US5466575A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for the manufacture of wholly microfabricated biosensors
Assignee: Abbott Point of Care Inc
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Filing: 1992-09-10
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Granted: 1995-11-14
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Expires: 2012-09-10
Abstract
Abstract An efficient method for the microfabrication of electronic devices which have been adapted for the analyses of biologically significant analyte species is described. The techniques of the present invention allow for close control over the dimensional features of the various components and layers established on a suitable substrate. Such control extends to those parts of the devices which incorporate the biological components which enable these devices to function as biological sensors. The materials and methods disclosed herein thus provide an effective means for the mass production of uniform wholly microfabricated biosensors. Various embodiments of the devices themselves are described herein which are especially suited for real time analyses of biological samples in a clinical setting. In particular, the present invention describes assays which can be performed using certain ligand/ligand receptor-based biosensor embodiments. The present invention also discloses a novel method for the electrochemical detection of particular analyte species of biological and physiological significance using an substrate/label signal generating pair which produces a change in the concentration of electroactive species selected from the group consisting of dioxygen and hydrogen peroxide.
Inventors
- 👤 Stephen N. Cozzette
- 👤 Graham Davis
- 👤 Imants R. Lauks
- 👤 Randall M. Mier
- 👤 Sylvia Piznik
- 👤 Nicolaas Smit
- 👤 Paul Van Der Werf
- 👤 Henry J. Wieck
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 11:45
CPC Classifications
B; B01; B01L; B01L3/00; B01L3/02; B01L3/0241; B01L3/0268; G; G01; G01N; G01N27/00; G01N27/26; B01L3/50; B01L3/502; B01L3/5027; C; C12; C12Q; C12Q1/00; C12Q1/001; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/543; G01N33/54366; G01N33/54373; G01N33/5438; G01N35/00; G01N35/0099; G01V; G01V9/00; G10; G10K; G10K11/00; G10K11/004; G10K11/006; B01L2200/00; B01L2200/12; B01L2300/00; B01L2300/06; B01L2300/0627; B01L2300/0636; B01L2300/0645; B01L2300/08; B01L2300/0861; B01L2300/0877; B01L3/508; B01L3/5088; G01N35/00029; G01N2035/00039; G01N2035/00059; G01N2035/00178; G01N2035/00237; G01N2035/00346; G01N2035/00455; G01N2035/00465; G01N2035/00534; G01N35/10; G01N2035/1027; G01N2035/1034; G01N35/1065; G01N2035/1076; G01N35/1081; G01N35/109; Y; Y10; Y10S; Y10S435/00; Y10S435/817; Y10S436/00; Y10S436/806
Claims Analysis
Total Claims: 55
Claim 1
Independent Claim
155 words
A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises: (a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; (c) applying a matrix, superimposed over at least a portion of said permselective layer and each of said base sensors, which matrix is selected from the group consisting of a photoformable proteinaceous material, a film-forming latex, and combinations thereof, and which is capable of incorporating a bioactive agent; and (d) incorporating into said matrix an amount of said bioactive agent sufficient to selectively interact with a particular analyte species, to form a plurality of uniform wafer level microfabricated sensing devices.
Claim 2
Independent Claim
155 words
A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises: (a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; (c) applying a matrix, superimposed over at least a portion of said permselective layer and each of said base sensors, which matrix is selected from the group consisting of a photoformable proteinaceous material, a film-forming latex, and combinations thereof, and which is capable of incorporating a bioactive agent; and (d) incorporating into said matrix an amount of said bioactive agent sufficient to selectively interact with a particular analyte species, to form a plurality of uniform wafer level microfabricated sensing devices.
Claim 3
Independent Claim
115 words
A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises: (a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer superimposed over at least a portion of each base sensor; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) a sufficient amount of a bioactive molecule, and (ii) a support matrix in which said bioactive molecule is incorporated, which matrix is formed from the group consisting of a photoformable .proteinaceous mixture, a film-forming latex, and combinations thereof to form a plurality of uniform wafer level microfabricated sensing devices.
Claim 4
Independent Claim
115 words
A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises: (a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer superimposed over at least a portion of each base sensor; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) a sufficient amount of a bioactive molecule, and (ii) a support matrix in which said bioactive molecule is incorporated, which matrix is formed from the group consisting of a photoformable .proteinaceous mixture, a film-forming latex, and combinations thereof to form a plurality of uniform wafer level microfabricated sensing devices.
