# US 11,906,463 B2 · Methods and systems for detecting bioanalytes

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,906,463 B2
- Document ID: US11906463B2
- Status: Granted
- Kind: B2
- Application number: 16/326,960
- Filed: 2017-08-22
- Published: 2019-07-25
- Granted: 2024-02-20
- Earliest claimed: 2016-08-22
- Assignees: Ramot at Tel-Aviv University Ltd.
- Applicants: Ramot at Tel-Aviv University Ltd.
- Inventors: Fernando Patolsky; Vadim Krivitsky; Marina Zverzhinetsky
- Web page: https://patentgrep.com/patent/US11906463B2

## CPC

- G01N 27/4145: {specially adapted for biomolecules, e.g. gate electrode with immobilised receptors}
- A61B 5/1486: using enzyme electrodes, e.g. with immobilised oxidase
- A61B 5/4842: {Monitoring progression or stage of a disease}
- C12M 1/34: Measuring or testing with condition measuring or sensing means, e.g. colony counters
- C12Q 1/00: Measuring or testing processes involving enzymes, nucleic acids or microorganisms (measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34); Compositions therefor; Processes of preparing such compositions
- G01N 27/4146: {involving nanosized elements, e.g. nanotubes, nanowires}
- G01N 33/48: Biological material, e.g. blood, urine (G01N33/02, G01N33/26, G01N33/44, G01N33/46 take precedence); Haemocytometers (counting blood corpuscules distributed over a surface by scanning the surface G06M11/02)
- G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q)
- G01N 33/5038: {involving detection of metabolites per se}
- G01N 33/54346: {Nanoparticles}
- G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings}
- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- A61B 2562/0285: Nanoscale sensors
- A61B 2562/164: the sensor is mounted in or on a conformable substrate or carrier
- A61B 2562/227: Sensors with electrical connectors
- B82Y 15/00: Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
- G01N 27/3275: {Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction}
- H10K 10/484: {characterised by the channel regions}
- H10K 85/60: Organic compounds having low molecular weight (H10K85/10 - H10K85/50 take precedence)
- H10K 85/761: {Biomolecules or bio-macromolecules, e.g. proteins, chlorophyl, lipids or enzymes}
- 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)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- 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
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- H10K: ORGANIC ELECTRIC SOLID-STATE DEVICES

## Abstract

A sensing system and a method utilizing same for determining and/or monitoring a presence and/or level of an analyte in a sample are provided. The sensing system is made of a nanostructure, or a plurality of nanostructures, having covalently attached thereto and a hydrogel having associated therewith a sensing moiety which selectively interacts with the analyte and being configured such that upon contacting the analyte, the nanostructure(s) exhibit a detectable change in an electrical property.

## Claims

### Claim 1

A sensing system for determining and/or monitoring a presence and/or level of an analyte in a sample, wherein the sample is a biological sample and wherein the analyte is a bioanalyte, the system comprising a field effect transistor having a source electrode, a drain electrode, a gate electrode, and a channel between said source and drain electrodes, said channel being a semiconducting nanostructure having a hydrogel covalently attached thereto, said hydrogel having incorporated therein a sensing moiety which is a bioanalyte-specific reagent and being configured such that upon contacting the bioanalyte, said nanostructure exhibits a detectable change in an electrical property, said electrical property comprising electron density on a surface of said nanostructure, wherein upon contacting the analyte, said hydrogel exhibits a deformation, said deformation leading to said detectable change in said electrical property of said nanostructure, wherein said nanostructure is a silicon nanowire, and wherein said hydrogel is selected capable of impregnating a biological moiety while maintaining an activity of said biological moiety.

### Claim 2 (depends on 1)

The sensing system of claim 1, wherein the bioanalyte is a metabolite.

### Claim 3 (depends on 2)

The sensing system of claim 2, wherein said sensing moiety is a redox enzyme specific to said metabolite.

### Claim 4 (depends on 1)

The sensing system of claim 1, wherein the bioanalyte is a biomarker protein.

### Claim 5 (depends on 4)

The system of claim 4, wherein the bioanalyte is an antigen and said sensing moiety is an antibody specific to said antigen.

### Claim 6 (depends on 1)

The sensing system of claim 1, wherein said hydrogel is covalently attached to said nanostructure via a linking moiety.

### Claim 7 (depends on 1)

The sensing system of claim 1, wherein said deformation comprises a change in a volume of said hydrogel.

### Claim 8 (depends on 1)

The sensing system of claim 1, wherein said deformation comprises a change in spatial distribution of molecules and/or charge in the hydrogel.

### Claim 9 (depends on 1)

The sensing system of claim 1, comprising a plurality of said nanostructures.

### Claim 10 (depends on 9)

The sensing system of claim 9, wherein said hydrogel is covalently attached to at least two of said nanostructures.

### Claim 11 (depends on 9)

The sensing system of claim 9, wherein in at least one portion of said nanostructures said hydrogel has a first sensing moiety incorporated therein and/or thereon and in at least another portion of said nanostructures said hydrogel has a second sensing moiety incorporated therein and/or thereon, said first and second sensing moieties being different from one another.

### Claim 12 (depends on 9)

The sensing system of claim 9, further comprising at least one nanostructure having a hydrogel covalently attached thereto, said hydrogel has a non-sensing moiety incorporated therein and/or thereon.

### Claim 13 (depends on 1)

The sensing system of claim 1, wherein said hydrogel is in a form of a nanoparticle or in a form of a film.

### Claim 14 (depends on 1)

The sensing system of claim 1, being in a form of a skin patch.

### Claim 15 (depends on 1)

A system comprising a sensing compartment comprising the sensing system of claim 1, and at least one additional compartment being in communication with the sensing compartment.

### Claim 16 (depends on 15)

The system of claim 15, wherein said at least one additional compartment is configured to contain at least a portion of said sample.

### Claim 17 (depends on 15)

The system of claim 15, wherein said at least one additional compartment is configured to contain a therapeutically active agent.

### Claim 18 (depends on 17)

The system of claim 17, wherein said additional compartment is configured to controllably release said therapeutically active agent.

### Claim 19 (depends on 18)

The system of claim 18, wherein said additional compartment is configured to controllably release said therapeutically active agent responsively to said detectable change in electrical property of said nanostructure.

### Claim 20 (depends on 15)

The system of claim 15, wherein said at least one additional compartment comprises an additional sensing system.

### Claim 21 (depends on 15)

The system of claim 15, being in a form of a skin patch.

### Claim 22 (depends on 1)

A method of determining or monitoring a presence and/or a level of at least one bioanalyte in a biological sample, the method comprising contacting at least a portion of the biological sample with the sensing system of claim 1, wherein said detectable change in said electrical property is indicative of the presence and/or level of the bioanalyte in the sample.

### Claim 23 (depends on 22)

The method of claim 22, being for diagnosing and/or monitoring a disease associated with said bioanalyte in a subject.

### Claim 24 (depends on 15)

A method of determining or monitoring a presence and/or a level of at least one bioanalyte in a biological sample, the method comprising contacting at least a portion of the biological sample with the system of claim 15, wherein said detectable change in said electrical property is indicative of the presence and/or level of the bioanalyte in the sample.

### Claim 25 (depends on 24)

The method of claim 24, being for diagnosing and/or monitoring a disease associated with said bioanalyte in a subject.

### Claim 26 (depends on 25)

The method of claim 25, wherein said system further comprises a compartment configured for releasing a therapeutically active agent, the method being for determining and/or monitoring an efficacy of said therapeutic agent towards said disease in said subject and/or for treating said disease.