Sweat cortisol continuous monitoring sensor based on efficient ion-doped carbon cloth grid

Abstract

The invention discloses a sweat cortisol continuous monitoring sensor based on an efficient ion-doped carbon cloth grid, and relates to the technical field of sweat detection, the sweat cortisol continuous monitoring sensor comprises a flexible substrate module, a three-electrode sensing system module, a microfluidic sweat management module and a signal processing and transmission module; through the synergistic effect of the capillary drainage characteristic of the carbon cloth three-dimensional porous structure and the sweat guiding and storing function of the micro-fluidic module, the problems that a traditional sensor is unstable in sweat collection and a detection interface is prone to drying are solved, and through a biological-nanometer synergistic signal amplification system, the detection accuracy is greatly improved. The electron transfer efficiency and the specific surface area are improved by the nano-material enhancement layer, high-sensitivity and high-specificity detection of trace cortisol is realized by combining the specific biological recognition layer and the redox mediator, in addition, the movement fitness of the sensor and the skin is ensured by the flexible substrate and the water-permeable pressure-sensitive adhesive, the external interference can be reduced by the air-permeable anti-pollution film, and the detection sensitivity is high. And meanwhile, the wireless transmission module is integrated to realize real-time data uploading, so that the monitoring stability is integrally improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of sweat detection, and particularly relates to a sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth gate. BACKGROUND

[0002] Sweat monitoring technology is a non-invasive detection method that tracks the physiological state of the human body in real time by analyzing sweat components. Human sweat contains rich biomarkers such as electrolytes (such as sodium and potassium), metabolic products (such as lactic acid and glucose), hormones, and small biological molecules. With the help of flexible electronics and micro-sensor technology, modern sweat monitoring equipment can be integrated into patches or wearable devices, which can collect and analyze sweat components in real time by contacting the skin. This technology can dynamically reflect the body's hydration status, fatigue level, electrolyte balance, and even some disease characteristics, providing key data for sports science, clinical monitoring, and personal health management.

[0003] Sweat cortisol monitoring technology is an important direction in the field of sweat monitoring, which aims to non-invasively and dynamically assess the stress state of the human body by detecting the concentration of cortisol in sweat. Cortisol is known as the "stress hormone", and its level fluctuations can directly reflect the psychological or physiological stress level. Compared with traditional blood tests, sweat cortisol monitoring technology uses micro-biosensors integrated into flexible patches to continuously collect and analyze sweat, providing more convenient and real-time long-term monitoring. It has great potential for mental health management (such as auxiliary diagnosis of anxiety and depression), occupational stress assessment, and athlete training load monitoring.

[0004] Existing sweat cortisol continuous monitoring sensors mostly use rigid electrodes, which have poor skin adhesion. Sweat collection relies on passive diffusion, which is prone to drying or leakage, and cannot achieve effective continuous monitoring. The carbon cloth substrate of existing sensors is not efficiently doped, and the conductivity and target molecule affinity are insufficient, resulting in weak signals and low sensitivity. In addition, the biological recognition layer of existing sensors is not fixed firmly and has poor specificity, and is easily affected by sweat interferents. At the same time, the reference electrode is prone to ion migration drift, and the detection stability is weak, which is difficult to meet the increasingly high requirements of sweat cortisol detection. Therefore, the present application proposes a sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth gate to solve the problems existing in the prior art. SUMMARY

[0005] In view of the above problems, the present application aims to provide a sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth gate to solve the problems of existing sweat cortisol continuous monitoring sensors, such as sweat collection relying on passive diffusion, being prone to drying or leakage, carbon cloth substrate not being efficiently doped, conductivity and target molecule affinity being insufficient, and detection stability being weak.

[0006] In order to achieve the purpose of the present application, the present application realizes the following technical solutions: a sweat cortisol continuous monitoring sensor based on an efficient ion-doped carbon cloth gate, comprising a flexible substrate module, a three-electrode sensing system module, a microfluidic sweat management module and a signal processing and transmission module, wherein:

[0007] The flexible substrate module adopts a sheet-shaped structure made of a biocompatible polymer material, and the back surface of the flexible substrate module is coated with a water-permeable pressure-sensitive adhesive layer.

[0008] The three-electrode sensing system module is integrated on the front surface of the flexible substrate module and comprises an ion-doped carbon cloth working electrode, an integrated reference electrode and an integrated counter electrode, which are prepared by screen printing or magnetron sputtering patterning.