Claim 5
Dependent Claim
16 words
The method of claim 1 or 2 in which said permselective layer comprises a polymer film.
Claim 6
Dependent Claim
15 words
The method of claim 3 in which an ionophore is incorporated in said polymer film.
Claim 7
Dependent Claim
14 words
The method of claim 4 in which said ionophore is an organic ammonium chloride.
Claim 8
Dependent Claim
31 words
The method of claim 4 in which said ionophore is selected from the group consisting of crown ethers, trialkylamines, phosphate esters, valinomycin, nonactin, monensin, methylmonensin, and mixtures of monensin and methylmonensin.
Claim 9
Dependent Claim
33 words
The method of claim 3 in which said polymer film is a polymeric substance selected from the group consisting of polyurethane, poly(vinyl chloride), poly(tetrafluoroethylene), cellulose acetate, cellulose nitrate, silicone rubber, and mixtures thereof.
Claim 10
Dependent Claim
14 words
The method of claim 7 in which said polymer film further comprises a plasticizer.
Claim 11
Dependent Claim
30 words
The method of claim 7 in which said plasticizer is selected from the group consisting of tris(2-ethylhexyl)phosphate, nitrocymene, 2-nitrophenyloctyl ether, dibutyl sebacate, diethyl adipate, propylene carbonate, 5-phenylpentanol, and mixtures thereof.
Claim 12
Dependent Claim
68 words
The method of claim 1 or 2 in which said permselective layer comprises a heat-treated film of a silane compound having the formula R' n Si(OR) 4-n , in which n is an integer selected from the group consisting of 0, 1, and 2; R, is a hydrocarbon radical comprising 3-12 carbon atoms; and R is a hydrogen radical or a lower alkyl radical comprising 1-4 carbon atoms.
Claim 13
Dependent Claim
32 words
The method of claim 10 in which said hydrocarbon radical further comprises at least one heteroatom selected from the group consisting of oxygen, nitrogen, phosphorus, sulfur, halogen, and stable heteroatom combinations thereof.
Claim 14
Dependent Claim
32 words
The method of claim 10 in which said hydrocarbon radical is selected from the group consisting of 3-aminopropyl, N-(2-aminoethyl)-3-aminopropyl, 3-methacryloxypropyl, 3-mercaptopropyl, 3-hydroxypropyl, 3-isocyanatopropyl, 10-aminodecyl, 11-aminoundecyl, 2-[p-(N-(2-aminoethyl)aminomethyl)phenyl]ethyl, n-propyl, phenyl, diethylphosphatoethyl, and N,N-bis(2-hydroxyethyl)aminopropyl groups.
Claim 15
Dependent Claim
33 words
The method of claim 10 in which said silane compound is selected from the group consisting of 3-aminopropyltriethoxysilane, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, 3-isocyanatopropyltriethoxysilane, 10-aminodecyltrimethoxysilane, 11-aminoundecyltrimethoxysilane, 2-[p-(N-(2-aminoethyl)aminomethyl)phenyl]ethyltrimethoxysilane, n-propyltrimethoxysilane, phenyltrimethoxysilane, diethylphosphatoethyltriethoxysilane, N,N-bis(2-hydroxyethyl)aminopropyltriethoxysilane, 3-chloropropyltriethoxysilane, and mixtures thereof.
Claim 16
Dependent Claim
12 words
The method of claim 10 in which said silane compound is N-(2-aminoethyl)-3-aminopropyltrimethoxysilane.
Claim 17
Dependent Claim
16 words
The method of claim 10 in which said silane compound is a tetraalkyl or tetrahydroxy orthosilicate.
Claim 18
Dependent Claim
26 words
The method of claim 10 in which the permselective layer is established by spin-coating or dispensing a solution of said silane compound on said substrate wafer.
Claim 19
Dependent Claim
64 words
The method of claim 1 or 2 which further comprises applying an electrolyte layer over at least a portion of each base sensor, prior to applying said permselective layer such that the electrolyte layer lies between the base sensor and the permselective layer and wherein said permselective layer covers at least the same portion of the base sensor as covered by the electrolyte layer.
