994, to form about 100 ⁇ m deep recess.
- the following sequence of droplets were deposited in the recess to form a four-layered structure.
- the innermost layer contained a hydrogen peroxide-sensing soybean peroxidase and redox polymer.
- the second layer was a hydrogen peroxide permeable insulating layer.
- the third layer was a silicone layer in which sol gel silica-immobilized glucose oxidase containing particles were dispersed.
- the fourth, cellulose acetate layer was oxygen permeable and glucose flux reducing.
- the redox polymer solution prepared as described for Example 1 was used at a concentration of 10 mg/mL.
- Soybean peroxidase (SBP) in deionized water was used at a concentration of 10 mg/mL.
- PEGDGE was used at 5 mg/mL.
- the redox polymer, SBP, and PEGDGE solutions were mixed at a 2:2: 1 ratio. Ten droplets of about 5nL each of the mixed solution were sequentially deposited within the recess to form the sensing layer, which was cured at 55°C for 20 minutes.
- the solution from which the second layer, the hydrogen peroxide permeable membrane, was cast consisted of 0.5%/weight% cellulose acetate (40% acetylated) in cyclohexanone. One 5 nL droplet of this solution was applied to the cured sensing layer in the recess.
- the hydrogen peroxide generating enzyme layer (third layer) was made of 0.5 parts of the sol-gel immobilized glucose oxidase of Example 15, 1 part of Dow Corning 3-5025 silicone water based elastomer that was thoroughly mixed and dispersed in 9 parts of water by grinding in an agate mortar for 30 minutes. Three drops of this mixture were applied on the cellulose acetate layer, and cured at 50°C for ten minutes.
- the fourth layer was made of 2 weight % cellulose acetate (40% acetylated) also containing 1.6 weight % TWEEN 80 in cyclohexane, of which one drop was applied onto the third layer.
- Recessed palladium electrodes were prepared as described by E. Cs ⁇ regi etal., Anaytical. Chemistry 67:1240, 1995, for gold electrodes, except that the solution in which the palladium was etched under galvanostatic control was not a potassium cyanide solution, but 6M Hcl. The recess formed was about lOO ⁇ m deep.
- Aqueous solutions of 10 mg/mL soybean peroxidase, 10 mg/mL POs-EA and 5 mg/mL PEGDGE were prepared.
- the electrode was poised at -0.045 V (SCE) in a phosphate buffer solution at pH 7.0 (20 mM phosphate, 0.14 M NaCl) and its current was measured as a function of the glucose concentration in the solution.
- the apparent K ⁇ of the electrode was
- 5mM glucose i.e., half of the maximum current was reached at 5 mM glucose.
- the response times i.e.,., the rise of the current from 10 to 90 %> of the maximum current, were less than one minute.
- the sensitivity of the electrode was 0.8 nA/mM glucose.
- a hydrated silica gel has an isoelectric point (pi) (i.e., the pH at which the net charge on the molecule is zero) near pH 5.
- pi isoelectric point
- Lactate oxidase (pi 4.6) and glycolate oxidase (pi « 9.6), on the other hand, each lost at least 70% of their activity upon immobilization in a hydrated silica gel and the stability of these two enzymes was not greatly improved.
- Glycolate oxidase and lactate oxidase belong to a family of flavin mononucleotide (FMN) oxidases that catalyze the oxidation of L- ⁇ -hydroxy acids.
- FMN flavin mononucleotide
- amino acid sequences for glycolate oxidase (Spinicia oleracea) and lactate oxidase (Aerococcus viridans) were aligned, as shown below in Table 1 with other members of the L- ⁇ -hydroxy oxidase family , the sequences are 34% identical and
- glycolate oxidase The crystal structure of glycolate oxidase has been determined to 2.2 A resolution (Lindqvist etal., 1989 J.Mol.Biol. 209:151-166) and, because of the similarity in sequences, this structure is assumed to be representative of lactate oxidase.
- Glucose oxidase is not a member of the L- ⁇ -hydroxy oxidase family, but belongs to a class of FAD-binding proteins.
- the crystal structure of glucose oxidase from Aspergillus niger has been previously reported to 2.3 A resolution (Hecht etal., 1993, J.Mol.Biol. 229:153).
- a flexible polycation buffer i.e., PVI and or PEI, depending on the isoelectric point of the enzyme
- the polysilicate anions interact with the cationic buffer molecules, and not with the cationic residues of the enzyme, thereby stabilizing the enzyme by encasement in the silica gel.
- PVI and PEI form adducts, acting as polycationic buffers for enzymes such as lactate oxidase.
- PEI also acts as a cationic buffer for enzymes such as glycolate oxidase. It is thought that PVI is not an effective buffer for glycolate oxidase, because its isoelectric point is lower than that of glycolate oxidase.
- the active site of glycolate oxidase is located within a channel that passes through its protein.
- a larger opening is located on the "front” of the molecule, and a smaller opening is on the "back”.
- residues R289, R290, and R309 Surrounding the front entrance to the channel are residues R289, R290, and R309, while the back entrance is surrounded by R164,
- the active site of glucose oxidase has been defined, as has the channel through which glucose passes on its way to the active site.
- GLYOX-So EVASTGP—GIRFFQLYVYKDRNWAQLVRRAERAGFKAIALTVDTPRLGRREADIKN-R HAOX-Rn DIVAAAPE-GFR FQLYMKSDWDFNKQMVQRAEALGFKALVITIDTPVLGNRRRDKRN-Q B2PRE-Pa EIADARIPGQQQWYQLYVNADRSITEKAVRHAEERGMKGLFITVDAPSLGRREKDMKM-K MANH-Pp DLARQCD—GDLWFQLYVIH-REIAQGMVLKALHTGYTTLVLTTDVAVNGYRERDLHN-R LOX-Ms DIRKHAGD-TPAYFQLYYPEDRDLAESFIRRAEEAGYDGLVITLDT IFGWRPRDLTISN LOX-Av EISEGLNG-GPRWFQIYMAKDDQQNRDILDEAKSDGATAIILTADSTVSGNRDRDVKN-
- a multiple sequence alignment of several members of the alpha-hydroxy acid oxidase family glycolate oxidase from Spinacia oleracea (GLYOX-So), (S) - 2 - hydroxy-acid oxidase from Rattusnorvegicus (HAOX-Rn), Cytochrome B2 precursor from Pichia anomala (B2PRE-Pa), Lactate oxidase from Aerococcus viridans (LOX-Av) and from Mycobacterium smegmatic (LOX-MS).
- GLYOX-So glycolate oxidase from Spinacia oleracea
- S 2 - hydroxy-acid oxidase from Rattusnorvegicus
- HEOX-Rn Rattusnorvegicus
- B2PRE-Pa Cytochrome B2 precursor from Pichia anomala
- B2PRE-Pa Cytochrome B2 precursor from Aerococcus viridans
- the first 180 residues of B2PRE-Pa were deleted, as were its last three residues, since they have no equivalent in the other enzymes.
- the first 17 residues of LOX-MS and the first 12 residues of LOX-Av were also deleted.
- the identical residues are marked with an *, highly conserved residues are marked with a : and moderately conserved residues are marked with a '.'.
- the 4 arginines discussed above have a ' ⁇ ' replacing the '*'.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP53495498A JP4054382B2 (en) | 1997-02-11 | 1998-02-11 | Electrochemical analyte sensor using thermostable soybean peroxidase |
AU63214/98A AU6321498A (en) | 1997-02-11 | 1998-02-11 | Electrochemical analyte sensors using thermostable soybean peroxidase |
EP98907399A EP0977984A2 (en) | 1997-02-11 | 1998-02-11 | Electrochemical analyte sensors using thermostable soybean peroxidase |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/798,596 | 1997-02-11 | ||
US08/798,596 US5972199A (en) | 1995-10-11 | 1997-02-11 | Electrochemical analyte sensors using thermostable peroxidase |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1998035053A2 true WO1998035053A2 (en) | 1998-08-13 |
WO1998035053A3 WO1998035053A3 (en) | 1998-09-17 |
Family
ID=25173808
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1998/002403 WO1998035053A2 (en) | 1997-02-11 | 1998-02-11 | Electrochemical analyte sensors using thermostable soybean peroxidase |
Country Status (5)
Country | Link |
---|---|
US (1) | US5972199A (en) |
EP (1) | EP0977984A2 (en) |
JP (1) | JP4054382B2 (en) |
AU (1) | AU6321498A (en) |
WO (1) | WO1998035053A2 (en) |
Cited By (101)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999056613A1 (en) | 1998-04-30 | 1999-11-11 | Therasense, Inc. | Analyte monitoring device and methods of use |
WO2002035222A1 (en) | 2000-10-27 | 2002-05-02 | Arkray, Inc. | Biosensor |
EP1235068A1 (en) * | 1999-11-15 | 2002-08-28 | ARKRAY, Inc. | Biosensor |
DE10212570A1 (en) * | 2002-03-12 | 2003-10-02 | Bst Bio Sensor Tech Gmbh | Production of amperometric biosensor used for determining hydrogen peroxide concentration comprises coating screen printed two electrode system with composition comprising polymer, mediator and enzyme |
US7632672B2 (en) | 2001-05-31 | 2009-12-15 | Instrumentation Laboratory Co. | Composite membrane containing a cross-linked enzyme matrix for a biosensor |
WO2011002694A1 (en) | 2009-06-30 | 2011-01-06 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
WO2011002692A1 (en) | 2009-06-30 | 2011-01-06 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
WO2011002693A1 (en) | 2009-06-30 | 2011-01-06 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
WO2011155943A1 (en) * | 2010-06-11 | 2011-12-15 | Empire Technology Development Llc | Detection and decomposition of bisphenol-a |
US9031630B2 (en) | 2006-02-28 | 2015-05-12 | Abbott Diabetes Care Inc. | Analyte sensors and methods of use |
US9039975B2 (en) | 2006-03-31 | 2015-05-26 | Abbott Diabetes Care Inc. | Analyte monitoring devices and methods therefor |
US9050041B2 (en) | 2009-10-30 | 2015-06-09 | Abbott Diabetes Care Inc. | Method and apparatus for detecting false hypoglycemic conditions |
US9060719B2 (en) | 2007-05-14 | 2015-06-23 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US9069536B2 (en) | 2011-10-31 | 2015-06-30 | Abbott Diabetes Care Inc. | Electronic devices having integrated reset systems and methods thereof |
US9066709B2 (en) | 2009-01-29 | 2015-06-30 | Abbott Diabetes Care Inc. | Method and device for early signal attenuation detection using blood glucose measurements |
US9088452B2 (en) | 2009-04-29 | 2015-07-21 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
US9326727B2 (en) | 2006-01-30 | 2016-05-03 | Abbott Diabetes Care Inc. | On-body medical device securement |
US9364149B2 (en) | 2006-02-28 | 2016-06-14 | Abbott Diabetes Care Inc. | Analyte sensor transmitter unit configuration for a data monitoring and management system |
US9541556B2 (en) | 2008-05-30 | 2017-01-10 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US9610046B2 (en) | 2008-08-31 | 2017-04-04 | Abbott Diabetes Care Inc. | Closed loop control with improved alarm functions |
US9615780B2 (en) | 2007-04-14 | 2017-04-11 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US9629578B2 (en) | 2006-10-02 | 2017-04-25 | Abbott Diabetes Care Inc. | Method and system for dynamically updating calibration parameters for an analyte sensor |
US9636068B2 (en) | 2009-02-03 | 2017-05-02 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US9636450B2 (en) | 2007-02-19 | 2017-05-02 | Udo Hoss | Pump system modular components for delivering medication and analyte sensing at seperate insertion sites |
US9649057B2 (en) | 2007-05-08 | 2017-05-16 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US9662056B2 (en) | 2008-09-30 | 2017-05-30 | Abbott Diabetes Care Inc. | Optimizing analyte sensor calibration |
US9669162B2 (en) | 2005-11-04 | 2017-06-06 | Abbott Diabetes Care Inc. | Method and system for providing basal profile modification in analyte monitoring and management systems |
US9675290B2 (en) | 2012-10-30 | 2017-06-13 | Abbott Diabetes Care Inc. | Sensitivity calibration of in vivo sensors used to measure analyte concentration |
US9687183B2 (en) | 2010-03-24 | 2017-06-27 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US9693713B2 (en) | 2011-12-11 | 2017-07-04 | Abbott Diabetes Care Inc. | Analyte sensor devices, connections, and methods |
US9730650B2 (en) | 2008-11-10 | 2017-08-15 | Abbott Diabetes Care Inc. | Alarm characterization for analyte monitoring devices and systems |
US9730584B2 (en) | 2003-06-10 | 2017-08-15 | Abbott Diabetes Care Inc. | Glucose measuring device for use in personal area network |
US9730623B2 (en) | 2008-03-28 | 2017-08-15 | Abbott Diabetes Care Inc. | Analyte sensor calibration management |
US9743862B2 (en) | 2011-03-31 | 2017-08-29 | Abbott Diabetes Care Inc. | Systems and methods for transcutaneously implanting medical devices |
US9743866B2 (en) | 2007-04-14 | 2017-08-29 | Abbott Diabetes Care Inc. | Method and apparatus for providing dynamic multi-stage signal amplification in a medical device |
US9743863B2 (en) | 2006-03-31 | 2017-08-29 | Abbott Diabetes Care Inc. | Method and system for powering an electronic device |
US9743865B2 (en) | 2007-10-23 | 2017-08-29 | Abbott Diabetes Care Inc. | Assessing measures of glycemic variability |
US9743872B2 (en) | 2011-11-23 | 2017-08-29 | Abbott Diabetes Care Inc. | Mitigating single point failure of devices in an analyte monitoring system and methods thereof |
US9750444B2 (en) | 2009-09-30 | 2017-09-05 | Abbott Diabetes Care Inc. | Interconnect for on-body analyte monitoring device |
US9750439B2 (en) | 2009-09-29 | 2017-09-05 | Abbott Diabetes Care Inc. | Method and apparatus for providing notification function in analyte monitoring systems |
US9770211B2 (en) | 2008-01-31 | 2017-09-26 | Abbott Diabetes Care Inc. | Analyte sensor with time lag compensation |
US9775563B2 (en) | 2005-09-30 | 2017-10-03 | Abbott Diabetes Care Inc. | Integrated introducer and transmitter assembly and methods of use |
US9788771B2 (en) | 2006-10-23 | 2017-10-17 | Abbott Diabetes Care Inc. | Variable speed sensor insertion devices and methods of use |
US9795326B2 (en) | 2009-07-23 | 2017-10-24 | Abbott Diabetes Care Inc. | Continuous analyte measurement systems and systems and methods for implanting them |
US9797880B2 (en) | 2007-05-14 | 2017-10-24 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US9795331B2 (en) | 2005-12-28 | 2017-10-24 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor insertion |
US9804148B2 (en) | 2007-10-23 | 2017-10-31 | Abbott Diabetes Care Inc. | Analyte sensor with lag compensation |
US9801545B2 (en) | 2007-03-01 | 2017-10-31 | Abbott Diabetes Care Inc. | Method and apparatus for providing rolling data in communication systems |