[0009] The microfluidic sweat management module covers the working electrode area of the three-electrode sensing system module and is composed of a hydrophilic microchannel and a liquid reservoir, which is used to guide the sweat to the working electrode of the three-electrode sensing system module.

[0010] The signal processing and transmission module is electrically connected with the three-electrode sensing system module and comprises a micro electrochemical detection circuit and a low-power Bluetooth chip, which can collect electrochemical signals in real time and transmit them to an external terminal through Bluetooth.

[0011] Further improvement lies in that the ion-doped carbon cloth working electrode adopts a basic carbon cloth doped with one of nitrogen ions or boron ions, the basic carbon cloth is a cleaned and pretreated polyacrylonitrile-based carbon cloth, the ion doping treatment of the basic carbon cloth adopts one of hydrothermal method or high-temperature calcination method to introduce nitrogen ions or boron ions, and the carbon cloth forms a three-dimensional porous network structure after doping.

[0012] Further improvement lies in that the ion-doped carbon cloth working electrode is modified with a molecular recognition and signal conversion layer, the molecular recognition and signal conversion layer is composed of a nano material enhancement layer and a biological recognition layer stacked in gradient, the nano material enhancement layer is loaded on the surface of the carbon cloth through electrodeposition or spin coating process and is composed of gold nanoparticles, reduced graphene oxide and MXene, the surface of the nano material enhancement layer is modified with a signal conversion medium, potassium ferricyanide / potassium ferrocyanide is used as a redox mediator, and the biological recognition layer is fixed on the nano material enhancement layer through covalent bonding or physical adsorption.

[0013] Further improvement lies in that the integrated reference electrode is a silver / silver chloride electrode, the surface of which is covered with a solidified polymer gel with a thickness of 10-20 μm, and the preparation method of the silver / silver chloride electrode is as follows:

[0014] An Ag layer is deposited on the flexible substrate module by magnetron sputtering, and then soaked in a saturated potassium chloride solution for electrochemical chlorination treatment to form an Ag / AgCl composite material layer.

[0015] Further improvement lies in that the integrated counter electrode is selected from a platinum sheet electrode or a carbon electrode, the platinum sheet electrode is formed by depositing Pt nanoparticles on a flexible substrate module through magnetron sputtering to form a porous Pt layer, and the carbon electrode is prepared by using a carbon paste printing process and is printed on the flexible substrate module after being mixed with an ethyl cellulose binder.

[0016] Further improvement lies in that the gas-permeable anti-pollution film of the microfluidic sweat management module covers the top of the liquid storage pool, the film material is selected from one of polydimethylsiloxane or polytetrafluoroethylene, the film thickness is 10-20 microns, and the film edges are sealed to the hydrophilic microchannel sidewalls through hot pressing or UV glue.

[0017] Further improvement lies in that the micro electrochemical detection circuit of the signal processing and transmission module comprises a working electrode lead for connecting the ion-doped carbon cloth working electrode to the same-phase input end of an operational amplifier, a reference electrode lead for connecting the integrated reference electrode to the opposite-phase input end of the operational amplifier, a counter electrode lead for connecting the integrated counter electrode to the output end of the operational amplifier, an analog-to-digital converter for converting an analog current signal into a digital signal, and a microcontroller.

[0018] Further improvement lies in that when the flexible substrate module is attached to the skin, the water permeability of the water-permeable pressure-sensitive adhesive layer allows sweat to penetrate into the microfluidic sweat management module, and the three-dimensional porous structure of the ion-doped carbon cloth working electrode actively draws sweat through capillary force.

[0019] The present application has the following advantages: through the synergistic effect of the capillary drainage characteristics of the three-dimensional porous structure of the carbon cloth and the sweat guiding and storing function of the microfluidic module, the present application solves the problems of unstable sweat collection and easy drying of the detection interface of traditional sensors, can ensure continuous and stable contact between sweat and the sensing interface, and guarantees the monitoring effect;

[0020] and through the bio-nano synergistic signal amplification system, the nano material enhancement layer enhances the electron transfer efficiency and specific surface area, and in combination with the specific biological recognition layer and the redox mediator, high-sensitivity and high-specificity detection of trace cortisol is realized;

[0021] In addition, the flexible substrate and the water-permeable pressure-sensitive adhesive ensure the motion attachment of the sensor to the skin, the gas-permeable anti-pollution film can reduce external interference, and the integrated wireless transmission module realizes real-time data uploading, thereby improving the stability and application convenience of continuous monitoring as a whole. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 is a structural framework schematic diagram of the sweat cortisol continuous monitoring sensor of the present application. DETAILED DESCRIPTION

[0023] With reference to the drawings and embodiments of the present application, the technical solutions in the embodiments of the present application will be described clearly and completely. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by a person of ordinary skill in the art without creative effort belong to the scope of protection of the present application.

