# US 2025/0082244 A1 · Wearable aptamer field-effect transistor sensing system for noninvasive cortisol monitoring and wearable system for stress sensing

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- Number: US 2025/0082244 A1
- Document ID: US20250082244A1
- Status: Published application
- Kind: A1
- Application number: 18/726,685
- Filed: 2023-01-04
- Published: 2025-03-13
- Earliest claimed: 2022-01-04
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Sam EMAMINEJAD; Anne ANDREWS; Bo WANG; Chuanzhen ZHAO
- Web page: https://patentgrep.com/patent/US20250082244A1

## CPC

- A61B 5/302: for capacitive or ionised electrodes, e.g. metal-oxide-semiconductor field-effect transistors [MOSFET]
- G01N 33/743: {Steroid hormones}
- A61B 5/14507: {specially adapted for measuring characteristics of body fluids other than blood (devices for taking samples of body liquids A61B10/0045)}
- A61B 5/14546: {for measuring analytes not otherwise provided for, e.g. ions, cytochromes}
- A61B 5/681: {Wristwatch-type devices}
- C12N 15/115: Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers}
- C12Q 1/6825: Nucleic acid detection involving sensors
- G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings}
- C12N 2310/16: Aptamers
- C12N 2310/531: Stem-loop; Hairpin
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol—a key stress biomarker—is present in sweat at low nanomolar concentrations. Previous wearable sensing systems are limited to analytes in the micromolar-millimolar ranges. To overcome these and other limitations, the present embodiments include a flexible field-effect transistor (FET) biosensor array that exploits a new cortisol aptamer coupled to nanometer-thin-film In2O3 FETs. Cortisol levels were determined via molecular recognition by aptamers where binding was transduced to electrical signals on FETs. The physiological relevance of cortisol as a stress biomarker was demonstrated by tracking salivary cortisol levels in participants in a Trier Social Stress Test and establishing correlations between cortisol in diurnal saliva and sweat samples. These correlations motivated the development and on-body validation of an aptamer-FET array-based smartwatch equipped with a custom, multi-channel, self-referencing autonomous source measurement unit enabling seamless, real-time cortisol sweat sensing.

## Claims

### Claim 1

A method of aptamer-FET sensing comprising:
preparing a stem-loop aptamer that contains oligonucleotide sequences with consecutive bases identical at least 80% to GGTCTG or 80% to TGTCTG; and
configuring the stem-loop aptamer to bind to cortisol with a dissociation constant between about 1×10−8 M to about 1×10−4 M,
wherein the stem-loop aptamer has at least four times higher binding affinity for cortisol compared to other steroid molecules present in retrievable biofluids.

### Claim 2

A device comprising:
a flexible or stiff field-effect transistor (FET) biosensor array including:
a cortisol aptamer or an aptamer for another biomarker coupled to a thin-film In2O3 FET.

### Claim 3 (depends on 2)

The device of claim 2 wherein cortisol levels or other biomarker levels are determined via molecular recognition by the aptamer wherein binding is transduced to electrical signals on the FET.

### Claim 4 (depends on 2)

A smartwatch or other wearable device based on the FET biosensor array of claim 2.

### Claim 5 (depends on 4)

The smartwatch or other wearable device of claim 4, including a custom, multi-channel, self-referencing, autonomous source measurement unit or other measurement unit enabling seamless, real-time, continuous cortisol or other biomarker measurements in biofluids including sweat, saliva, interstitial fluid, tears, urine, or blood.

### Claim 6

A device for wearable sensing applications, comprising:
a substrate embedded in a microfluidic device to form a skin-adherable biofluid sampling, routing, and analysis module; and
a cortisol-aptamer-FET sensor or an aptamer-FET sensor for another biomarker formed on the substrate.

### Claim 7 (depends on 6)

The device of claim 6, wherein the substrate comprises a flexible polyimide substrate or a substrate comprising another flexible material.

### Claim 8 (depends on 6)

The device of claim 6, wherein the sensor comprises an aptamer-FET array.

### Claim 9 (depends on 6)

The device of claim 6, further comprising an on-board multi-channel source measurement unit (SMU).

### Claim 10 (depends on 6)

The device of claim 6, wherein the sensor comprises quasi-2D FETs employing In2O3 or another inorganic semiconductor or graphene fabricated on hard or soft substrates.

### Claim 11

A method of fabricating a device for wearable sensing applications, comprising:
forming a layer of thin-film In2O3 on polyimide via spin coating or other methods of deposition;
patterning the In2O3 layer to form channel regions; and
forming source and drain contacts.

### Claim 12 (depends on 11)

The method of claim 11, wherein patterning is performed by photolithography or other chemical patterning methods and reactive ion etching.

### Claim 13 (depends on 11)

The method of claim 11, wherein forming source and drain contacts includes patterning interdigitated Au/Ti or other metal electrodes.

### Claim 14 (depends on 11)

The method of claim 11, wherein the polyimide comprises a flexible substrate.

### Claim 15

A method of operating a biosensor comprising:
preparing an aptamer-FET sensing interface;
translating target binding events into measurable surface charge perturbations; and
measuring the perturbations as changes in effective VGS and subsequently IDS.

### Claim 16 (depends on 15)

The method of claim 15, wherein the target binding events include exposure to human sweat or other retrievable biofluids.

### Claim 17 (depends on 15)

The method of claim 15, wherein the target binding events include exposure to human saliva.

### Claim 18 (depends on 15)

The method of claim 15, wherein the target binding events include exposure to cortisol or other biomarkers.