US9801571B2 (en) | 2007-05-14 | 2017-10-31 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US9804150B2 (en) | 2007-05-14 | 2017-10-31 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US9808186B2 (en) | 2006-09-10 | 2017-11-07 | Abbott Diabetes Care Inc. | Method and system for providing an integrated analyte sensor insertion device and data processing unit |
US9814428B2 (en) | 2006-10-25 | 2017-11-14 | Abbott Diabetes Care Inc. | Method and system for providing analyte monitoring |
US9814416B2 (en) | 2009-08-31 | 2017-11-14 | Abbott Diabetes Care Inc. | Displays for a medical device |
US9833181B2 (en) | 2006-08-09 | 2017-12-05 | Abbot Diabetes Care Inc. | Method and system for providing calibration of an analyte sensor in an analyte monitoring system |
US9882660B2 (en) | 2006-10-26 | 2018-01-30 | Abbott Diabetes Care Inc. | Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors |
US9907492B2 (en) | 2012-09-26 | 2018-03-06 | Abbott Diabetes Care Inc. | Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data |
US9913600B2 (en) | 2007-06-29 | 2018-03-13 | Abbott Diabetes Care Inc. | Analyte monitoring and management device and method to analyze the frequency of user interaction with the device |
US9931075B2 (en) | 2008-05-30 | 2018-04-03 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US9943644B2 (en) | 2008-08-31 | 2018-04-17 | Abbott Diabetes Care Inc. | Closed loop control with reference measurement and methods thereof |
US9949678B2 (en) | 2007-05-08 | 2018-04-24 | Abbott Diabetes Care Inc. | Method and device for determining elapsed sensor life |
US9968302B2 (en) | 2009-08-31 | 2018-05-15 | Abbott Diabetes Care Inc. | Analyte signal processing device and methods |
US9968306B2 (en) | 2012-09-17 | 2018-05-15 | Abbott Diabetes Care Inc. | Methods and apparatuses for providing adverse condition notification with enhanced wireless communication range in analyte monitoring systems |
US9980670B2 (en) | 2002-11-05 | 2018-05-29 | Abbott Diabetes Care Inc. | Sensor inserter assembly |
US9980669B2 (en) | 2011-11-07 | 2018-05-29 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods |
US10002233B2 (en) | 2007-05-14 | 2018-06-19 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10009244B2 (en) | 2009-04-15 | 2018-06-26 | Abbott Diabetes Care Inc. | Analyte monitoring system having an alert |
US10028680B2 (en) | 2006-04-28 | 2018-07-24 | Abbott Diabetes Care Inc. | Introducer assembly and methods of use |
US10031002B2 (en) | 2007-05-14 | 2018-07-24 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10039881B2 (en) | 2002-12-31 | 2018-08-07 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
US10045739B2 (en) | 2008-09-30 | 2018-08-14 | Abbott Diabetes Care Inc. | Analyte sensor sensitivity attenuation mitigation |
US10082493B2 (en) | 2011-11-25 | 2018-09-25 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods of use |
US10089446B2 (en) | 2009-01-29 | 2018-10-02 | Abbott Diabetes Care Inc. | Method and device for providing offset model based calibration for analyte sensor |
US10092229B2 (en) | 2010-06-29 | 2018-10-09 | Abbott Diabetes Care Inc. | Calibration of analyte measurement system |
US10111608B2 (en) | 2007-04-14 | 2018-10-30 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US10117614B2 (en) | 2006-02-28 | 2018-11-06 | Abbott Diabetes Care Inc. | Method and system for providing continuous calibration of implantable analyte sensors |
US10132793B2 (en) | 2012-08-30 | 2018-11-20 | Abbott Diabetes Care Inc. | Dropout detection in continuous analyte monitoring data during data excursions |
US10136816B2 (en) | 2009-08-31 | 2018-11-27 | Abbott Diabetes Care Inc. | Medical devices and methods |
US10173007B2 (en) | 2007-10-23 | 2019-01-08 | Abbott Diabetes Care Inc. | Closed loop control system with safety parameters and methods |
US10194863B2 (en) | 2005-09-30 | 2019-02-05 | Abbott Diabetes Care Inc. | Integrated transmitter unit and sensor introducer mechanism and methods of use |
US10226207B2 (en) | 2004-12-29 | 2019-03-12 | Abbott Diabetes Care Inc. | Sensor inserter having introducer |
US10349877B2 (en) | 2007-04-14 | 2019-07-16 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US10429250B2 (en) | 2009-08-31 | 2019-10-01 | Abbott Diabetes Care, Inc. | Analyte monitoring system and methods for managing power and noise |
US10463310B2 (en) | 2007-05-14 | 2019-11-05 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10555695B2 (en) | 2011-04-15 | 2020-02-11 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US10610137B2 (en) | 2005-03-10 | 2020-04-07 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
USD902408S1 (en) | 2003-11-05 | 2020-11-17 | Abbott Diabetes Care Inc. | Analyte sensor control unit |
US10874338B2 (en) | 2010-06-29 | 2020-12-29 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US10991456B2 (en) | 2007-05-14 | 2021-04-27 | Abbott Diabetes Care Inc. | Method and system for determining analyte levels |
US11000215B1 (en) | 2003-12-05 | 2021-05-11 | Dexcom, Inc. | Analyte sensor |
USD924406S1 (en) | 2010-02-01 | 2021-07-06 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
US11213226B2 (en) | 2010-10-07 | 2022-01-04 | Abbott Diabetes Care Inc. | Analyte monitoring devices and methods |
US11264133B2 (en) | 2007-06-21 | 2022-03-01 | Abbott Diabetes Care Inc. | Health management devices and methods |
US11298058B2 (en) | 2005-12-28 | 2022-04-12 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor insertion |
US11307201B2 (en) | 2007-09-17 | 2022-04-19 | Red Ivory Llc | Self-actuating signal producing detection devices and methods |
US11331022B2 (en) | 2017-10-24 | 2022-05-17 | Dexcom, Inc. | Pre-connected analyte sensors |
US11350862B2 (en) | 2017-10-24 | 2022-06-07 | Dexcom, Inc. | Pre-connected analyte sensors |
USD980986S1 (en) | 2015-05-14 | 2023-03-14 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
USD982762S1 (en) | 2020-12-21 | 2023-04-04 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
US11793936B2 (en) | 2009-05-29 | 2023-10-24 | Abbott Diabetes Care Inc. | Medical device antenna systems having external antenna configurations |
USD1002852S1 (en) | 2019-06-06 | 2023-10-24 | Abbott Diabetes Care Inc. | Analyte sensor device |
US11883164B2 (en) | 2004-07-13 | 2024-01-30 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
Families Citing this family (406)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5593852A (en) * | 1993-12-02 | 1997-01-14 | Heller; Adam | Subcutaneous glucose electrode |
US5956501A (en) * | 1997-01-10 | 1999-09-21 | Health Hero Network, Inc. | Disease simulation system and method |
US5620850A (en) | 1994-09-26 | 1997-04-15 | President And Fellows Of Harvard College | Molecular recognition at surfaces derivatized with self-assembled monolayers |
US6179817B1 (en) * | 1995-02-22 | 2001-01-30 | Boston Scientific Corporation | Hybrid coating for medical devices |
US6558798B2 (en) | 1995-02-22 | 2003-05-06 | Scimed Life Systems, Inc. | Hydrophilic coating and substrates coated therewith having enhanced durability and lubricity |
US6689265B2 (en) * | 1995-10-11 | 2004-02-10 | Therasense, Inc. | Electrochemical analyte sensors using thermostable soybean peroxidase |
US7014992B1 (en) | 1996-11-05 | 2006-03-21 | Clinical Micro Sensors, Inc. | Conductive oligomers attached to electrodes and nucleoside analogs |
US9155496B2 (en) | 1997-03-04 | 2015-10-13 | Dexcom, Inc. | Low oxygen in vivo analyte sensor |
US7899511B2 (en) | 2004-07-13 | 2011-03-01 | Dexcom, Inc. | Low oxygen in vivo analyte sensor |
US6001067A (en) | 1997-03-04 | 1999-12-14 | Shults; Mark C. | Device and method for determining analyte levels |
US8527026B2 (en) | 1997-03-04 | 2013-09-03 | Dexcom, Inc. | Device and method for determining analyte levels |
US6060327A (en) | 1997-05-14 | 2000-05-09 | Keensense, Inc. | Molecular wire injection sensors |
US6699667B2 (en) | 1997-05-14 | 2004-03-02 | Keensense, Inc. | Molecular wire injection sensors |
US7220550B2 (en) * | 1997-05-14 | 2007-05-22 | Keensense, Inc. | Molecular wire injection sensors |
WO1998057159A1 (en) | 1997-06-12 | 1998-12-17 | Clinical Micro Sensors, Inc. | Electronic methods for the detection of analytes |
US6036924A (en) | 1997-12-04 | 2000-03-14 | Hewlett-Packard Company | Cassette of lancet cartridges for sampling blood |
US6134461A (en) | 1998-03-04 | 2000-10-17 | E. Heller & Company | Electrochemical analyte |
US6103033A (en) | 1998-03-04 | 2000-08-15 | Therasense, Inc. | Process for producing an electrochemical biosensor |
US6391005B1 (en) | 1998-03-30 | 2002-05-21 | Agilent Technologies, Inc. | Apparatus and method for penetration with shaft having a sensor for sensing penetration depth |
US8974386B2 (en) | 1998-04-30 | 2015-03-10 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US6949816B2 (en) | 2003-04-21 | 2005-09-27 | Motorola, Inc. | Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same |
US8480580B2 (en) | 1998-04-30 | 2013-07-09 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9066695B2 (en) | 1998-04-30 | 2015-06-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US6294281B1 (en) * | 1998-06-17 | 2001-09-25 | Therasense, Inc. | Biological fuel cell and method |
US6281006B1 (en) * | 1998-08-24 | 2001-08-28 | Therasense, Inc. | Electrochemical affinity assay |
US6338790B1 (en) | 1998-10-08 | 2002-01-15 | Therasense, Inc. | Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator |
JP4469504B2 (en) * | 1998-10-08 | 2010-05-26 | メドトロニック ミニメド インコーポレイテッド | Remote trait monitor system |
US7766873B2 (en) | 1998-10-29 | 2010-08-03 | Medtronic Minimed, Inc. | Method and apparatus for detecting occlusions in an ambulatory infusion pump |
US7621893B2 (en) * | 1998-10-29 | 2009-11-24 | Medtronic Minimed, Inc. | Methods and apparatuses for detecting occlusions in an ambulatory infusion pump |
JP3395673B2 (en) * | 1998-11-18 | 2003-04-14 | 株式会社豊田中央研究所 | Specific binding pair measurement method using micro oxygen electrode |
US6579673B2 (en) * | 1998-12-17 | 2003-06-17 | Kimberly-Clark Worldwide, Inc. | Patterned deposition of antibody binding protein for optical diffraction-based biosensors |
US6565738B1 (en) * | 1999-01-28 | 2003-05-20 | Abbott Laboratories | Diagnostic test for the measurement of analyte in abiological fluid |
US7806886B2 (en) | 1999-06-03 | 2010-10-05 | Medtronic Minimed, Inc. | Apparatus and method for controlling insulin infusion with state variable feedback |
AU1631101A (en) * | 1999-10-07 | 2001-05-10 | Pepex Biomedical, Llc | Sensor for measuring a bioanalyte such as lactate |
US7167615B1 (en) | 1999-11-05 | 2007-01-23 | Board Of Regents, The University Of Texas System | Resonant waveguide-grating filters and sensors and methods for making and using same |
US8268143B2 (en) * | 1999-11-15 | 2012-09-18 | Abbott Diabetes Care Inc. | Oxygen-effect free analyte sensor |
US8444834B2 (en) | 1999-11-15 | 2013-05-21 | Abbott Diabetes Care Inc. | Redox polymers for use in analyte monitoring |
WO2001036660A2 (en) | 1999-11-15 | 2001-05-25 | Therasense, Inc. | Transition metal complexes attached to a polymer via a flexible chain |
WO2001038873A2 (en) * | 1999-11-24 | 2001-05-31 | Biotronic Technologies, Inc. | Devices and methods for detecting analytes using electrosensor having capture reagent |
US6399295B1 (en) | 1999-12-17 | 2002-06-04 | Kimberly-Clark Worldwide, Inc. | Use of wicking agent to eliminate wash steps for optical diffraction-based biosensors |
US6716577B1 (en) | 2000-02-02 | 2004-04-06 | Lifescan, Inc. | Electrochemical test strip for use in analyte determination |
US6824669B1 (en) | 2000-02-17 | 2004-11-30 | Motorola, Inc. | Protein and peptide sensors using electrical detection methods |
KR100518921B1 (en) * | 2000-08-29 | 2005-10-06 | 소시에떼 데 프로듀이 네슬레 소시에떼아노님 | Flexible container having flat walls |
US8641644B2 (en) | 2000-11-21 | 2014-02-04 | Sanofi-Aventis Deutschland Gmbh | Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means |
US6558528B1 (en) * | 2000-12-20 | 2003-05-06 | Lifescan, Inc. | Electrochemical test strip cards that include an integral dessicant |
US6560471B1 (en) | 2001-01-02 | 2003-05-06 | Therasense, Inc. | Analyte monitoring device and methods of use |
US6855243B2 (en) * | 2001-04-27 | 2005-02-15 | Lifescan, Inc. | Electrochemical test strip having a plurality of reaction chambers and methods for using the same |
WO2002090961A2 (en) * | 2001-05-03 | 2002-11-14 | Immunetics, Inc. | Systems and methods for detection of analytes in biological fluids |
US7262019B2 (en) * | 2001-05-03 | 2007-08-28 | Immunetics, Inc. | System and methods for detection of Bacillus anthracis related analytes in biological fluids |
US6676816B2 (en) * | 2001-05-11 | 2004-01-13 | Therasense, Inc. | Transition metal complexes with (pyridyl)imidazole ligands and sensors using said complexes |
US8226814B2 (en) * | 2001-05-11 | 2012-07-24 | Abbott Diabetes Care Inc. | Transition metal complexes with pyridyl-imidazole ligands |
US8070934B2 (en) | 2001-05-11 | 2011-12-06 | Abbott Diabetes Care Inc. | Transition metal complexes with (pyridyl)imidazole ligands |
US6932894B2 (en) | 2001-05-15 | 2005-08-23 | Therasense, Inc. | Biosensor membranes composed of polymers containing heterocyclic nitrogens |
US7005273B2 (en) * | 2001-05-16 | 2006-02-28 | Therasense, Inc. | Method for the determination of glycated hemoglobin |
US9493806B2 (en) * | 2001-06-01 | 2016-11-15 | Colorado State University Research Foundation | Enzymatic biosensing systems |
US9493805B2 (en) * | 2001-06-01 | 2016-11-15 | Colorado State University Research Foundation | Enzymatic biosensors with enhanced activity retention for detection of organic compounds |
US8323956B2 (en) * | 2001-06-01 | 2012-12-04 | Colorado State University Research Foundation | Distal tip of biosensor transducer comprising enzyme for deamination |
WO2003025627A2 (en) * | 2001-06-01 | 2003-03-27 | Colorado State University Research Foundation | Optical biosensor with enhanced activity retention for detection of halogenated organic compounds |
US6674635B1 (en) | 2001-06-11 | 2004-01-06 | Avx Corporation | Protective coating for electrolytic capacitors |
