WO2024096729A1 - Appareil de détection de biomarqueurs à partir d'une biomolécule - Google Patents

Appareil de détection de biomarqueurs à partir d'une biomolécule Download PDF

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Publication number
WO2024096729A1
WO2024096729A1 PCT/MY2023/050088 MY2023050088W WO2024096729A1 WO 2024096729 A1 WO2024096729 A1 WO 2024096729A1 MY 2023050088 W MY2023050088 W MY 2023050088W WO 2024096729 A1 WO2024096729 A1 WO 2024096729A1
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WO
WIPO (PCT)
Prior art keywords
biomolecule
electrodes
biomarkers
analytes
printed circuit
Prior art date
Application number
PCT/MY2023/050088
Other languages
English (en)
Inventor
Vengadesh Periasamy
Sara TALEBI
Gnana kumar GEORGEPETER
Original Assignee
Universiti Malaya
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universiti Malaya filed Critical Universiti Malaya
Publication of WO2024096729A1 publication Critical patent/WO2024096729A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/48785—Electrical and electronic details of measuring devices for physical analysis of liquid biological material not specific to a particular test method, e.g. user interface or power supply

Definitions

  • the present invention relates to an apparatus for detecting biomarkers from biomolecule, more particularly an apparatus for detecting various types of analytes present in body fluids.
  • wearable biosensors have been receiving considerable attention due to their potential in clinical and physiological applications. Despite significant progress made in printed and flexible biosensors in the field, a majority of wearable devices focus on monitoring of the physical activities or major electrophysiological parameters and provide very limited information regarding physiological changes of our complex biological systems. Typically, wearable electrochemical sensors are able to measure the chemical compositions in body fluid at a molecular level, which further allows accurate measurement of biomolecules including sweat analytes through signal processing and calibration. However, it still is a challenge for conventional wearable biosensors to enable sufficient sweat extraction to provide accurate results pertaining to the various analytes within sweat.
  • a wearable sweat monitoring sensor which comprises a bonding layer, an electrochemical sensor electrode layer, and a microfluidic structure layer, whereby the top of the bonding layer is connected with the electrochemical sensor electrode layer, and the bottom of the bonding layer is bonded with the user’s skin.
  • a first through hole is formed in the bonding layer to receive sweat such that the electrochemical sensor electrode layer is able to detect analytes in the sweat upon receiving the sweat.
  • An international patent application WO2017192836A1 recites a potentiometric sensor that includes a housing and working electrode.
  • the housing includes a reference electrode, a first hydrogel that contains a reference solution, and a salt bridge. Further, the sensor is wearable and can be used for continuous on-body sweat measurements.
  • Another international patent application WO2021216614A1 discloses a microfluidic patch that allows continuous analysis of natural sweat at various body locations of sedentary individuals, whereby the path provides integrated electrical sweat rate sensor and electrochemical sensors to enable simultaneous detection of sweat rate and compositions such as pH, Cl, and levodopa.
  • Another technology as disclosed in a United States patent application with publication no. US20180070870A1 discloses a device for on-demand sweat extraction and analysis which comprises a microcontroller, an iontophoresis circuit, a sensing circuit, and an electrode array having electrodes for sweat induction and sweat sensing.
  • An object of the present invention is to establish a database of electrochemical signatures of various types of analytes present in biomolecule including body fluid such as blood, sweat, urine, tears and saliva, which would enumerate the fast sensing and significantly limit the sample volume. It is also an object of the present invention to substantially reduce diagnostics cost in terms of analysing the analytes present in biomolecule using a drastically reduced sample size. Further an objection of the present invention is to provide a miniaturized universal electrochemical sensor for detecting the fingerprint electrochemical signatures of the variant constituents of biomolecules including lactate, urea, glucose, betaine, ammonia, and chloride, sodium and potassium ions by placing the sample biomolecule on the printed circuit board.
  • the sensor being the apparatus for detecting the biomarker of biomolecule is sensitive and allows selective sensing.
  • the biomolecule can be collected directed on the sensor that enables instant detection of the biomarker. It is also an object of the present invention to allow the sensor to be inserted into or connected to a device that further processes or analyses the detected biomarker.
  • the sensor can be disposed after each detection.
  • an apparatus for detecting biomarkers from biomolecule comprising a printed circuit board having three electrodes for sensing analytes in the biomolecule that define the biomarkers; wherein the printed circuit board is formed with a gap where the biomolecule is collected thereon, and where the electrodes are exposed to for detecting the biomarkers from the biomolecule.
  • the electrodes are made of a same metallic material.
  • the electrodes include a reference electrode, and a counter electrode and a working electrode.
  • the electrodes are evenly spaced apart with a gap of 2.00mm to 4.00mm.
  • the biomolecule is body fluid including any one of sweat, blood, urine, tears, or saliva.
  • the analytes in the biomolecule include any one or a combination of lactate, urea, glucose, betaine, ammonia, and mineral ions.
  • the apparatus is connected to a device which analyses the analytes in the biomolecule upon detection.
  • a system for detecting biomarkers from biomolecule comprises an apparatus including a printed circuit board having three electrodes for sensing analytes in the biomolecule that define the biomarkers; and a device connected to the apparatus which analyses the analytes in the biomolecule upon detection of the biomarkers; wherein the printed circuit board is exposed to for detecting the biomarkers from the biomolecule.
  • the device is configured to allow the apparatus to be inserted therein to establish connection with the device for sending information about the detected biomarker to the device to analyze.
  • FIG. 1 illustrates a preferred embodiment of an apparatus for detecting biomarkers from biomolecule.
  • FIG. 2 is a flowchart illustrating a pre-treatment or cleaning procedure of electrodes of the apparatus prior to usage.
  • FIG. 3A illustrates an exemplary embodiment of a cyclic voltammetry profile of a bare working electrode as a function of sweep rates.
  • FIG. 3B illustrates an exemplary embodiment of the cyclic voltammetry profile of the working electrode when in contact with the biomolecule.
  • FIG. 1 illustrates a preferred embodiment of an apparatus for detecting biomarkers in biomolecule, comprising a printed circuit board 100 three electrodes lOlfor sensing analytes in the biomolecule.
