A cortisol sensor and its preparation method, a wearable device and its preparation method and application
By developing a wearable device that combines a cortisol sensor and an HRV sensor to monitor heart rate and cortisol concentration in real time, the problem of accurate assessment of mental stress in existing technologies has been solved, and timely and accurate assessment and feedback of mental stress has been achieved.
Patent Information
- Application Number
- CN202410925921.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-07-10
- Publication Date
- 2025-09-16
- Estimated Expiration
- 2044-07-10
AI Technical Summary
Existing technologies make it difficult to accurately assess mental stress, especially among adolescents due to the lack of effective monitoring methods, which makes it difficult to detect and intervene in mental stress-related diseases in a timely manner.
Develop a cortisol sensor that uses an organic electrochemical transistor to detect cortisol concentration in sweat, combines it with an HRV sensor for comprehensive analysis, and monitors heart rate and cortisol concentration in real time through wearable devices to assess mental stress.
It achieves a more accurate assessment of mental stress, can detect changes in mental stress in a timely manner, and provides a non-invasive means of mental stress assessment to help users closely observe changes in psychological emotions and respond in a timely manner.
Smart Images
Figure CN118817806B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of sensor preparation, and specifically relates to a cortisol sensor and a preparation method thereof, a wearable device and a preparation method and application thereof. Background Art
[0002] Long-term, recurring mental stress often leads to various illnesses, such as depression, anxiety, and decreased immune function, posing a serious threat to both physical and mental health. However, chronic mental stress can be highly insidious, especially for adolescents, who often lack communication with their caregivers, making it difficult for professionals to detect and intervene in the early stages. Currently, mental stress assessments typically involve professional evaluations by psychologists and involve complex processes such as invasive blood tests.
[0003] With the rapid development of wearable devices, especially smartwatches and wristbands, these convenient intelligent electronic products are widely used in office, entertainment, and sports scenarios. Current wristbands generally use photoplethysmography to analyze heart rate variability (HRV) by monitoring blood flow at the wrist. This method can provide a simple assessment of psychological stress, but accurate judgment based on this single signal is difficult and prone to errors, causing distress to the wearer. Summary of the Invention
[0004] The purpose of the present invention is to provide a cortisol sensor and a preparation method thereof, a wearable device and a preparation method and application thereof. The data obtained by the wearable device provided by the present invention is more accurate.
[0005] In order to achieve the above object, the present invention provides the following technical solutions:
[0006] The present invention provides a cortisol sensor, comprising an organic electrochemical transistor; the organic electrochemical transistor comprises a substrate, and a gate, a source electrode, a drain electrode, and a channel covered on the surface of the substrate; the surface of the channel is poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) (PEDOT:PSS); the gate is a gold-chromium alloy; and the surface of the gate is modified with a cortisol molecularly imprinted methacrylic acid polymer (PBMIP) doped with Prussian blue.
[0007] Preferably, the channel has a width of 0.5 to 2 mm, a length of 3 to 8 mm, and a distance from the gate of 0.5 to 2 cm.
[0008] Preferably, the gold-chromium alloy comprises a superimposed chromium layer and a gold layer; the thickness of the chromium layer is 1 to 10 nm; and the thickness of the gold layer is 10 to 50 nm.
[0009] Preferably, a sweat absorbing layer is further provided on the surface of the Prussian blue-doped cortisol molecularly imprinted methacrylic acid polymer.
[0010] Preferably, a waterproof film is also provided on the surfaces of the gate, source and drain.
[0011] Preferably, the substrate is a silicon wafer or a flexible material; the thickness of the substrate is 0.01 to 1 mm.
[0012] The present invention also provides a method for preparing the cortisol sensor described in the above scheme, comprising the following steps:
[0013] (1) coating a substrate surface with photoresist and then performing photolithography and development processes in sequence to obtain a substrate with exposed channels;
[0014] (2) coating a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) mixed solution (PEDOT:PSS mixed solution) on the exposed channel surface of the substrate, and then sequentially performing curing, debonding, and electrode evaporation to obtain a basic transistor, wherein the electrodes include a gate, a drain, and a source;
[0015] (3) A Prussian blue-doped cortisol molecularly imprinted methacrylic acid polymer solution (PBMIP solution) and a perfluorinated resin solution (Nafion solution) were coated on the gate surface and dried to obtain a cortisol sensor.