ES2352998T3 (en) | 2001-06-12 | 2011-02-24 | Pelikan Technologies Inc. | LANCETA ELECTRIC ACTUATOR. |
US8337419B2 (en) | 2002-04-19 | 2012-12-25 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
WO2002100254A2 (en) | 2001-06-12 | 2002-12-19 | Pelikan Technologies, Inc. | Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge |
US9795747B2 (en) | 2010-06-02 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Methods and apparatus for lancet actuation |
AU2002344825A1 (en) | 2001-06-12 | 2002-12-23 | Pelikan Technologies, Inc. | Method and apparatus for improving success rate of blood yield from a fingerstick |
US9427532B2 (en) | 2001-06-12 | 2016-08-30 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
CA2448902C (en) | 2001-06-12 | 2010-09-07 | Pelikan Technologies, Inc. | Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties |
CA2448905C (en) | 2001-06-12 | 2010-09-07 | Pelikan Technologies, Inc. | Blood sampling apparatus and method |
US7025774B2 (en) | 2001-06-12 | 2006-04-11 | Pelikan Technologies, Inc. | Tissue penetration device |
US7981056B2 (en) | 2002-04-19 | 2011-07-19 | Pelikan Technologies, Inc. | Methods and apparatus for lancet actuation |
US9226699B2 (en) | 2002-04-19 | 2016-01-05 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling module with a continuous compression tissue interface surface |
US6794649B2 (en) | 2001-07-09 | 2004-09-21 | Pharmaceutical Systems, Inc. | Spectrophotometric determination of gas phase compositions |
US20030032874A1 (en) | 2001-07-27 | 2003-02-13 | Dexcom, Inc. | Sensor head for use with implantable devices |
US20030036202A1 (en) | 2001-08-01 | 2003-02-20 | Maria Teodorcyzk | Methods and devices for use in analyte concentration determination assays |
US6827702B2 (en) | 2001-09-07 | 2004-12-07 | Medtronic Minimed, Inc. | Safety limits for closed-loop infusion pump control |
US7767437B2 (en) * | 2001-11-02 | 2010-08-03 | Genefluidics, Inc. | System for detection of a component in a liquid |
AU2002351164A1 (en) * | 2001-11-26 | 2003-06-10 | Molecular Reflections, Inc. | Microscale immobilization of molecules using a hydrogel and methods of use thereof |
US7102752B2 (en) * | 2001-12-11 | 2006-09-05 | Kimberly-Clark Worldwide, Inc. | Systems to view and analyze the results from diffraction-based diagnostics |
US7613491B2 (en) | 2002-05-22 | 2009-11-03 | Dexcom, Inc. | Silicone based membranes for use in implantable glucose sensors |
US8260393B2 (en) | 2003-07-25 | 2012-09-04 | Dexcom, Inc. | Systems and methods for replacing signal data artifacts in a glucose sensor data stream |
US8010174B2 (en) | 2003-08-22 | 2011-08-30 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US8364229B2 (en) | 2003-07-25 | 2013-01-29 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US9247901B2 (en) | 2003-08-22 | 2016-02-02 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US7909778B2 (en) | 2002-04-19 | 2011-03-22 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US9248267B2 (en) | 2002-04-19 | 2016-02-02 | Sanofi-Aventis Deustchland Gmbh | Tissue penetration device |
US7717863B2 (en) | 2002-04-19 | 2010-05-18 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7901362B2 (en) | 2002-04-19 | 2011-03-08 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US9795334B2 (en) | 2002-04-19 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US7331931B2 (en) | 2002-04-19 | 2008-02-19 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7232451B2 (en) | 2002-04-19 | 2007-06-19 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7371247B2 (en) | 2002-04-19 | 2008-05-13 | Pelikan Technologies, Inc | Method and apparatus for penetrating tissue |
US7491178B2 (en) | 2002-04-19 | 2009-02-17 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7674232B2 (en) | 2002-04-19 | 2010-03-09 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7713214B2 (en) | 2002-04-19 | 2010-05-11 | Pelikan Technologies, Inc. | Method and apparatus for a multi-use body fluid sampling device with optical analyte sensing |
US7297122B2 (en) | 2002-04-19 | 2007-11-20 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7229458B2 (en) | 2002-04-19 | 2007-06-12 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US8360992B2 (en) | 2002-04-19 | 2013-01-29 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US7648468B2 (en) | 2002-04-19 | 2010-01-19 | Pelikon Technologies, Inc. | Method and apparatus for penetrating tissue |
US9314194B2 (en) | 2002-04-19 | 2016-04-19 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US7976476B2 (en) | 2002-04-19 | 2011-07-12 | Pelikan Technologies, Inc. | Device and method for variable speed lancet |
US8579831B2 (en) | 2002-04-19 | 2013-11-12 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US7892183B2 (en) | 2002-04-19 | 2011-02-22 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
US7547287B2 (en) | 2002-04-19 | 2009-06-16 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7175642B2 (en) | 2002-04-19 | 2007-02-13 | Pelikan Technologies, Inc. | Methods and apparatus for lancet actuation |
US8221334B2 (en) | 2002-04-19 | 2012-07-17 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US8267870B2 (en) | 2002-04-19 | 2012-09-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for body fluid sampling with hybrid actuation |
US8372016B2 (en) | 2002-04-19 | 2013-02-12 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for body fluid sampling and analyte sensing |
US8702624B2 (en) | 2006-09-29 | 2014-04-22 | Sanofi-Aventis Deutschland Gmbh | Analyte measurement device with a single shot actuator |
US8784335B2 (en) | 2002-04-19 | 2014-07-22 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling device with a capacitive sensor |
US7291117B2 (en) | 2002-04-19 | 2007-11-06 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US20070227907A1 (en) * | 2006-04-04 | 2007-10-04 | Rajiv Shah | Methods and materials for controlling the electrochemistry of analyte sensors |
US7813780B2 (en) * | 2005-12-13 | 2010-10-12 | Medtronic Minimed, Inc. | Biosensors and methods for making and using them |
US7368190B2 (en) * | 2002-05-02 | 2008-05-06 | Abbott Diabetes Care Inc. | Miniature biological fuel cell that is operational under physiological conditions, and associated devices and methods |
US7343188B2 (en) * | 2002-05-09 | 2008-03-11 | Lifescan, Inc. | Devices and methods for accessing and analyzing physiological fluid |
US7226978B2 (en) | 2002-05-22 | 2007-06-05 | Dexcom, Inc. | Techniques to improve polyurethane membranes for implantable glucose sensors |
US6864147B1 (en) | 2002-06-11 | 2005-03-08 | Avx Corporation | Protective coating for electrolytic capacitors |
US20040068230A1 (en) | 2002-07-24 | 2004-04-08 | Medtronic Minimed, Inc. | System for providing blood glucose measurements to an infusion device |
US7278983B2 (en) | 2002-07-24 | 2007-10-09 | Medtronic Minimed, Inc. | Physiological monitoring device for controlling a medication infusion device |
US8512276B2 (en) * | 2002-07-24 | 2013-08-20 | Medtronic Minimed, Inc. | System for providing blood glucose measurements to an infusion device |
US7291256B2 (en) * | 2002-09-12 | 2007-11-06 | Lifescan, Inc. | Mediator stabilized reagent compositions and methods for their use in electrochemical analyte detection assays |
US7162289B2 (en) * | 2002-09-27 | 2007-01-09 | Medtronic Minimed, Inc. | Method and apparatus for enhancing the integrity of an implantable sensor device |
US7727181B2 (en) | 2002-10-09 | 2010-06-01 | Abbott Diabetes Care Inc. | Fluid delivery device with autocalibration |
US7501053B2 (en) * | 2002-10-23 | 2009-03-10 | Abbott Laboratories | Biosensor having improved hematocrit and oxygen biases |
US7670853B2 (en) * | 2002-11-05 | 2010-03-02 | Abbott Diabetes Care Inc. | Assay device, system and method |
US20040106163A1 (en) * | 2002-11-12 | 2004-06-03 | Workman Jerome James | Non-invasive measurement of analytes |
AU2003287735A1 (en) | 2002-11-12 | 2004-06-03 | Argose, Inc. | Non-invasive measurement of analytes |
GB0227424D0 (en) * | 2002-11-25 | 2002-12-31 | Univ Warwick | Coatings |
WO2004053483A2 (en) * | 2002-12-11 | 2004-06-24 | Instrumentation Laboratory Company | Multi-analyte reference solutions |
US20040122353A1 (en) | 2002-12-19 | 2004-06-24 | Medtronic Minimed, Inc. | Relay device for transferring information between a sensor system and a fluid delivery system |
US8574895B2 (en) | 2002-12-30 | 2013-11-05 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus using optical techniques to measure analyte levels |
US20040154933A1 (en) * | 2003-02-11 | 2004-08-12 | Instrumentation Laboratory Company | Polymeric membranes for use in electrochemical sensors |
US20040256227A1 (en) * | 2003-02-11 | 2004-12-23 | Jungwon Shin | Electrochemical urea sensors and methods of making the same |
US7312197B2 (en) * | 2003-02-24 | 2007-12-25 | University Of Maryland, Baltimore | Method of modifying glucose activity using polypeptides selectively expressed in fat tissue |
US7679407B2 (en) | 2003-04-28 | 2010-03-16 | Abbott Diabetes Care Inc. | Method and apparatus for providing peak detection circuitry for data communication systems |
US7875293B2 (en) | 2003-05-21 | 2011-01-25 | Dexcom, Inc. | Biointerface membranes incorporating bioactive agents |
EP2238892A3 (en) | 2003-05-30 | 2011-02-09 | Pelikan Technologies Inc. | Apparatus for body fluid sampling |
US7850621B2 (en) | 2003-06-06 | 2010-12-14 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
WO2006001797A1 (en) | 2004-06-14 | 2006-01-05 | Pelikan Technologies, Inc. | Low pain penetrating |
US7220034B2 (en) * | 2003-07-11 | 2007-05-22 | Rudolph Technologies, Inc. | Fiber optic darkfield ring light |
WO2005011520A2 (en) | 2003-07-25 | 2005-02-10 | Dexcom, Inc. | Oxygen enhancing membrane systems for implantable devices |
US9763609B2 (en) | 2003-07-25 | 2017-09-19 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US7074307B2 (en) | 2003-07-25 | 2006-07-11 | Dexcom, Inc. | Electrode systems for electrochemical sensors |
US7761130B2 (en) | 2003-07-25 | 2010-07-20 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
US7494465B2 (en) | 2004-07-13 | 2009-02-24 | Dexcom, Inc. | Transcutaneous analyte sensor |
US7778680B2 (en) | 2003-08-01 | 2010-08-17 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US8676287B2 (en) | 2003-08-01 | 2014-03-18 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US8275437B2 (en) | 2003-08-01 | 2012-09-25 | Dexcom, Inc. | Transcutaneous analyte sensor |
US20080119703A1 (en) | 2006-10-04 | 2008-05-22 | Mark Brister | Analyte sensor |
US20140121989A1 (en) | 2003-08-22 | 2014-05-01 | Dexcom, Inc. | Systems and methods for processing analyte sensor data |
JP4769412B2 (en) * | 2003-09-02 | 2011-09-07 | 積水メディカル株式会社 | Electron mediator, electron mediator fixed electrode, and biofuel cell using the same |
WO2005033659A2 (en) | 2003-09-29 | 2005-04-14 | Pelikan Technologies, Inc. | Method and apparatus for an improved sample capture device |
WO2005037095A1 (en) | 2003-10-14 | 2005-04-28 | Pelikan Technologies, Inc. | Method and apparatus for a variable user interface |
US7299082B2 (en) | 2003-10-31 | 2007-11-20 | Abbott Diabetes Care, Inc. | Method of calibrating an analyte-measurement device, and associated methods, devices and systems |
US20080245664A1 (en) * | 2003-11-12 | 2008-10-09 | Yu-Hong Chang | Biosensor test strips for multiple tests |
US20050100880A1 (en) * | 2003-11-12 | 2005-05-12 | Yu-Hong Chang | Biosensor test strips of multiple function for multiple uses |
US9247900B2 (en) | 2004-07-13 | 2016-02-02 | Dexcom, Inc. | Analyte sensor |
US8423114B2 (en) | 2006-10-04 | 2013-04-16 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
US11633133B2 (en) | 2003-12-05 | 2023-04-25 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
EP2256493B1 (en) | 2003-12-05 | 2014-02-26 | DexCom, Inc. | Calibration techniques for a continuous analyte sensor |
US8364231B2 (en) | 2006-10-04 | 2013-01-29 | Dexcom, Inc. | Analyte sensor |
US8287453B2 (en) | 2003-12-05 | 2012-10-16 | Dexcom, Inc. | Analyte sensor |
US7476360B2 (en) | 2003-12-09 | 2009-01-13 | Genefluidics, Inc. | Cartridge for use with electrochemical sensor |
WO2005065241A2 (en) | 2003-12-24 | 2005-07-21 | Argose, Inc. | Smmr (small molecule metabolite reporters) for use as in vivo glucose biosensors |
US8668656B2 (en) | 2003-12-31 | 2014-03-11 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for improving fluidic flow and sample capture |
US7822454B1 (en) | 2005-01-03 | 2010-10-26 | Pelikan Technologies, Inc. | Fluid sampling device with improved analyte detecting member configuration |
US7699964B2 (en) * | 2004-02-09 | 2010-04-20 | Abbott Diabetes Care Inc. | Membrane suitable for use in an analyte sensor, analyte sensor, and associated method |
US8165651B2 (en) | 2004-02-09 | 2012-04-24 | Abbott Diabetes Care Inc. | Analyte sensor, and associated system and method employing a catalytic agent |
US20070135697A1 (en) * | 2004-04-19 | 2007-06-14 | Therasense, Inc. | Method and apparatus for providing sensor guard for data monitoring and detection systems |
US8792955B2 (en) | 2004-05-03 | 2014-07-29 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8277713B2 (en) | 2004-05-03 | 2012-10-02 | Dexcom, Inc. | Implantable analyte sensor |
EP1751546A2 (en) | 2004-05-20 | 2007-02-14 | Albatros Technologies GmbH & Co. KG | Printable hydrogel for biosensors |
WO2005120365A1 (en) | 2004-06-03 | 2005-12-22 | Pelikan Technologies, Inc. | Method and apparatus for a fluid sampling device |
US9775553B2 (en) | 2004-06-03 | 2017-10-03 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for a fluid sampling device |
WO2005119524A2 (en) | 2004-06-04 | 2005-12-15 | Therasense, Inc. | Diabetes care host-client architecture and data management system |
US20070100222A1 (en) * | 2004-06-14 | 2007-05-03 | Metronic Minimed, Inc. | Analyte sensing apparatus for hospital use |
US20060000710A1 (en) | 2004-06-30 | 2006-01-05 | Klaus Peter Weidenhaupt | Fluid handling methods |
US20070045902A1 (en) | 2004-07-13 | 2007-03-01 | Brauker James H | Analyte sensor |
