# US 12,599,319 B2 · Electrochemical detection device and method > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,599,319 B2 - Document ID: US12599319B2 - Status: Granted - Kind: B2 - Application number: 16/618,944 - Filed: 2018-06-04 - Published: 2020-05-07 - Granted: 2026-04-14 - Earliest claimed: 2017-06-04 - Assignees: B.G. Negev Technologies and Applications Ltd., At Ben-Gurion University - Applicants: B.G. Negev Technologies and Applications Ltd., At Ben-Gurion University - Inventors: Hadar Shmuel Ben-Yoav; Alon Mazafi - Web page: https://patentgrep.com/patent/US12599319B2 ## CPC - A61B 5/14507: {specially adapted for measuring characteristics of body fluids other than blood (devices for taking samples of body liquids A61B10/0045)} - A61B 5/0022: {Monitoring a patient using a global network, e.g. telephone networks, internet} - A61B 5/14546: {for measuring analytes not otherwise provided for, e.g. ions, cytochromes} - A61B 5/1477: non-invasive - A61B 5/7267: {involving training the classification device} - G01N 27/3277: {being a redox reaction, e.g. detection by cyclic voltammetry (voltammetry per se G01N27/42, G01N27/48)} - G01N 33/493: urine - G06N 3/02: Neural networks - G16H 40/67: for remote operation - G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems - A61B 2562/0209: Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053 - A61B 2562/046: in a matrix array - G16H 50/70: for mining of medical data, e.g. analysing previous cases of other patients - 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) - G06N: COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA ## Abstract An electrochemical sensor comprising a counter electrode, optionally a reference electrode, and an array of multiple working electrodes, wherein at least one of the working electrodes is a film-coated electrode, and wherein the film-forming material has repeat unit that comprises six-membered non-aromatic ring. A device for electrochemical detection that comprises the sensor (an electrochemical tongue) and a method for detecting analytes with the aid of the sensor are also disclosed. ## Claims ### Claim 1 An electrochemical sensor comprising one counter electrode, optionally a reference electrode, and an array of multiple working electrodes, wherein the array of working electrodes comprises: a first subarray consisting of one or more bare electrodes; a second subarray consisting of one or more film-coated electrodes; a third subarray consisting of one or more conductive additive-incorporated film-coated electrodes; wherein a film-forming material has a repeat unit that comprises a six-membered non-aromatic ring such that the film coated electrodes are partially selective and can cross-react with multiple redox molecules. ### Claim 2 (depends on 1) An electrochemical sensor according to claim 1, wherein the six-membered, non-aromatic ring bears amine group, carboxylic acid group, hydroxyl group or sulfonic acid group covalently bonded to a carbon atom of said ring. ### Claim 3 (depends on 1) An electrochemical sensor according to claim 1, wherein the film-forming material is polysaccharide. ### Claim 4 (depends on 3) An electrochemical sensor according to claim 3, wherein the polysaccharide is chitosan. ### Claim 5 (depends on 1) An electrochemical sensor according to claim 1, wherein the conductive additive that is incorporated into the one or more conductive additive-incorporated film-coated electrodes is carbon nanotubes. ### Claim 6 (depends on 1) An electrochemical sensor according to claim 1, wherein at least one of the working electrodes is a carbon nanotubes-incorporated chitosan-coated electrode. ### Claim 7 (depends on 1) An electrochemical sensor according to claim 1, wherein the working electrodes comprise: one or more bare gold electrodes; and one or more chitosan-coated gold electrodes. ### Claim 8 (depends on 1) An electrochemical sensor according to claim 1, wherein the working electrodes comprise: one or more bare gold electrodes; one or more chitosan-coated gold electrodes; and one or more carbon nanotubes-incorporated chitosan-coated gold electrodes. ### Claim 9 (depends on 1) An electrochemical sensor according to claim 1, wherein the working electrodes comprise: one or more bare electrodes; one or more chitosan-coated electrodes; one or more carbon nanotubes-incorporated chitosan-coated electrodes; and one or more reduced graphene oxide-coated electrodes; and wherein the film made of chitosan and the film made of reduced graphene oxide are electrodeposited films. ### Claim 10 (depends on 1) A method of electrochemical detection of one or more analytes in a liquid sample, the method comprising the steps of: bringing a liquid sample into contact with an electrochemical sensor as defined in claim 1; applying variable voltage, fixed