# US 2014/0197042 A1 · Saliva Glucose Monitoring System

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- Number: US 2014/0197042 A1
- Document ID: US20140197042A1
- Status: Published application
- Kind: A1
- Application number: 14/153,647
- Filed: 2014-01-13
- Published: 2014-07-17
- Earliest claimed: 2013-01-11
- Assignees: Northeastern University
- Applicants: Northeastern University
- Inventors: Wenjun Zhang; Ming L. Wang
- Web page: https://patentgrep.com/patent/US20140197042A1

## CPC

- G01N 27/3273: {Devices therefor, e.g. test element readers, circuitry (details not specific to biochemical electrodes G01N33/4875)}
- G01N 27/3271: {Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood (amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001)}
- 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

A glucose sensor suitable for measuring glucose levels in human saliva is provided. Systems containing the glucose sensor and methods for making and using the sensor are also provided. The glucose sensor is highly sensitive and can detect glucose levels at least down to 5 ppm. Fabrication of the sensor involves depositing single-walled carbon nanotubes onto the surface of a working electrode in a 3 electrode electrochemical detector and functionalizing the nanotubes by depositing layers of polymers, metallic nanoparticles, and glucose oxidase enzyme onto the nanotubes. The sensor can be used as a disposable, single-use device or as part of an analytical system, such as a microfluidics system, for the analysis of multiple analytes. The sensor enables the diagnosis and monitoring of diabetes to be performed without pain or the need for finger pricks in a home or clinical setting.

## Claims

### Claim 1

A glucose sensor for determining a concentration of glucose in a liquid sample, the sensor comprising:
an insulating or semiconducting substrate;
at least one working electrode, a counter electrode, and a reference electrode, and
a sample placement area on a surface of the substrate for containing the liquid sample during a determination of the glucose concentration in the liquid sample;
wherein each of the working electrode(s), counter electrode, and reference electrode comprises a conductive metal layer deposited on the substrate in the sample placement area; wherein the working electrode is optionally coated in the sample placement area with a plurality of sensor elements; wherein the sensor elements or the working electrode in the sample placement area is functionalized with a coating comprising glucose oxidase; wherein the working electrode, counter electrode, and reference electrode are connected to an amperometry circuit; and
wherein an output voltage of the amperometry circuit correlates with a glucose concentration in the liquid sample deposited in the sample placement area.

### Claim 2 (depends on 1)

The glucose sensor of claim 1, wherein the substrate comprises a material selected from the group consisting of silicon, glass, ceramic, a non-conductive polymer, and combinations thereof.

### Claim 3 (depends on 1)

The glucose sensor of claim 1, wherein the working electrode comprises one or more materials selected from the group consisting of gold, platinum, iridium, silver, silver/silver chloride, and combinations thereof.

### Claim 4 (depends on 1)

The glucose sensor of claim 1, wherein the sensor elements comprise a material selected from the group consisting of single-walled carbon nanotubes (SWNT), graphite, graphene, carbon nanofibers, carbon nanowires, and combinations thereof.

### Claim 5 (depends on 1)

The glucose sensor of claim 1, wherein the sensor element functionalization coating comprises one or more layers, each layer comprising a sublayer of chitosan, a sublayer of gold nanoparticles disposed on the sublayer of chitosan, and a sublayer of glucose oxidase disposed on the sublayer of gold nanoparticles.

### Claim 6 (depends on 1)

The glucose sensor of claim 1, further comprising a layer comprising a polycationic polymer deposited on the surface of the working electrode and beneath the sensor elements.

### Claim 7 (depends on 6)

The glucose sensor of claim 6, wherein the polycationic polymer is selected from the group consisting of polyallylamine, poly(L-lysine), polyethyleneimine, polyamidoamine dendrimers, and combinations thereof.

### Claim 8 (depends on 1)

The glucose sensor of claim 1, wherein the sensor element functionalization coating comprises one or more materials selected from the group consisting of carbon nanotubes, graphite, graphene, gold nanoparticles, platinum nanoparticles, serum albumin, chitosan, and Prussian Blue.

### Claim 9 (depends on 1)

The glucose sensor of claim 1, further comprising a sensor element protective membrane.

### Claim 10 (depends on 9)

The glucose sensor of claim 9, wherein the sensor element protective membrane comprises Nafion, a lipid bilayer, or another semi-permeable membrane.

### Claim 11 (depends on 1)

The glucose sensor of claim 1 that is a component of a microfluidics device, wherein the microfluidics device comprises one or more channels that deliver a liquid sample to the sample placement area.