US8452368B2 (en) | 2004-07-13 | 2013-05-28 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8565848B2 (en) | 2004-07-13 | 2013-10-22 | Dexcom, Inc. | Transcutaneous analyte sensor |
US7783333B2 (en) | 2004-07-13 | 2010-08-24 | Dexcom, Inc. | Transcutaneous medical device with variable stiffness |
US8886272B2 (en) | 2004-07-13 | 2014-11-11 | Dexcom, Inc. | Analyte sensor |
US7344500B2 (en) | 2004-07-27 | 2008-03-18 | Medtronic Minimed, Inc. | Sensing system with auxiliary display |
US7303543B1 (en) | 2004-12-03 | 2007-12-04 | Medtronic Minimed, Inc. | Medication infusion set |
JP4595517B2 (en) * | 2004-12-13 | 2010-12-08 | パナソニック株式会社 | Biosensor, its inspection device, and its inspection method |
US9398882B2 (en) | 2005-09-30 | 2016-07-26 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor and data processing device |
US8571624B2 (en) | 2004-12-29 | 2013-10-29 | Abbott Diabetes Care Inc. | Method and apparatus for mounting a data transmission device in a communication system |
US9572534B2 (en) | 2010-06-29 | 2017-02-21 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US7731657B2 (en) | 2005-08-30 | 2010-06-08 | Abbott Diabetes Care Inc. | Analyte sensor introducer and methods of use |
US9259175B2 (en) | 2006-10-23 | 2016-02-16 | Abbott Diabetes Care, Inc. | Flexible patch for fluid delivery and monitoring body analytes |
US8545403B2 (en) | 2005-12-28 | 2013-10-01 | Abbott Diabetes Care Inc. | Medical device insertion |
US8652831B2 (en) | 2004-12-30 | 2014-02-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for analyte measurement test time |
US7704229B2 (en) | 2005-02-03 | 2010-04-27 | Medtronic Minimed, Inc. | Insertion device |
US20090076360A1 (en) | 2007-09-13 | 2009-03-19 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8133178B2 (en) | 2006-02-22 | 2012-03-13 | Dexcom, Inc. | Analyte sensor |
WO2006102412A2 (en) | 2005-03-21 | 2006-09-28 | Abbott Diabetes Care, Inc. | Method and system for providing integrated medication infusion and analyte monitoring system |
WO2006110193A2 (en) * | 2005-04-08 | 2006-10-19 | Dexcom, Inc. | Cellulosic-based interference domain for an analyte sensor |
US8744546B2 (en) | 2005-05-05 | 2014-06-03 | Dexcom, Inc. | Cellulosic-based resistance domain for an analyte sensor |
US8060174B2 (en) | 2005-04-15 | 2011-11-15 | Dexcom, Inc. | Analyte sensing biointerface |
US7768408B2 (en) | 2005-05-17 | 2010-08-03 | Abbott Diabetes Care Inc. | Method and system for providing data management in data monitoring system |
US20060272652A1 (en) * | 2005-06-03 | 2006-12-07 | Medtronic Minimed, Inc. | Virtual patient software system for educating and treating individuals with diabetes |
US20070033074A1 (en) * | 2005-06-03 | 2007-02-08 | Medtronic Minimed, Inc. | Therapy management system |
US20070016449A1 (en) * | 2005-06-29 | 2007-01-18 | Gary Cohen | Flexible glucose analysis using varying time report deltas and configurable glucose target ranges |
US20070066956A1 (en) * | 2005-07-27 | 2007-03-22 | Medtronic Minimed, Inc. | Systems and methods for entering temporary basal rate pattern in an infusion device |
US20090227855A1 (en) | 2005-08-16 | 2009-09-10 | Medtronic Minimed, Inc. | Controller device for an infusion pump |
US20070093786A1 (en) * | 2005-08-16 | 2007-04-26 | Medtronic Minimed, Inc. | Watch controller for a medical device |
US7737581B2 (en) | 2005-08-16 | 2010-06-15 | Medtronic Minimed, Inc. | Method and apparatus for predicting end of battery life |
JP2009507224A (en) | 2005-08-31 | 2009-02-19 | ユニヴァーシティー オブ ヴァージニア パテント ファンデーション | Improving the accuracy of continuous glucose sensors |
US7713240B2 (en) | 2005-09-13 | 2010-05-11 | Medtronic Minimed, Inc. | Modular external infusion device |
US9072476B2 (en) | 2005-09-23 | 2015-07-07 | Medtronic Minimed, Inc. | Flexible sensor apparatus |
US7725148B2 (en) | 2005-09-23 | 2010-05-25 | Medtronic Minimed, Inc. | Sensor with layered electrodes |
US8880138B2 (en) | 2005-09-30 | 2014-11-04 | Abbott Diabetes Care Inc. | Device for channeling fluid and methods of use |
US9521968B2 (en) | 2005-09-30 | 2016-12-20 | Abbott Diabetes Care Inc. | Analyte sensor retention mechanism and methods of use |
US7583190B2 (en) | 2005-10-31 | 2009-09-01 | Abbott Diabetes Care Inc. | Method and apparatus for providing data communication in data monitoring and management systems |
US8160670B2 (en) | 2005-12-28 | 2012-04-17 | Abbott Diabetes Care Inc. | Analyte monitoring: stabilizer for subcutaneous glucose sensor with incorporated antiglycolytic agent |
US8515518B2 (en) * | 2005-12-28 | 2013-08-20 | Abbott Diabetes Care Inc. | Analyte monitoring |
US20070169533A1 (en) | 2005-12-30 | 2007-07-26 | Medtronic Minimed, Inc. | Methods and systems for detecting the hydration of sensors |
US20070173712A1 (en) * | 2005-12-30 | 2007-07-26 | Medtronic Minimed, Inc. | Method of and system for stabilization of sensors |
US8114269B2 (en) | 2005-12-30 | 2012-02-14 | Medtronic Minimed, Inc. | System and method for determining the point of hydration and proper time to apply potential to a glucose sensor |
US7985330B2 (en) * | 2005-12-30 | 2011-07-26 | Medtronic Minimed, Inc. | Method and system for detecting age, hydration, and functional states of sensors using electrochemical impedance spectroscopy |
US8114268B2 (en) * | 2005-12-30 | 2012-02-14 | Medtronic Minimed, Inc. | Method and system for remedying sensor malfunctions detected by electrochemical impedance spectroscopy |
US7774038B2 (en) | 2005-12-30 | 2010-08-10 | Medtronic Minimed, Inc. | Real-time self-calibrating sensor system and method |
US9757061B2 (en) | 2006-01-17 | 2017-09-12 | Dexcom, Inc. | Low oxygen in vivo analyte sensor |
JP4858143B2 (en) * | 2006-02-22 | 2012-01-18 | セイコーエプソン株式会社 | Film forming method, film-coated substrate, sensor, and liquid composition |
US9326709B2 (en) | 2010-03-10 | 2016-05-03 | Abbott Diabetes Care Inc. | Systems, devices and methods for managing glucose levels |
US9392969B2 (en) | 2008-08-31 | 2016-07-19 | Abbott Diabetes Care Inc. | Closed loop control and signal attenuation detection |
US20100012049A1 (en) * | 2006-04-12 | 2010-01-21 | Jms Co., Ltd | Cavitation heating system and method |
WO2007120381A2 (en) | 2006-04-14 | 2007-10-25 | Dexcom, Inc. | Analyte sensor |
US7942844B2 (en) | 2006-04-28 | 2011-05-17 | Medtronic Minimed, Inc. | Remote monitoring for networked fluid infusion systems |
US8073008B2 (en) | 2006-04-28 | 2011-12-06 | Medtronic Minimed, Inc. | Subnetwork synchronization and variable transmit synchronization techniques for a wireless medical device network |
US7699973B2 (en) * | 2006-06-30 | 2010-04-20 | Abbott Diabetes Care Inc. | Rapid analyte measurement assay |
US7831287B2 (en) | 2006-10-04 | 2010-11-09 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
US20080119702A1 (en) * | 2006-10-31 | 2008-05-22 | Abbott Diabetes Care, Inc. | Analyte meter having alert, alarm and test reminder capabilities and methods of use |
US20080119710A1 (en) * | 2006-10-31 | 2008-05-22 | Abbott Diabetes Care, Inc. | Medical devices and methods of using the same |
US8579853B2 (en) | 2006-10-31 | 2013-11-12 | Abbott Diabetes Care Inc. | Infusion devices and methods |
EP2091430A4 (en) | 2006-11-30 | 2010-01-06 | Abbott Diabetes Care Inc | Lyotropic liquid crystal coated analyte monitoring device and methods of use |
US20080139910A1 (en) * | 2006-12-06 | 2008-06-12 | Metronic Minimed, Inc. | Analyte sensor and method of using the same |
US10154804B2 (en) | 2007-01-31 | 2018-12-18 | Medtronic Minimed, Inc. | Model predictive method and system for controlling and supervising insulin infusion |
US8808515B2 (en) | 2007-01-31 | 2014-08-19 | Abbott Diabetes Care Inc. | Heterocyclic nitrogen containing polymers coated analyte monitoring device and methods of use |
US8930203B2 (en) | 2007-02-18 | 2015-01-06 | Abbott Diabetes Care Inc. | Multi-function analyte test device and methods therefor |
US9796998B2 (en) | 2007-04-09 | 2017-10-24 | Colorado State University Research Foundation | Oxygenase-based biosensing systems for measurement of halogenated alkene concentrations |
EP2146623B1 (en) | 2007-04-14 | 2014-01-08 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US20080269723A1 (en) * | 2007-04-25 | 2008-10-30 | Medtronic Minimed, Inc. | Closed loop/semi-closed loop therapy modification system |
US20080269714A1 (en) | 2007-04-25 | 2008-10-30 | Medtronic Minimed, Inc. | Closed loop/semi-closed loop therapy modification system |
US8080385B2 (en) | 2007-05-03 | 2011-12-20 | Abbott Diabetes Care Inc. | Crosslinked adduct of polyaniline and polymer acid containing redox enzyme for electrochemical sensor |
US7928850B2 (en) | 2007-05-08 | 2011-04-19 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US8461985B2 (en) | 2007-05-08 | 2013-06-11 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US8444560B2 (en) | 2007-05-14 | 2013-05-21 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US20200037875A1 (en) | 2007-05-18 | 2020-02-06 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
WO2008150917A1 (en) | 2007-05-31 | 2008-12-11 | Abbott Diabetes Care, Inc. | Insertion devices and methods |
US8834366B2 (en) | 2007-07-31 | 2014-09-16 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor calibration |
WO2009032760A2 (en) | 2007-08-30 | 2009-03-12 | Pepex Biomedical Llc | Electrochmical sensor and method for manufacturing |
WO2009051901A2 (en) * | 2007-08-30 | 2009-04-23 | Pepex Biomedical, Llc | Electrochemical sensor and method for manufacturing |
US8163146B2 (en) | 2007-10-12 | 2012-04-24 | Abbott Diabetes Care Inc. | Mediator stabilized reagent compositions for use in biosensor electrodes |
US20090247984A1 (en) * | 2007-10-24 | 2009-10-01 | Masimo Laboratories, Inc. | Use of microneedles for small molecule metabolite reporter delivery |
US8417312B2 (en) | 2007-10-25 | 2013-04-09 | Dexcom, Inc. | Systems and methods for processing sensor data |
US20090164239A1 (en) | 2007-12-19 | 2009-06-25 | Abbott Diabetes Care, Inc. | Dynamic Display Of Glucose Information |
US8313467B2 (en) | 2007-12-27 | 2012-11-20 | Medtronic Minimed, Inc. | Reservoir pressure equalization systems and methods |
US8431011B2 (en) | 2008-01-31 | 2013-04-30 | Abbott Diabetes Care Inc. | Method for automatically and rapidly distinguishing between control and sample solutions in a biosensor strip |
US20090275815A1 (en) * | 2008-03-21 | 2009-11-05 | Nova Biomedical Corporation | Temperature-compensated in-vivo sensor |
US8396528B2 (en) | 2008-03-25 | 2013-03-12 | Dexcom, Inc. | Analyte sensor |
US8583204B2 (en) | 2008-03-28 | 2013-11-12 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US11730407B2 (en) | 2008-03-28 | 2023-08-22 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US8682408B2 (en) | 2008-03-28 | 2014-03-25 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US9386944B2 (en) | 2008-04-11 | 2016-07-12 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for analyte detecting device |
US8262874B2 (en) * | 2008-04-14 | 2012-09-11 | Abbott Diabetes Care Inc. | Biosensor coating composition and methods thereof |
US9295786B2 (en) | 2008-05-28 | 2016-03-29 | Medtronic Minimed, Inc. | Needle protective device for subcutaneous sensors |
US7826382B2 (en) | 2008-05-30 | 2010-11-02 | Abbott Diabetes Care Inc. | Close proximity communication device and methods |
US8876755B2 (en) | 2008-07-14 | 2014-11-04 | Abbott Diabetes Care Inc. | Closed loop control system interface and methods |
US8700114B2 (en) * | 2008-07-31 | 2014-04-15 | Medtronic Minmed, Inc. | Analyte sensor apparatuses comprising multiple implantable sensor elements and methods for making and using them |
US20100025238A1 (en) * | 2008-07-31 | 2010-02-04 | Medtronic Minimed, Inc. | Analyte sensor apparatuses having improved electrode configurations and methods for making and using them |
US20100057040A1 (en) | 2008-08-31 | 2010-03-04 | Abbott Diabetes Care, Inc. | Robust Closed Loop Control And Methods |
WO2010033724A2 (en) | 2008-09-19 | 2010-03-25 | Dexcom, Inc. | Particle-containing membrane and particulate electrode for analyte sensors |
US8208973B2 (en) | 2008-11-05 | 2012-06-26 | Medtronic Minimed, Inc. | System and method for variable beacon timing with wireless devices |
US8951377B2 (en) | 2008-11-14 | 2015-02-10 | Pepex Biomedical, Inc. | Manufacturing electrochemical sensor module |
WO2010056878A2 (en) | 2008-11-14 | 2010-05-20 | Pepex Biomedical, Llc | Electrochemical sensor module |
WO2010056876A2 (en) | 2008-11-14 | 2010-05-20 | Pepex Biomedical, Llc | Manufacturing electrochemical sensor module |
US20100160740A1 (en) * | 2008-12-24 | 2010-06-24 | Gary Cohen | Use of Patterns in a Therapy Management System |
US9330237B2 (en) * | 2008-12-24 | 2016-05-03 | Medtronic Minimed, Inc. | Pattern recognition and filtering in a therapy management system |
US9375169B2 (en) | 2009-01-30 | 2016-06-28 | Sanofi-Aventis Deutschland Gmbh | Cam drive for managing disposable penetrating member actions with a single motor and motor and control system |
US20100213057A1 (en) | 2009-02-26 | 2010-08-26 | Benjamin Feldman | Self-Powered Analyte Sensor |
WO2010129375A1 (en) | 2009-04-28 | 2010-11-11 | Abbott Diabetes Care Inc. | Closed loop blood glucose control algorithm analysis |
WO2010127050A1 (en) | 2009-04-28 | 2010-11-04 | Abbott Diabetes Care Inc. | Error detection in critical repeating data in a wireless sensor system |
WO2010127051A1 (en) | 2009-04-29 | 2010-11-04 | Abbott Diabetes Care Inc. | Method and system for providing real time analyte sensor calibration with retrospective backfill |
US20110027458A1 (en) | 2009-07-02 | 2011-02-03 | Dexcom, Inc. | Continuous analyte sensors and methods of making same |
US9351677B2 (en) | 2009-07-02 | 2016-05-31 | Dexcom, Inc. | Analyte sensor with increased reference capacity |
US8344847B2 (en) | 2009-07-09 | 2013-01-01 | Medtronic Minimed, Inc. | Coordination of control commands in a medical device system having at least one therapy delivery device and at least one wireless controller device |
US8487758B2 (en) | 2009-09-02 | 2013-07-16 | Medtronic Minimed, Inc. | Medical device having an intelligent alerting scheme, and related operating methods |