[0024] Sweat sensing technology has great application potential in sports, neonatology, pharmacological monitoring, individual digital health, etc. This is because sweat contains many biomarkers, chemicals or solutes that are the same as those carried in blood, which can provide important information, enabling even the diagnosis of diseases, health conditions, toxins, behavioral performance and other physiological properties before any signs appear. In addition, the sweat itself and the behavior of sweating or other parameters, properties, solutes or features on or near or under the skin can be measured to further reveal physiological information;

[0025] Cortisol, also known as "stress hormone", is secreted by the adrenal gland, 3-5% of which circulates in the body as free cortisol, has biological activity, can bind to glucocorticoid receptors and affect metabolism. Excessive release of cortisol often leads to metabolic disorders, muscle weakness, osteoporosis, anxiety, depression, schizophrenia. The concentration of cortisol in sweat is usually in the range of 23-390 nM, and shows a strong correlation with serum cortisol. Therefore, non-invasive sweat cortisol monitoring is a feasible method for evaluating human cortisol levels.

[0026] It should be noted that the technical means not described in detail in the following embodiments are conventional means in the art, which are not the key points of the present application and will not be described here.

[0027] Embodiment 1

[0028] According to Figure 1 As shown in the figure, the present embodiment provides a sweat cortisol continuous monitoring sensor based on high-efficiency ion-doped carbon cloth gate, which is composed of a flexible substrate module, a three-electrode sensing system module, a microfluidic sweat management module and a signal processing and transmission module, which are sequentially stacked from bottom to top. Among them:

[0029] The flexible substrate module is a thin sheet structure made of biocompatible polymer material (polydimethylsiloxane PDMS), with a thickness of 50 μm. The back of the flexible substrate module is coated with a water-permeable pressure-sensitive adhesive layer (acrylate, water flux ≥100 mL / (cm 2 ·h), peel strength 0.2 N / cm), used to fit the human skin and fix the functional components;

[0030] The three-electrode sensing system module is integrated on the front surface of the flexible substrate module, and contains an ion-doped carbon cloth working electrode, an integrated reference electrode and an integrated counter electrode. The three electrodes are prepared by screen printing process, and the electrode spacing is 0.5 mm, thereby forming a stable three-electrode detection system.

[0031] The microfluidic sweat management module covers the working electrode area of the three-electrode sensing system module, and is composed of a hydrophilic microchannel (width 0.5 mm, depth 0.2 mm, and surface treated by plasma to improve hydrophilicity) and a liquid storage pool (volume 50 μL, opening diameter 2 mm), and is used for guiding sweat to the working electrode and maintaining the stability of the sweat at the detection interface.

[0032] The signal processing and transmission module includes a micro electrochemical detection circuit (flexible PCB, thickness ≤50 μm, integrated operational amplifier and analog-to-digital converter) and a low-power Bluetooth chip (packaged in a PDMS flexible shell, and the signal is not attenuated when the bending radius is ≤10 mm), which is electrically connected with the three-electrode sensing system module, and is used for real-time acquisition of electrochemical signals and transmission to an external terminal through Bluetooth.

[0033] In this embodiment, the ion-doped carbon cloth working electrode is the core sensing unit, and the basic carbon cloth is doped with nitrogen ions, which is specifically as follows:

[0034] The basic carbon cloth is a polyacrylonitrile-based carbon cloth (carbon fiber diameter 50 nm, single filament number 1000 / cm 2 ), which is cleaned and pretreated (soaked in concentrated nitric acid for 30 min to remove surface impurities, washed with deionized water and dried at 60°C);

[0035] The doping treatment is as follows:

[0036] Nitrogen doping: the basic carbon cloth is immersed in an ethanol-water mixed solution (volume ratio 1:1) containing 0.1 mol / L ammonium nitrate, and hydrothermal reaction is carried out at a temperature of 120°C for 6h, and nitrogen elements are anchored on the surface of the carbon cloth in the form of pyridine nitrogen and graphite nitrogen;

[0037] After doping, the carbon cloth forms a three-dimensional porous network structure, the porosity is ≥80%, the specific surface area is ≥150 m 2 / g, the conductivity is improved to 100 S / cm (2 times higher than that of the undoped carbon cloth), and the introduced heteroatoms on the surface enhance the π-π interaction and hydrogen bond affinity to cortisol molecules.