Claim 20
Dependent Claim
15 words
The method of claim 17 in which said permselective layer substantially encloses said electrolyte layer.
Claim 21
Dependent Claim
50 words
The method of claim 1 or 2 which further comprises applying an analyte attenuation layer, superimposed over a substantial portion of said matrix, which attenuation layer is characterized as having a thickness sufficient to attenuate the transport therethrough of analyte species having a molecular weight of about 120 or more.
Claim 22
Dependent Claim
15 words
The method of claim 19 in which said analyte attenuation layer comprises a polymer film.
Claim 23
Dependent Claim
18 words
The method of claim 19 which further comprises applying a photoresist cap superimposed over said analyte attenuation layer.
Claim 24
Dependent Claim
23 words
The method of claim 3 or 20 in which said polymer film comprises a copolymer of a siloxane compound and a nonsiloxane compound.
Claim 25
Dependent Claim
31 words
The method of claim 22 in which said copolymer is selected from the group consisting of dimethylsiloxanealkene oxide, tetramethyldisiloxane-divinylbenzene, tetramethyldisiloxane-ethylene, dimethylsiloxanesilphenylene, dimethylsiloxane-silphenylene oxide, dimethylsiloxane-methylstyrene, and dimethylsiloxanebisphenol A carbonate, and mixtures thereof.
Claim 26
Dependent Claim
13 words
The method of claim 22 in which said copolymer is dimethylsiloxane-bisphenol A carbonate.
Claim 27
Dependent Claim
29 words
The method of claim 20 or 22 in which said analyte attenuation layer is established by spin-coating or dispensing a solution of said polymer film on said substrate wafer.
Claim 28
Dependent Claim
16 words
The method of claim 1 or 2 in which said base sensor comprises an electrochemical transducer.
Claim 29
Dependent Claim
12 words
The method of claim 26 in which said electrochemical transducer is amperometric.
Claim 30
Dependent Claim
12 words
The method of claim 26 in which said electrochemical transducer is potentiometric.
Claim 31
Dependent Claim
17 words
The method of claim 26 in which said electrochemical transducer further comprises a silver/silver halide reference electrode.
Claim 32
Dependent Claim
42 words
The method of claim 1 or 2 in which said base sensor comprises an amperometric electrochemical transducer comprising an indicator electrode which includes an electrocatalyst selected from the group consisting of carbon, platinum, gold, silver, rhodium, iridium, ruthenium, mercury, palladium, and osmium.
Claim 33
Dependent Claim
29 words
The method of claim 1 or 2 in which said base sensor comprises a potentiometric electrochemical transducer comprising an indicator electrode which comprises a mixed metal oxide alloy electrocatalyst.
Claim 34
Dependent Claim
30 words
The method of claim 1 or 2 in which said photoformable proteinaceous material comprises: (i) a proteinaceous substance; (ii) a photosensitizer uniformly dispersed in said proteinaceous substance; and (iii) water.
Claim 35
Dependent Claim
25 words
The method of claim 32 in which said proteinaceous material is selected from the group consisting of albumin, casein, gamma-globulin, collagen, gelatin and mixtures thereof.
Claim 36
Dependent Claim
13 words
The method of claim 32 in which said proteinaceous material is fish gelatin.
Claim 37
Dependent Claim
14 words
The method of claim 32 in which said photosensitizer is a transition metal compound.
Claim 38
Dependent Claim
40 words
The method of claim 32 in which said photosensitizer is selected from the group consisting of ferric chloride, ferric ammonium citrate, ferric potassium citrate, ferric ammonium oxalate, ferric sodium oxalate, ferric potassium oxalate, ferric oxalate, potassium dichromate, and ammonium dichromate.
Claim 39
Dependent Claim
27 words
The method of claim 1 or 2 in which said film-forming latex comprises an aqueous emulsion of a polymer or copolymer derived from synthetic or natural sources.
Claim 40
Dependent Claim
20 words
The method of claim 1 or 2 in which said film-forming latex comprises an aqueous emulsion of an isoprene-based polymer.
Claim 41
Independent Claim
136 words
A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises: (a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) an amount of a bioactive agent, and (ii) a support matrix, in which said bioactive agent is incorporated, which matrix is a photoformable proteinaceous material, to form a plurality of uniform wafer level microfabricated sensing devices.