US8386042B2 (en) | 2009-11-03 | 2013-02-26 | Medtronic Minimed, Inc. | Omnidirectional accelerometer device and medical device incorporating same |
US8574201B2 (en) | 2009-12-22 | 2013-11-05 | Medtronic Minimed, Inc. | Syringe piston with check valve seal |
US8755269B2 (en) | 2009-12-23 | 2014-06-17 | Medtronic Minimed, Inc. | Ranking and switching of wireless channels in a body area network of medical devices |
US8965476B2 (en) | 2010-04-16 | 2015-02-24 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US8603032B2 (en) | 2010-10-15 | 2013-12-10 | Medtronic Minimed, Inc. | Medical device with membrane keypad sealing element, and related manufacturing method |
US8562565B2 (en) | 2010-10-15 | 2013-10-22 | Medtronic Minimed, Inc. | Battery shock absorber for a portable medical device |
US8603033B2 (en) | 2010-10-15 | 2013-12-10 | Medtronic Minimed, Inc. | Medical device and related assembly having an offset element for a piezoelectric speaker |
US8474332B2 (en) | 2010-10-20 | 2013-07-02 | Medtronic Minimed, Inc. | Sensor assembly and medical device incorporating same |
US8479595B2 (en) | 2010-10-20 | 2013-07-09 | Medtronic Minimed, Inc. | Sensor assembly and medical device incorporating same |
US8495918B2 (en) | 2010-10-20 | 2013-07-30 | Medtronic Minimed, Inc. | Sensor assembly and medical device incorporating same |
WO2012071471A2 (en) | 2010-11-22 | 2012-05-31 | Colorado State University Research Foundation | Biosensing systems for measurement of lactose |
US8628510B2 (en) | 2010-12-22 | 2014-01-14 | Medtronic Minimed, Inc. | Monitoring the operating health of a force sensor in a fluid infusion device |
US8690855B2 (en) | 2010-12-22 | 2014-04-08 | Medtronic Minimed, Inc. | Fluid reservoir seating procedure for a fluid infusion device |
US8197444B1 (en) | 2010-12-22 | 2012-06-12 | Medtronic Minimed, Inc. | Monitoring the seating status of a fluid reservoir in a fluid infusion device |
US8469942B2 (en) | 2010-12-22 | 2013-06-25 | Medtronic Minimed, Inc. | Occlusion detection for a fluid infusion device |
US9463309B2 (en) | 2011-02-22 | 2016-10-11 | Medtronic Minimed, Inc. | Sealing assembly and structure for a fluid infusion device having a needled fluid reservoir |
US9283318B2 (en) | 2011-02-22 | 2016-03-15 | Medtronic Minimed, Inc. | Flanged sealing element and needle guide pin assembly for a fluid infusion device having a needled fluid reservoir |
US9393399B2 (en) | 2011-02-22 | 2016-07-19 | Medtronic Minimed, Inc. | Sealing assembly for a fluid reservoir of a fluid infusion device |
US8864726B2 (en) | 2011-02-22 | 2014-10-21 | Medtronic Minimed, Inc. | Pressure vented fluid reservoir having a movable septum |
CA2827196A1 (en) | 2011-02-28 | 2012-11-15 | Jai Karan | Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same |
US10136845B2 (en) | 2011-02-28 | 2018-11-27 | Abbott Diabetes Care Inc. | Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same |
US8614596B2 (en) | 2011-02-28 | 2013-12-24 | Medtronic Minimed, Inc. | Systems and methods for initializing a voltage bus and medical devices incorporating same |
US9101305B2 (en) | 2011-03-09 | 2015-08-11 | Medtronic Minimed, Inc. | Glucose sensor product and related manufacturing and packaging methods |
US8564447B2 (en) | 2011-03-18 | 2013-10-22 | Medtronic Minimed, Inc. | Battery life indication techniques for an electronic device |
US9018893B2 (en) | 2011-03-18 | 2015-04-28 | Medtronic Minimed, Inc. | Power control techniques for an electronic device |
JP5930810B2 (en) | 2011-04-26 | 2016-06-08 | アークレイ株式会社 | Analysis tool |
US9585605B2 (en) | 2011-05-19 | 2017-03-07 | Pepex Biomedical, Inc. | Fluid management and patient monitoring system |
US9504162B2 (en) | 2011-05-20 | 2016-11-22 | Pepex Biomedical, Inc. | Manufacturing electrochemical sensor modules |
US9499853B2 (en) | 2011-08-02 | 2016-11-22 | Colorado State University Research Foundation | Biosensing system with extended lifetime via cofactor recycling |
US9317656B2 (en) | 2011-11-23 | 2016-04-19 | Abbott Diabetes Care Inc. | Compatibility mechanisms for devices in a continuous analyte monitoring system and methods thereof |
US9610401B2 (en) | 2012-01-13 | 2017-04-04 | Medtronic Minimed, Inc. | Infusion set component with modular fluid channel element |
US8523803B1 (en) | 2012-03-20 | 2013-09-03 | Medtronic Minimed, Inc. | Motor health monitoring and medical device incorporating same |
US8603027B2 (en) | 2012-03-20 | 2013-12-10 | Medtronic Minimed, Inc. | Occlusion detection using pulse-width modulation and medical device incorporating same |
US8603026B2 (en) | 2012-03-20 | 2013-12-10 | Medtronic Minimed, Inc. | Dynamic pulse-width modulation motor control and medical device incorporating same |
US20130338629A1 (en) | 2012-06-07 | 2013-12-19 | Medtronic Minimed, Inc. | Diabetes therapy management system for recommending basal pattern adjustments |
US9333292B2 (en) | 2012-06-26 | 2016-05-10 | Medtronic Minimed, Inc. | Mechanically actuated fluid infusion device |
US8808269B2 (en) | 2012-08-21 | 2014-08-19 | Medtronic Minimed, Inc. | Reservoir plunger position monitoring and medical device incorporating same |
US9849239B2 (en) | 2012-08-30 | 2017-12-26 | Medtronic Minimed, Inc. | Generation and application of an insulin limit for a closed-loop operating mode of an insulin infusion system |
US9526834B2 (en) | 2012-08-30 | 2016-12-27 | Medtronic Minimed, Inc. | Safeguarding measures for a closed-loop insulin infusion system |
US9623179B2 (en) | 2012-08-30 | 2017-04-18 | Medtronic Minimed, Inc. | Safeguarding techniques for a closed-loop insulin infusion system |
US10496797B2 (en) | 2012-08-30 | 2019-12-03 | Medtronic Minimed, Inc. | Blood glucose validation for a closed-loop operating mode of an insulin infusion system |
US9878096B2 (en) | 2012-08-30 | 2018-01-30 | Medtronic Minimed, Inc. | Generation of target glucose values for a closed-loop operating mode of an insulin infusion system |
US9662445B2 (en) | 2012-08-30 | 2017-05-30 | Medtronic Minimed, Inc. | Regulating entry into a closed-loop operating mode of an insulin infusion system |
US10130767B2 (en) | 2012-08-30 | 2018-11-20 | Medtronic Minimed, Inc. | Sensor model supervisor for a closed-loop insulin infusion system |
US8870818B2 (en) | 2012-11-15 | 2014-10-28 | Medtronic Minimed, Inc. | Systems and methods for alignment and detection of a consumable component |
WO2014089058A1 (en) | 2012-12-03 | 2014-06-12 | Pepex Biomedical, Inc. | Sensor module and method of using a sensor module |
US20140166503A1 (en) * | 2012-12-13 | 2014-06-19 | Broadmaster Biotech Corp. | Method and device for measuring hematocrit |
US9107994B2 (en) | 2013-01-18 | 2015-08-18 | Medtronic Minimed, Inc. | Systems for fluid reservoir retention |
US9033924B2 (en) | 2013-01-18 | 2015-05-19 | Medtronic Minimed, Inc. | Systems for fluid reservoir retention |
US9522223B2 (en) | 2013-01-18 | 2016-12-20 | Medtronic Minimed, Inc. | Systems for fluid reservoir retention |
US9308321B2 (en) | 2013-02-18 | 2016-04-12 | Medtronic Minimed, Inc. | Infusion device having gear assembly initialization |
US8920381B2 (en) | 2013-04-12 | 2014-12-30 | Medtronic Minimed, Inc. | Infusion set with improved bore configuration |
US9433731B2 (en) | 2013-07-19 | 2016-09-06 | Medtronic Minimed, Inc. | Detecting unintentional motor motion and infusion device incorporating same |
US9402949B2 (en) | 2013-08-13 | 2016-08-02 | Medtronic Minimed, Inc. | Detecting conditions associated with medical device operations using matched filters |
US9889257B2 (en) | 2013-08-21 | 2018-02-13 | Medtronic Minimed, Inc. | Systems and methods for updating medical devices |
US9880528B2 (en) | 2013-08-21 | 2018-01-30 | Medtronic Minimed, Inc. | Medical devices and related updating methods and systems |
US9259528B2 (en) | 2013-08-22 | 2016-02-16 | Medtronic Minimed, Inc. | Fluid infusion device with safety coupling |
US9750877B2 (en) | 2013-12-11 | 2017-09-05 | Medtronic Minimed, Inc. | Predicted time to assess and/or control a glycemic state |
US9750878B2 (en) | 2013-12-11 | 2017-09-05 | Medtronic Minimed, Inc. | Closed-loop control of glucose according to a predicted blood glucose trajectory |
US9849240B2 (en) | 2013-12-12 | 2017-12-26 | Medtronic Minimed, Inc. | Data modification for predictive operations and devices incorporating same |
US10105488B2 (en) | 2013-12-12 | 2018-10-23 | Medtronic Minimed, Inc. | Predictive infusion device operations and related methods and systems |
US9694132B2 (en) | 2013-12-19 | 2017-07-04 | Medtronic Minimed, Inc. | Insertion device for insertion set |
CN105899132B (en) | 2013-12-31 | 2020-02-18 | 雅培糖尿病护理公司 | Self-powered analyte sensor and devices using same |
US9399096B2 (en) | 2014-02-06 | 2016-07-26 | Medtronic Minimed, Inc. | Automatic closed-loop control adjustments and infusion systems incorporating same |
US9861748B2 (en) | 2014-02-06 | 2018-01-09 | Medtronic Minimed, Inc. | User-configurable closed-loop notifications and infusion systems incorporating same |
US9610402B2 (en) | 2014-03-24 | 2017-04-04 | Medtronic Minimed, Inc. | Transcutaneous conduit insertion mechanism with a living hinge for use with a fluid infusion patch pump device |
US10001450B2 (en) | 2014-04-18 | 2018-06-19 | Medtronic Minimed, Inc. | Nonlinear mapping technique for a physiological characteristic sensor |
US10232113B2 (en) | 2014-04-24 | 2019-03-19 | Medtronic Minimed, Inc. | Infusion devices and related methods and systems for regulating insulin on board |
US9681828B2 (en) | 2014-05-01 | 2017-06-20 | Medtronic Minimed, Inc. | Physiological characteristic sensors and methods for forming such sensors |
US10275572B2 (en) | 2014-05-01 | 2019-04-30 | Medtronic Minimed, Inc. | Detecting blockage of a reservoir cavity during a seating operation of a fluid infusion device |
US10274349B2 (en) | 2014-05-19 | 2019-04-30 | Medtronic Minimed, Inc. | Calibration factor adjustments for infusion devices and related methods and systems |
US10152049B2 (en) | 2014-05-19 | 2018-12-11 | Medtronic Minimed, Inc. | Glucose sensor health monitoring and related methods and systems |
US10007765B2 (en) | 2014-05-19 | 2018-06-26 | Medtronic Minimed, Inc. | Adaptive signal processing for infusion devices and related methods and systems |
CN107003264B (en) | 2014-06-04 | 2020-02-21 | 普佩克斯生物医药有限公司 | Electrochemical sensor and method of manufacturing an electrochemical sensor using advanced printing techniques |
US9839753B2 (en) | 2014-09-26 | 2017-12-12 | Medtronic Minimed, Inc. | Systems for managing reservoir chamber pressure |
US9833563B2 (en) | 2014-09-26 | 2017-12-05 | Medtronic Minimed, Inc. | Systems for managing reservoir chamber pressure |
US10279126B2 (en) | 2014-10-07 | 2019-05-07 | Medtronic Minimed, Inc. | Fluid conduit assembly with gas trapping filter in the fluid flow path |
US9833564B2 (en) | 2014-11-25 | 2017-12-05 | Medtronic Minimed, Inc. | Fluid conduit assembly with air venting features |
US10195341B2 (en) | 2014-11-26 | 2019-02-05 | Medtronic Minimed, Inc. | Systems and methods for fluid infusion device with automatic reservoir fill |
US9987420B2 (en) | 2014-11-26 | 2018-06-05 | Medtronic Minimed, Inc. | Systems and methods for fluid infusion device with automatic reservoir fill |
US9636453B2 (en) | 2014-12-04 | 2017-05-02 | Medtronic Minimed, Inc. | Advance diagnosis of infusion device operating mode viability |
US9943645B2 (en) | 2014-12-04 | 2018-04-17 | Medtronic Minimed, Inc. | Methods for operating mode transitions and related infusion devices and systems |
US9937292B2 (en) | 2014-12-09 | 2018-04-10 | Medtronic Minimed, Inc. | Systems for filling a fluid infusion device reservoir |
US10307535B2 (en) | 2014-12-19 | 2019-06-04 | Medtronic Minimed, Inc. | Infusion devices and related methods and systems for preemptive alerting |
US10265031B2 (en) | 2014-12-19 | 2019-04-23 | Medtronic Minimed, Inc. | Infusion devices and related methods and systems for automatic alert clearing |
US10307528B2 (en) | 2015-03-09 | 2019-06-04 | Medtronic Minimed, Inc. | Extensible infusion devices and related methods |
US10449298B2 (en) | 2015-03-26 | 2019-10-22 | Medtronic Minimed, Inc. | Fluid injection devices and related methods |
CA2984939A1 (en) | 2015-05-14 | 2016-11-17 | Abbott Diabetes Care Inc. | Compact medical device inserters and related systems and methods |
US10137243B2 (en) | 2015-05-26 | 2018-11-27 | Medtronic Minimed, Inc. | Infusion devices with distributed motor control and related operating methods |
US9999721B2 (en) | 2015-05-26 | 2018-06-19 | Medtronic Minimed, Inc. | Error handling in infusion devices with distributed motor control and related operating methods |
US10575767B2 (en) | 2015-05-29 | 2020-03-03 | Medtronic Minimed, Inc. | Method for monitoring an analyte, analyte sensor and analyte monitoring apparatus |
US10010668B2 (en) | 2015-06-22 | 2018-07-03 | Medtronic Minimed, Inc. | Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and a force sensor |
US9878095B2 (en) | 2015-06-22 | 2018-01-30 | Medtronic Minimed, Inc. | Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and multiple sensor contact elements |
US9879668B2 (en) | 2015-06-22 | 2018-01-30 | Medtronic Minimed, Inc. | Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and an optical sensor |
US9987425B2 (en) | 2015-06-22 | 2018-06-05 | Medtronic Minimed, Inc. | Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and sensor contact elements |
US9993594B2 (en) | 2015-06-22 | 2018-06-12 | Medtronic Minimed, Inc. | Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and rotor position sensors |
US10201657B2 (en) | 2015-08-21 | 2019-02-12 | Medtronic Minimed, Inc. | Methods for providing sensor site rotation feedback and related infusion devices and systems |
US20170053084A1 (en) | 2015-08-21 | 2017-02-23 | Medtronic Minimed, Inc. | Data analytics and reporting of glucose-related information |
US10463297B2 (en) | 2015-08-21 | 2019-11-05 | Medtronic Minimed, Inc. | Personalized event detection methods and related devices and systems |