voltage, current or impedance across the working electrodes; measuring the current flowing or the impedance between each of the working electrodes and a counter electrode, or the potential between each of the working electrodes and a reference electrode, to obtain a raw data set consisting of plurality of electrochemical signals; preprocessing the raw data set; and applying chemometric method(s) to the preprocessed data, to qualitatively or quantitively characterize the analyte of interest. ### Claim 11 (depends on 10) A method according to claim 10, wherein the liquid sample is a biofluid sample and the analyte is an organic redox compound, wherein an interferant is optionally present in said biofluid sample. ### Claim 12 (depends on 11) A method according to claim 11, wherein the analyte is a neurotransmitter. ### Claim 13 (depends on 12) A method according to claim 12, wherein the analyte of interest is dopamine and/or norepinephrine and the interferant is uric acid. ### Claim 14 (depends on 10) A method according to claim 10, comprising applying variable voltage and measuring current as the electrochemical signal. ### Claim 15 (depends on 14) A method according to claim 14, wherein the raw data is reduced in dimensions and normalized, the reduction being achieved using extracted electrochemical features recorded by voltammetry. ### Claim 16 (depends on 15) A method according to claim 15, comprising applying one or more chemometric method(s) selected from partial least square regression or a trained artificial neural network model (ANN). ### Claim 17 (depends on 16) A method according to claim 16, comprising applying trained artificial neural network model to the preprocessed raw data. ### Claim 18 (depends on 17) A method according to claim 17, wherein the raw data that is obtained from a biofluid is used to calibrate the model that was previously trained using non-biofluid samples. ### Claim 19 A device for electrochemical detection, comprising: one counter electrode, optionally a reference electrode, and an array of multiple working electrodes, wherein at least one of the working electrodes is a first film-coated electrode, with a film-forming material that has a repeat unit that comprises a six-membered non-aromatic ring, wherein the array of working electrodes further comprises at least one bare electrode and/or at least one second film-coated electrode that is different from the first film-coated electrode, wherein each film coated electrode is partially selective and can cross-react with multiple redox molecules; a potentiostat or galvanostat to which the electrodes are electrically connected to allow control of the potential or current of the working electrodes, respectively, to create a data set of electrochemical signals when the electrodes are immersed in a sample; and a processor configured to analyze the data set of electrochemical signals by one or more chemometric techniques. ### Claim 20 (depends on 19) A device according to claim 19, comprising the potentiostat, the potentiostat being configured to record current signals measured by voltammetry. ### Claim 21 (depends on 20) A device according to claim 20, wherein the one or more chemometric techniques include a regression method, a supervised or unsupervised machine learning algorithm, or both. ### Claim 22 (depends on 21) A device according to claim 21, wherein the regression method is partial least square regression (PLSR). ### Claim 23 (depends on 21) A device according to claim 21, wherein the supervised machine learning algorithm is a trained artificial neural network (ANN). ### Claim 24 (depends on 20) A device according to claim 20, wherein the processor is configured to reduce the dimensions of the data set by extracting electrochemical features recorded by voltammetry of a biofluid sample. ### Claim 25 (depends on 19) A device for electrochemical detection according to claim 19, wherein the array of working electrodes comprises the one or more bare electrodes. ### Claim 26 (depends on 25) A device for electrochemical detection according to claim 25, wherein the first film-coated electrode is coated with a chitosan film. ### Claim 27 (depends on 25) A device for electrochemical detection according to claim 25, wherein the array of working electrodes further comprises the at least one second film-coated electrode, each second film-coated electrode being a conductive additive-incorporated film-coated electrode. ### Claim 28 (depends on 27) A device for electrochemical detection according to claim 27, wherein each second film-coated electrode is coated with a carbon nanotubes-incorporated chitosan film. ### Claim 29 (depends on 27) A device for electrochemical detection according to claim 27, further comprising one or more reduced graphene oxide-coated electrodes.