[0038] In this embodiment, the ion-doped carbon cloth working electrode is modified with a molecular recognition and signal conversion layer, which is composed of a nano material enhancement layer and a biological recognition layer stacked in gradient, wherein:

[0039] Nanomaterial-enhanced layer: loaded on the surface of carbon cloth by electrodeposition process, composed of gold nanoparticles (particle size 10 nm, prepared by sodium citrate reduction method), reduced graphene oxide (thickness 5 layers, prepared by Hummers method to prepare graphene oxide and then reduced by hydrazine hydrate) and MXene (Ti3C2Tx, thickness ≤1 μm, prepared by etching MAX phase with HF), mass ratio 1:1:1, the composite structure makes the specific surface area increase by 2 times and the electron transfer rate increase by 1 order of magnitude, the surface of the nanomaterial-enhanced layer is modified with a signal conversion medium, potassium ferricyanide (K3[Fe(CN)6], concentration 5 mM) is used as a redox mediator, after the binding of cortisol and antibody, the exchange rate of the mediator and the electrode surface changes, producing a measurable change in current signal (detection limit ≤0.1 ng / mL, linear range 0.5-100 ng / mL);

[0040] Biological recognition layer: fixed on the nanomaterial-enhanced layer by covalent bonding (EDC / NHS activated carboxyl group and then coupled with amino-modified cortisol antibody or aptamer), the amount of antibody / aptamer fixed is 0.5 μg / cm 2 Specific recognition affinity constant (Ka) of cortisol ≥10 8 M -1 .

[0041] In this embodiment, the integrated reference electrode is a silver / silver chloride electrode, and its preparation method is as follows:

[0042] An Ag layer (thickness 50 nm) is deposited on the flexible substrate module by magnetron sputtering, and then soaked in a saturated potassium chloride solution for electrochemical chlorination treatment to form an Ag / AgCl composite material layer (Cl - The concentration is matched with sweat, about 10 mM);

[0043] The integrated reference electrode surface is covered with a solidified polymer gel (polyacrylamide / sodium alginate composite gel containing 10 mM KCl) with a thickness of 10 μm, and the gel layer porosity is ≥70%, which not only fixes Cl - The concentration prevents the reference potential from drifting, and also allows ion migration to maintain electrical neutrality.

[0044] In this embodiment, the integrated counter electrode is a platinum sheet electrode: Pt nanoparticles (particle size 5 nm) are deposited on the flexible substrate module by magnetron sputtering to form a porous Pt layer (thickness 20 nm), which has a large specific surface area and high catalytic activity, and is used to accelerate electron transfer.

[0045] In this embodiment, the breathable anti-pollution membrane of the microfluidic sweat management module is covered on the top of the liquid reservoir, and the specific parameters are as follows:

[0046] The membrane material is polydimethylsiloxane (PDMS), the pore size is 0.22 μm, and the water vapor transmission rate is ≥1000 g / (m2 • 24h), allowing sweat evaporation and air exchange to maintain a stable microenvironment humidity;

[0047] Membrane thickness 10 pm, interception rate of PM2.5 particles (particle size ≤2.5 pm) ≥99%, adsorption capacity of skin oil ≤0.1 pg / cm 2 , to avoid pollutants blocking the hydrophilic microchannel or polluting the sensing interface;

[0048] The membrane edge is sealed to the microchannel side wall by heat pressing to form a closed space with the liquid pool, preventing sweat leakage.

[0049] In this embodiment, the specific composition of the micro electrochemical detection circuit of the signal processing and transmission module is:

[0050] Working electrode lead: connect the ion-doped carbon cloth working electrode to the non-inverting input terminal of the operational amplifier;

[0051] Reference electrode lead: connect the integrated reference electrode to the inverting input terminal of the operational amplifier;

[0052] Counter electrode lead: connect the platinum sheet counter electrode to the output terminal of the operational amplifier to form a differential amplification circuit to suppress environmental noise interference;

[0053] Analog-to-digital converter: sampling frequency 1 Hz, resolution 12 bits, convert analog current signal to digital signal;

[0054] Microcontroller: built-in algorithm corrects temperature drift (compensation range 20-40℃, error ≤5%) and sweat pH fluctuation (pH 4.5-7.5, error ≤8%), improves detection stability.

