Optical determination of glucose utilizing boronic acid adducts

• US 8,394,357 B2
• Filed: 08/08/2008
• Issued: 03/12/2013
• 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:
  US12/189,082
• Publication Number:
  US 20090148344A1
• Time in Patent Office: 1,677 Days
• Field of Search: 424/1.11, 424/1.65, 424/1.81, 424/185, 424/9.1, 424/9.2, 424/9.6, 568/18, 568/300, 436/106, 436/131, 436/172, 514/741, 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. A device for optically determining an analyte concentration, which device comprises:

an analyte permeable component;

a fluorophore confined by, immobilized in, or covalently attached to the analyte permeable component, which fluorophore absorbs light at a first wavelength and emits light at a second wavelength, wherein the fluorophore comprises a substituted pyrene sulfonate;

a quencher confined by, immobilized in, or covalently attached to the analyte permeable component, which quencher modifies the light emitted by the fluorophore by an amount related to the analyte concentration;

a light source; and

a detector.

2. The device of claim 1, wherein the analyte permeable component comprises a polymer matrix.

3. The device of claim 1 wherein the analyte permeable component comprises a polymer, wherein the polymer is made from a monomer independently selected from the group consisting of 2-hydroxyethylmethacrylate (HEMA), polyethylene glycol methacrylate (PEGMA), methacrylic acid, hydroxyethyl acrylate, N-vinyl pyrrolidone, acrylamide, N,N′

-dimethyl acrylamide, methacryloylaminopropyl trimethylammonium chloride, diallyl dimethyl ammonium. chloride, vinyl benzyl trimethyl ammonium chloride, sodium sulfopropyl methacrylate, and combinations thereof.

4. The device of claim 3, wherein the polymer is further made with crosslinkers selected from the group consisting of ethylene dimethacrylate, polyethylene glycol dimethacrylate (PEGDMA), methylene bis acrylamide, trimethylolpropane triacrylate, and combinations thereof.

5. The device of claim 2, wherein the polymer matrix is insoluble in water and the water-insoluble polymer matrix is prepared from monomers selected from the group consisting of HPTS(Lys-MA)₃, HPTS-MA, HPTS-CO₂-MA, APTS-BuMA, and APTS-DegMA.

6. The device of claim 5 wherein the water-insoluble polymer matrix comprises copolymers 2-hydroxyethylmethacrylate (HEMA) and polyethylene glycol dimethacrylate or N,N′

-dimethylacrylamide and methylene-bis-acrylamide.

7. The device of claim 1, wherein the analyte permeable component comprises a membrane, which confines the fluorophore and the quencher.

8. The device of claim 2, wherein the polymer matrix comprises copolymers of 8-hydroxypyrene-1-N-(methacrylamidopropylsulfonamido)-N′

,N″

-3,6-bis(carboxypropylsulfonamide) HPTS-CO₂-MA with HEMA or PEGMA.

9. The device of claim 1, wherein the analyte permeable component comprises a biocompatible coating.

10. The device of claim 2, wherein the fluorophore is bonded to the polymer matrix.

11. The device of claim 1, wherein the substituted pyrene sulfonate is a pyranine derivative selected from the structure:

12. The device of claim 1, wherein the fluorophore is

13. The device of claim 1, wherein the quencher is a boronic acid substituted viologen.

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

15. The device of claim 1, wherein the light source is a blue light emitting diode (LED).