US10543314B2 (en) | 2015-08-21 | 2020-01-28 | Medtronic Minimed, Inc. | Personalized parameter modeling with signal calibration based on historical data |
US10293108B2 (en) | 2015-08-21 | 2019-05-21 | Medtronic Minimed, Inc. | Infusion devices and related patient ratio adjustment methods |
US10117992B2 (en) | 2015-09-29 | 2018-11-06 | Medtronic Minimed, Inc. | Infusion devices and related rescue detection methods |
US11666702B2 (en) | 2015-10-19 | 2023-06-06 | Medtronic Minimed, Inc. | Medical devices and related event pattern treatment recommendation methods |
US11501867B2 (en) | 2015-10-19 | 2022-11-15 | Medtronic Minimed, Inc. | Medical devices and related event pattern presentation methods |
US10146911B2 (en) | 2015-10-23 | 2018-12-04 | Medtronic Minimed, Inc. | Medical devices and related methods and systems for data transfer |
US10037722B2 (en) | 2015-11-03 | 2018-07-31 | Medtronic Minimed, Inc. | Detecting breakage in a display element |
US10449306B2 (en) | 2015-11-25 | 2019-10-22 | Medtronics Minimed, Inc. | Systems for fluid delivery with wicking membrane |
US10589038B2 (en) | 2016-04-27 | 2020-03-17 | Medtronic Minimed, Inc. | Set connector systems for venting a fluid reservoir |
WO2018049170A1 (en) * | 2016-09-09 | 2018-03-15 | Board Of Regents, The University Of Texas System | Sensors and methods for making and using the same |
US11097051B2 (en) | 2016-11-04 | 2021-08-24 | Medtronic Minimed, Inc. | Methods and apparatus for detecting and reacting to insufficient hypoglycemia response |
US10238030B2 (en) | 2016-12-06 | 2019-03-26 | Medtronic Minimed, Inc. | Wireless medical device with a complementary split ring resonator arrangement for suppression of electromagnetic interference |
US10272201B2 (en) | 2016-12-22 | 2019-04-30 | Medtronic Minimed, Inc. | Insertion site monitoring methods and related infusion devices and systems |
CN110461217B (en) | 2017-01-23 | 2022-09-16 | 雅培糖尿病护理公司 | Systems, devices, and methods for analyte sensor insertion |
US10500135B2 (en) | 2017-01-30 | 2019-12-10 | Medtronic Minimed, Inc. | Fluid reservoir and systems for filling a fluid reservoir of a fluid infusion device |
US10532165B2 (en) | 2017-01-30 | 2020-01-14 | Medtronic Minimed, Inc. | Fluid reservoir and systems for filling a fluid reservoir of a fluid infusion device |
US10552580B2 (en) | 2017-02-07 | 2020-02-04 | Medtronic Minimed, Inc. | Infusion system consumables and related calibration methods |
US10363365B2 (en) | 2017-02-07 | 2019-07-30 | Medtronic Minimed, Inc. | Infusion devices and related consumable calibration methods |
US10646649B2 (en) | 2017-02-21 | 2020-05-12 | Medtronic Minimed, Inc. | Infusion devices and fluid identification apparatuses and methods |
US11207463B2 (en) | 2017-02-21 | 2021-12-28 | Medtronic Minimed, Inc. | Apparatuses, systems, and methods for identifying an infusate in a reservoir of an infusion device |
CA3104533A1 (en) * | 2018-06-29 | 2020-01-02 | Profusa, Inc. | Layered sensors and methods of using |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0390390A1 (en) * | 1989-03-20 | 1990-10-03 | Associated Universities, Inc. | Electrochemical biosensor based on immobilized enzymes and redox polymers |
EP0439318A2 (en) * | 1990-01-23 | 1991-07-31 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Doped sol-gel glasses for obtaining chemical interactions |
US5264092A (en) * | 1991-10-02 | 1993-11-23 | Moltech Corporation | Redox polymer modified electrode for the electrochemical regeneration of coenzyme |
WO1993023748A1 (en) * | 1992-05-08 | 1993-11-25 | E. Heller & Company | Electrode and method for the detection of hydrogen peroxide |
US5278046A (en) * | 1991-09-16 | 1994-01-11 | The Mead Corporation | Soybean peroxidase assays |
US5334296A (en) * | 1992-01-15 | 1994-08-02 | Andcare, Inc. | Peroxidase colloidal gold oxidase biosensors for mediatorless glucose determination |
WO1997013870A1 (en) * | 1995-10-11 | 1997-04-17 | Adam Heller | Soybean peroxidase electrochemical sensor |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3796634A (en) * | 1970-03-19 | 1974-03-12 | Us Health Education & Welfare | Insolubilized biologically active enzymes |
US3911901A (en) * | 1974-07-24 | 1975-10-14 | Gen Electric | In vivo hydrogen ion sensor |
US4102746A (en) * | 1975-08-29 | 1978-07-25 | Amerace Corporation | Immobilized proteins |
US4458686A (en) * | 1979-08-02 | 1984-07-10 | Children's Hospital Medical Center | Cutaneous methods of measuring body substances |
US4781798A (en) * | 1985-04-19 | 1988-11-01 | The Regents Of The University Of California | Transparent multi-oxygen sensor array and method of using same |
US5352348A (en) * | 1987-04-09 | 1994-10-04 | Nova Biomedical Corporation | Method of using enzyme electrode |
US5165407A (en) * | 1990-04-19 | 1992-11-24 | The University Of Kansas | Implantable glucose sensor |
RU2049991C1 (en) * | 1992-06-25 | 1995-12-10 | Гиндилис Андрей Львович | Method and active member for detecting metabolites in biological fluids |
-
1997
- 1997-02-11 US US08/798,596 patent/US5972199A/en not_active Expired - Lifetime
-
1998
- 1998-02-11 WO PCT/US1998/002403 patent/WO1998035053A2/en not_active Application Discontinuation
- 1998-02-11 EP EP98907399A patent/EP0977984A2/en not_active Withdrawn
- 1998-02-11 AU AU63214/98A patent/AU6321498A/en not_active Abandoned
- 1998-02-11 JP JP53495498A patent/JP4054382B2/en not_active Expired - Fee Related
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0390390A1 (en) * | 1989-03-20 | 1990-10-03 | Associated Universities, Inc. | Electrochemical biosensor based on immobilized enzymes and redox polymers |
EP0439318A2 (en) * | 1990-01-23 | 1991-07-31 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Doped sol-gel glasses for obtaining chemical interactions |
US5278046A (en) * | 1991-09-16 | 1994-01-11 | The Mead Corporation | Soybean peroxidase assays |
US5264092A (en) * | 1991-10-02 | 1993-11-23 | Moltech Corporation | Redox polymer modified electrode for the electrochemical regeneration of coenzyme |
US5334296A (en) * | 1992-01-15 | 1994-08-02 | Andcare, Inc. | Peroxidase colloidal gold oxidase biosensors for mediatorless glucose determination |
WO1993023748A1 (en) * | 1992-05-08 | 1993-11-25 | E. Heller & Company | Electrode and method for the detection of hydrogen peroxide |
WO1997013870A1 (en) * | 1995-10-11 | 1997-04-17 | Adam Heller | Soybean peroxidase electrochemical sensor |
Non-Patent Citations (6)
Title |
---|
DATABASE WPI Section Ch, Week 9638 Derwent Publications Ltd., London, GB; Class A89, AN 96-383023 XP002070475 & RU 2 049 991 C (GINDILIS A L) * |
H. LIU ET AL: "Reagentless amperometric biosensors highly sensitive to hydrogen peroxide, glucose and lactose based on N-methyl phenazine methosulfate incorporated in a Nafion film as an electron transfer mediator between horseradish peroxidase and an electrode." ANALYTICA CHIMICA ACTA, vol. 344, no. 3, 10 June 1997, pages 187-199, XP002070474 * |
KENAUSIS G ET AL: "ELECTROCHEMICAL GLUCOSE AND LACTATE SENSORS BASED ON "WIRED" THERMOSTABLE SOYBEAN POROXIDASE OPERATING CONTINUOUSLY AND STABLY AT 37 C" ANALYTICAL CHEMISTRY, vol. 69, no. 6, 15 March 1997, pages 1054-1060, XP000686380 * |
MARCINKEVICIENCE J ET AL: "BIENZYME STRIP-TYPE GLUCOSE SENSOR" BIOSENSORS & BIOELECTRONICS, vol. 8, no. 3/04, 1 January 1993, pages 209-212, XP000579124 * |
VREEKE M S ET AL: "A THERMOSTABLE HYDROGEN PEROXIDE SENSOR BASED ON "WIRING" OF SOYBEAN PEROXIDASE" ANALYTICAL CHEMISTRY, vol. 67, no. 23, 1 December 1995, pages 4247-4249, XP000540111 * |
Y. LIU ET AL: "Entrapment of both glucose and peroxidase in regenerated silk fibroin membrane. Characterization of the membrane structure and its application to an amperometric glucose sensor employing methylene green as an electron transfer mediator." FRESENIUS' JOURNAL OF ANALYTICAL CHEMISTRY, vol. 355, no. 1, May 1996, pages 78-82, XP002070473 * |
Cited By (263)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999056613A1 (en) | 1998-04-30 | 1999-11-11 | Therasense, Inc. | Analyte monitoring device and methods of use |
EP1235068A1 (en) * | 1999-11-15 | 2002-08-28 | ARKRAY, Inc. | Biosensor |
EP1235068A4 (en) * | 1999-11-15 | 2003-02-19 | Arkray Inc | Biosensor |
US6916410B2 (en) | 1999-11-15 | 2005-07-12 | Arkray, Inc. | Biosensor |
WO2002035222A1 (en) | 2000-10-27 | 2002-05-02 | Arkray, Inc. | Biosensor |
EP1336839A1 (en) * | 2000-10-27 | 2003-08-20 | ARKRAY, Inc. | Biosensor |
EP1336839A4 (en) * | 2000-10-27 | 2006-05-24 | Arkray Inc | Biosensor |
US8426192B2 (en) | 2001-05-31 | 2013-04-23 | Instrumentation Laboratory Company | Composite membrane containing a cross-linked enzyme matrix for a biosensor |
US7632672B2 (en) | 2001-05-31 | 2009-12-15 | Instrumentation Laboratory Co. | Composite membrane containing a cross-linked enzyme matrix for a biosensor |
US9388503B2 (en) | 2001-05-31 | 2016-07-12 | Instrumentation Laboratory Company | Cross-linked enzyme matrix and uses thereof |
DE10212570A1 (en) * | 2002-03-12 | 2003-10-02 | Bst Bio Sensor Tech Gmbh | Production of amperometric biosensor used for determining hydrogen peroxide concentration comprises coating screen printed two electrode system with composition comprising polymer, mediator and enzyme |
DE10212570B4 (en) * | 2002-03-12 | 2004-02-19 | Bst Bio Sensor Technologie Gmbh | Amperometric thick-film biosensor for determining the hydrogen peroxide concentration in a solution and method for producing the sensor |
US10973443B2 (en) | 2002-11-05 | 2021-04-13 | Abbott Diabetes Care Inc. | Sensor inserter assembly |
US11141084B2 (en) | 2002-11-05 | 2021-10-12 | Abbott Diabetes Care Inc. | Sensor inserter assembly |
US9980670B2 (en) | 2002-11-05 | 2018-05-29 | Abbott Diabetes Care Inc. | Sensor inserter assembly |
US11116430B2 (en) | 2002-11-05 | 2021-09-14 | Abbott Diabetes Care Inc. | Sensor inserter assembly |
US10039881B2 (en) | 2002-12-31 | 2018-08-07 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
US9730584B2 (en) | 2003-06-10 | 2017-08-15 | Abbott Diabetes Care Inc. | Glucose measuring device for use in personal area network |
USD914881S1 (en) | 2003-11-05 | 2021-03-30 | Abbott Diabetes Care Inc. | Analyte sensor electronic mount |
USD902408S1 (en) | 2003-11-05 | 2020-11-17 | Abbott Diabetes Care Inc. | Analyte sensor control unit |
US11000215B1 (en) | 2003-12-05 | 2021-05-11 | Dexcom, Inc. | Analyte sensor |
US11627900B2 (en) | 2003-12-05 | 2023-04-18 | Dexcom, Inc. | Analyte sensor |
US11020031B1 (en) | 2003-12-05 | 2021-06-01 | Dexcom, Inc. | Analyte sensor |
US11883164B2 (en) | 2004-07-13 | 2024-01-30 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10226207B2 (en) | 2004-12-29 | 2019-03-12 | Abbott Diabetes Care Inc. | Sensor inserter having introducer |
US11160475B2 (en) | 2004-12-29 | 2021-11-02 | Abbott Diabetes Care Inc. | Sensor inserter having introducer |
US10709364B2 (en) | 2005-03-10 | 2020-07-14 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10925524B2 (en) | 2005-03-10 | 2021-02-23 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US11000213B2 (en) | 2005-03-10 | 2021-05-11 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10610137B2 (en) | 2005-03-10 | 2020-04-07 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10716498B2 (en) | 2005-03-10 | 2020-07-21 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10617336B2 (en) | 2005-03-10 | 2020-04-14 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US11051726B2 (en) | 2005-03-10 | 2021-07-06 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10743801B2 (en) | 2005-03-10 | 2020-08-18 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10918316B2 (en) | 2005-03-10 | 2021-02-16 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10918318B2 (en) | 2005-03-10 | 2021-02-16 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10856787B2 (en) | 2005-03-10 | 2020-12-08 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10610136B2 (en) | 2005-03-10 | 2020-04-07 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10918317B2 (en) | 2005-03-10 | 2021-02-16 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10898114B2 (en) | 2005-03-10 | 2021-01-26 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10610135B2 (en) | 2005-03-10 | 2020-04-07 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US10342489B2 (en) | 2005-09-30 | 2019-07-09 | Abbott Diabetes Care Inc. | Integrated introducer and transmitter assembly and methods of use |
US10194863B2 (en) | 2005-09-30 | 2019-02-05 | Abbott Diabetes Care Inc. | Integrated transmitter unit and sensor introducer mechanism and methods of use |
US9775563B2 (en) | 2005-09-30 | 2017-10-03 | Abbott Diabetes Care Inc. | Integrated introducer and transmitter assembly and methods of use |
US9669162B2 (en) | 2005-11-04 | 2017-06-06 | Abbott Diabetes Care Inc. | Method and system for providing basal profile modification in analyte monitoring and management systems |
US11538580B2 (en) | 2005-11-04 | 2022-12-27 | Abbott Diabetes Care Inc. | Method and system for providing basal profile modification in analyte monitoring and management systems |
US11298058B2 (en) | 2005-12-28 | 2022-04-12 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor insertion |
US9795331B2 (en) | 2005-12-28 | 2017-10-24 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor insertion |
US10307091B2 (en) | 2005-12-28 | 2019-06-04 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor insertion |
US9326727B2 (en) | 2006-01-30 | 2016-05-03 | Abbott Diabetes Care Inc. | On-body medical device securement |
USD961778S1 (en) | 2006-02-28 | 2022-08-23 | Abbott Diabetes Care Inc. | Analyte sensor device |
US10117614B2 (en) | 2006-02-28 | 2018-11-06 | Abbott Diabetes Care Inc. | Method and system for providing continuous calibration of implantable analyte sensors |
US9031630B2 (en) | 2006-02-28 | 2015-05-12 | Abbott Diabetes Care Inc. | Analyte sensors and methods of use |
US9364149B2 (en) | 2006-02-28 | 2016-06-14 | Abbott Diabetes Care Inc. | Analyte sensor transmitter unit configuration for a data monitoring and management system |
US11872039B2 (en) | 2006-02-28 | 2024-01-16 | Abbott Diabetes Care Inc. | Method and system for providing continuous calibration of implantable analyte sensors |