[0055] In this embodiment, the composite structure of the nanomaterial enhancement layer and the biological recognition layer optimizes signal amplification in the following ways:

[0056] Gold nanoparticles provide high-density active sites, promoting the directional fixation of antibodies / aptamers and electron transfer;

[0057] The two-dimensional sheet structure of reduced graphene oxide forms a "nanobridge" connecting the carbon cloth substrate and gold nanoparticles, shortening the electron transport path;

[0058] The high electrical conductivity and mechanical flexibility of MXene enhance the signal consistency of the sensor in a bent state (current response deviation ≤3% when the bending radius is 5 mm);

[0059] The three work together to increase the current change caused by cortisol binding by 3 times, with a detection sensitivity of 0.05 nA / (ng / mL).

[0060] In this embodiment, when the flexible substrate module is attached to the skin, stable monitoring is achieved through the following mechanisms:

[0061] The water permeability of the water-permeable pressure-sensitive adhesive layer allows sweat to permeate to the microfluidic sweat management module, avoiding the accumulation of sweat between the skin and the flexible substrate module, which leads to interface sliding;

[0062] The three-dimensional porous structure of the ion-doped carbon cloth working electrode actively draws sweat through capillary force (capillary rise height ≥ 5 mm), even in a stationary or low-sweat state (sweat output ≤ 2 μL / min), still maintaining a sweat layer thickness on the working electrode surface ≥ 100 μm;

[0063] The volume design (50 μL) of the liquid reservoir combined with the sweat secretion rate (5 μL / min in a sports state) ensures that the sensor does not need to be replaced for 6 h of continuous monitoring.

[0064] Embodiment 2

[0065] Referring to Figure 1 , the present embodiment provides a continuous monitoring sensor for cortisol based on an efficient ion-doped carbon cloth gate, which is composed of a flexible substrate module, a three-electrode sensor system module, a microfluidic sweat management module, and a signal processing and transmission module, which are sequentially stacked from bottom to top, wherein:

[0066] The flexible substrate module is a thin sheet structure made of biocompatible polymer material (polyurethane PU) with a thickness of 200 μm. The back of the flexible substrate module is coated with a water-permeable pressure-sensitive adhesive layer (acrylate, water flux ≥ 100 mL / (cm 2 ·h), peel strength 0.5 N / cm) for attaching to the human skin and fixing the functional components;

[0067] The three-electrode sensor system module is integrated on the front of the flexible substrate module, including an ion-doped carbon cloth working electrode, an integrated reference electrode, and an integrated counter electrode. The three electrodes are patterned by magnetron sputtering process, with an electrode spacing of 1 mm, forming a stable three-electrode detection system.

[0068] The microfluidic sweat management module covers the working electrode area of the three-electrode sensor system module, which is composed of a hydrophilic microchannel (width 1 mm, depth 0.5 mm, surface treated by plasma to improve hydrophilicity) and a liquid reservoir (volume 200 μL, opening diameter 3 mm), which is used to guide sweat to the working electrode and maintain the stability of the detection interface;

[0069] The signal processing and transmission module includes a micro electrochemical detection circuit (flexible PCB, thickness ≤ 50 μm, integrated operational amplifier and analog-to-digital converter) and a low-power Bluetooth chip (packaged in a PU flexible shell, with no signal attenuation when the bending radius is ≤ 10 mm), which is electrically connected with the three-electrode sensing system module, for real-time collection of electrochemical signals and transmission to an external terminal through Bluetooth.

[0070] In this embodiment, the ion-doped carbon cloth working electrode is the core sensing unit, which is based on carbon cloth doped with boron ions, as follows:

[0071] The basic carbon cloth is polyacrylonitrile-based carbon cloth (carbon fiber diameter 200 nm, single filament number 2000 / cm 2 ), which is cleaned and pretreated (soaked in concentrated nitric acid for 30 min to remove surface impurities, rinsed with deionized water and dried at 60°C);

[0072] The doping treatment is as follows:

[0073] Boron doping: place the carbon cloth in a tube furnace, heat to 1000°C at 10°C / min under argon atmosphere, and introduce trimethyl borate vapor for 4 h, with boron element doped into the carbon skeleton by substitution;

[0074] After doping, the carbon cloth forms a three-dimensional porous network structure with a porosity of ≥ 80%, a specific surface area of ≥ 150 m 2 / g, and an electrical conductivity of 300 S / cm (5 times higher than that of undoped carbon cloth), while the surface-introduced heteroatoms enhance the π-π interaction and hydrogen bond affinity of the cortisol molecules.

