Apparatus for monitoring glucose

• US 4,981,779 A
• Filed: 06/26/1986
• Issued: 01/01/1991
• Est. Priority Date: 06/26/1986
• Status: Expired due to Fees

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Wagner, Daniel B.
• Primary Examiner(s): Warden, Robert J.
• Assistant Examiner(s): McMahon, Timothy M.
• Application Number:
  US06/878,560
• Time in Patent Office: 1,650 Days
• Field of Search: 422/58, 422/68.09, 422/68.10, 422/82.09, 422/82.10, 356/39, 356/445, 128/637, 128/665, 435/14.25, 435/288, 435/310, 436/95, 436/136, 436/138, 436/800, 436/805, 436/904
• US Class Current: 435/287.9
• CPC Class Codes: C12M 21/18 Apparatus specially designed for the use of free, immobilized or carrier-bound enzymes
• CPC Class Codes: C12M 23/20 Material Coatings immunocoatings C12M25/00
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• 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
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/904 Oxidation - reduction indicators
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/207497 Molecular oxygen
• CPC Class Codes: Y10T 436/209163 Dissolved or trace oxygen or oxygen content of a sealed environment

Abstract

A method for monitoring the glucose level in a body fluid uses an apparatus which includes a conjugate of glucose oxidase with a fluorescent dye coated onto an optical fiber in contact with the body fluid, a source of excitation light and a fluorescence emission detector. Glucose is oxidized by oxygen in the body fluid causing a decrease in oxygen concentration at the enzyme. The fluorescent dye is sensitive to oxygen quenching so that, when the oxygen concentration decreases, fluorescence emission increases in direct proportion to the glucose concentration in the fluid.

Claims

1. An apparatus for monitoring glucose concentration in a body fluid comprising:

(a) a first cable comprising first and second optical fibers having immobilized thereon a first conjugate comprising active glucose oxidase and a fluorescent dye, emission from said dye being sensitive to oxygen quenching;

(b) a second cable comprising third and fourth optical fibers having immobilized thereon a second conjugate comprising inactive glucose oxidase and the same aforementioned fluorescent dye;

(c) a light source in excitation light transmissive communication with said first conjugate through said first fiber and with said second conjugate through said third fiber; and

(d) a detector in fluorescence emission transmissive communication with said first conjugate through said second fiber and with said second conjugate through said fourth fiber.

2. The apparatus of claim 1 wherein said dye is selected from the group of dyes consisting of perylene dibutyrate and fluoranthrene.

3. The apparatus of claim 1 wherein said active and inactive glucose oxidase are conjugated to said dye by a covalent bond.

4. The apparatus of claim 3 wherein said active and inactive glucose oxidase are conjugated to said dye through a linking group.

5. The apparatus of claim 1 wherein said light source is a light emitting diode.

6. The apparatus of claim 1 wherein said detector is a photocell.

7. An apparatus for monitoring glucose concentration in a body fluid comprising:

(a) first light transmissive means having positioned adjacent thereto a first material comprising a conjugate of active glucose oxidase and a fluorescent dye, emission from said dye being sensitive to oxygen quenching;

(b) second light transmissive means having positioned adjacent thereto a second material comprising the same aforementioned fluorescent dye conjugated to inactive glucose oxidase;

(c) means for providing excitation light to said first material through said first light transmissive means and to said second material through said second light transmissive means; and

(d) means for detecting fluorescence emission from said first material through said first light transmissive means and from said second material through said second light transmissive means.

9. The apparatus of claim 7 wherein said first material is coated on said first light transmissive means and said second material is coated on said second light transmissive means.

10. The apparatus of claim 7 further comprising a first solid support adjacent said first light transmissive means and having said first material coated thereon and a second solid support adjacent said second light transmissive means and having said second material coated thereon.

8. An apparatus for monitoring glucose concentration in a body fluid comprising:

(a) a first cable comprising first and second optical fibers having immobilized thereon a first conjugate comprising glucose oxidase covalently conjugated to a fluorescent dye, emission from said dye being sensitive to oxygen quenching, said first conjugate being coated with a membrane permeable to glucose;

(b) a second cable comprising third and fourth optical fibers having immobilized thereon a second conjugate comprising glucose oxidase covalently conjugated to the same fluorescent dye, said second conjugate being coated with a membrane permeable to oxygen but impermeable to glucose;

(c) a light emitting diode in excitation light transmissive communication with said first conjugate through said first fiber and with said second conjugate through said third fiber; and

(d) a photocell in fluorescence emission transmissive communication with said first conjugate through said second fiber and with said second conjugate through said fourth fiber.