  • the biomolecule is body fluid that can be either sweat, blood, urine, saliva or tears.
  • the printed circuit board 100 is formed with a recess 105where the biomolecule is disposed and collected thereon.
  • the electrodes may be made from a same metallic material, and is preferably gold due to its electrochemical inertness.
  • the polarization of the electrodes 101 often results in significant potential drops that reduces the sensitivity on analyte detection in the biomolecule, thereby the electrodes 101 of the same material would avoid electrode polarization at an electrode-electrolyte interface.
  • the analytes include any one or a combination of lactate, urea, glucose, betaine, ammonia and mineral ions.
  • the apparatus is a portable and miniature in size.
  • the apparatus is a chip that can be attached to any parts of the body of a user for collection of the biomolecule in the recess 105 and then detection of the biomarker. After usage of the apparatus, it can be disposed.
  • the apparatus may be made in a size and form that allows it to be insertable into a device for the device to read data from the apparatus which includes information of the detected biomarker.
  • the device can be a device that further processes the data or analyses the data.
  • the printed circuit board lOOof the apparatus comprises one or more electrodes lOlwhich include a reference electrodelOla, a counter electrodelOlb, and a working electrodelOlc.
  • the electrodeslOl comprises a plurality of rectangular padslOla, 102b, 102c representing the reference electrodelOla, the counter electrodelOlb and the working electrode lOlrespectively.
  • the first padsl02a, 102b, 102c are rectangular and dimensioned at 3.00 mm x 4.00 mm, with each first pad 102a, 102b, 102cof the electrodes lOlbeing evenly spaced apart with a gap in between of 2.00mm to 4.00mm, but is most preferred to be spaced at 3.00mm apart between two adjacent first padsl02a, 102b, 102c.
  • each first pad 102a, 102b, 102c of the electrodes is connected to an electronic trace, whereby the tip of the trace is provided with a second pad which is preferably square with a dimension of 0.70mmx0.70mm.
  • the pads at the tip of the traces are evenly spaced apart with a gap of 0.40mm to 0.60mm, and most preferably spaced apart with a gap of 0.50mm.
  • the traces 104 have a width of between 0.60mm and 0.80mm, but is most preferably etched with a 0.70mm width.
  • Therecessl05 is formed with a solder mask where the tips of the traces including the second pads at the tips are within the territory of the recess 105.
  • the recess allows the biomolecule collected from the body of a user to be disposed thereon for the electrodes 101 to be in contact with the biomolecule and perform detection of the analytes from the biomolecule.
  • the electrodeslOl are pre-treated or cleaned prior to usage.
  • the electrodes lOl may undergo a process of sonication using acetone and are washed with deionized water thereafter, in which the deionized water, also known as DI water, is purified water with shallow ion content, meaning it does not contain any minerals such as sodium or potassium ions in the form of salts, at Step 201 and Step 202 respectively.
  • Sonication is a process of cleaning printed circuit boards lOOto remove solder paste and flux residue, thereby increasing reliability of the printed circuit board lOOwhen analysing the analytes in the biomolecule which is in the form of a fluid.
  • the working electrodelOlc may be fully pre-treated or cleaned to enhance the detection and analysis of the analytes in the biomolecule when submerged in the reference solution 106 thereafter, as illustrated in FIG. 3.
  • a system for detecting biomarkers from biomolecule comprises the apparatus that is connected to a device which analyses the analytes in the biomolecule upon detection by the electrodes 101.
  • the device which can be a potentiostat that functions by maintaining a potential of the working electrode lOlcat a constant level with respect to the reference electrodelOla by adjusting current at the counter electrodelOlb, which is also known as an auxiliary electrode.
  • the device is configured to receive the apparatus through having a port where the apparatus is inserted thereto to establish communication with the device such that information of the detected biomarker from the apparatus can be sent to the device. Therefore, it is preferred that the apparatus is portable and miniature in size.
  • the apparatus is a chip that can be attached to any parts of the body of a user for collection of the biomolecule in the recess 105 and then detection of the biomarker. Upon collection of the biomolecule and detection of the biomarker, the apparatus can be inserted into the device for analysis to be carried out on the biomarker.
  • the device may be connected to a computing device that is part of the system.
  • the computing device is linked to a database to allow storage of data relating to the detected analytes.
  • the database stores the analysis results regarding the electrochemical signatures of various types of analytes present in the biomolecule.
  • the computing device is also provided with a graph generating module to generate graphs based on the information of the biomarkers and analysis results from the device. Examples of graphs are illustrated in FIG.
  • 3A and 3B that shows analysis regarding the potential of the working electrodelOlc against input current
  • the analysis of the analytes in the biomolecule being sweat utilizes a method known as voltammetry to obtain information of the various analytes present in the sweat by measuring the current as the potential of the working electrodelOlc is varied, particularly half-cell reactivity of any one of the analytes being measured.
  • analytical data from the device being the potentiostat comes in a form of a voltammogram which plots the current produced by any one of the analytes versus the potential of the working electrodelOlc, which can be seen in FIG.
  • FIG. 3A as a cyclic voltammetry profile of a bare working electrode 101b as a function of sweep rates, in which the graph shows a consistent profile for each sweep rate applied.
  • FIG. 3B illustrates an example of the cyclic voltammetry profile of the working electrodelOlb when in contact with the sweat, also as the function of sweep rates.
  • the computing device is provided with a display to show the generated graphs and analysis results of the biomarkers through computer software programmes.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention concerne un appareil de détection de biomarqueurs à partir d'une biomolécule, comprenant une carte de circuit imprimé (100) comportant trois électrodes (101) constituées du même matériau métallique servant à détecter des analytes dans la biomolécule qui définissent les biomarqueurs ; la carte de circuit imprimé (100) présentant un espace (105), la biomolécule étant collectée sur celui-ci, et les électrodes (101) y étant exposées afin de détecter les biomarqueurs à partir de la biomolécule.
PCT/MY2023/050088 2022-11-01 2023-10-31 Appareil de détection de biomarqueurs à partir d'une biomolécule WO2024096729A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
MYPI2022006111 2022-11-01
MYPI2022006111 2022-11-01