[0075] In this embodiment, the ion-doped carbon cloth working electrode is surface-modified with a molecular recognition and signal conversion layer, which is composed of a nanomaterial enhancement layer and a biological recognition layer stacked in gradient, wherein:

[0076] Nanomaterial enhancement layer: loaded on the surface of the carbon cloth by spin coating process, composed of gold nanoparticles (particle size 30 nm, prepared by sodium citrate reduction method), reduced graphene oxide (thickness 10 layers, prepared by Hummers method to prepare oxidized graphite and then reduced by hydrazine hydrate), and MXene (Ti3C2Tx, thickness ≤ 1 μm, prepared by HF etching MAX phase), with a mass ratio of 1:1:1. The composite structure increases the specific surface area by 5 times and the electron transfer rate by 3 orders of magnitude. The surface of the nanomaterial enhancement layer is modified with a signal conversion medium, using potassium ferrocyanide (K4[Fe(CN)6], concentration 10 mM) as the redox mediator. After the combination of cortisol and antibody, the exchange rate of the mediator and the electrode surface changes, producing a measurable change in current signal (detection limit ≤ 0.1 ng / mL, linear range 0.5-100 ng / mL);

[0077] Biological recognition layer: immobilized on the nanomaterial enhanced layer by physical adsorption, the fixed amount is 2 μg / cm 2 Specific recognition affinity constant (Ka) of cortisol ≥10 8 M -1 .

[0078] In this embodiment, the integrated reference electrode is a silver / silver chloride electrode, and its preparation method is:

[0079] An Ag layer (thickness 100 nm) is deposited on the flexible substrate module by magnetron sputtering, and then soaked in a saturated potassium chloride solution for electrochemical chlorination treatment to form an Ag / AgCl composite material layer (Cl - Concentration matched with sweat, about 30 mM);

[0080] The integrated reference electrode surface is covered with a solidified polymer gel (polyacrylamide / sodium alginate composite gel containing 30 mM KCl) with a thickness of 20 μm, and the gel layer porosity is ≥70%, which not only fixes Cl - Concentration to prevent reference potential drift, but also allows ion migration to maintain electrical neutrality.

[0081] In this embodiment, the integrated counter electrode is a carbon electrode: prepared by carbon paste printing process, carbon powder particle size 5 μm, mixed with ethyl cellulose binder and printed on a flexible substrate with a thickness of 80 μm, low cost and good compatibility with sweat.

[0082] In this embodiment, the breathable anti-pollution membrane of the microfluidic sweat management module is covered on the top of the reservoir, and the specific parameters are as follows:

[0083] The membrane material is polytetrafluoroethylene (PTFE), the pore size is 0.45 μm, and the water vapor transmission rate is ≥1000 g / (m 2 ·24h), allowing sweat evaporation and air exchange to maintain stable microenvironment humidity;

[0084] The membrane thickness is 20 μm, the interception rate of PM2.5 particles (particle size ≤2.5 μm) is ≥99%, and the adsorption amount of skin oil is ≤0.1 μg / cm 2 , to avoid contamination of hydrophilic microchannels or contamination of sensing interface;

[0085] The membrane edge is sealed to the microchannel sidewall by UV glue to form a closed space with the reservoir to prevent sweat leakage.

[0086] In this embodiment, the specific composition of the micro electrochemical detection circuit of the signal processing and transmission module is:

[0087] Working electrode lead: connect ion-doped carbon cloth working electrode to the same-phase input terminal of the operational amplifier;

[0088] Reference electrode lead: connecting the integrated reference electrode to the inverting input of the operational amplifier;

[0089] Counter electrode lead: connecting the carbon counter electrode to the output of the operational amplifier, forming a differential amplification circuit to suppress environmental noise interference;

[0090] Analog-to-digital converter: sampling frequency 10 Hz, resolution 16 bits, converting analog current signals to digital signals;

[0091] Microcontroller: built-in algorithm to correct temperature drift (compensation range 20-40℃, error ≤5%) and sweat pH fluctuation (pH 4.5-7.5, error ≤8%), improving detection stability.

