WO2019069109A1 - Dispositif biocapteur et procédé de mesure de glucose de manière non invasive - Google Patents

Dispositif biocapteur et procédé de mesure de glucose de manière non invasive Download PDF

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WO2019069109A1
WO2019069109A1 PCT/IB2017/001209 IB2017001209W WO2019069109A1 WO 2019069109 A1 WO2019069109 A1 WO 2019069109A1 IB 2017001209 W IB2017001209 W IB 2017001209W WO 2019069109 A1 WO2019069109 A1 WO 2019069109A1
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glucose
biosensor
working electrode
measurement
template
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David SHIMOMOTO-SANCHEZ
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1477—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means non-invasive
    • 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

Definitions

  • the present invention is related to the principles and techniques of the
  • Iontophoresis is a technique that facilitates the delivery of drugs through the skin, by applying a small current and a small voltage to an anode and a cathode, which in turn form an electric field.
  • This technique also serves to extract analytes from the skin of an individual's body and is known as reverse iontophoresis.
  • the reverse iontophoresis generates movement of neutral and positive charges towards the cathode, while the negative ones move towards the anode, that is to say the molecules that are not charged are dragged towards the cathode by the anions.
  • This technique is currently implemented in devices in order to extract the glucose that is in the interstitial fluid of the skin, for which the current that is applied between two printed electrodes is 0.2 mA or more.
  • the traditional glucometers make the measurements through an electro-enzymatic means, that is they make use of an enzyme to generate different products.
  • the enzyme glucose oxidase catalyzes the reaction of glucose with molecular oxygen, which causes an increase in pH, low concentration of molecular oxygen by its consumption, and production of hydrogen peroxide as a by-product.
  • test strips are used, which are elongated rectangles made of plastic, which work in a similar way to microchips, with sensor bars at one end to determine the sugar level contained in the blood of a user just by placing a drop of capillary blood in it and then entered in a glucometer to visualize the level of glucose contained in the blood.
  • One end of the strip contains an enzyme called glucose oxidase that, upon contact with the glucose in the blood sample, undergoes a change that is subsequently translated as an electrochemical reaction that generates a very small discharge of low intensity electric current. , that the glucometer interprets and shows how the sugar or glucose level is expressed in the mg / dl unit.
  • glucose oxidase that, upon contact with the glucose in the blood sample, undergoes a change that is subsequently translated as an electrochemical reaction that generates a very small discharge of low intensity electric current.
  • test strips measure changes in one or several intervals and present a three-electrode design, which is composed of:
  • An approximate voltage of -0.4 V is applied to the reference electrode.
  • the blood touches the test strip it is absorbed by capillarity, generating a small current related to the concentration of glucose.
  • the signal generated by the test strip is a current that represents the concentration of glucose. This current is then converted to voltage, using a current-to-voltage converter, which is also filtered for better signal processing.
  • the non-invasive glucose biosensor of the present invention was developed.
  • Glucotrack of Israeli origin, which is intended for adults (over 18 years old), type 2 diabetics and pre-diabetics. This device is in the process of being registered, so it is not yet available for sale to the public.
  • Non-invasive glucose biosensor is the Symphony device, which is a meter that allows continuous monitoring of glucose in blood in healthy patients, or Type I or Type II diabetics.
  • This device is of American origin, is intended for adults (over 18 years), diabetics type I and type II and is comprised of a glucose biosensor, an App to be used in a smartphone and / or smartwatch and a skin scrub. The company started in 2007 and still do not have any commercially available device.
  • GlucoWatch currently under development, has been identified in the state of the art.
  • the device consists of a bracelet for the measurement of glucose in a non-invasive way, which uses the reverse iontophoresis technique to extract glucose through the skin to control glycaemia in diabetes.
  • Said glucose meter is an advantage over conventional blood glucose monitoring which requires an invasive daily measurement using a lancet.
  • patent application KR20030047971 A discloses a biosensor that employs a new penetration method in the skin, which can measure and utilize the concentration of glucose extracted from a body while minimizing pain.