[0016] The present invention also provides a wearable device, comprising a circuit board, a cortisol sensor connected to the circuit board, and a heart pulse sensor connected to the circuit board; the circuit board is provided with a signal amplification module; the cortisol sensor is the cortisol sensor described in the above scheme or the cortisol sensor obtained by the preparation method described in the above scheme.
[0017] Preferably, the wearable device is a wearable watch.
[0018] The present invention also provides the use of the wearable device described in the above scheme or the wearable device obtained by the preparation method described in the above scheme in obtaining heart rate and cortisol concentration data.
[0019] The present invention provides a cortisol sensor. This invention innovatively uses sweat on the skin surface as an analysis source. When people face a stressful environment, the cortisol concentration increases. The cortisol sensor accurately identifies cortisol molecules in sweat that can be used for psychological stress analysis. The molecularly imprinted polymer (PBMIP) doped with Prussian blue can capture cortisol molecules and block the conduction path of PBMIP, causing the channel current to decrease, thereby realizing the detection of cortisol molecules (such as Figure 1As shown), the cortisol data is obtained by cooperating with the sensor signal amplification and transmission. The cortisol sensor of the present invention has good flexibility, sensitivity, selectivity and stability, and can continuously monitor sweat for a day.
[0020] The present invention also provides a method for preparing the cortisol sensor described in the above scheme. The preparation method provided by the present invention is easy to operate, has good feasibility, good stability, and has good market prospects.
[0021] The present invention also provides a wearable device. The wearable device is based on multiple sensors, such as a cortisol sensor and an HRV sensor. The present invention utilizes the aforementioned cortisol sensor to acquire cortisol data. Simultaneously, the present invention incorporates analysis from an HRV sensor, which utilizes the established photoplethysmography method, along with sensor signal amplification and transmission, to provide an alternative method for acquiring heartbeat data. By acquiring heartbeat and cortisol concentration data through both sweat and skin, the present invention can help users more accurately detect and record changes in psychological stress, allowing for a non-invasive assessment of mental stress.
[0022] The wearable device provided by the present invention is easy to use and operate, does not require professional operation, is user-friendly, can continuously monitor for a long time, helps users closely observe their own psychological and emotional changes, and respond to abnormal anxiety states in a timely manner, and has good prospects for large-scale application.
[0023] The present invention also provides the use of the wearable device described in the above scheme, or the wearable device obtained by the preparation method described in the above scheme, for obtaining heart rate and cortisol concentration data. The wearable device provided by the present invention does not require professional operation and can provide continuous monitoring for a long time, helping relevant personnel closely observe the wearer's psychological and emotional changes and respond promptly to abnormal anxiety states, thus having promising application prospects. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.
[0025] Figure 1 This is a schematic diagram of the principle of PBMIP recognizing cortisol molecules and electrical signal changes in the cortisol sensor provided by the present invention;
[0026] Figure 2 This is a schematic diagram of the structure of the organic electrochemical transistor in the cortisol sensor provided by the present invention;
[0027] Figure 3 It is the software signal receiving interface for the mobile phone APP (a) and the computer host computer (b);
[0028] Figure 4 A schematic structural diagram of the wearable device provided by the present invention;
[0029] Figure 5 A physical picture of the wearable device provided by the present invention;
[0030] Figure 6 The current change diagram of different concentrations of cortisol in artificial sweat (a) and the linear relationship diagram of current size and cortisol concentration (b);
[0031] Figure 7 The sensor current changes (a) and cortisol concentration changes (b) during the test of spinning exercise are shown.
[0032] Figure 1: 1 is a sweat absorption layer, 2 is a waterproof film, 3 is a Prussian blue-doped cortisol molecular imprinted methacrylic acid polymer, 4 is poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid), 5 is a gold-chromium alloy, 6 is a substrate, 7 is a source electrode, 8 is a drain electrode, 9 is a gate electrode, 11 is an LCD screen, 12 is Bluetooth, 13 is a single-chip microcomputer (MCU), 14 is a battery interface, and 15 is a USB interface. DETAILED DESCRIPTION
[0033] The present invention provides a cortisol sensor, comprising an organic electrochemical transistor; the organic electrochemical transistor comprises a substrate, and a gate, a source electrode, a drain electrode, and a channel covered on the surface of the substrate; the surface of the channel is poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) (PEDOT:PSS); the gate is a gold-chromium alloy; and the surface of the gate is modified with a cortisol molecularly imprinted methacrylic acid polymer (PBMIP) doped with Prussian blue.