[0092] In this embodiment, the composite structure of the nanomaterial enhancement layer and the biological recognition layer optimizes signal amplification in the following way:

[0093] Gold nanoparticles provide high-density active sites, promoting the directional fixation of antibodies / aptamers and electron transfer;

[0094] The two-dimensional sheet structure of reduced graphene oxide forms a "nanobridge", connecting the carbon cloth substrate and gold nanoparticles, shortening the electron transport path;

[0095] The high electrical conductivity and mechanical flexibility of MXene enhance the signal consistency of the sensor in a bent state (current response deviation ≤3% when the bending radius is 5mm);

[0096] The synergistic effect of the three makes the current change caused by cortisol binding increase by 8 times, with a detection sensitivity of 0.05nA / (ng / mL).

[0097] In this embodiment, when the flexible substrate module is attached to the skin, stable monitoring is achieved through the following mechanisms:

[0098] The water permeability of the water-permeable pressure-sensitive adhesive layer allows sweat to penetrate into the microfluidic sweat management module, preventing the accumulation of sweat between the skin and the flexible substrate module, which can cause interfacial sliding;

[0099] The three-dimensional porous structure of the ion-doped carbon cloth working electrode actively draws sweat through capillary force (capillary rise height ≥5mm), ensuring that the sweat layer thickness on the surface of the working electrode is ≥100μm even when the human body is still or in a low-sweat state (sweat output ≤2μL / min);

[0100] The volume design (200μL) of the liquid reservoir combined with the sweat secretion rate (15μL / min in a motion state) ensures that the sensor does not need to be replaced for 24h continuous monitoring.

[0101] The sweat cortisol continuous monitoring sensor based on high-efficiency ion-doped carbon cloth gate is realized through multi-module cooperation to realize continuous monitoring of sweat cortisol, and the specific process is as follows:

[0102] 1. Sweat collection and guidance (microfluidic sweat management module dominant)

[0103] The sweat secreted by the human skin first contacts the water-permeable pressure-sensitive adhesive layer on the back of the sensor (allowing sweat to penetrate), and then is collected to the top liquid pool through the microfluidic microchannel on the surface of the flexible substrate module (hydrophilic design, driven by capillary force). The air-permeable anti-pollution film on the top of the liquid pool allows the sweat to evaporate in a small amount, maintains the stability of the microenvironment humidity, and at the same time blocks dust, grease and other pollutants from blocking the channel or polluting the sensing interface, ensuring that the sweat is continuously and cleanly supplied to the working electrode area.

[0104] 2. Sweat interface stabilization and sensing contact (ion-doped carbon cloth working electrode dominant)

[0105] The ion-doped carbon cloth working electrode actively draws sweat from the liquid pool using its high capillary force to form a stable and uniform sweat layer on the electrode surface. Even in the case of human body stillness or low sweat volume, the capillary action of the porous structure can still maintain sufficient interface sweat, avoiding detection interruption caused by dryness.

[0106] 3. Cortisol specific recognition (molecular recognition and signal conversion layer dominant)

[0107] Cortisol in sweat diffuses to the biological recognition layer (cortisol antibody / aptamer) on the surface of the working electrode, and selective capture is achieved through antibody-antigen specific binding or aptamer-target high affinity action. The biological recognition layer is fixed on the nanomaterial enhancement layer, and the high specific surface area of the nanomaterial increases the recognition site density and enhances the electron transfer efficiency.

[0108] 4. Electrochemical signal generation and amplification (three-electrode system and signal medium cooperation)

[0109] After the recognition reaction is triggered, the electrochemical environment of the working electrode changes:

[0110] Redox mediator effect: The pre-modified potassium ferricyanide / potassium ferrocyanide acts as a mediator and transfers electrons through reversible redox reaction. After cortisol binds to the antibody, the exchange rate of the mediator and the electrode surface changes, resulting in a change in the current signal.

[0111] Nanomaterials synergistic amplification: Gold nanoparticles provide high-density active sites, reduced graphene oxide shortens the electron transport path, and MXene enhances mechanical flexibility. The three synergistically amplify the signal, with a sensitivity of 0.05 nA / (ng / mL).

[0112] 5. Signal processing and transmission (signal processing and transmission module dominant)

[0113] The micro electrochemical detection circuit collects the current change signal of the working electrode, after differential amplification (noise suppression) and analog-to-digital conversion, the temperature and pH drift are corrected by the microcontroller, and finally the real-time data (such as concentration value, time stamp) are wirelessly transmitted to the external mobile terminal or cloud server through the low-power Bluetooth chip, completing continuous monitoring.

[0114] The above shows and describes the basic principles, main features and advantages of the present application. Those skilled in the art should understand that the present application is not limited to the above embodiments, and the above embodiments and descriptions in the specification are only to illustrate the principles of the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the claimed present application. The scope of protection of the present application is defined by the appended claims and their equivalents.