  • the invention relates to a proposal and an evaluation of the performance of a biosensor of the continuous use type, capable of extracting and analyzing efficiently Glucose molecules in the body through skin tissues in a short time, using a reverse osmosis method.
  • the penetration-type biosensor of the skin is divided into three parts: 1) an extraction electrode (EE) to apply a fine continuous current through the skin tissue to extract glucose molecules by reverse osmosis; 2) a second electrode that has good adhesion with the skin (direct contact), between the skin and the extraction electrode is placed a hydrogel of an electrolytic material that suppresses the irritation of the skin caused by electricity, since the hydrogel can contain glucose oxidase (GOx), acts as a reaction medium that converts intermolecular glucose glucose molecules extracted from skin tissue into substances that generate signals such as hydrogen peroxide (H2O2); and, 3) a working electrode (WE), to measure the electrons emitted when the hydrogen peroxide molecule is electrochemically oxidized.
  • the technique described in the document entitled "A stretchable and screenprinted electrochemical sensor for glucose determination in human perspiration, Biosensors and Bioelectronic, Bbios.2017.01.058” (Abellán-Llobregat, et al.)
  • a biosensor device glucose consisting of two types of totally printable, highly stretchable and economical devices, based on graphite decorated with platinum (Pt) for the determination of glucose in physiological fluids.
  • Said devices are: a non-enzymatic sensor and an enzymatic biosensor.
  • Glucose has been quantified by reduction of peroxide (H2O2) by chronoamperometry at -0.35 V (vs pseudo Ag / AgCI) using glucose-oxidase immobilized in graphite decorated with Pt.
  • the sensor works well for glucose quantification in buffer solution of phosphate (0.25 M PBS, pH 7.0), with a working range between 33 ⁇ and 0.9 mM, high sensitivity and selectivity, and low detection limit (LOD). Therefore, it provides a non-invasive alternative form of quantification of glucose levels in human transpiration.
  • This biosensor has been applied successfully in real samples of human transpiration and the results also show a significant correlation between the concentration of glucose in perspiration and the concentration of glucose in the blood measured by a commercial glucose meter.
  • said biosensor uses Prussian Blue ink as an ink that generates a conductive surface which is printed on the template by a curing step with the electrodes to carry out the desired determination of the biosensor.
  • the measurement of glucose is carried out by means of an extraction through the iontophoresis technique, without the use of Prussian blue; and, the electrochemical analysis is carried out through a biosensor, which detects glucose levels in the interstitial fluid between the skin cells of an individual, in particular a person.
  • the objective of the present invention is to provide a biosensor device that allows the measurement of glucose in an individual non-invasively, without the need to prick a finger or any other part of the body of the individual, to obtain a blood sample which is then analyzed by carrying out a measurement from an electrochemical measurement on the surface of the individual's skin, using a glucose measurement biosensor mounted on a template.
  • the device of the present invention basically comprises a primary working electrode, composed of single-walled nanotubes with copper nanoparticles covalently linked and which are embedded in a polymer that can be of chitosan; a secondary working electrode composed of ink containing nitrogen-doped nanotubes embedded in a polymer that can be chitosan; a counter-electrode composed of ink containing nitrogen-doped nanotubes embedded in a polymer that can be chitosan; a reference electrode, composed of silver ink - commercial silver chloride from Ercon Inc. -; and, two iontophoresis electrodes for the extraction of glucose; wherein all the electrodes are printed on a substrate which may be a polyimide or a textile material.
  • the present device applies a current on the surface of the skin, in order to initiate the process of reverse iontophoresis, by which the analyte (glucose) is obtained through an electroosmotic flow, ie, ions that transport glucose to the surface, which interacts with the electrode ink where nanotubes are doped with nitrogen and nanotubes doped with copper particles.
  • analyte glucose
  • ie electroosmotic flow
  • the contact of the extracted glucose with the ink of the electrode generates an electrical response that is measured in the main circuit of the biosensor, generating a response that is detected and quantified by an electrochemical technique called time curve vs. amperometric current or also known as chronoamperometry .