[0034] In the present invention, the substrate is preferably a silicon wafer or a flexible material; the flexible material is preferably a PET film; the thickness of the substrate is preferably 0.01 to 1 mm, more preferably 0.1 mm; the surface of the silicon wafer is preferably provided with a silicon oxide surface layer; the thickness of the silicon oxide surface layer is preferably 100 to 500 nm, more preferably 300 nm.
[0035] In the present invention, the gate is a gold-chromium alloy, which preferably includes a superimposed chromium layer and a gold layer; the thickness of the chromium layer in the gate is preferably 1 to 10 nm, more preferably 10 nm; the thickness of the gold layer is preferably 10 to 50 nm, more preferably 30 nm.
[0036] In the present invention, the source electrode is preferably a gold-chromium alloy; the gold-chromium alloy preferably includes a superimposed chromium layer and a gold layer; the thickness of the chromium layer in the source electrode is preferably 1 to 10 nm, more preferably 10 nm; the thickness of the gold layer is preferably 10 to 50 nm, more preferably 30 nm.
[0037] In the present invention, the drain electrode is preferably a gold-chromium alloy; the gold-chromium alloy preferably includes a superimposed chromium layer and a gold layer; the thickness of the chromium layer in the drain electrode is preferably 1 to 10 nm, more preferably 10 nm; the thickness of the gold layer is preferably 10 to 50 nm, more preferably 30 nm.
[0038] In the present invention, the gate, source, and drain electrodes are preferably provided with a waterproof film; the waterproof film is preferably a PE adhesive film, a PET adhesive film, or a PVC adhesive film. By covering the surface with the waterproof film, the present invention ensures that there will be no leakage during use.
[0039] In the present invention, the width of the channel is preferably 0.5 to 2 mm, more preferably 1 to 1.5 mm, the length is preferably 3 to 8 mm, more preferably 5 to 7 mm, and the distance from the gate is preferably 0.5 to 2 cm, more preferably 1 to 1.5 cm.
[0040] In the present invention, the surface of the Prussian blue-doped cortisol molecularly imprinted methacrylic acid polymer is preferably further provided with a sweat-absorbing layer; the sweat-absorbing layer is preferably a hydrogel. The present invention uses a hydrogel as a sweat-absorbing layer to direct sweat into the sensor's sensing area, thereby avoiding discomfort caused by contact between the sensor and the skin surface and ensuring that the sensor is not damaged during use.
[0041] In the present invention, the sweat absorbing layer is preferably fixed by gluing or mold fixing; the glue used for gluing is preferably plastic-specific glue or 502 glue.
[0042] In the present invention, the hydrogel is preferably prepared by heating and mixing polyvinyl alcohol (PVA), a pore-forming agent and water, and then allowing to stand and soaking in sequence.
[0043] In the present invention, the weight average molecular weight of the polyvinyl alcohol is preferably 70,000 to 100,000, more preferably 98,000.
[0044] In the present invention, the pore-forming agent is preferably sucrose; the mass ratio of the pore-forming agent to polyvinyl alcohol is preferably 14-28:20-60, more preferably 18-24:30-50, and further preferably 21:40.
[0045] In the present invention, the mass ratio of the polyvinyl alcohol to water is preferably 2-6:20-60, more preferably 4-5:40-50.
[0046] In the present invention, the temperature of the heating and mixing is preferably 80 to 120° C., more preferably 90 to 110° C., and the mixing time is preferably 2 to 4 hours, more preferably 3 hours; and the heating and mixing is preferably stirring and mixing.
[0047] In the present invention, the standing is preferably performed in a culture dish; the standing temperature is preferably room temperature until dry.
[0048] In the present invention, the soaking agent is preferably distilled water, and the soaking time is preferably 24 hours. In the present invention, the pore-forming agent is dissolved by soaking.