Publications (1)

Publication Number Publication Date
WO2024096729A1 true WO2024096729A1 (fr) 2024-05-10

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009034284A1 (fr) * 2007-09-05 2009-03-19 Lifescan Scotland Ltd Bandelette pour dispositif de mesure électrochimique
WO2011144904A1 (fr) * 2010-05-19 2011-11-24 Lifescan Scotland Limited Bande de test analytique comportant une électrode ayant des zones électrochimiquement actives et inertes d'une taille et d'une distribution prédéterminées
KR101531384B1 (ko) * 2013-07-02 2015-06-24 주식회사 인포피아 바이오센서용 시약조성물 및 이를 포함하는 바이오센서
WO2017085280A1 (fr) * 2015-11-19 2017-05-26 Roche Diabetes Care Gmbh Détecteur et ensemble de détection pour détecter un analyte dans un liquide corporel
KR20210042486A (ko) * 2019-10-10 2021-04-20 숭실대학교산학협력단 전기화학적 혈당센서 및 그 제조방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009034284A1 (fr) * 2007-09-05 2009-03-19 Lifescan Scotland Ltd Bandelette pour dispositif de mesure électrochimique
WO2011144904A1 (fr) * 2010-05-19 2011-11-24 Lifescan Scotland Limited Bande de test analytique comportant une électrode ayant des zones électrochimiquement actives et inertes d'une taille et d'une distribution prédéterminées
KR101531384B1 (ko) * 2013-07-02 2015-06-24 주식회사 인포피아 바이오센서용 시약조성물 및 이를 포함하는 바이오센서
WO2017085280A1 (fr) * 2015-11-19 2017-05-26 Roche Diabetes Care Gmbh Détecteur et ensemble de détection pour détecter un analyte dans un liquide corporel
KR20210042486A (ko) * 2019-10-10 2021-04-20 숭실대학교산학협력단 전기화학적 혈당센서 및 그 제조방법

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