A flexible sweat sensor based on conductive porous membrane electrode and preparation process

Abstract

The application relates to the field of body fluid sensors, and particularly discloses a flexible sweat sensor based on a conductive porous film electrode and a preparation process, the sensor comprising a flexible substrate, a three-electrode system, a conductive circuit, an insulating layer and a water absorption layer, wherein the working electrode in the three-electrode system is a conductive porous film loaded with biological enzymes; the preparation process of the sensor comprises the following steps: performing surface hydrophilization treatment on the flexible substrate; depositing a conductive layer and a conductive circuit on the flexible substrate, preparing, integrating and cleaning the three-electrode system; modifying biological enzymes on the working electrode; and packaging the sensor. The conductive porous film adopted in the application has a high specific surface area conductive three-dimensional structure, can increase the contact area of the reaction while tightly fixing the biological enzymes, and realizes high-sensitivity detection of physiological substances in sweat; the working electrode can be independently replaced, which is favorable for reducing the use cost.

Description

Technical Field

[0001] This application relates to the field of body fluid sensors, and in particular to a flexible sweat sensor based on a conductive porous thin film electrode and its fabrication process. Background Technology

[0002] Various metabolites in the human body are inextricably linked to human health, and their indicators play a vital role in disease prevention, diagnosis, and treatment. With increasing attention and demand for health monitoring, achieving low-cost, real-time, portable, and easy-to-operate metabolite detection is of significant research importance for health management and medical diagnosis.

[0003] Traditional metabolite testing typically employs invasive blood tests, which can cause pain and increase the risk of wound infection for patients. Furthermore, blood tests are often cumbersome and lack real-time monitoring capabilities. In addition to blood tests, interstitial fluid testing, as a novel technology, can also detect various metabolite indicators in the human body. This technology has lower pain and infection risks than blood tests and offers some real-time monitoring, but its high cost makes widespread adoption difficult. In contrast, the metabolites and electrolytes in sweat are very similar to those in blood. Non-invasive sweat monitoring methods effectively avoid the risks of pain and infection and can achieve convenient and low-cost real-time monitoring. Although research teams both domestically and internationally have conducted extensive research on sweat sensors, they still face many challenges. For example, enzymatic sweat sensors suffer from accuracy and sensitivity issues due to the easy shedding and inactivation of enzymes, while non-enzymatic sweat sensors face difficulties in material preparation, high costs, and poor selectivity. Summary of the Invention

[0004] To address the shortcomings of existing sweat sensors, this application provides a flexible sweat sensor based on a conductive porous thin-film electrode and its fabrication process.

[0005] The flexible sweat sensor based on a conductive porous thin-film electrode provided in this application adopts the following technical solution:

[0006] A flexible sweat sensor based on a conductive porous thin-film electrode includes:

[0007] Flexible substrate;

[0008] The three-electrode system includes a conductive layer, a counter electrode, a reference electrode, and a working electrode; wherein the conductive layer is deposited on the flexible substrate, the counter electrode and the reference electrode are respectively deposited on the conductive layer, and the working electrode is a conductive porous film fixed on the flexible substrate and loaded with a biological enzyme, the biological enzyme being able to undergo an oxidation-reduction reaction with the analyte in sweat;

[0009] Conductive circuitry, deposited on the flexible substrate, is used to connect external analytical instruments to the three-electrode system;

[0010] An insulating layer, made of flexible insulating material, covers the conductive lines;

[0011] The absorbent layer is a flexible absorbent film that covers the three-electrode system.

[0012] The sensor provided in this application can be used for wearable detection. In use, the sensor's absorbent layer is attached to the skin. Sweat on the skin's surface is absorbed by the absorbent layer and diffuses into the three-electrode system. The analyte in the sweat reacts with the bio-enzyme in the working electrode to produce an active substance. Under an applied potential, this active substance undergoes a redox reaction, generating electrons. These electrons are transferred along conductive lines to an external analytical instrument. The magnitude of the current is proportional to the concentration of the analyte; by detecting the magnitude of the current, the concentration of the analyte in the sweat can be determined. The sensor provided in this application can also be used for non-wearable detection, i.e., by directly dripping the sweat to be tested onto the absorbent layer of the sensor's working area.