[0049] In the present invention, the soaking step preferably includes cutting, wherein the target size of the cutting is preferably 1 cm*1 cm. The present invention makes the hydrogel more conformable to the sensor surface by cutting, and the hydrogel is soaked in PBS buffer solution after cutting for later use.
[0050] In the cortisol sensor provided by the present invention, the structure of the organic electrochemical transistor is as follows: Figure 2 As shown, it includes a substrate, and a gate, a source, a drain and a channel covered on the surface of the substrate, the gate surface is covered with a PEDOT:PSS film, a Prussian blue-doped cortisol molecular imprinted methacrylic acid polymer and a waterproof film, and the surface of the Prussian blue-doped cortisol molecular imprinted methacrylic acid polymer is covered with a sweat absorption layer.
[0051] The present invention also provides a method for preparing the cortisol sensor described in the above scheme, comprising the following steps:
[0052] (1) coating a substrate surface with photoresist and then performing photolithography and development processes in sequence to obtain a substrate with exposed channels;
[0053] (2) coating a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) mixed solution (PEDOT:PSS mixed solution) on the exposed channel surface of the substrate, and then sequentially performing curing, debonding, and electrode evaporation to obtain a basic transistor, wherein the electrodes include a gate, a drain, and a source;
[0054] (3) A Prussian blue-doped cortisol molecularly imprinted methacrylic acid polymer solution (PBMIP solution) and a perfluorinated resin solution (Nafion solution) were coated on the gate surface and dried to obtain a cortisol sensor.
[0055] The present invention coats a substrate surface with photoresist and then sequentially performs photolithography and development processes to obtain a substrate with exposed channels. In the present invention, the substrate is preferably cleaned before use; the cleaning preferably includes sequential water washing and alcohol washing; the water used for the water washing is preferably deionized water; the number of water washings is preferably 3 to 5, more preferably 4; the alcohol used for the alcohol washing is preferably ethanol; the number of alcohol washings is preferably 3 to 5, more preferably 4.
[0056] In the present invention, the coating amount of the photoresist is preferably 1 to 100 kg / m 2 , more preferably 5 to 10 kg / m 2 The present invention uses photoresist to cover the entire surface, and then uses a standard photolithography process to perform photolithography to expose the channel.
[0057] In the present invention, the development treatment preferably further includes washing the substrate; the washing is preferably plasma cleaning; the washing equipment is preferably a plasma cleaning machine; the washing time is preferably 10 to 60 seconds, more preferably 30 to 50 seconds.
[0058] After obtaining a substrate with exposed channels, the present invention applies a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) mixed solution (PEDOT:PSS mixed solution) to the exposed channel surface of the substrate (referred to as the first coating), followed by curing, debonding, and electrode evaporation to obtain a basic transistor. The electrodes include a gate, a drain, and a source. In the present invention, the PEDOT-PSS mixed solution preferably includes the following components: PEDOT, PSS, 3-glycidoxypropyltrimethoxysilane, dodecylbenzenesulfonic acid, ethylene glycol, and water.
[0059] In the present invention, the volume ratio of PEDOT to PSS is preferably 1:4-8, more preferably 1:5-7, and even more preferably 1:6.
[0060] In the present invention, the volume ratio of the total volume of PEDOT and PSS to water is preferably 0.5 to 5:100, more preferably 1.5:100.
[0061] In the present invention, the volume ratio of the 3-glycidyloxypropyltrimethoxysilane to water is preferably 0.1-0.8:8-10, more preferably 0.3-0.6:9.
[0062] In the present invention, the volume ratio of dodecylbenzenesulfonic acid to water is preferably 0.04-0.12:8-10, more preferably 0.07-0.09:9.
[0063] In the present invention, the volume ratio of ethylene glycol to water is preferably 0.2-0.8:8-10, more preferably 0.4-0.6:9.
[0064] In the present invention, the PEDOT-PSS mixed solution is preferably stored at 4°.
[0065] In the present invention, the PEDOT:PSS mixed solution is preferably filtered before use. The present invention removes solid impurities by filtering.
[0066] In the present invention, the first coating is preferably drop coating followed by spin coating; the rotation speed of the spin coating is preferably 1000-3000 rpm, more preferably 1500-2500 rpm, and the time is preferably 10-60 s, more preferably 30-50 s.
