Optical determination of glucose utilizing boronic acid adducts

• US 8,951,503 B2
• Filed: 08/08/2008
• Issued: 02/10/2015
• Est. Priority Date: 12/05/2000
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Singaram, Bakthan, Wessling, Ritchie A.
• Primary Examiner(s): Jones, D L
• Application Number:
  US12/189,094
• Publication Number:
  US 20090148956A1
• Time in Patent Office: 2,377 Days
• Field of Search: 424/1.11, 424/1.65, 424/1.81, 424/1.85, 424/9.1, 424/9.2, 424/9.6, 568/18, 568/300, 436/95, 436/172, 546/13, 546/257, 546/268.1, 560/205, 560/250, 422/400, 514/765
• US Class Current: 424/9.6
• CPC Class Codes: A61K 49/0019 characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07D 213/82 in position 3
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C09K 2211/1007 Non-condensed systems
• CPC Class Codes: C09K 2211/1011 Condensed systems
• CPC Class Codes: C09K 2211/1029 containing one nitrogen atom as the heteroatom
• CPC Class Codes: C09K 9/02 Organic tenebrescent materials
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

The present invention concerns an improved optical method and optical sensing device for determining the levels of polyhydroxyl-substituted organic molecules in vitro and/or in vivo in aqueous media. The range of detection is between about 400 and 800 nm. In particular, a sensory devise is implemented in a mammal to determine sugar levels. Specifically, a dye is combined with a conjugated nitrogen-containing heterocyclic aromatic boronic acid-substituted bis-onium compound in the presence of a sugar, such as fructose or glucose. The viologens are preferred as the aromatic conjugated nitrogen-containing boronic acid substituted compounds. The method is useful to determine sugar levels in a human being.

Claims

1. An analyte sensor, comprising:

a fluorophore dye comprising a pyrene sulfonate

selected from the structure;

2. The analyte sensor of claim 1, wherein the fluorophore comprises at least one negative charge.

3. The analyte sensor of claim 1, wherein the fluorophore is a compound formed by reacting 8-acetoxypyrene-1,3,6-trisulfonylchloride with an amino acid.

4. The analyte sensor of claim 3, wherein the amino acid is amino butyric acid or lysine.

5. The analyte sensor of claim 1, wherein the fluorophore is

6. The analyte sensor of claim 1, wherein the boronic acid substituted viologen further comprises an aromatic boronic acid moiety.

7. The analyte sensor of claim 1, wherein the quencher comprises an aromatic boronic acid moiety covalently bonded to a polymer, wherein the aromatic boronic acid moiety is selected from the group consisting of:

8. The analyte sensor of claim 1, wherein the quencher comprises an aromatic boronic acid moiety covalently bonded to a polymer, wherein the aromatic boronic acid moiety is selected from the group consisting of:

9. The analyte sensor of claim 1, wherein the quencher comprises an aromatic boronic acid moiety covalently bonded to a polymer, wherein the aromatic boronic acid moiety has the structure:

10. The analyte sensor of claim 9, wherein the aromatic boronic acid moiety is selected from the group consisting of:

11. The analyte sensor of claim 1, wherein the analyte permeable component comprises a polymer matrix.

12. The analyte sensor of claim 11, wherein the polymer matrix is a hydrogel.

13. The analyte sensor of claim 1, wherein the analyte permeable component confines the fluorophore and the quencher.

14. The analyte sensor of claim 13, wherein the fluorophore is bonded to the polymer matrix.

15. The analyte sensor of claim 1, wherein the analyte permeable component further comprises a biocompatible coating.

16. The analyte sensor of claim 1, wherein the analyte is a polyhydroxyl-substituted organic molecule.