Glucose sensors and methods of manufacture thereof

• US 8,771,500 B2
• Filed: 10/22/2008
• Issued: 07/08/2014
• Est. Priority Date: 10/22/2007
• Status: Active Grant

• Current Assignee: University of Connecticut (State of Connecticut)
• Original Assignee: University of Connecticut (State of Connecticut)
• Inventors: Papadimitrakopoulos, Fotios, Vaddiraju, Santhisagar
• Primary Examiner(s): Van, Luan
• Assistant Examiner(s): Kessel, Maris R
• Application Number:
  US12/256,043
• Publication Number:
  US 20090101498A1
• Time in Patent Office: 2,085 Days
• Field of Search: 600/309, 600345-366, 20440301-40315, 205/775, 205/777.5, 205/778, 205/792, 205/793
• US Class Current: 205/777.5
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: C01B 13/0248 Physical processing only
• CPC Class Codes: C01B 13/0259 by adsorption on solids
• CPC Class Codes: C01B 13/0285 by absorption in liquids
• CPC Class Codes: C12Q 1/003 Functionalisation
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

Disclosed herein is a device that functions as a glucose sensor. The device has a reference electrode; a counter electrode, a working electrode; an electrically conducting membrane; an enzyme layer; a semi-permeable membrane; a first layer of a first hydrogel in operative communication with the working electrode; the first layer of the first hydrogel being operative to store oxygen; wherein the amount of stored oxygen is proportional to the number of freeze-thaw cycles that the hydrogel is subjected to; and a second layer of the second hydrogel. Disclosed too is a method that comprises using periodically biased amperometry towards interrogation of implantable glucose sensors to improve both sensor'"'"'s sensitivity and linearity while at the same time enable internal calibration against sensor drifts that originate from changes in either electrode activity or membrane permeability as a result of fouling, calcification and/or fibrosis.

Claims

1. A method comprising:

performing periodic biasing amperometry on a sensor, the sensor comprising;

a reference electrode;

a counter electrode;

a working electrode;

the working electrode being disposed in the vicinity of the reference and counter electrode;

an electrically conducting membrane;

the electrically conducting membrane being in operative communication with the working electrode;

an enzyme layer;

the enzyme layer being in operative communication with the working electrode;

a semi-permeable membrane;

the semi-permeable membrane being in operative communication with the working electrode introducing a sample comprising an analyte being measured to the sensor;

the periodic biasing amperometry comprising;

determining a normal operating state for the sensor by biasing the working electrode for the same duration of time at intervals (t_wait) having the same periods of time at a number of testing potentials;

repeating the periodic biasing for all the testing potentials;

continuing the periodic biasing until a steady state is attained for all the testing potentials;

conducting an internal calibration of the sensor after the analyte being measured has reached a steady state;

the internal calibration comprising a time interval (t_cal) where the periodic biasing is not applied;

where t_cal=n×

t_wait, where n is a number of about 2 to about 10;

measuring a periodic biasing amperometric signal difference immediately before and immediately after the time interval (t_cal);

comparing the differential with a calibration chart to obtain sensitivity factors; and

applying the sensitivity factors to the sensor to correct against drifts; and

performing biasing amperometry at a time interval of t_eq to ensure that the sensor returns to its normal operating state;

where t_eq is less than t_wait.

2. The method of claim 1, where the sensitivity factors are applied to gradually prorate recorded values obtained from the sensor.

3. The method of claim 1, where the drifts originate from changes in electro-activity of the working electrode.

4. The method of claim 3, wherein the changes in electro-activity of the working electrode are determined by comparing signal differentials from two different internal calibration routines at two different analyte concentrations.

5. The method of claim 3, wherein the changes in electro-activity of the working electrode are determined by comparing the time dependent decay of the amperometric signal immediately before and immediately after the time interval t_cal.

6. The method of claim 5, wherein the time-dependent decay involves determining a slope of a time-dependent decay curve.

7. The method of claim 5, wherein the slope of the time-dependent curve is determined by interrogating the sensor at two different biasing time intervals.

8. The method of claim 5, where the slope of the time-dependent decay curve is obtained by comparing at a signal value at a mid-point and a final of the curve.