Barrier layer for glucose sensor

• US 9,970,940 B2
• Filed: 08/08/2012
• Issued: 05/15/2018
• Est. Priority Date: 08/17/2011
• Status: Active Grant

• Current Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Original Assignee: Lightship Medical Limited
• Inventors: Crane, Barry, Paterson, William, Barwell, Nicholas Paul, Culbert, Bruce
• Primary Examiner(s): Chin, Chris L
• Application Number:
  US14/239,132
• Publication Number:
  US 20140349307A1
• Time in Patent Office: 2,106 Days
• Field of Search: None
• CPC Class Codes: G01N 2021/6434 Optrodes
• 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: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: Y10T 29/49 Method of mechanical manufacture

Abstract

An optical glucose sensor for detecting and/or quantifying the amount of glucose in a sample comprising:

• • a sensing region comprising a boronic acid receptor for binding to glucose and a fluorophore associated with said receptor;
  • an optical waveguide for directing incident light onto the sensing region; and
  • a glucose-permeable barrier layer comprising a semi-permeable membrane having pores and a hydrophilic polymer within the pores of the semi-permeable membrane, the barrier layer overlying at least a part of the sensing region;
    wherein the sensor is adapted so that glucose enters the sensing region of the sensor through the glucose-permeable barrier layer, and an ROS-quenching agent is present in the sensing region and/or the glucose-permeable barrier layer.

Claims

1. A glucose sensor for detecting and/or quantifying the amount of glucose comprising:

a sensing region comprising a boronic acid receptor for binding to glucose and a fluorophore associated with the boronic acid receptor;

an optical waveguide for directing light onto the sensing region; and

a glucose-permeable barrier layer comprising a semi-permeable membrane comprising pores and a hydrophilic polymer within the pores of the semi-permeable membrane, the glucose-permeable barrier layer overlying at least a part of the sensing region;

wherein the glucose enters the sensing region of the sensor through the glucose-permeable barrier layer, and an ROS-quenching agent which is platinum in the form of nanoparticles is present in the glucose-permeable barrier layer.

2. A glucose sensor according to claim 1, wherein the semi-permeable membrane restricts the passage of proteins and glycated proteins having a molecular weight of 6000 or greater.

3. A glucose sensor according to claim 1, wherein the semi-permeable membrane restricts the passage of proteins and glycated proteins having a molecular weight of 5000 or greater.

4. A glucose sensor according to claim 1, wherein the semi-permeable membrane has an effective pore size of from 1 to 20 nm.

5. A glucose sensor according to claim 1, wherein a negatively charged polymer is present within the pores of the membrane.

6. A glucose sensor according to claim 1, wherein the semi-permeable membrane is formed by generating the hydrophilic and optionally the negatively charged polymer in situ by diffusing a monomer mixture comprising one or more hydrophilic monomer(s), optionally one or more negatively charged monomer(s) and optionally an ROS-quenching agent into the pores of a membrane and initiating polymerisation.

7. A glucose sensor according to claim 1, wherein the ROS-quenching agent is immobilised within the hydrophilic polymer which is present within the pores of the membrane.

8. A glucose sensor according to claim 1, wherein the hydrophilic polymer present within the pores of the semi-permeable membrane is a hydrogel.

9. A glucose sensor according to claim 1, wherein the barrier layer comprises heparin.

10. A glucose sensor according to claim 1, wherein the membrane is a microporous membrane and the barrier layer forms a support structure on the sensing region.

11. A method of manufacturing a glucose sensor for detecting and/or quantifying the amount of glucose comprising:

a sensing region comprising a boronic acid receptor for binding to glucose and a fluorophore associated with the boronic acid receptor;

an optical waveguide for directing light onto the sensing region; and

a glucose-permeable barrier layer comprising a semi-permeable membrane comprising pores and a hydrophilic polymer within the pores of the semi-permeable membrane, the glucose-permeable barrier layer overlying at least a part of the sensing region;

wherein the glucose enters the sensing region of the sensor through the glucose-permeable barrier layer, and an ROS-quenching agent which is platinum in the form of nanoparticles is present in the glucose-permeable barrier layer;

wherein the method comprises

providing a sensing region comprising a boronic acid receptor for binding to glucose and a fluorophore associated with said receptor;

providing an optical waveguide for directing incident light onto the sensing region; and

providing a glucose-permeable barrier layer comprising a semi-permeable membrane having pores and a hydrophilic polymer within the pores of the semi-permeable membrane, the glucose-permeable barrier overlying at least a part of the sensing region;

wherein the glucose enters the sensing region of the sensor through the glucose-permeable barrier layer, and an ROS-quenching agent which is platinum in the form of nanoparticles is present in the glucose-permeable barrier layer.

12. A method according to claim 11, wherein the method comprises diffusing a monomer mixture comprising one or more hydrophilic monomer(s), an ROS-quenching agent which is platinum in the form of nanoparticles and optionally one or more negatively charged monomer(s) into the pores of a membrane and initiating polymerisation, to provide a semi-permeable membrane comprising an ROS-quenching agent and a hydrophilic and optionally negatively charged polymer within the pores of the membrane.

13. A method according to claim 11, wherein the polymer formed within the pores of the membrane is a hydrogel.

14. A method according to claim 13, wherein the monomer mixture further comprises a boronic acid receptor and a fluorophore.

15. A method of detecting and/or quantifying the amount of glucose in a sample, the method comprising:

inserting into the sample a glucose sensor;

providing incident light to the sensing region of the sensor; and

detecting an emission pattern of a fluorophore associated with a boronic acid receptor for binding to glucose;

wherein the glucose sensor comprises;

a sensing region comprising the boronic acid receptor and the fluorophore associated with the boronic acid receptor;

an optical waveguide for directing light onto the sensing region; and

a glucose-permeable barrier layer comprising a semi-permeable membrane comprising pores and a hydrophilic polymer within the pores of the semi-permeable membrane, the glucose-permeable barrier layer overlying at least a part of the sensing region;

wherein the glucose enters the sensing region of the sensor through the glucose-permeable barrier layer, and an ROS-quenching agent which is platinum in the form of nanoparticles is present in the glucose-permeable barrier layer.