# US 10,309,918 B2 · Quantum capacitance sensing > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,309,918 B2 - Document ID: US10309918B2 - Status: Granted - Kind: B2 - Application number: 15/643,208 - Filed: 2017-07-06 - Published: 2017-12-28 - Granted: 2019-06-04 - Earliest claimed: 2015-01-26 - Assignees: Oxford University Innovation Limited; Universidade Estadual Paulista “Julio De Mesquita Filho” —UNESP - Applicants: Oxford University Innovation Limited; Universidade Estadual Paulista “JúLio De Mesquita Filho”-Unesp - Inventors: Jason Davis; Paulo Roberto Bueno - Web page: https://patentgrep.com/patent/US10309918B2 ## CPC - G01N 27/221: {by investigating the dielectric properties (using microwaves G01N22/00; measuring loss factors or dielectric constants per se G01R27/26)} - G01N 27/026: {Dielectric impedance spectroscopy (electrochemical impedance spectroscopy for measuring corrosion G01N17/02)} - G01N 27/227: {Sensors changing capacitance upon adsorption or absorption of fluid components, e.g. electrolyte-insulator-semiconductor sensors, MOS capacitors (G01N27/225 takes precedence)} - G01N 27/27: Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter - G01N 33/5438: {Electrodes} - G01N 33/68: involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} - G01R 27/2605: {Measuring capacitance (capacitive sensors G01D5/24)} - H10D 62/882: {Graphene} - H10F 30/29: the devices being sensitive to radiation having very short wavelengths, e.g. X-rays, gamma-rays or corpuscular radiation - G01N 2333/4737: C-reactive protein - 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) - G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12) - H10D: INORGANIC ELECTRIC SEMICONDUCTOR DEVICES - H10F: INORGANIC SEMICONDUCTOR DEVICES SENSITIVE TO INFRARED RADIATION, LIGHT, ELECTROMAGNETIC RADIATION OF SHORTER WAVELENGTH OR CORPUSCULAR RADIATION ## Abstract The present application relates to a sensing method that is carried out using an electrode that comprises an electrode substrate functionalized with sensing elements. The method involves conducting electrochemical impedance spectroscopy at a plurality of applied voltages and then integrating measurement data as a function of voltage. Also provided is an apparatus for carrying out the sensing method. The method and apparatus are suitable for a broad range of sensing applications, including the detection of diagnostic biomarkers, drug screening, development of glycoarray systems and the sensing of environmental parameters such as light intensity, temperature and humidity. ## Claims ### Claim 1 A sensing method for sensing a chemical substance, the method comprising: (A) obtaining, by electrochemical impedance spectroscopy conducted across a range of applied potentials, a plurality of measurements of the complex impedance, Z*, of a system that has a working electrode that is in contact with a carrier medium that may comprise said chemical substance, the working electrode comprising receptor moieties that are capable of binding to said chemical substance, wherein the working electrode comprises an electrode substrate functionalized with sensing elements whose electrochemical response to the applied potentials is sensitive to the binding of said chemical substance to said receptor moieties, the sensing elements having a dimension of from 0.5 to 10 nm; (B) converting said plurality of measurements of Z* into a plurality of measurements of the real component of the complex capacitance, C′, at a selected frequency ω and/or the imaginary component of the complex capacitance, C″, at a selected frequency ω; (C) integrating the measurements of (a) C′, (b) C″, or (c) any combination of C′ and C″, at the selected frequency ω as a function of applied voltage to obtain an integrated measurement value; and (D) sensing whether the chemical substance is present in the carrier medium from said integrated measurement value. ### Claim 2 (depends on 1) The sensing method according to claim 1, wherein in step (A) said obtaining, by electrochemical impedance spectroscopy conducted across a range of applied potentials, a plurality of measurements of the complex impedance, comprises obtaining at least five measurements of the complex impedance at different applied potentials. ### Claim 3 (depends on 1) The sensing method according to claim 1, wherein said sensing in step (D) is performed by comparing said integrated measurement value with one or more reference values obtained by performing the steps (A), (B) and (C) under conditions where the local environment of the electrode is known. ### Claim 4 (depends on 1) The sensing method according to claim 