[0013] Furthermore, the conductive porous film is a porous film loaded with carbon nanotubes, wherein the carbon nanotubes are loaded onto the porous film by adsorption, and the porous film is a polylactic acid porous film and a polyethylene glycol disulfide porous film.

[0014] Furthermore, the bio-enzyme is loaded onto the conductive porous film by adsorption.

[0015] The porous membrane retains its porous structure after fully adsorbing carbon nanotubes, enabling it to conduct electricity while further loading biological enzymes. The conductive porous membrane possesses a high specific surface area and a conductive three-dimensional structure, which can increase the contact area for the reaction while tightly immobilizing biological enzymes. This results in a larger detection current at the same analyte concentration, improving signal resolution and detection accuracy, and achieving highly sensitive detection of target physiological substances in sweat.

[0016] Furthermore, the conductive layer and conductive circuit are both inkjet-printed silver nanoparticles on the flexible substrate, the counter electrode is carbon nanotubes deposited on the conductive layer, and the reference electrode is an Ag / AgCl electrode obtained by chlorinating the conductive layer.

[0017] This application also provides a fabrication process for a flexible sweat sensor based on a conductive porous thin-film electrode, comprising the following steps:

[0018] The flexible substrate is subjected to surface hydrophilization treatment;

[0019] Depositing conductive layers and conductive lines on a flexible substrate;

[0020] Counter electrode and reference electrode are fabricated on the conductive layer, respectively;

[0021] A flexible porous thin film was prepared and then subjected to conductive treatment to obtain a working electrode;

[0022] The working electrode, counter electrode, and reference electrode are integrated into a three-electrode system.

[0023] Clean the three-electrode system;

[0024] Modify the working electrode with biological enzymes;

[0025] The three-electrode system region and the conductive line region on the flexible substrate are encapsulated.

[0026] Furthermore, the preparation method of the porous film includes solution casting-particle leaching and solvent evaporation.

[0027] Furthermore, the method for conductive treatment of the porous film is as follows: a carbon nanotube dispersion is dropped onto the surface of the porous film, so that the carbon nanotubes penetrate into the porous structure of the porous film.

[0028] Furthermore, the method for modifying the working electrode with biological enzymes is as follows: a biological enzyme solution is dropped onto the surface of the working electrode, allowing the biological enzymes to penetrate into the porous structure of the working electrode.

[0029] Furthermore, the encapsulation process for the three-electrode system region and the conductive line region on the flexible substrate includes: covering the three-electrode system region with a flexible absorbent film, covering the conductive line region with a flexible insulating material, and exposing the ends of the conductive lines.

[0030] This application also provides a wearable device, including a flexible sweat sensor based on a conductive porous thin-film electrode.

[0031] In summary, this application includes at least one of the following beneficial technical effects:

[0032] 1. The flexible sweat sensor based on conductive porous thin film electrodes provided in this application has good wearability and biocompatibility, and can be easily integrated into wearable devices to realize non-invasive monitoring of users' health information and improve the convenience and real-time access to health indicators for users.

[0033] 2. The flexible sweat sensor based on conductive porous film electrode provided in this application uses a conductive porous film with a high specific surface area and a conductive three-dimensional structure. It can achieve a good enzyme immobilization effect without the participation of other modification materials. It can increase the contact area of ​​the reaction while tightly immobilizing biological enzymes, obtain a larger detection current at the same analyte concentration, improve signal resolution and detection accuracy, and achieve high-sensitivity detection of target physiological substances in sweat.

[0034] 3. In the flexible sweat sensor based on conductive porous thin film electrode provided in this application, the thin film working electrode and other electrodes are fabricated and then integrated separately, so that the working electrode can be replaced independently and the counter electrode and reference electrode can be reused, which helps to reduce the cost of use.

[0035] 4. The flexible sweat sensor based on conductive porous thin film electrode provided in this application uses inkjet printing technology. The working electrode is prepared separately from other electrodes and then integrated, which can realize array-type mass production to a certain extent. The production process is convenient, fast and low cost. Attached Figure Description

[0036] Figure 1 This is a schematic diagram of the overall structure of the flexible sweat sensor based on a conductive porous thin film electrode according to an embodiment of this application;

[0037] Figure 2 This is an exploded structural diagram of a flexible sweat sensor based on a conductive porous thin film electrode according to an embodiment of this application;

[0038] Figure 3 This application presents the current-time response curves of a flexible sweat sensor based on a conductive porous thin film electrode at different glucose concentrations according to embodiments of this application.