  • the technical problem that solves the device and method of this invention is to provide a non-invasive, reliable and efficient glucose measurement biosensor based on a glucose detection method utilizing nitrogen-doped nanotubes and single-walled nanotubes with copper nanoparticles covalently linked.
  • an object of the present invention is to provide a device for measuring glucose in a non-invasive manner, which allows the determination of the blood glucose concentration of an individual, without the need to take the sample with a lancet, for get a drop of blood.
  • a further object of the present invention is to provide a biosensor device for the measurement of glucose in a non-invasive manner, which allows to determine the blood glucose concentration of an individual, in a fast, practical and simple manner.
  • Another object of the present invention is to provide a method for measuring glucose in a non-invasive manner, which employs reverse iontophoresis and a plurality of electrodes mounted on a substrate to effect the measurement.
  • FIG. 1 shows a biosensor device for non-invasively measuring glucose, constructed in accordance with a preferred embodiment of the present invention, which employs a template with two printed biosensor elements.
  • Figure 2 shows a top view of the template with two biosensor elements printed thereon.
  • Figure 3 shows a first embodiment of the biosensor element for glucose measurement, which includes two working electrodes.
  • Figure 4 shows a second embodiment of the biosensor element for the glucose measurement, which includes a single working electrode.
  • Figure 5 shows a schematic diagram of the method of operation of the device for non-invasively measuring glucose of the present invention.
  • Figures 6A and 6B show the results obtained when using the device for glucose measurement in a non-invasive manner shown in Figure 2.
  • Figure 6A the amperometries of 0, 1 and 2 hours after ingesting 75g of glucosam while in Figure 6B a comparative analysis of the detected value with the biosensor of the present invention with respect to the measurement obtained with a traditional glucometer is shown.
  • Figures 7A and 7B show the results obtained by using the device for glucose measurement in a non-invasive manner shown in Figure 4.
  • Figure 7A the amperometries of 0, 1 and 2 hours after ingesting 75g of glucose are observed.
  • glucose while in Figure 7B a comparative analysis of the detected value with the biosensor of the present invention is shown with respect to the measurement obtained with a traditional glucometer.
  • FIG. 8 schematically illustrates the operation of the non-invasive glucose measurement device of the present invention, wherein step 801 is to initiate the application on the electronic device that will display the graph of measurement results, where the application sends the start signal to the next module that is a minicomputer called Beaglebone, in step 802, the Beaglebone transmits the start signal to the module called Control Electronics, which is a switch type element with the on / off function only, whereby, in step 803, the electrical signal is sent to the template where the electrodes that perform the glucose measurement are located.
  • step 801 is to initiate the application on the electronic device that will display the graph of measurement results, where the application sends the start signal to the next module that is a minicomputer called Beaglebone
  • the Beaglebone transmits the start signal to the module called Control Electronics, which is a switch type element with the on / off function only, whereby, in step 803, the electrical signal is sent to the template where the electrodes that perform the glucose measurement are located.
  • the template performs the steps of glucose extraction and measurement in step 804, sending back a voltaic signal to the control Electronics once the measurement is completed in step 805, the control electronics receives the signal back from the template and sends it back to the Beaglebone in step 806. Subsequently, the Beaglebone processes and normalizes the signal from the control electronics in step 807 and then sends it to the application, where the data they are received and shown in graphical form, also giving the result of the measurement in mg of glucose per deciliter in step 808.
  • a device 100 for glucose measurement in a non-invasive manner constructed in accordance with the principles of the present invention.
  • the device 100 in the manner described, comprises an information processing module 101 that incorporates a screen for displaying information; a wrist-type fastener element 102, for attaching to the extremity of an individual, where the information processing module 101 is placed on its external face with the display for displaying information; and, a template 103 including at least one glucose biosensor element 200, which is located on the internal face of the fastener element 102, on the side opposite the processing module.
  • the processing module 101 includes in addition to the display for displaying information, a central processing unit that allows to execute the instructions of the software that uses the biosensor element 103, to be able to perform the measurement of the glucose and its subsequent deployment of the results in the screen.
