# US 4,396,464 A · Method for sensing the concentration of glucose in biological fluids

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- Number: US 4,396,464 A
- Document ID: US4396464A
- Status: Granted
- Kind: A
- Application number: 06/370,735
- Filed: 1982-04-22
- Granted: 1983-08-02
- Earliest claimed: 1980-06-02
- Assignees: Joslin Diabetes Center, Inc.
- Inventors: Jose D. Giner; Harry Lerner; John S. Soeldner
- Web page: https://patentgrep.com/patent/US4396464A

## CPC

- A61B 5/14865: {invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors}
- G01N 27/3274: {Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration (coding of calibration information G01N33/48771)}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Glucose sensing apparatus for use in biological fluids comprising an electrode and a voltage source connected to the electrode to cause a current to flow therethrough, in which the voltage applied to the electrode is varied in a sweep ranging from a first limit to a second limit and back toward the first limit, and the current at the electrode is integrated with respect to time during at least a portion of the voltage variation selected to produce a total charge sensitive to glucose concentration and relatively insensitive to other components in the fluid; alternatively the current is measured at a point in a specific region of the voltage variation.

## Claims

### Claim 1

A method for sensing the concentration of glucose in biological fluids comprising the steps of
applying a variable voltage to an electrode to cause a current flow therethrough
sweeping said voltage over a range in a first direction from a first limit to a second limit and in the reverse direction back toward said first limit, and
integrating current at the electrode with respect to time during a period including at least a portion of said sweep in both directions selected to produce a total charge sensitive to glucose concentration and relatively insensitive to other components in the fluid.

### Claim 2 (depends on 1)

The method of claim 1 wherein said portion is selected so that the charge responsive to glucose concentration has predominantly the same algebraic sign throughout said period, and so that the charge responsive to interfering components of said fluid has a positive sign in one segment of said period and a negative sign in another segment of said period, whereby the glucose-responsive charge, and thus sensitivity to glucose, is reinforced, and the charge responsive to interfering substances at least partially cancels, thus reducing such interference.

### Claim 3 (depends on 1, 2)

The method of claim 1 or 2 wherein the lower limit of such voltage sweep is between -1.0 and -0.6 volts and the upper limit is between 0.7 and 1.1 volts, said sweep including an anodic sweep from said lower to said upper limit and a cathodic sweep from said upper to said lower limit.

### Claim 4 (depends on 1, 2)

The method of claim 1 or 2 wherein said voltage sweep includes dwell periods at said upper and lower limits, and the rate of voltage change during said anodic and cathodic sweeps is constant.

### Claim 5 (depends on 1, 2)

The method of claim 1 or 2 wherein said integration takes place continuously during one complete voltage sweep.

### Claim 6 (depends on 1, 2)

The method of claim 1 or 2 wherein said integration occurs substantially including the anodic sweep between -0.45 volts and said upper limit, the dwell at said upper limit, and the entire cathodic voltage sweep.

### Claim 7 (depends on 1, 2)

The method of claim 1 or 2 wherein the rate of voltage change during said cathodic voltage sweep is more rapid than during said anodic voltage sweep.

### Claim 8 (depends on 1, 2)

The method of claim 1 or 2 wherein said varying of said applied voltage ceases during holding periods between said limits, said holding periods being at potentials at which glucose undergoes an electrochemical reaction.

### Claim 9 (depends on 1, 2)

The method of claim 1 or 2 wherein said portion is selected so that the charge attributable to any specific interfering component of the fluid cancels, whereby changes in concentration of that specific component do not affect the charge measured.

### Claim 10 (depends on 9)

The method of claim 9 wherein said voltage variation includes an anodic sweep and a cathodic sweep, said rate of voltage variation being between 0.5 volts/min and 4 volts/min.

### Claim 11 (depends on 1, 2)

The method of claim 1 or 2 further comprising the step of forming the ratio of said total charge to the total absolute value of charge during said portion.

### Claim 12

A method for sensing the concentration of glucose in biological fluids comprising
applying a voltage to an electrode arranged for interaction with said fluids to cause a current to flow through said electrode,
sweeping said voltage in a first direction from a first limit to a second limit and thereafter in the reverse direction, said sweep including voltages between 0.2 and 0.6 volts,
measuring said current at at least one isolated point, between 0.2 volts and 0.6 volts, during the anodic variation of the voltage sweep, said point being selected to be sensitive to change in levels of glucose concentration in said fluid, but relatively insensitive to levels of other constituents of said fluid, and
determining the glucose concentration level based on the current measurement at said isolated point.

### Claim 13 (depends on 12)

The method of claim 12 wherein said lower limit of said voltage variation is between -1.0 and -0.6 volts and the upper limit is between 0.7 and 1.1 volts.

### Claim 14 (depends on 13)

The method of claim 13 wherein said dwell periods are greater than 2 seconds.

### Claim 15 (depends on 14)

The method of claim 14 wherein the rate of voltage change during said cathodic sweep is more rapid than during said anodic sweep.

### Claim 16 (depends on 12)

The method of claim 12 wherein the rate of change of said voltage variation is constant between said limits, and includes dwell periods at each limit.