[0039] Figure 4 This is a linear calibration curve of the flexible sweat sensor based on conductive porous thin film electrode according to the embodiments of this application, showing the relationship between Ampere current and glucose concentration in the glucose concentration range of 50 μM to 300 μM.

[0040] Figure 5 This is a process flow diagram of the fabrication of a flexible sweat sensor based on a conductive porous thin film electrode according to an embodiment of this application.

[0041] Reference numerals: 1. Flexible substrate; 2. Three-electrode system; 201. Conductive layer; 201-1. Conductive layer one; 201-2. Conductive layer two; 202. Counter electrode; 203. Reference electrode; 204. Working electrode; 3. Conductive circuit; 301. Conductive circuit one; 302. Conductive circuit two; 303. Conductive circuit three; 4. Insulating layer; 5. Water-absorbing layer. Detailed Implementation

[0042] The following is in conjunction with the appendix Figure 1-5 This application will be described in further detail.

[0043] Example 1

[0044] This application discloses a flexible sweat sensor based on a conductive porous thin-film electrode. (Refer to...) Figure 1 and Figure 2The flexible sweat sensor based on conductive porous thin film electrodes includes a flexible substrate 1, a three-electrode system 2, a conductive circuit 3, an insulating layer 4, and an absorbent layer 5.

[0045] The flexible substrate 1 is made of a flexible biocompatible material, such as polyimide or polydimethylsiloxane, and the average thickness of the flexible substrate 1 is 25 μm.

[0046] Reference Figure 1 and Figure 2 The three-electrode system 2 includes a conductive layer 201, a counter electrode 202, a reference electrode 203, and a working electrode 204.

[0047] Reference Figure 2 The conductive layer 201 is made of nano-silver inkjet printed on the flexible substrate 1 and serves to conduct electricity. The conductive layer 201 includes conductive layer one 201-1 and conductive layer two 201-2, wherein conductive layer one 201-1 is located below the counter electrode 202 and conductive layer two 201-2 is located below the reference electrode 203.

[0048] The counter electrode 202 is obtained by depositing carbon nanotubes on the conductive layer 201-1. The counter electrode 202 provides electrons for the redox reaction of the working electrode 204, forming a closed conductive circuit.

[0049] The reference electrode 203 is an Ag / AgCl pseudo-reference electrode obtained by chlorinating the conductive layer 201-2 with sodium hypochlorite. The reference electrode 203 provides a reference voltage for the working electrode 204 to ensure the accuracy of the measurement.

[0050] The working electrode 204 is a conductive porous film fixed on a flexible substrate 1 and loaded with a biological enzyme. The biological enzyme can undergo a redox reaction with the analyte in sweat, generating a current proportional to the concentration of the analyte. Specifically, the conductive porous film used in the working electrode 204 is a porous film loaded with carbon nanotubes. The porous film can be a polylactic acid (PLA) porous film or a polyethylene glycol (PEG) porous film. The carbon nanotubes are loaded onto the porous film by adsorption. The biological enzyme is loaded onto the conductive porous film by adsorption; in this embodiment, the biological enzyme is glucose oxidase.

[0051] Porous membranes possess high porosity and retain their porous structure even after sufficient adsorption of carbon nanotubes, enabling them to conduct electricity while further loading biological enzymes. Conductive porous membranes, with their high specific surface area and conductive three-dimensional structure, can tightly immobilize biological enzymes while increasing the contact area for the reaction. This results in a larger detection current at the same analyte concentration, improving signal resolution and detection accuracy, and achieving highly sensitive detection of target physiological substances in sweat.

[0052] Reference Figure 1 and Figure 2 The working electrode 204 is a circular disc with a diameter of 5 mm and a thickness of 25 μm; the counter electrode 202 and the reference electrode 203 are both arc-shaped with a width of 0.7 mm, of which the counter electrode 202 is an arc with a larger arc; the distance between the outer periphery of the working electrode 204 and the inner ring of the counter electrode 202 is 0.6 mm.