Claim 42
Independent Claim
136 words
A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises: (a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) an amount of a bioactive agent, and (ii) a support matrix, in which said bioactive agent is incorporated, which matrix is a photoformable proteinaceous material, to form a plurality of uniform wafer level microfabricated sensing devices.
Claim 43
Independent Claim
144 words
A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises: (a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) an amount of bioactive agent sufficient to selectively interact with an analyte species, and (ii) a support matrix, in which said bioactive agent is incorporated, which matrix is formed from a film-forming latex, to form a plurality of uniform wafer level microfabricated sensing devices.
Claim 44
Independent Claim
144 words
A method of manufacturing a plurality of uniform wafer level microfabricated sensing devices which comprises: (a) applying a plurality of base sensors on a substrate wafer; (b) applying a permselective layer, superimposed over at least a portion of each base sensor, having a thickness sufficient to exclude substantially all molecules having a molecular weight of greater than about 120 while allowing the free permeation of molecules having a molecular weight of about 50 or less; and (c) applying a biolayer, superimposed over at least a portion of said permselective layer and each of said base sensors, said biolayer comprising (i) an amount of bioactive agent sufficient to selectively interact with an analyte species, and (ii) a support matrix, in which said bioactive agent is incorporated, which matrix is formed from a film-forming latex, to form a plurality of uniform wafer level microfabricated sensing devices.
Claim 45
Dependent Claim
18 words
The method of claim 39 or 40 in which said bioactive molecule is an enzyme or mixtures thereof.
Claim 46
Dependent Claim
69 words
The method of claim 39 or 40 in which said bioactive molecule is an enzyme selected from the group consisting of glucose oxidase, glucose dehydrogenase, NADH oxidase, uricase, urease, creatininase, sarcosine oxidase, creatinase, creatine kinase, creatine amidohydrolase, cholesterol esterase, cholesterol oxidase, glycerol kinase, hexokinase, glycerol-3-phosphate oxidase, lactate dehydrogenase, alkaline phosphatase, alanine transaminase, aspartate transaminase, amylase, lipase, esterase, gamma-glutamyl transpeptidase, L-glutamate oxidase, pyruvate oxidase, diaphorase, bilirubin oxidase, and their mixtures.
Claim 47
Dependent Claim
53 words
The method of claim 39 or 40 in which said bioactive molecule is selected from the group consisting of ionophores, cofactors, polypeptides, proteins, glycoproteins, enzymes, immunoglobulins, antibodies, antigens, lectins, neurochemical receptors, oligonucleotides, polynucleotides, molecules of DNA, molecules of RNA, active fragments or subunits or single strands of the preceding molecules, and mixtures thereof.
Claim 48
Dependent Claim
26 words
The method of claim 39 or 40 in which said bioactive molecule is selected from the group consisting of creatininase, creatinase, sarcosine oxidase, and combinations thereof.
Claim 49
Dependent Claim
26 words
The method of claim 39 or 40 in which said bioactive molecule is selected from the group consisting of cholesterol esterase, cholesterol oxidase, and combinations thereof.
Claim 50
Dependent Claim
28 words
The method of claim 39 or 40 in which said bioactive molecule is selected from the group consisting of lipase, esterase, glycerol kinase, glycerol-3-phosphate oxidase, and combinations thereof.
Claim 51
Dependent Claim
26 words
The method of claim 39 or 40 in which said bioactive molecule is selected from the group consisting of glycerol kinase, glycerol-3-phosphate oxidase, and combinations thereof.
Claim 52
Dependent Claim
15 words
The method of claim 39 or 40 in which said bioactive molecule is glucose oxidase.
Claim 53
Dependent Claim
14 words
The method of claim 39 or 40 in which said bioactive molecule is urease.
Claim 54
Dependent Claim
18 words
The method of claim 1, 2 or 40 in which said film-forming latex further comprises a crosslinking agent.
Claim 55
Dependent Claim
34 words
The method of claim 1, 2, 39, or 40 in which said support matrix or biolayer is established by spin-coating or dispensing a solution of said support matrix or biolayer on said substrate wafer.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1998-11-13 | 1999-05-15 | 1999-11-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2002-11-13 | 2003-05-15 | 2003-11-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2006-11-13 | 2007-05-15 | 2007-11-14 | $7700.00 | Window Closed / Lapsed |