[0067] In the present invention, the curing temperature is preferably 60-180°C, more preferably 90-150°C, further preferably 120°C, the holding time is preferably 20-60 min, more preferably 30-50 min, further preferably 40 min; the curing equipment is preferably an oven.
[0068] In the present invention, the debonding is preferably performed using a debonding liquid. In the present invention, a PEDOT:PSS film attached to a specific position of the substrate is obtained by debonding.
[0069] In the present invention, the electrode evaporation is preferably performed by attaching a mask to the surface of the PEDOT:PSS film obtained by curing and debonding, and performing evaporation using chromium and gold.
[0070] In the present invention, the evaporation current of the electrode evaporation is preferably 120 to 140 A, more preferably 130 A, and the evaporation rate is preferably 0.1 nm / s.
[0071] After obtaining the basic transistor, the present invention coats (referred to as the second coating) a Prussian blue-doped cortisol molecularly imprinted methacrylic acid polymer solution (PBMIP solution) and a perfluorinated resin solution (Nafion solution) on the gate surface and then dries to obtain a cortisol sensor.
[0072] In the present invention, the preparation method of the Prussian blue-doped molecularly imprinted polymer (PBMIP) is preferably as follows: in a protective atmosphere, using cortisol as a template, mixing an initiator, methacrylic acid, a crosslinking agent, Prussian blue and a good solvent for polymerization reaction.
[0073] In the present invention, the molar ratio of cortisol to methacrylic acid is preferably 1-6:16-28, more preferably 3-5:19-25, and even more preferably 4:21-22.
[0074] In the present invention, the initiator is preferably azobisisobutyronitrile; the molar ratio of methacrylic acid to initiator is preferably 160-280:5-9, more preferably 190-240:6-8, and further preferably 210-220:7.
[0075] In the present invention, the cross-linking agent is preferably ethylene glycol methacrylate; the molar ratio of the cross-linking agent to methacrylic acid is preferably 80-140:16-28, more preferably 100-130:20-25, and further preferably 110-120:22-23.
[0076] In the present invention, the molar ratio of Prussian blue to methacrylic acid is preferably 2-8:16-28, more preferably 4-6:18-25, and even more preferably 5:20-22.
[0077] In the present invention, the good solvent is preferably dichloromethane; the molar volume ratio of methacrylic acid to the good solvent is preferably (1.6-2.8) mmol: (4-10) mL, more preferably (1.8-2.5) mmol: (6-8) mL.
[0078] In the present invention, the polymerization reaction device is preferably a quartz round-bottom flask; and nitrogen is preferably used for purge before the polymerization reaction. In the present invention, air in the device is removed by purge.
[0079] In the present invention, the polymerization reaction is preferably carried out under ultraviolet irradiation and protective gas; the protective gas is preferably nitrogen; the temperature of the polymerization reaction is preferably -4 to 4°C, more preferably 0°C, and the insulation time is preferably 24 hours; the present invention preferably controls the temperature of the polymerization reaction to the above target value by cooling in an ice bath.
[0080] In the present invention, after the polymerization reaction, the obtained reaction product is preferably subjected to post-treatment; the post-treatment preferably includes grinding, washing and drying performed in sequence.
[0081] In the present invention, the washing reagent is preferably methanol and acetic acid; the volume ratio of methanol to acetic acid is preferably 8:2; the number of washings is preferably 1 or more, more preferably 3 times; the drying is preferably vacuum drying; the vacuum degree of the vacuum drying is preferably >0.8 kg / cm 3 The drying time is preferably 12 to 24 hours, more preferably 18 hours.
[0082] In the present invention, the PBMIP solution is preferably prepared by mixing PBMIP powder and water; the mass ratio of the PBMIP powder to water is preferably 1:2 to 8, more preferably 1:3 to 6, and even more preferably 1:4 to 5. After the preparation of the present invention, the PBMIP solution is sealed and set aside.
[0083] In the present invention, the concentration of the Nafion solution is preferably 1-10 wt%, more preferably 5 wt%. The Nafion solution is preferably prepared by diluting a commercially available Nafion solution with water and sealing it for later use. The present invention uses the Nafion solution to immobilize the imprinted molecules, preventing them from falling off during use.
