Optical glucose sensor

• US 5,605,152 A
• Filed: 07/18/1994
• Issued: 02/25/1997
• Est. Priority Date: 07/18/1994
• Status: Expired due to Term

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Minimed, Inc. (Medtronic Plc)
• Inventors: Lord, Peter C., Slate, John B.
• Primary Examiner(s): Sykes, Angela D.
• Assistant Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US08/276,453
• Time in Patent Office: 953 Days
• Field of Search: 128/634, 128/632, 128/633, 128/637, 422/58, 422/55, 422/82.08, 436/805, 436/95, 436/136, 436/138, 436/172, 356/445, 356/39, 435/14
• US Class Current: 600/316
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/7759 Dipstick; Test strip
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B

Abstract

An improved glucose sensor adapted for in vivo implantation includes one or more optical fiber optrodes mounted within a semipermeable probe housing designed for differential diffusion of glucose and oxygen. In a preferred form, an enzyme optrode comprises an optical fiber with an enzyme coating such as glucose oxidase for catalyzing glucose in the presence of oxygen (O₂) to produce gluconic acid and hydrogen peroxide. An oxygen sensitive coating such as a fluorescent dye is provided on the enzyme optrode in close proximity with the enzymatic reaction, and also on a reference optrode at a position spaced substantially from the enzymatic reaction. Optical monitoring of the fluorescent activity of the optrode coatings provides an indication of oxygen depletion as a result of the enzymatic reaction, and thus also indicates glucose concentration level. The semipermeable housing is designed to ensure that the reaction proceeds with a stoichiometric excess of oxygen (O₂).

Claims

1. A glucose sensor, comprising:

a semipermeable probe housing defining an interior sensor chamber, said housing being formed from a material permeable to glucose and oxygen (O₂) entrained in a patient fluid and adapted to be contacted therewith; and

optrode means for monitoring glucose concentration in the patient fluid, said optrode means being disposed within said sensor chamber and comprising an enzyme optrode including a first optical fiber having a selected enzyme coating thereon for generating an enzymatic reaction to catalyze glucose in the presence of oxygen (O₂), and an oxygen sensitive coating on said first optical fiber at a position to generate a light signal representative of oxygen (O₂) depletion in response to the enzymatic reaction, and a reference optrode having an additional oxygen sensitive coating on a second optical fiber at a position spaced from said enzyme and oxygen sensitive coatings on said first optical fiber;

said optrode means further including means for supporting and retaining said first and second optical fibers in a spaced array within said housing, said supporting and retaining means comprising a gel permeable to glucose and oxygen.

2. The glucose sensor of claim 1 wherein said probe housing has a first portion formed from a material permeable to oxygen (O₂) and substantially impermeable to glucose, and a second portion formed from a material permeable to glucose, said first portion having a surface area for exposure to the patient fluid which is substantially greater than a surface area of said second portion for exposure to the patient fluid, whereby the enzymatic reaction occurs with a stoichiometric excess of oxygen (O₂).

3. The glucose sensor of claim 2 wherein said first portion is formed from a silicone material.

4. The glucose sensor of claim 2 wherein said second portion is formed from a material permeable to glucose and oxygen (O₂).

5. The glucose sensor of claim 4 wherein said second portion is formed from a hydrogel.

6. The glucose sensor of claim 1 wherein said enzyme coating is glucose oxidase.

7. The glucose sensor of claim 1 wherein said oxygen sensitive coating is a fluorescent dye.

8. The glucose sensor of claim 1 further including an optical monitor connected to said at least one optical fiber.

9. A glucose sensor, comprising:

a semipermeable probe housing defining an interior sensor chamber, said housing being formed from a material permeable to glucose and oxygen (O₂) entrained in a patient fluid and adapted to be contacted therewith; and

optrode means for monitoring glucose concentration in the patient fluid, said optrode means being disposed within said sensor chamber and including an optical fiber having a selected enzyme coating thereon for generating an enzymatic reaction to catalyze glucose in the presence of oxygen (O₂), said optrode means further including a first oxygen sensitive coating on said optical fiber at a position in close proximity to said enzyme coating to generate a light signal representative of oxygen (O₂) depletion in response to the enzymatic reaction;

and a second oxygen sensitive coating on said optical fiber at a position spaced from said enzyme and first oxygen sensitive coatings, said first and second oxygen sensitive coatings responding to the presence of oxygen to generating light signals of different wave lengths.

10. A glucose sensor adapted for in vivo implantation into the body of a patient, said sensor comprising:

a semipermeable probe housing defining an interior sensor chamber, said housing being formed from a material permeable to glucose and oxygen (O₂) entrained in a patient fluid and adapted to be contacted therewith; and

optrode means for monitoring glucose concentration in the patient fluid, said optrode means including an enzyme optrode having a first optical fiber adapted for transcutaneous passage into the body of a patient and having a distal end disposed within said sensor chamber, an enzyme coating on said first fiber generally at said distal end for generating an enzymatic reaction to catalyze glucose in the presence of oxygen (O₂), and an oxygen sensitive coating on said first fiber generally at said distal end in close proximity with the enzyme coating to generate a light signal representative of oxygen (O₂) depletion in response to the enzymatic reaction, and a reference optrode having an additional oxygen sensitive coating on a second optical fiber at a position spaced from said enzyme and oxygen sensitive coatings on said first optical fiber;

said optrode means further including means for supporting and retaining said first and second optical fibers in a spaced array within said housing, said supporting and retaining means comprising a gel permeable to glucose and oxygen.

11. The glucose sensor of claim 10 wherein said housing has a first portion formed from a material permeable to oxygen (O₂) and substantially impermeable to glucose, and a second portion formed from a material permeable to glucose, said first portion having a surface area for exposure to the patient fluid which is substantially greater than a surface area of said second portion for exposure to the patient fluid, whereby the en zymatic reaction occurs with a stoichiometric excess of oxygen (O₂).

12. The glucose sensor of claim 10 further including an optical monitor for connection to a proximal end of said fiber outside the body of the patient.