  • the fastener element 102 consists of a tape of polymeric material (bracelet type), so that when the device 100 is in use, it is firmly attached to the extremity of an individual, preferably on the wrist of a user.
  • the polymeric material used in the bracelet is preferably a hypoallergenic plastic material, with a firmness that allows to hold on one side the screen to display information (external face) and on the opposite side (internal face), the template 103 for glucose measurement.
  • the biosensor element 200 shown in Figures 2 and 3, consists of a first working electrode 201, which is printed on the template 103 by a screen printing process, consisting of single-walled nanotubes with copper nanoparticles covalently bonded and which are embedded in a polymer selected from chitosan, styrene butadiene rubber, ethyl cellulose polymer, among others, preferably using chitosan; a counter electrode 202, printed on the template 103 also by a screenprinting process, wherein the ink that is printed on the template contains nitrogen-doped nanotubes embedded in a polymer selected from chitosan, styrene butadiene rubber, ethylcellulose polymer, among others , preferably using chitosan; a second working electrode 203, printed on the template 103 also by a screenprinting process, wherein the ink that is printed on the template contains nitrogen-doped nanotubes embedded in a polymer selected from chito
  • the biosensor element 300 shown in Figure 4 consists of a first working electrode 301, which is printed on the template 103 by a screen-printing process, consisting of single-walled nanotubes with copper nanoparticles covalently linked and which are embedded in a polymer selected from chitosan, styrene butadiene rubber, ethyl cellulose polymer, among others, preferably using chitosan; a counter electrode 302, printed on the template 103 also by a screenprinting process, wherein the ink that is printed on the template contains nitrogen-doped nanotubes embedded in a polymer selected from chitosan, styrene butadiene rubber, ethylcellulose polymer, among others , preferably using chitosan; a reference electrode 303, printed on the template 103 also by a screen printing process, formed by a support based on Ag-AgCI (silver-silver chloride) ink; and, a glucose extraction electrode 304
  • the electrodes of the biosensor element 200 of the device 100 of the present invention are printed as already mentioned, in the template 103 formed by a substrate that can be a polyamide or a textile material.
  • an ink is obtained that can be printed by means of screen printing.
  • the secondary working electrode contains carbon nanotubes doped with nitrogen where the detection of hydrogen peroxide that occurs in the primary working electrode is carried out.
  • CNx-MWCNT nanotubes doped with nitrogen
  • benzylamine C7H9N
  • ferrocene (CsHs ⁇ Fe)
  • 10 ml of ferrocene are used with 2.5% of benzylamine; which is used is iron, which acts as an initiator of root growth and is found in the ferrocene molecule.
  • the synthesis method used is chemical vapor deposition (CVD).
  • the method of the present invention is based on the chemical reaction of the breakdown of the glucose molecule that generates hydrogen peroxide, which is measured in the working electrodes, which allows the detection of glucose.
  • the measurement of glucose in the skin of a user, using the device 100 of the present invention, is based on the extraction of the interstitial fluid found in the skin.
  • the interstitial fluid is a liquid that surrounds the cells that in turn form the tissues; in the particular case, said interstitial fluid is analyzed on the surface of the user's skin, where the extraction is made.
  • the extraction is done through the reverse iontophoresis technique, which is based on applying a stable current between the terminals of the extraction electrode that are in contact with the skin.
  • the extraction consists of applying a current that can vary depending on:
  • the values of the current extraction range from 200 micro-amperes to 2,000 micro-amperes, it being understood that it is the adequate current to carry out the extraction without causing any adverse effect on the user.
  • the biosensor element 200 as already mentioned, in a first embodiment has the particularity of including first and second working electrodes, 201 and 203 respectively, a counter-electrode 202, a reference electrode 204 and an extraction electrode. 205, wherein the following is carried out: a) the reaction for obtaining glucose from the interstitial cellular fluid; b) the breakdown of glucose molecules present in the fluid; and, c) the subsequent measurement of the byproduct of glucose breakdown, such as hydrogen peroxide.
  • the first working electrode 201 has the particularity of having single-walled carbon nanotubes (SWCNT), where the synthesis of single-walled carbon nanotubes with copper nanoparticles is carried out through a hydrothermal synthesis.
