Detection of biological molecules using chemical amplification and optical sensors

• US 6,804,544 B2
• Filed: 08/21/2001
• Issued: 10/12/2004
• Est. Priority Date: 11/22/1995
• Status: Expired due to Term

• Current Assignee: Minimed, Inc. (Medtronic Plc)
• Original Assignee: Minimed, Inc. (Medtronic Plc)
• Inventors: Mastrototaro, John Joseph, Van Antwerp, William Peter
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/934,390
• Publication Number:
  US 20020018843A1
• Time in Patent Office: 1,148 Days
• Field of Search: 600/310, 600/317, 600/322, 600/342, 422/68.1, 422/87.07, 422/87.08, 424/9.6, 436/95, 436/501, 436/805, 436/807
• US Class Current: 600/317
• 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 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence

Abstract

Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

Claims

1. A system comprising a biocompatible polymer matrix and an amplification component incorporated within the biocompatible polymer matrix that is capable of producing a polyhydroxylated analyze signal upon interrogation by an optical system, wherein said amplification component in covalently attached to said biocompatible polymer matrix and requires a photo-induced electron transfer for production of said signal, and further wherein said biocompatible polymer matrix permeable to glucose.

2. The biocompatible polymer matrix in accordance with claim 1, wherein said biocompatible polymer matrix lea solid substrate.

3. The biocompatible polymer matrix in accordance with claim 2, wherein said solid substrate is a member selected from thin group consisting of polyurethane, silicon, silicon-containing polymer, chronoflex, P-HEMA or sol-gel.

4. The biocompatible polymer matrix in accordance with claim 1, wherein said biocompatible polymer matrix comprises a hydrophilic polymer.

5. The biocompatible polymer matrix in accordance with claim 1, wherein said biocompatible polymer is a member selected from the group consisting of a polyurethane a silicone, an acrylic, and a silicone containing polyurethane.

6. The biocompatible polymer matrix in accordance with claim 1, wherein said biocompatible polymer matrix is a member selected from the group consisting of a disk, a cylinder, a patch, a microsphere and a refillable sack.

7. The biocompatible polymer matrix in accordance with claim 6, wherein said biocompatible polymer matrix is a microsphere.

8. The biocompatible polymer matrix in accordance with claim 1, wherein said biocompatible polymer matrix is adapted to be implanted subdermally.

9. The biocompatible polymer matrix in accordance with claim 1, wherein amid biocompatible polymer matrix is permeable to oxygen.

10. The biocompatible polymer matrix in accordance with claim 1, wherein said biocompatible polymer matrix is optically transparent.

11. The biocompatible polymer matrix in accordance with claim 1, further comprising a biocompatible shell.

12. The biocompatible polymer matrix in accordance with claim 1, wherein said biocompatible shell is a member selected from the group consisting of dialysis fiber, teflon cloth, resorbable polymers and islet encapsulation materials.

13. The biocompatible polymer matrix in accordance with claim 1, wherein said amplification component comprises a boronic acid moiety.

14. A system comprising a biocompatible polymer matrix and a fluorescent transducer component incorporated within the biocompatible polymer matrix that binds polyhydroxylate analyte and whose fluorescence is modulated by a photo-induced electron transfer process, wherein upon illumination of the fluorescent transducer component in the presence of polyhydroxylate analyte a change in fluorescence is observable that is correlatable with the concentration of bound polyhydroxylate analyte and wherein polyhydroxylate analyte binding to the fluorescent transducer component produces a decrease in the fluorescence of the fluorescent transducer component.

15. The biocompatible polymer matrix of claim 14, wherein the change in fluorescence is measured as a change in fluorescent intensity.

16. The biocompatible polymer matrix of claim 14, wherein the change in fluorescence is measured as a change in the average fluorescent lifetime of the fluorescent transducer component.

17. The biocompatible polymer matrix of claim 14, wherein the photoinduced electron transfer process of the fluorescent transducer component is modulated by polyhydroxylate analyte binding.

18. The biocompatible polymer matrix in accordance with claim 14, wherein said fluorescent transducer component comprises a boronic acid moiety.

19. A system comprising a biocompatible polymer matrix and an amplification component incorporated within the biocompatible polymer matrix that is capable of producing a signal upon interrogation by an optical system, wherein the signal is modulated by polyhydroxylate analyte binding and wherein polyhydroxylate analyte binding modulates a photo-induced electron transfer process, and further wherein bound polyhydroxylate analyte produces a decrease in the signal.

20. The biocompatible polymer matrix of claim 19, wherein the signal is measured as a change in fluorescent intensity of the amplification component.

21. The biocompatible polymer matrix of claim 19, wherein the signal is measured as a change in the average fluorescent lifetime of the amplification component.

22. The biocompatible polymer matrix of claim 19, wherein the photoinduced electron transfer process is modulated by bound polyhydroxylate analyte.

23. The biocompatible polymer matrix in accordance with claim 19, wherein said amplification component comprises a boronic acid moiety.

24. A system comprising a biocompatible polymer matrix having a mesh incorporated therein and in amplification component incorporated within the biocompatible polymer matrix that is capable of producing a polyhydroxylated analyte signal upon interrogation by an optical system, wherein said amplification component requires a photo-induced electron transfer for production of said signal, and further wherein said biocompatible polymer matrix is permeable to glucose.