Implantable glucose sensor
First Claim
1. An implantable sensor for sensing a concentration of an organic substrate, the sensor comprising:
- a conductive electrode; and
a stabilized enzyme emulsion in contact with the electrode, the enzyme emulsion comprising;
an enzyme that quantitatively oxidizes the organic substrate;
a water immiscible oxygen dissolving compound emulsified into intimate contact with the enzyme to provide oxygen; and
a protein crosslinking agent to crosslink and insolubilize the enzyme forming a stabilized gel comprising crosslinked protein and particles of the oxygen dissolving substance.
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Accused Products
Abstract
The sensitivity of enzyme-based polarographic electrodes to oxygen concentration can be significantly reduced or eliminated by providing an oxygen-reservoir in intimate contact with the oxidative enzyme. This is achieved by making a stabilized emulsion between the enzyme and a compound in which oxygen is extremely soluble. An aqueous glucose oxidase solution is emulsified with a perfluorocarbon liquid, and the resulting emulsion is stabilized by chemically crosslinking the mixture to form a gel. Thin layers of the emulsion are fabricated by spreading a layer of the liquid emulsion before gelation occurs. Additional carrier proteins such as albumin may be added to the enzyme prior to crosslinking to protect enzymatic activity and enhance gel strength. Additional electron transport compounds may be added to further reduce sensitivity to oxygen concentration.
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Citations
26 Claims
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1. An implantable sensor for sensing a concentration of an organic substrate, the sensor comprising:
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a conductive electrode; and
a stabilized enzyme emulsion in contact with the electrode, the enzyme emulsion comprising;
an enzyme that quantitatively oxidizes the organic substrate;
a water immiscible oxygen dissolving compound emulsified into intimate contact with the enzyme to provide oxygen; and
a protein crosslinking agent to crosslink and insolubilize the enzyme forming a stabilized gel comprising crosslinked protein and particles of the oxygen dissolving substance. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19)
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14. An implantable glucose sensor for sensing a concentration of glucose, the sensor comprising:
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a metal electrode; and
a stabilized enzyme emulsion in contact with the electrode, the enzyme emulsion comprising;
a solution of glucose oxidase protein for oxidizing glucose to quantitatively produce hydrogen peroxide;
a perfluorocarbon liquid emulsified with the glucose oxidase; and
a crosslinking agent to crosslink covalently said protein to form a stabilized gel comprising crosslinked protein and particles of the perfluorocarbon liquid.
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20. A method for producing a stabilized enzyme emulsion for use with a polarographic or amperometric sensor comprising the steps of:
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making an aqueous solution of a water soluble enzyme that oxidizes an organic substrate to produce hydrogen peroxide;
emulsifying a volume of a water immiscible oxygen dissolving substance into the aqueous solution to form an emulsion;
contacting the emulsion with a protein crosslinking agent; and
spreading a mixture of the protein crosslinking agent and the emulsion into a uniform layer whereby the emulsion becomes crosslinked to form a solid gel. - View Dependent Claims (21, 22, 23, 24, 26)
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25. A method for producing a stabilized enzyme emulsion for use with a polarographic sensor comprising the steps of:
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making an aqueous solution of a carrier protein;
emulsifying a volume of a perfluorocarbon liquid into the aqueous solution to form an emulsion;
contacting the emulsion with a water soluble enzyme that oxidizes an organic substrate to produce hydrogen peroxide to form a mixture;
contacting the mixture with a protein crosslinking agent; and
spreading a mixture of the protein crosslinking agent and the emulsion into a uniform layer whereby the emulsion becomes crosslinked to form a solid gel.
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Specification