  • SWCNT single-walled carbon nanotubes
  • the biosensor element 300 has the particular feature of including a single working electrode 301, a counter-electrode 302, a reference electrode 303 and an extraction electrode 304.
  • the glucose measurement method of the invention is generally carried out by means of a biosensor device 100 for measuring glucose in a non-invasive manner and employing two working electrodes (mode 1), or well, a single working electrode (mode 2), said method comprising the following general steps:
  • (501) apply agarose hydrogel containing PBS buffer, on the external surface of a user's skin and place on it, a device 100 for the measurement of glucose non-invasively, so that the template 103 that includes at least one biosensor element 200, is in direct contact with the skin of the user, so that at least one voltage measurement is carried out;
  • (501) apply agarose hydrogel containing PBS buffer, on the external surface of a user's skin and place on it, a device 100 for the measurement of glucose non-invasively, so that the template 103 that includes at least one biosensor element 200, is in direct contact with the skin of the user, so that at least one voltage measurement is carried out;
  • the working electrode 301 (Potentiostat 1) of the biosensor element 200, wherein the working electrode 301 comprises nitrogen nanotubes doped with nitrogen and also comprises the enzyme glucose oxidase responsible for carrying out the glucose break in the same working electrode.
  • GlucoseValue (pot2Value + 11.42) / 0.832) * 18 Obtaining in this way a graph of the glucose measurement as well as a numerical result of the concentration of glucose in the subject expressed in milligrams per deciliter (mg / dL), which allows give a numerical result representative of the glucose concentration in the user.
  • Biosensor device
  • the biosensor device for the non-invasive measurement of glucose of the present invention is capable of being operated from a software application (App) through a visible graphic interface, whether in a computer, Smartphone, Tablet or any other electronic device that is capable of generating a graphical interface visible on a screen.
  • App software application
  • visible graphic interface whether in a computer, Smartphone, Tablet or any other electronic device that is capable of generating a graphical interface visible on a screen.
  • the App allows you to start a measurement by sending a start instruction that is processed and sent from the device where the user interface is displayed, so that once the process is started, the electronic board of the biosensor is turned on, once it is turned on , sends an electrical signal to the biosensor template; wherein the template contains the electrodes where the detection method of the present invention is carried out, said electrodes fulfill the function of extracting glucose from the interstitial space between the cells of the epidermis, as well as the function of breaking said glucose obtained and subsequently measure the concentration of the hydrogen peroxide molecule resulting from said breakdown of the glucose molecule.
  • the output electrodes send back a signal to a biosensor module in charge of pre-processing the hydrogen peroxide measurement signal before converting said signals into numerical data that are then sent to the user interface software, where the return values obtained from the measurement made in the template, are plotted to obtain a blood glucose concentration value in a patient with total absence of the technique of pricking a finger to get a drop of blood.
  • the biosensor element of the present invention provides a user interface module that allows the execution of the software application to carry out the measurement.
  • the App receives the information from the measurement, processes it and stores it, and then generates a graph, where the final calculation of the user's glucose measurement is carried out.
  • FIG. 8 it schematically shows the operation of the device 100 for non-invasively measuring glucose of the present invention
  • the user of the device gives instruction 801 from the application for the start of the measurement once the template has been placed in contact with the skin, whereby the start signal is sent to the next module 802 called Beaglebone, which is a mini computer, whose functions are to receive the signals of the beginning of the measurement, as well as to receive the electrical signals resulting from the measurement made in the template, said signals are normalized and converted into data that are sent back to the application.
  • Beaglebone which is a mini computer, whose functions are to receive the signals of the beginning of the measurement, as well as to receive the electrical signals resulting from the measurement made in the template, said signals are normalized and converted into data that are sent back to the application.
  • control electronics which is a switch type controller with on / off functions.
  • first and second work electrodes are arranged in the first mode, and a single working electrode in the second mode, as well as a counter-electrode operating with the first working electrode, an extraction electrode and a reference electrode, by means of which the extraction of glucose is carried out, the measurement of the concentration value thereof and the emission of an electrical signal 805 back to the control electronics module 803.