US9844329B2 (en) | 2006-02-28 | 2017-12-19 | Abbott Diabetes Care Inc. | Analyte sensors and methods of use |
US9039975B2 (en) | 2006-03-31 | 2015-05-26 | Abbott Diabetes Care Inc. | Analyte monitoring devices and methods therefor |
US9625413B2 (en) | 2006-03-31 | 2017-04-18 | Abbott Diabetes Care Inc. | Analyte monitoring devices and methods therefor |
US9743863B2 (en) | 2006-03-31 | 2017-08-29 | Abbott Diabetes Care Inc. | Method and system for powering an electronic device |
US10028680B2 (en) | 2006-04-28 | 2018-07-24 | Abbott Diabetes Care Inc. | Introducer assembly and methods of use |
US10736547B2 (en) | 2006-04-28 | 2020-08-11 | Abbott Diabetes Care Inc. | Introducer assembly and methods of use |
US10278630B2 (en) | 2006-08-09 | 2019-05-07 | Abbott Diabetes Care Inc. | Method and system for providing calibration of an analyte sensor in an analyte monitoring system |
US11864894B2 (en) | 2006-08-09 | 2024-01-09 | Abbott Diabetes Care Inc. | Method and system for providing calibration of an analyte sensor in an analyte monitoring system |
US9833181B2 (en) | 2006-08-09 | 2017-12-05 | Abbot Diabetes Care Inc. | Method and system for providing calibration of an analyte sensor in an analyte monitoring system |
US9808186B2 (en) | 2006-09-10 | 2017-11-07 | Abbott Diabetes Care Inc. | Method and system for providing an integrated analyte sensor insertion device and data processing unit |
US9629578B2 (en) | 2006-10-02 | 2017-04-25 | Abbott Diabetes Care Inc. | Method and system for dynamically updating calibration parameters for an analyte sensor |
US9788771B2 (en) | 2006-10-23 | 2017-10-17 | Abbott Diabetes Care Inc. | Variable speed sensor insertion devices and methods of use |
US10194868B2 (en) | 2006-10-25 | 2019-02-05 | Abbott Diabetes Care Inc. | Method and system for providing analyte monitoring |
US9814428B2 (en) | 2006-10-25 | 2017-11-14 | Abbott Diabetes Care Inc. | Method and system for providing analyte monitoring |
US11282603B2 (en) | 2006-10-25 | 2022-03-22 | Abbott Diabetes Care Inc. | Method and system for providing analyte monitoring |
US11722229B2 (en) | 2006-10-26 | 2023-08-08 | Abbott Diabetes Care Inc. | Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors |
US10903914B2 (en) | 2006-10-26 | 2021-01-26 | Abbott Diabetes Care Inc. | Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors |
US9882660B2 (en) | 2006-10-26 | 2018-01-30 | Abbott Diabetes Care Inc. | Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors |
US9636450B2 (en) | 2007-02-19 | 2017-05-02 | Udo Hoss | Pump system modular components for delivering medication and analyte sensing at seperate insertion sites |
US9801545B2 (en) | 2007-03-01 | 2017-10-31 | Abbott Diabetes Care Inc. | Method and apparatus for providing rolling data in communication systems |
US10194846B2 (en) | 2007-04-14 | 2019-02-05 | Abbott Diabetes Care Inc. | Method and apparatus for providing dynamic multi-stage signal amplification in a medical device |
US9743866B2 (en) | 2007-04-14 | 2017-08-29 | Abbott Diabetes Care Inc. | Method and apparatus for providing dynamic multi-stage signal amplification in a medical device |
US10111608B2 (en) | 2007-04-14 | 2018-10-30 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US11039767B2 (en) | 2007-04-14 | 2021-06-22 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US10349877B2 (en) | 2007-04-14 | 2019-07-16 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US9615780B2 (en) | 2007-04-14 | 2017-04-11 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US10952611B2 (en) | 2007-05-08 | 2021-03-23 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US10653317B2 (en) | 2007-05-08 | 2020-05-19 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US10178954B2 (en) | 2007-05-08 | 2019-01-15 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US11696684B2 (en) | 2007-05-08 | 2023-07-11 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US9949678B2 (en) | 2007-05-08 | 2018-04-24 | Abbott Diabetes Care Inc. | Method and device for determining elapsed sensor life |
US9649057B2 (en) | 2007-05-08 | 2017-05-16 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US11300561B2 (en) | 2007-05-14 | 2022-04-12 | Abbott Diabetes Care, Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10143409B2 (en) | 2007-05-14 | 2018-12-04 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US11828748B2 (en) | 2007-05-14 | 2023-11-28 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10031002B2 (en) | 2007-05-14 | 2018-07-24 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10119956B2 (en) | 2007-05-14 | 2018-11-06 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10463310B2 (en) | 2007-05-14 | 2019-11-05 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US9804150B2 (en) | 2007-05-14 | 2017-10-31 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10002233B2 (en) | 2007-05-14 | 2018-06-19 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US11125592B2 (en) | 2007-05-14 | 2021-09-21 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10653344B2 (en) | 2007-05-14 | 2020-05-19 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10634662B2 (en) | 2007-05-14 | 2020-04-28 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10976304B2 (en) | 2007-05-14 | 2021-04-13 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10991456B2 (en) | 2007-05-14 | 2021-04-27 | Abbott Diabetes Care Inc. | Method and system for determining analyte levels |
US9801571B2 (en) | 2007-05-14 | 2017-10-31 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US9737249B2 (en) | 2007-05-14 | 2017-08-22 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US11119090B2 (en) | 2007-05-14 | 2021-09-14 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US9060719B2 (en) | 2007-05-14 | 2015-06-23 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US11076785B2 (en) | 2007-05-14 | 2021-08-03 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US9797880B2 (en) | 2007-05-14 | 2017-10-24 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US11264133B2 (en) | 2007-06-21 | 2022-03-01 | Abbott Diabetes Care Inc. | Health management devices and methods |
US11276492B2 (en) | 2007-06-21 | 2022-03-15 | Abbott Diabetes Care Inc. | Health management devices and methods |
US11678821B2 (en) | 2007-06-29 | 2023-06-20 | Abbott Diabetes Care Inc. | Analyte monitoring and management device and method to analyze the frequency of user interaction with the device |
US9913600B2 (en) | 2007-06-29 | 2018-03-13 | Abbott Diabetes Care Inc. | Analyte monitoring and management device and method to analyze the frequency of user interaction with the device |
US10856785B2 (en) | 2007-06-29 | 2020-12-08 | Abbott Diabetes Care Inc. | Analyte monitoring and management device and method to analyze the frequency of user interaction with the device |
US11307201B2 (en) | 2007-09-17 | 2022-04-19 | Red Ivory Llc | Self-actuating signal producing detection devices and methods |
US11083843B2 (en) | 2007-10-23 | 2021-08-10 | Abbott Diabetes Care Inc. | Closed loop control system with safety parameters and methods |
US10173007B2 (en) | 2007-10-23 | 2019-01-08 | Abbott Diabetes Care Inc. | Closed loop control system with safety parameters and methods |
US9804148B2 (en) | 2007-10-23 | 2017-10-31 | Abbott Diabetes Care Inc. | Analyte sensor with lag compensation |
US9743865B2 (en) | 2007-10-23 | 2017-08-29 | Abbott Diabetes Care Inc. | Assessing measures of glycemic variability |
US9770211B2 (en) | 2008-01-31 | 2017-09-26 | Abbott Diabetes Care Inc. | Analyte sensor with time lag compensation |
US9730623B2 (en) | 2008-03-28 | 2017-08-15 | Abbott Diabetes Care Inc. | Analyte sensor calibration management |
US10463288B2 (en) | 2008-03-28 | 2019-11-05 | Abbott Diabetes Care Inc. | Analyte sensor calibration management |
US11779248B2 (en) | 2008-03-28 | 2023-10-10 | Abbott Diabetes Care Inc. | Analyte sensor calibration management |
US11735295B2 (en) | 2008-05-30 | 2023-08-22 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US9541556B2 (en) | 2008-05-30 | 2017-01-10 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US9931075B2 (en) | 2008-05-30 | 2018-04-03 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US9610046B2 (en) | 2008-08-31 | 2017-04-04 | Abbott Diabetes Care Inc. | Closed loop control with improved alarm functions |
US9943644B2 (en) | 2008-08-31 | 2018-04-17 | Abbott Diabetes Care Inc. | Closed loop control with reference measurement and methods thereof |
US11202592B2 (en) | 2008-09-30 | 2021-12-21 | Abbott Diabetes Care Inc. | Optimizing analyte sensor calibration |
US11464434B2 (en) | 2008-09-30 | 2022-10-11 | Abbott Diabetes Care Inc. | Optimizing analyte sensor calibration |
US9662056B2 (en) | 2008-09-30 | 2017-05-30 | Abbott Diabetes Care Inc. | Optimizing analyte sensor calibration |
US11013439B2 (en) | 2008-09-30 | 2021-05-25 | Abbott Diabetes Care Inc. | Optimizing analyte sensor calibration |
US11484234B2 (en) | 2008-09-30 | 2022-11-01 | Abbott Diabetes Care Inc. | Optimizing analyte sensor calibration |
US10045739B2 (en) | 2008-09-30 | 2018-08-14 | Abbott Diabetes Care Inc. | Analyte sensor sensitivity attenuation mitigation |
US10980461B2 (en) | 2008-11-07 | 2021-04-20 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US11272890B2 (en) | 2008-11-10 | 2022-03-15 | Abbott Diabetes Care Inc. | Alarm characterization for analyte monitoring devices and systems |
US11678848B2 (en) | 2008-11-10 | 2023-06-20 | Abbott Diabetes Care Inc. | Alarm characterization for analyte monitoring devices and systems |
US9730650B2 (en) | 2008-11-10 | 2017-08-15 | Abbott Diabetes Care Inc. | Alarm characterization for analyte monitoring devices and systems |
US11464430B2 (en) | 2009-01-29 | 2022-10-11 | Abbott Diabetes Care Inc. | Method and device for providing offset model based calibration for analyte sensor |
US10089446B2 (en) | 2009-01-29 | 2018-10-02 | Abbott Diabetes Care Inc. | Method and device for providing offset model based calibration for analyte sensor |
US9066709B2 (en) | 2009-01-29 | 2015-06-30 | Abbott Diabetes Care Inc. | Method and device for early signal attenuation detection using blood glucose measurements |
USD957642S1 (en) | 2009-02-03 | 2022-07-12 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
US11166656B2 (en) | 2009-02-03 | 2021-11-09 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US11213229B2 (en) | 2009-02-03 | 2022-01-04 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US11006872B2 (en) | 2009-02-03 | 2021-05-18 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US11006870B2 (en) | 2009-02-03 | 2021-05-18 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US10786190B2 (en) | 2009-02-03 | 2020-09-29 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US9636068B2 (en) | 2009-02-03 | 2017-05-02 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US11006871B2 (en) | 2009-02-03 | 2021-05-18 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US9993188B2 (en) | 2009-02-03 | 2018-06-12 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
USD957643S1 (en) | 2009-02-03 | 2022-07-12 | Abbott Diabetes Care Inc. | Analyte sensor device |
US11202591B2 (en) | 2009-02-03 | 2021-12-21 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
USD882432S1 (en) | 2009-02-03 | 2020-04-28 | Abbott Diabetes Care Inc. | Analyte sensor on body unit |
US10009244B2 (en) | 2009-04-15 | 2018-06-26 | Abbott Diabetes Care Inc. | Analyte monitoring system having an alert |
US9088452B2 (en) | 2009-04-29 | 2015-07-21 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
US9693688B2 (en) | 2009-04-29 | 2017-07-04 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
US10172518B2 (en) | 2009-04-29 | 2019-01-08 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
US9949639B2 (en) | 2009-04-29 | 2018-04-24 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
US10617296B2 (en) | 2009-04-29 | 2020-04-14 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
US11872370B2 (en) | 2009-05-29 | 2024-01-16 | Abbott Diabetes Care Inc. | Medical device antenna systems having external antenna configurations |
US11793936B2 (en) | 2009-05-29 | 2023-10-24 | Abbott Diabetes Care Inc. | Medical device antenna systems having external antenna configurations |
WO2011002692A1 (en) | 2009-06-30 | 2011-01-06 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
WO2011002694A1 (en) | 2009-06-30 | 2011-01-06 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
WO2011002693A1 (en) | 2009-06-30 | 2011-01-06 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9795326B2 (en) | 2009-07-23 | 2017-10-24 | Abbott Diabetes Care Inc. | Continuous analyte measurement systems and systems and methods for implanting them |
US11241175B2 (en) | 2009-08-31 | 2022-02-08 | Abbott Diabetes Care Inc. | Displays for a medical device |
US10136816B2 (en) | 2009-08-31 | 2018-11-27 | Abbott Diabetes Care Inc. | Medical devices and methods |
US11045147B2 (en) | 2009-08-31 | 2021-06-29 | Abbott Diabetes Care Inc. | Analyte signal processing device and methods |
USD1010133S1 (en) | 2009-08-31 | 2024-01-02 | Abbott Diabetes Care Inc. | Analyte sensor assembly |
US9968302B2 (en) | 2009-08-31 | 2018-05-15 | Abbott Diabetes Care Inc. | Analyte signal processing device and methods |
US10918342B1 (en) | 2009-08-31 | 2021-02-16 | Abbott Diabetes Care Inc. | Displays for a medical device |
US10429250B2 (en) | 2009-08-31 | 2019-10-01 | Abbott Diabetes Care, Inc. | Analyte monitoring system and methods for managing power and noise |
USRE47315E1 (en) | 2009-08-31 | 2019-03-26 | Abbott Diabetes Care Inc. | Displays for a medical device |
US10881355B2 (en) | 2009-08-31 | 2021-01-05 | Abbott Diabetes Care Inc. | Displays for a medical device |
US11202586B2 (en) | 2009-08-31 | 2021-12-21 | Abbott Diabetes Care Inc. | Displays for a medical device |
US10456091B2 (en) | 2009-08-31 | 2019-10-29 | Abbott Diabetes Care Inc. | Displays for a medical device |
USD962446S1 (en) | 2009-08-31 | 2022-08-30 | Abbott Diabetes Care, Inc. | Analyte sensor device |