[0053] The circular working electrode 204 and the arc-shaped counter electrode 202 are more in line with the trend of liquid diffusion flow. In the radial direction of the circular electrode, the distance between corresponding positions on the circular electrode and the arc-shaped electrode is equal everywhere. Therefore, compared with other shapes, the electric field and current density generated by the circular-arc electrode are more uniform, which helps to accelerate the ion transfer rate and bring better detection performance.

[0054] Reference Figure 1 and Figure 2 The conductive line 3 is made of nano-silver inkjet-printed on the flexible substrate 1, used to connect external analytical instruments to the three-electrode system 2. The conductive line 3 includes three lines: conductive line one 301, conductive line two 302, and conductive line three 303; wherein conductive line one 301 is connected to conductive layer one 201-1, conductive line three 303 is connected to conductive layer two 201-2, and conductive line two 302 is connected to the working electrode 204. In this embodiment, each line has a width of 0.5 mm, a length of 11.5 cm, and a spacing of 2.5 cm between adjacent lines. The conductive line 3 and conductive layer 201 can be printed together or separately.

[0055] Reference Figure 1 and Figure 2 The insulating layer 4 is made of a flexible insulating material with dielectric properties and covers the conductive lines 3 to protect the stability and integrity of the conductive lines 3; the ends of the three conductive lines 3 are exposed outside the insulating layer 4. In this embodiment, the insulating layer 4 is made of polydimethylsiloxane, with a thickness of 100 μm, a width of 7 cm, and a length of 9.5 cm.

[0056] Reference Figure 1 and Figure 2 The absorbent layer 5 is a flexible absorbent film that covers the three-electrode system 2 to absorb sweat and prevent it from overflowing into other areas. In this embodiment, the absorbent layer 5 is made of polyglycolic acid with good adhesion and absorbency, with a thickness of 20-25 μm, and its size completely covers the three-electrode system 2 and does not exceed the edge of the flexible substrate 1.

[0057] The sensor provided in this embodiment can be used for wearable detection. In use, the absorbent layer 5 of the sensor is attached to the human skin. Sweat on the skin surface is absorbed by the absorbent layer 5 and diffuses into the three-electrode system 2. Glucose in the sweat reacts with glucose oxidase in the working electrode 204 to produce hydrogen peroxide. When a certain potential is applied externally, the hydrogen peroxide decomposes to generate electrons. The higher the glucose concentration, the more hydrogen peroxide is produced, i.e., the more electrons are generated, and the greater the current. Therefore, the glucose concentration in the sweat can be analyzed by detecting the magnitude of the current. The sensor provided in this embodiment can also be used for non-wearable detection, i.e., the sweat to be tested is directly dripped into the absorbent layer 5 of the sensor's working area.

[0058] The current-time response curves of different glucose concentrations measured using the sensor provided in this embodiment are as follows: Figure 3 As shown, the linear calibration curve of the response current versus glucose concentration at 20 s is as follows. Figure 4 As shown. Figure 4 The calibration curve in the figure shows good linearity, with a linear function of I = 0.0157c + 0.348, where I represents the current (in μA) and c represents the glucose concentration (in μM).

[0059] Once the response current of the sweat sample is obtained, the glucose concentration in the sweat can be calculated using the calibration curve equation. Sweat samples taken from the subject 30 minutes after a meal were used for current detection at a working voltage of 0.195V. The resulting current value was 1.929 μA. Substituting this into the linear function of the calibration curve, the glucose concentration was calculated to be 100.73 μM.

[0060] Integrating the flexible sweat sensor based on a conductive porous thin film electrode provided in this embodiment into a wearable device enables non-invasive monitoring of the user's health information, improving the convenience and real-time access to health indicators for the user.

[0061] It should be noted that this embodiment only takes the detection of glucose in sweat as an example; when it is necessary to detect the concentration of other target physiological substances in sweat, the glucose oxidase loaded on the working electrode 204 is replaced with the corresponding biological enzyme.

[0062] Example 2

[0063] This application discloses a fabrication process for a flexible sweat sensor based on a conductive porous thin-film electrode, referring to... Figure 5 This includes the following steps:

[0064] S1. Perform surface hydrophilization treatment on the flexible substrate:

[0065] Materials with good flexibility and biocompatibility, such as polyimide or polydimethylsiloxane, are selected as substrates, and the surface of the substrate materials is hydrophilized. Specifically, the polyimide substrate is treated under UV light for about 55 seconds, and the polydimethylsiloxane substrate is treated in a plasma cleaner with a power of 30W for about 30 seconds.