  • the control electronics 803 receives the signal 805 from the template and forwards it 806 to the beaglebone module 802, where the resulting electrical signals are received, which must be normalized 807 and converted into data before the beaglebone sends the data of the measurement to the user interface, where the software immediately processes the received data and produces a graph where the value of the glucose determination is indicated for quick reading by the user when providing a graph 808 with the information of the measurement as a numerical value expressed in milligrams per deciliter.
  • the operation of the template is described below, which is where the glucose concentration detection of the user is carried out.
  • the template of the biosensor device of the present invention contains inkjet printed electrodes, the technique of which is to pass a conductive ink through a template and deposit it on a flat substrate after baking.
  • the template is made of stainless steel and this makes the electrode acquire a desired shape and thickness.
  • own inks are used for each variant of the biosensor, so there are electrodes with nanotubes doped with nitrogen, with single-walled nanotubes and with commercial silver-silver-chloride ink.
  • the template is configured to carry out the technique of transduction in biosensors based on electrochemistry, in particular, the cyclic voltammetry is used, which consists of an arrangement of three electrodes bearing the name: working electrode, reference electrode and auxiliary electrode .
  • the working electrode is in contact with the analyte and it must apply a potential in a controlled manner and with easy electron transfer
  • the reference potential is a cell that has a known reduction potential, that is, it controls the potential of the working electrode more electrons do not pass in this.
  • the auxiliary electrode all the current passes to balance the current observed in the working electrode.
  • the chemical reaction by which it is possible to determine the glucose concentration is a reaction of glucose oxidation by the enzyme glucose oxidase, where the breakdown of glucose generates hydrogen peroxide (H2O2) and gluconic acid (C6H12O7).
  • H2O2 hydrogen peroxide
  • C6H12O7 gluconic acid
  • the extraction of the interstitial fluid is carried out by the reverse iontophoresis method, which is achieved by applying the previously described current to the skin of the individual in a superficial and non-invasive manner; Once the biosensor patch is placed, the glucose measurement is carried out in a time that varies from individual to individual, since the extraction time is a factor that directly depends on the hydration, conductivity and heart rate of the user. why this has observed that the glucose measurement varies between 3 and 10 minutes.
  • Vs time curve amperometric current also known as amperometry.
  • the glucose is extracted by applying a current of between 200 ⁇ and 2000 ⁇ for a period of between 3 and 10 minutes.
  • a potential is set between the reference electrodes, counter electrode and working electrode 1 of single-walled nanotubes with copper nanoparticles (SWNCT / CuNp) of between 0.4 and 0.6 (0.46V) volts for 1 minute using the amperometric technique , this reaction will generate hydrogen peroxide.
  • SWNCT / CuNp copper nanoparticles
  • a potential is set between the reference electrodes, counter electrode and working electrode 2 (carbon nanotubes doped with nitrogen) of 0.4 volts to detect an oxidation and one between 0.1 and 0.06 volts to detect a reduction if it is used either of doping with nitrogen.
  • a graph of amperometry related to hydrogen peroxide is generated which indicates the concentration of glucose in micro amperes, by means of a calibration curve the equivalent to milligrams per deciliter is obtained.
  • a template having a single working electrode, a counter electrode, a reference electrode and an extraction electrode.
  • the enzyme glucose oxidase is integrated, whose functions are to decompose the glucose molecule and subsequently, the working electrode determines the amount of hydrogen peroxide resulting from said glucose breakage, where the second embodiment of the invention measures the reduction or dismutation of hydrogen peroxide in order to generate an electrical signal that can be processed and graphed as well as being able to provide a user glucose concentration data in mg / dL.
  • the measurement made with the second embodiment of the biosensor device generates electrical current data that is directly related to the glucose concentration, by means of an algorithm that integrates the cardiac rhythm variable, skin conductivity, skin sweat, step counter and pH.