Claims

1. A continuous monitoring sensor for cortisol in sweat based on a high-efficiency ion-doped carbon cloth gate, comprising a flexible substrate module, a three-electrode sensing system module, a microfluidic sweat management module, and a signal processing and transmission module, characterized in that: The flexible substrate module is a sheet-like structure made of biocompatible polymer material, and the back of the flexible substrate module is coated with a water-permeable pressure-sensitive adhesive layer. The three-electrode sensing system module is integrated on the front of the flexible substrate module and includes an ion-doped carbon cloth working electrode, an integrated reference electrode, and an integrated counter electrode, which are patterned by screen printing or magnetron sputtering. The microfluidic sweat management module covers the working electrode area of ​​the three-electrode sensing system module and consists of hydrophilic microchannels and a liquid storage tank, which is used to guide sweat to the working electrode of the three-electrode sensing system module. The signal processing and transmission module is electrically connected to the three-electrode sensing system module, including a micro electrochemical detection circuit and a low-power Bluetooth chip, which collects electrochemical signals in real time and transmits them to an external terminal via Bluetooth.

2. The sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth grid according to claim 1, characterized in that: The ion-doped carbon cloth working electrode uses a base carbon cloth and is doped with either nitrogen ions or boron ions. The base carbon cloth is a polyacrylonitrile-based carbon cloth that has undergone cleaning and pretreatment. The ion doping treatment of the base carbon cloth is carried out by hydrothermal method or high-temperature calcination method to introduce either nitrogen ions or boron ions. After doping, the carbon cloth forms a three-dimensional porous network structure.

3. The sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth grid according to claim 1, characterized in that: The surface of the ion-doped carbon cloth working electrode is modified with a molecular recognition and signal conversion layer. The molecular recognition and signal conversion layer is composed of a gradient stack of a nanomaterial reinforcement layer and a biorecognition layer. The nanomaterial reinforcement layer is loaded onto the carbon cloth surface by electrodeposition or spin coating and is composed of gold nanoparticles, reduced graphene oxide and MXene. The surface of the nanomaterial reinforcement layer is modified with a signal conversion medium, using potassium ferricyanide / potassium ferrocyanide as a redox mediator. The biorecognition layer is fixed to the nanomaterial reinforcement layer by covalent bonding or physical adsorption.

4. The sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth grid according to claim 1, characterized in that: The integrated reference electrode is a silver / silver chloride electrode, with a surface covered by a 10-20 μm thick cured polymer gel. The preparation method of the silver / silver chloride electrode is as follows: An Ag layer was deposited on a flexible substrate module by magnetron sputtering, followed by electrochemical chlorination treatment by immersion in a saturated potassium chloride solution to form an Ag / AgCl composite layer.

5. The sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth grid according to claim 1, characterized in that: The integrated electrode is selected from platinum sheet electrode or carbon electrode. The platinum sheet electrode is deposited on the flexible substrate module by magnetron sputtering to form a porous Pt layer. The carbon electrode is prepared by carbon paste printing process and printed on the flexible substrate module after being mixed with ethyl cellulose binder.

6. The sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth grid according to claim 1, characterized in that: The breathable and anti-fouling membrane of the microfluidic sweat management module covers the top of the liquid storage tank. The membrane material is selected from polydimethylsiloxane or polytetrafluoroethylene, and the membrane thickness is 10-20 μm. The membrane edge is sealed to the hydrophilic microchannel sidewall by hot pressing or UV adhesive.

7. The sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth grid according to claim 1, characterized in that: The micro electrochemical detection circuit of the signal processing and transmission module includes a working electrode lead connecting the ion-doped carbon cloth working electrode to the non-inverting input of the operational amplifier, a reference electrode lead connecting the integrated reference electrode to the inverting input of the operational amplifier, a counter electrode lead connecting the integrated counter electrode to the output of the operational amplifier, an analog-to-digital converter that converts the analog current signal into a digital signal, and a microcontroller.

8. The sweat cortisol continuous monitoring sensor based on a high-efficiency ion-doped carbon cloth grid according to claim 1, characterized in that: When the flexible substrate module is attached to the skin, the water permeability of the water-permeable pressure-sensitive adhesive layer allows sweat to penetrate into the microfluidic sweat management module, and the three-dimensional porous structure of the ion-doped carbon cloth working electrode actively absorbs sweat through capillary force.

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