[0066] S2. Deposit conductive layers and conductive lines on a flexible substrate:

[0067] A flexible substrate with a hydrophilic surface is placed on an inkjet printer substrate, and nano-silver circuits are printed on the flexible substrate according to the designed circuit pattern. The printed sample is then placed in a vacuum drying oven for high-temperature evaporation treatment, typically sintering at 150°C for 45 minutes.

[0068] S3. Fabricate the counter electrode and reference electrode on the conductive layer, including the following steps:

[0069] Preparation of counter electrode: Carbon nanotubes are deposited in the corresponding region on the conductive layer. Specifically, a carbon nanotube dispersion with a mass fraction of 3.15 wt% is used to drop-coat the conductive layer using a mask.

[0070] Preparation of reference electrode: Chlorine nanoparticles of silver are chlorinated by adding a chlorine-containing solution to the corresponding region on the conductive layer to prepare an Ag / AgCl pseudo-reference electrode, wherein the chlorine-containing solution is a 0.1 mol / L sodium hypochlorite solution.

[0071] S4. Prepare a flexible porous thin film and perform conductive treatment to obtain the working electrode, including the following steps:

[0072] S4-1, Preparation of porous thin films:

[0073] L-type polylactic acid porous films were prepared using a solution casting-particle leaching method, as detailed below:

[0074] L-polylactic acid (PLA) material is dissolved in a volatile solvent, such as ethyl acetate or hexafluoroisopropanol. Soluble porogen particles of appropriate size, such as potassium chloride, are added. The PLA solution is then poured into a mold containing the porogen, and the solvent is removed by vacuum drying to obtain a polymer-porogen composite. The porogen particles in the composite are removed by leaching with a solvent insoluble in PLA but soluble in the porogen, such as deionized water. After drying, a PLA film is obtained, which is then cut to obtain a porous film with a diameter of 5 mm.

[0075] Poly(glycolic acid) porous films were prepared using a solvent evaporation method, as detailed below:

[0076] Polyglycolic acid crystals were completely dissolved in a strong organic solvent, such as hexafluoroisopropanol. The polyethylene glycol solution was then dropped onto a smooth, clean silicon wafer and placed in a ventilated area to allow the organic solvent to evaporate completely, resulting in a porous polyethylene glycol film. After cutting, the porous film with a diameter of 5 mm was obtained.

[0077] L-polylactic acid porous films and polyglycolic acid porous films have large porosity, and their spatial porous structure can provide more attachment sites for biological enzymes.

[0078] S4-2. Conductive treatment of porous thin films:

[0079] A carbon nanotube dispersion with a mass fraction of 3.15 wt% was dropwise added to the surface of a porous film. Due to the large porosity of the porous film, the carbon nanotube dispersion easily penetrated into the porous structure of the film. After the porous film fully adsorbed the carbon nanotubes, it still maintained its porous structure, enabling it to achieve conductivity while further loading biological enzymes.

[0080] S5. Integrate the working electrode, counter electrode, and reference electrode into a three-electrode system:

[0081] Before the conductive porous film is completely dry, its own adhesive properties are used to adhere it to a flexible substrate on which the counter and reference electrodes have already been fabricated, thus completing the integration of the three electrodes. The conductive porous film is fixed to the flexible substrate by its own adhesive properties, making it easy to replace the working electrode.

[0082] S6. Clean the three-electrode system:

[0083] The preliminarily prepared three-electrode system was cleaned using phosphate-hydrochloric acid buffer under cyclic voltammetry to remove some impurities introduced by the carbon nanotube dispersion from the porous film. Cyclic voltammetry was performed on an electrochemical workstation with the scanning voltage range set to -0.8V to 0.8V, the scan rate to 0.05mV / s, and the number of scan cycles to 5.

[0084] S7. Modify the working electrode with biological enzymes:

[0085] Add 2 μL of 500 U / L glucose oxidase solution dropwise to the cleaned working electrode surface and dry it to allow the enzyme to penetrate into the porous structure of the working electrode.