### Claim 12 (depends on 1)

The glucose sensor of claim 1 that is capable of detecting glucose at concentrations down to 5 ppm (0.5 mg/dL) or lower.

### Claim 13 (depends on 1)

The glucose sensor of claim 1 that is configured as a disposable device or a reusable device.

### Claim 14 (depends on 1)

The glucose sensor of claim 1 that is configured for determination of glucose concentration in saliva.

### Claim 15 (depends on 1)

The glucose sensor of claim 1 comprising one or more working electrodes having functionalized sensor elements capable of detecting an analyte other than glucose.

### Claim 16 (depends on 1)

A glucose analysis system comprising:
the glucose sensor of claim 1;
a signal conditioning and/or analysis device that processes an electrical signal from the sensor.

### Claim 17 (depends on 16)

The glucose analysis system of claim 16, further comprising a transmitter device for sending a radio signal to a remote receiver and/or to a data processing device, wherein the radio signal carries information related to a glucose concentration in the liquid sample, the information obtained from the signal conditioning and/or analysis device.

### Claim 18 (depends on 16)

The glucose analysis system of claim 16, further comprising a memory device for accumulating data related to the glucose concentration in the liquid sample, the data obtained at different times or from different liquid samples.

### Claim 19 (depends on 16)

The glucose analysis system of claim 16, further comprising a device for chemically or physically processing a liquid sample and delivering the processed sample to the sample placement area of the device.

### Claim 20 (depends on 1)

A method of determining a glucose concentration in a liquid sample, the method comprising the steps of:
(a) providing the glucose sensor of claim 1;
(b) introducing a liquid sample into the sample placement area of the sensor; and
(c) determining the glucose concentration in the liquid sample from an electrical output of the sensor.

### Claim 21 (depends on 20)

The method of claim 20 further comprising the steps of:
(d) removing the liquid sample introduced in step (b);
(e) introducing a new liquid sample into the sample placement area of the sensor; and
(f) determining a new glucose concentration in the new liquid sample from an electrical output of the sensor.

### Claim 22 (depends on 20)

The method of claim 20, wherein the liquid sample is from a subject who has diabetes, is suspected of having diabetes, or is healthy.

### Claim 23 (depends on 20)

The method of claim 20, wherein the liquid sample is a saliva sample.

### Claim 24 (depends on 1)

A glucose sensor array comprising a plurality of sensors according to claim 1 sharing a common substrate.

### Claim 25

A method of fabricating a glucose sensor, comprising the steps of:
(a) microfabricating one or more working electrodes, a reference electrode, and a counter electrode on the surface of an insulating substrate, wherein each of said electrodes contacts a sample placement area on the substrate;
(b) optionally depositing a layer of a polycationic polymer onto the working electrode;
(c) optionally depositing a plurality of sensor elements onto the polycationic polymer layer or onto the working electrode;
(d) depositing a plurality of functionalization layers onto the sensor elements or onto the working electrode; wherein the functionalization layers comprise sublayers of chitosan, gold nanoparticles, and glucose oxidase.

### Claim 26 (depends on 25)

The method of claim 25, further comprising:
(e) depositing a sensor element protective membrane over the functionalization layers of the sensor elements.

### Claim 27 (depends on 25)

The method of claim 25, wherein the substrate comprises a material selected from the group consisting of silicon, glass, ceramic, a non-conductive polymer, and combinations thereof; wherein the working electrode comprises one or more materials selected from the group consisting of gold, platinum, iridium, silver, silver/silver chloride, and combinations thereof; wherein the sensor elements comprise a material selected from the group consisting of single-walled carbon nanotubes (SWNT), graphite, graphene, carbon nanofibers, carbon nanowires, and combinations thereof; and wherein the polycationic polymer is selected from the group consisting of polyallylamine, poly(L-lysine), polyethyleneimine, polyamidoamine dendrimers, and combinations thereof.

### Claim 28 (depends on 25)

The method of claim 25, wherein the sensor elements are deposited on the working electrode by a self-assembly process comprising depositing a liquid suspension of sensor elements onto the layer of polycationic polymer.

### Claim 29 (depends on 25)

The method of claim 25, comprising depositing two or more working electrodes, each having differently functionalized sensor elements.

### Claim 30 (depends on 25)

The method of claim 25, wherein one or more of the working electrode(s), reference electrode, and counter electrode is not coplanar with respect to the other electrodes.