US11150145B2 (en) | 2009-08-31 | 2021-10-19 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods for managing power and noise |
US10772572B2 (en) | 2009-08-31 | 2020-09-15 | Abbott Diabetes Care Inc. | Displays for a medical device |
US9814416B2 (en) | 2009-08-31 | 2017-11-14 | Abbott Diabetes Care Inc. | Displays for a medical device |
US11730429B2 (en) | 2009-08-31 | 2023-08-22 | Abbott Diabetes Care Inc. | Displays for a medical device |
US10492685B2 (en) | 2009-08-31 | 2019-12-03 | Abbott Diabetes Care Inc. | Medical devices and methods |
US11635332B2 (en) | 2009-08-31 | 2023-04-25 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods for managing power and noise |
US10123752B2 (en) | 2009-08-31 | 2018-11-13 | Abbott Diabetes Care Inc. | Displays for a medical device |
US10349874B2 (en) | 2009-09-29 | 2019-07-16 | Abbott Diabetes Care Inc. | Method and apparatus for providing notification function in analyte monitoring systems |
US9750439B2 (en) | 2009-09-29 | 2017-09-05 | Abbott Diabetes Care Inc. | Method and apparatus for providing notification function in analyte monitoring systems |
US11259725B2 (en) | 2009-09-30 | 2022-03-01 | Abbott Diabetes Care Inc. | Interconnect for on-body analyte monitoring device |
US10765351B2 (en) | 2009-09-30 | 2020-09-08 | Abbott Diabetes Care Inc. | Interconnect for on-body analyte monitoring device |
US9750444B2 (en) | 2009-09-30 | 2017-09-05 | Abbott Diabetes Care Inc. | Interconnect for on-body analyte monitoring device |
US9050041B2 (en) | 2009-10-30 | 2015-06-09 | Abbott Diabetes Care Inc. | Method and apparatus for detecting false hypoglycemic conditions |
US11207005B2 (en) | 2009-10-30 | 2021-12-28 | Abbott Diabetes Care Inc. | Method and apparatus for detecting false hypoglycemic conditions |
US10117606B2 (en) | 2009-10-30 | 2018-11-06 | Abbott Diabetes Care Inc. | Method and apparatus for detecting false hypoglycemic conditions |
USD924406S1 (en) | 2010-02-01 | 2021-07-06 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
US10881341B1 (en) | 2010-03-24 | 2021-01-05 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US11266335B2 (en) | 2010-03-24 | 2022-03-08 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US11058334B1 (en) | 2010-03-24 | 2021-07-13 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US10881340B2 (en) | 2010-03-24 | 2021-01-05 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US11064922B1 (en) | 2010-03-24 | 2021-07-20 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US10292632B2 (en) | 2010-03-24 | 2019-05-21 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US10010280B2 (en) | 2010-03-24 | 2018-07-03 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US11013440B2 (en) | 2010-03-24 | 2021-05-25 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
USD948722S1 (en) | 2010-03-24 | 2022-04-12 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
US11000216B2 (en) | 2010-03-24 | 2021-05-11 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US10772547B1 (en) | 2010-03-24 | 2020-09-15 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
USD987830S1 (en) | 2010-03-24 | 2023-05-30 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
US9687183B2 (en) | 2010-03-24 | 2017-06-27 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US10945649B2 (en) | 2010-03-24 | 2021-03-16 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US11246519B2 (en) | 2010-03-24 | 2022-02-15 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
USD997362S1 (en) | 2010-03-24 | 2023-08-29 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
US10952657B2 (en) | 2010-03-24 | 2021-03-23 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
US10959654B2 (en) | 2010-03-24 | 2021-03-30 | Abbott Diabetes Care Inc. | Medical device inserters and processes of inserting and using medical devices |
WO2011155943A1 (en) * | 2010-06-11 | 2011-12-15 | Empire Technology Development Llc | Detection and decomposition of bisphenol-a |
US9206459B2 (en) | 2010-06-11 | 2015-12-08 | Empire Technology Development Llc | Detection and decomposition of bisphenol-A |
US10092229B2 (en) | 2010-06-29 | 2018-10-09 | Abbott Diabetes Care Inc. | Calibration of analyte measurement system |
US10973449B2 (en) | 2010-06-29 | 2021-04-13 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US11064921B2 (en) | 2010-06-29 | 2021-07-20 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US11478173B2 (en) | 2010-06-29 | 2022-10-25 | Abbott Diabetes Care Inc. | Calibration of analyte measurement system |
US10966644B2 (en) | 2010-06-29 | 2021-04-06 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US10874338B2 (en) | 2010-06-29 | 2020-12-29 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US10959653B2 (en) | 2010-06-29 | 2021-03-30 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US11213226B2 (en) | 2010-10-07 | 2022-01-04 | Abbott Diabetes Care Inc. | Analyte monitoring devices and methods |
US9743862B2 (en) | 2011-03-31 | 2017-08-29 | Abbott Diabetes Care Inc. | Systems and methods for transcutaneously implanting medical devices |
US10610141B2 (en) | 2011-04-15 | 2020-04-07 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US10561354B2 (en) | 2011-04-15 | 2020-02-18 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US10682084B2 (en) | 2011-04-15 | 2020-06-16 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US10835162B2 (en) | 2011-04-15 | 2020-11-17 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US10722162B2 (en) | 2011-04-15 | 2020-07-28 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US10555695B2 (en) | 2011-04-15 | 2020-02-11 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US10624568B2 (en) | 2011-04-15 | 2020-04-21 | Dexcom, Inc. | Advanced analyte sensor calibration and error detection |
US9069536B2 (en) | 2011-10-31 | 2015-06-30 | Abbott Diabetes Care Inc. | Electronic devices having integrated reset systems and methods thereof |
US9980669B2 (en) | 2011-11-07 | 2018-05-29 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods |
US9743872B2 (en) | 2011-11-23 | 2017-08-29 | Abbott Diabetes Care Inc. | Mitigating single point failure of devices in an analyte monitoring system and methods thereof |
US10136847B2 (en) | 2011-11-23 | 2018-11-27 | Abbott Diabetes Care Inc. | Mitigating single point failure of devices in an analyte monitoring system and methods thereof |
US10939859B2 (en) | 2011-11-23 | 2021-03-09 | Abbott Diabetes Care Inc. | Mitigating single point failure of devices in an analyte monitoring system and methods thereof |
US10082493B2 (en) | 2011-11-25 | 2018-09-25 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods of use |
US11391723B2 (en) | 2011-11-25 | 2022-07-19 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods of use |
US9693713B2 (en) | 2011-12-11 | 2017-07-04 | Abbott Diabetes Care Inc. | Analyte sensor devices, connections, and methods |
USD903877S1 (en) | 2011-12-11 | 2020-12-01 | Abbott Diabetes Care Inc. | Analyte sensor device |
US11051724B2 (en) | 2011-12-11 | 2021-07-06 | Abbott Diabetes Care Inc. | Analyte sensor devices, connections, and methods |
US11179068B2 (en) | 2011-12-11 | 2021-11-23 | Abbott Diabetes Care Inc. | Analyte sensor devices, connections, and methods |
USD915601S1 (en) | 2011-12-11 | 2021-04-06 | Abbott Diabetes Care Inc. | Analyte sensor device |
USD915602S1 (en) | 2011-12-11 | 2021-04-06 | Abbott Diabetes Care Inc. | Analyte sensor device |
US9931066B2 (en) | 2011-12-11 | 2018-04-03 | Abbott Diabetes Care Inc. | Analyte sensor devices, connections, and methods |
US11051725B2 (en) | 2011-12-11 | 2021-07-06 | Abbott Diabetes Care Inc. | Analyte sensor devices, connections, and methods |
US10132793B2 (en) | 2012-08-30 | 2018-11-20 | Abbott Diabetes Care Inc. | Dropout detection in continuous analyte monitoring data during data excursions |
US10942164B2 (en) | 2012-08-30 | 2021-03-09 | Abbott Diabetes Care Inc. | Dropout detection in continuous analyte monitoring data during data excursions |
US10345291B2 (en) | 2012-08-30 | 2019-07-09 | Abbott Diabetes Care Inc. | Dropout detection in continuous analyte monitoring data during data excursions |
US10656139B2 (en) | 2012-08-30 | 2020-05-19 | Abbott Diabetes Care Inc. | Dropout detection in continuous analyte monitoring data during data excursions |
US11612363B2 (en) | 2012-09-17 | 2023-03-28 | Abbott Diabetes Care Inc. | Methods and apparatuses for providing adverse condition notification with enhanced wireless communication range in analyte monitoring systems |
US9968306B2 (en) | 2012-09-17 | 2018-05-15 | Abbott Diabetes Care Inc. | Methods and apparatuses for providing adverse condition notification with enhanced wireless communication range in analyte monitoring systems |
US11896371B2 (en) | 2012-09-26 | 2024-02-13 | Abbott Diabetes Care Inc. | Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data |
US10842420B2 (en) | 2012-09-26 | 2020-11-24 | Abbott Diabetes Care Inc. | Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data |
US9907492B2 (en) | 2012-09-26 | 2018-03-06 | Abbott Diabetes Care Inc. | Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data |
US9675290B2 (en) | 2012-10-30 | 2017-06-13 | Abbott Diabetes Care Inc. | Sensitivity calibration of in vivo sensors used to measure analyte concentration |
US10188334B2 (en) | 2012-10-30 | 2019-01-29 | Abbott Diabetes Care Inc. | Sensitivity calibration of in vivo sensors used to measure analyte concentration |
US9801577B2 (en) | 2012-10-30 | 2017-10-31 | Abbott Diabetes Care Inc. | Sensitivity calibration of in vivo sensors used to measure analyte concentration |
USD980986S1 (en) | 2015-05-14 | 2023-03-14 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
US11706876B2 (en) | 2017-10-24 | 2023-07-18 | Dexcom, Inc. | Pre-connected analyte sensors |
US11331022B2 (en) | 2017-10-24 | 2022-05-17 | Dexcom, Inc. | Pre-connected analyte sensors |
US11350862B2 (en) | 2017-10-24 | 2022-06-07 | Dexcom, Inc. | Pre-connected analyte sensors |
US11382540B2 (en) | 2017-10-24 | 2022-07-12 | Dexcom, Inc. | Pre-connected analyte sensors |
US11943876B2 (en) | 2017-10-24 | 2024-03-26 | Dexcom, Inc. | Pre-connected analyte sensors |
USD1002852S1 (en) | 2019-06-06 | 2023-10-24 | Abbott Diabetes Care Inc. | Analyte sensor device |
USD1006235S1 (en) | 2020-12-21 | 2023-11-28 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
USD999913S1 (en) | 2020-12-21 | 2023-09-26 | Abbott Diabetes Care Inc | Analyte sensor inserter |
USD982762S1 (en) | 2020-12-21 | 2023-04-04 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
Also Published As
Publication number | Publication date |
---|---|
JP4054382B2 (en) | 2008-02-27 |
US5972199A (en) | 1999-10-26 |
AU6321498A (en) | 1998-08-26 |
JP2001512567A (en) | 2001-08-21 |
EP0977984A2 (en) | 2000-02-09 |
WO1998035053A3 (en) | 1998-09-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5972199A (en) | Electrochemical analyte sensors using thermostable peroxidase | |
US6689265B2 (en) | Electrochemical analyte sensors using thermostable soybean peroxidase | |
US5665222A (en) | Soybean peroxidase electrochemical sensor | |
JP3242923B2 (en) | Electrode and method for detecting hydrogen peroxide | |
Yu et al. | Glucose sensor for flow injection analysis of serum glucose based on immobilization of glucose oxidase in titania sol–gel membrane | |
US5356786A (en) | Interferant eliminating biosensor | |
Ohara et al. | " Wired" enzyme electrodes for amperometric determination of glucose or lactate in the presence of interfering substances | |
Huang et al. | Electrochemistry and electrocatalysis with heme proteins in chitosan biopolymer films | |
Kandimalla et al. | A conductive ormosil encapsulated with ferrocene conjugate and multiwall carbon nanotubes for biosensing application | |
US5262305A (en) | Interferant eliminating biosensors | |
Vidal et al. | A chronoamperometric sensor for hydrogen peroxide based on electron transfer between immobilized horseradish peroxidase on a glassy carbon electrode and a diffusing ferrocene mediator | |
US5225064A (en) | Peroxidase colloidal gold oxidase biosensors for mediatorless glucose determination | |
Choi et al. | Amperometric glucose biosensor based on sol–gel-derived metal oxide/Nafion composite films | |
JP2009031283A (en) | Cm sensor with covalently bound enzyme | |
Wang et al. | Biocomposite of cobalt phthalocyanine and lactate oxidase for lactate biosensing with MnO2 nanoparticles as an eliminator of ascorbic acid interference | |
Xu et al. | A new film for the fabrication of an unmediated H2O2 biosensor | |
Boguslavsky et al. | Thin film bienzyme amperometric biosensors based on polymeric redox mediators with electrostatic bipolar protecting layer | |
Niu et al. | Reagentless mediated biosensors based on polyelectrolyte and sol–gel derived silica matrix | |
Deng et al. | Self-gelatinizable copolymer immobilized glucose biosensor based on Prussian Blue modified graphite electrode | |
Haiying et al. | Amperometric glucose sensor using tetrathiafulvalene in Nafion gel as electron shuttle | |
Kutner et al. | Condensation α‐cyclodextrin polymer membrane with covalently immobilized glucose oxidase and molecularly included mediator for amperometric glucose biosensor | |
Rahman et al. | The potential use of hydrazine as an alternative to peroxidase in a biosensor: comparison between hydrazine and HRP-based glucose sensors | |
Park | Amperometric determination of hydrogen peroxide by utilizing a sol-gel-derived biosensor incorporating an osmium redox polymer as mediator | |
Jezkova et al. | Stabilization of an osmium bis‐bipyridyl polymer‐modified carbon paste amperometric glucose biosensor using polyethyleneimine | |
JP3204980B2 (en) | Peroxidase colloidal gold oxidase biosensor for mediator-free glucose measurement |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM GW HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 1998 534954 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1998907399 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 1998907399 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1998907399 Country of ref document: EP |