  • the second embodiment of the invention is based on a single working electrode, in addition to containing carbon nanotubes doped with nitrogen that allow determine the amount of peroxide resulting from the breakdown of glucose, said break is carried out in the same working electrode by the inclusion of the enzyme glucose oxidase, capable of breaking the glucose molecule in situ, so that the need to a second working electrode.
  • Anti-electrode composed of ink of nanotubes doped with nitrogen embedded in a polymer, preferably chitosan.
  • Work Electode composed of ink of nanotubes doped with nitrogen embedded in a polymer, preferably chitosan and also a single wall nanotube ink with copper nanoparticles.
  • Reference electrode composed of silver ink - commercial silver chloride from Ercon Inc.
  • Example 1 In the following, illustrative examples are described, but in no way limiting the present invention.
  • Example 1
  • a glucose measurement was carried out under the conditions of the first embodiment of the invention, for which, a 35-year-old female was selected with diagnosis of Diabetes Mellitus type 2, in a general state of good health and appearing in fasting to the experiment.
  • agarose hydrogel was placed in addition to PBS buffer in the skin of an individual to then place the biosensor device, connected to the processing unit of the signals generated in the patch of the biosensor element.
  • the measurement was carried out with the biosensor element of the present invention, where a blood glucose value of 121 mg / dL was obtained Likewise, a glucose measurement was carried out by the conventional method, that is, the patient's finger was pricked until a small drop of blood was obtained, which was placed on a test strip, leaving the strip will impregnate perfectly; subsequently, the test strip previously impregnated with the blood drop of the subject of the experiment was placed in a conventional reader, resulting in 84 mg / dL.
  • Example 2 The results of the glucose measurement performed on the individual in example 1 are shown in Figures 6A and 6B.
  • Example 2
  • the result of the glucose measurement under the conditions of the second embodiment of the invention was carried out in a time of 4 minutes, giving a blood glucose value of 117 mg / dL.
  • the measurement made with a conventional glucometer resulted in a blood glucose value of 121 mg / dL, so that a minimum variation is observed with respect to the result obtained with the biosensor of the present invention.

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  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

La présente invention concerne un dispositif biocapteur et un procédé de mesure du glucose de manière non invasive. Le dispositif biocapteur comprend un module de traitement des informations; un élément de fixation pour se fixer à l'extrémité d'un utilisateur, qui comprend sur sa surface externe, le module de traitement des informations; et un normographe qui comprend au moins un élément biocapteur de glucose, lequel est placé dans la face interne de l'élément de fixation. Le dispositif biocapteur permet de réaliser la mesure du glucose chez un individu de manière non invasive, sans avoir à piquer un doigt ou n'importe quelle autre partie du corps de l'individu pour obtenir un échantillon de sang, qui est ensuite analysé pour réaliser une mesure électrochimique à la surface de la peau de l'individu.
PCT/IB2017/001209 2017-10-04 2017-10-04 Dispositif biocapteur et procédé de mesure de glucose de manière non invasive Ceased WO2019069109A1 (fr)

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WO2022231591A1 (fr) * 2021-04-29 2022-11-03 Biosense Inc. Biocapteur de suivi multi-métabolite
WO2024080889A1 (fr) * 2022-10-10 2024-04-18 Олег Олегович ТИХОНЕНКО Dispositif pour le contrôle non invasif de la teneur en glucose dans le sang
EP4358842A4 (fr) * 2021-06-22 2024-10-02 Ege Üniversitesi Dispositifs biomédicaux portables pour le diagnostic, l'identification, la surveillance et la prédiction d'événements cardiaques majeurs et de cas de syndrome coronaire aigu

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022231591A1 (fr) * 2021-04-29 2022-11-03 Biosense Inc. Biocapteur de suivi multi-métabolite
EP4358842A4 (fr) * 2021-06-22 2024-10-02 Ege Üniversitesi Dispositifs biomédicaux portables pour le diagnostic, l'identification, la surveillance et la prédiction d'événements cardiaques majeurs et de cas de syndrome coronaire aigu
WO2024080889A1 (fr) * 2022-10-10 2024-04-18 Олег Олегович ТИХОНЕНКО Dispositif pour le contrôle non invasif de la teneur en glucose dans le sang

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