1, wherein said chemical substance is a target species to which said receptor moieties are capable of specifically binding, and wherein said method is a method for the determining the concentration of said target species in said carrier medium. ### Claim 5 (depends on 4) The sensing method according to claim 4, wherein said target species is selected from the group consisting of CRP protein, insulin and a marker of one or more of neurodegeneration, cancer, myocardial infarction, diabetes and general trauma. ### Claim 6 (depends on 1) The sensing method according claim 1, wherein said chemical substance is selected from a lectin protein, a glycoenzyme and a carbohydrate-binding antibody, and wherein said receptor moieties are carbohydrate moieties. ### Claim 7 (depends on 6) The sensing method according to claim 6, where said working electrode forms part of a glycoarray comprising a plurality of working electrodes that are each functionalized with different carbohydrate moieties. ### Claim 8 (depends on 1) The sensing method according to claim 1, wherein said chemical substance is drug candidate and wherein said receptor moieties are moieties that are capable of binding to a reference drug. ### Claim 9 (depends on 8) The sensing method according to claim 8, wherein said working electrode forms part of an array comprising a plurality of working electrode that are each functionalized with said receptor moieties, said array thereby being suitable for use in the simultaneous screening of a plurality of drug candidates. ### Claim 10 (depends on 1) The sensing method according to claim 1, wherein said sensing elements comprise one or more of redox active species, a molecular film, nanoparticles, graphene, carbon nanotubes or quantum dots. ### Claim 11 (depends on 1) The sensing method according to claim 1, wherein said working electrode is not functionalized with a redox active species. ### Claim 12 (depends on 1) The sensing method according to claim 1, wherein said receptor moieties that are capable of binding to said chemical substance comprise an antibody or an antibody fragment. ### Claim 13 (depends on 1) The sensing method according to claim 1 wherein said sensing elements comprise graphene. ### Claim 14 (depends on 1) The sensing method according to claim 1, wherein said sensing method is a quantum capacitance sensing method. ### Claim 15 An apparatus for use in a sensing method for sensing a chemical substance, which apparatus comprises: an electrochemical spectrometer that comprises a working electrode, a counter electrode and a potentiostat, said working electrode comprising receptor moieties that are capable of binding to said chemical substance, wherein said working electrode comprises an electrode substrate functionalized with sensing elements whose electrochemical response to applied potentials is sensitive to the binding of said chemical substance to said receptor moieties, the sensing elements having a dimension of from 0.5 to 10 nm; a receiver configured to receive, from said electrochemical spectrometer, input data comprising a plurality of measurements of complex impedance, Z*, across a range of applied potentials; and a processor configured to (i) convert said plurality of measurements of Z* into a plurality of measurements of the real component of the complex capacitance, C′, at a selected frequency ω and/or the imaginary component of the complex capacitance, C″, at a selected frequency ω, and (ii) integrate said measurements of (a) C′, (b) C″, or (c) any combination of C′ and C″, at the selected frequency ω as a function of applied voltage to obtain an integrated measurement value. ### Claim 16 (depends on 15) The apparatus according to claim 15, further comprising an output unit configured to output data generated from said integrated measurement value. ### Claim 17 A storage medium storing computer readable code for implementation by a computer or network of computers, the code, when implemented, causing the computer or network of computers to implement the steps of: obtaining, from an electrochemical spectrometer, input data comprising a plurality of measurements of complex impedance, Z*, across a range of applied potentials; converting said plurality of measurements of Z* into a plurality of measurements of the real component of the complex capacitance, C′, at a selected frequency ω and/or the imaginary component of the complex capacitance, C″, at a selected frequency ω; and integrating said measurements of (a) C′, (b) C″, or (c) any combination of C′ and C″, at the selected frequency ω as a function of applied voltage to obtain an integrated measurement value.