[0086] S8. Encapsulate the three-electrode system region and conductive line region on the flexible substrate. Specific steps include:

[0087] A polylactic acid (PLA) film or a polyethylene glycol (PEG) film is used as an absorbent layer to cover the three-electrode system area, and a polydimethylsiloxane (PDMS) film is used as an insulating layer to cover the conductive circuit area, exposing the ends of the conductive circuit, thus completing the sensor encapsulation.

[0088] The above are all preferred embodiments of this application, and are not intended to limit the scope of protection of this application. Therefore, all equivalent changes made in accordance with the structure, shape and principle of this application should be covered within the scope of protection of this application.

Claims

1. A flexible sweat sensor based on a conductive porous thin-film electrode, characterized in that: include: Flexible substrate; The three-electrode system includes a conductive layer, a counter electrode, a reference electrode, and a working electrode. The conductive layer is deposited on the flexible substrate. The counter electrode and the reference electrode are respectively deposited on the conductive layer. The working electrode is a conductive porous membrane fixed on the flexible substrate and loaded with a biological enzyme, which can undergo a redox reaction with the analyte in sweat. The conductive porous membrane is a porous membrane loaded with carbon nanotubes, specifically a polylactic acid (PLA) porous membrane and a polyethylene glycol (PEG) porous membrane. The carbon nanotubes are loaded onto the porous membrane via adsorption. The loading step includes: dropping a carbon nanotube dispersion onto the surface of the porous membrane, allowing the carbon nanotubes to penetrate into the porous structure of the membrane. Conductive circuitry, deposited on the flexible substrate, is used to connect external analytical instruments to the three-electrode system; An insulating layer, made of flexible insulating material, covers the conductive lines; The absorbent layer is a flexible absorbent film that covers the three-electrode system.

2. The flexible sweat sensor based on a conductive porous thin-film electrode according to claim 1, characterized in that: The bio-enzyme is loaded onto the conductive porous film by adsorption.

3. A flexible sweat sensor based on a conductive porous thin-film electrode according to claim 1, characterized in that: The conductive layer and conductive circuit are both inkjet-printed silver nanoparticles on the flexible substrate. The counter electrode is carbon nanotubes deposited on the conductive layer. The reference electrode is an Ag / AgCl electrode obtained by chlorinating the conductive layer.

4. A fabrication process for a flexible sweat sensor based on a conductive porous thin-film electrode, used to fabricate the flexible sweat sensor based on a conductive porous thin-film electrode as described in any one of claims 1-3, characterized in that: Includes the following steps: The flexible substrate is subjected to surface hydrophilization treatment; Depositing conductive layers and conductive lines on a flexible substrate; Counter electrode and reference electrode are fabricated on the conductive layer, respectively; A flexible porous thin film was prepared and then subjected to conductive treatment to obtain a working electrode; The working electrode, counter electrode, and reference electrode are integrated into a three-electrode system. Clean the three-electrode system; Modify the working electrode with biological enzymes; The three-electrode system region and the conductive line region on the flexible substrate are encapsulated.

5. The fabrication process of a flexible sweat sensor based on a conductive porous thin-film electrode according to claim 4, characterized in that: The methods for preparing the porous film include solution casting-particle leaching and solvent evaporation.

6. The fabrication process of a flexible sweat sensor based on a conductive porous thin-film electrode according to claim 4, characterized in that: The method for conductive treatment of the porous film is as follows: a carbon nanotube dispersion is dropped onto the surface of the porous film, so that the carbon nanotubes penetrate into the porous structure of the porous film.

7. The fabrication process of a flexible sweat sensor based on a conductive porous thin-film electrode according to claim 5, characterized in that: The method for modifying the working electrode with biological enzymes is as follows: add the biological enzyme solution dropwise to the surface of the working electrode, so that the biological enzymes penetrate into the porous structure of the working electrode.

8. The fabrication process of a flexible sweat sensor based on a conductive porous thin-film electrode according to claim 4, characterized in that: The steps for encapsulating the three-electrode system region and the conductive line region on the flexible substrate include: covering the three-electrode system region with a flexible absorbent film, covering the conductive line region with a flexible insulating material, and exposing the ends of the conductive lines.

9. A wearable device comprising a flexible sweat sensor based on a conductive porous thin-film electrode as described in any one of claims 1-3.

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