[0084] In the present invention, the volume ratio of the PBMIP solution to the Nafion solution is preferably 1:1-6, more preferably 1:2-5, and even more preferably 1:3-4.
[0085] In the present invention, the second coating is preferably drop coating; the coating amount of the second coating is preferably 0.2 to 20 μL / cm 2 , more preferably 2 to 10 μL / cm 2 .
[0086] In the present invention, the drying is preferably carried out until the surface moisture evaporates to form a stable film, and then the product is vacuum-sealed and stored; the drying is preferably carried out by infrared irradiation.
[0087] The present invention also provides a wearable device, comprising a circuit board, a cortisol sensor connected to the circuit board, and a heart pulse sensor connected to the circuit board; the circuit board is provided with a signal amplification module; the cortisol sensor is the cortisol sensor described in the above scheme or the cortisol sensor obtained by the preparation method described in the above scheme.
[0088] The wearable device provided by the present invention includes a circuit board; the circuit board is preferably further provided with a single-chip microcomputer, a power supply circuit, a Bluetooth module and an interface; the interface preferably includes a battery interface and a USB interface (micro-USB data line interface). The present invention has developed the above-mentioned signal collection scheme, and the data collected by the two sensors are transmitted to the single-chip microcomputer for analysis. The results can be transmitted to a mobile phone via a Bluetooth module or connected to a computer using a microprogram controller on the circuit board, and the mobile phone APP and the host computer software (interface as shown) are produced. Figure 3 As shown), used for signal collection and cloud upload (specific structure as shown Figure 4 and Figure 5 shown).
[0089] The wearable device provided by the present invention preferably also includes a current and voltage measuring device. The present invention first uses the current and voltage measuring device to detect the sensor's signal current. Based on the obtained data, a signal amplification module on the circuit board amplifies the signal current. The amplification circuit is used to eliminate bias current and improve accuracy.
[0090] In the present invention, the wearable device is preferably a wearable watch.
[0091] The present invention also provides a method for preparing the wearable device described in the above scheme, comprising the following steps:
[0092] The cortisol sensor and the heart pulse sensor are connected to the circuit board respectively to obtain a wearable device.
[0093] The present invention also provides the use of the wearable device described in the above scheme or the wearable device obtained by the preparation method described in the above scheme in obtaining heart rate and cortisol concentration data.
[0094] The wearable device provided by the present invention is easy to use and operate, does not require professional operation, is user-friendly, can continuously monitor for a long time, helps relevant personnel closely observe the wearer's psychological and emotional changes, and responds to abnormal anxiety states in a timely manner, and has good application prospects.
[0095] In order to further illustrate the present invention, the scheme of the present invention is described in detail below with reference to the accompanying drawings and embodiments, but they should not be understood as limiting the scope of protection of the present invention.
[0096] Example 1
[0097] (1) Preparation of PEDOT:PSS mixed solution
[0098] 0.2 mL of ethylene glycol, 0.1 mL of 3-glycidoxypropyltrimethoxysilane, 8 mL of PEDOT:PSS solution (the volume ratio of PEDOT:PSS is 1:4, water is used as the dispersant, and the mass concentration is 1.5%), and 0.04 mL of dodecylbenzenesulfonic acid are stirred evenly and sealed and stored in a refrigerator at 4°C.
[0099] (2) Construction of organic electrochemical transistors
[0100] The substrate is a silicon wafer with a 300nm silicon oxide surface layer and a thickness of 0.1mm; the substrate surface is rinsed with deionized water and ethanol three times respectively, and then the surface is completely covered with photoresist. The standard photolithography process is used to expose the channel where PEDOT:PSS is to be spin-coated, and then the substrate is developed to obtain a substrate with a channel exposed with PEDOT:PSS; then, the developed substrate is treated with a plasma plasma cleaning machine for 10s, and after being taken out, the PEDOT:PSS mixed solution prepared in step 1 is filtered with a filter membrane, and then drop-coated on the position of the exposed channel, spin-coated at 1000rpm for 60s, and then placed in an oven at 60°C and heated for 60min. After being taken out, the substrate is debonded with a debonding solution to obtain a substrate with a partially attached PEDOT:PSS film (such as Figure 2); then, electrodes were deposited using thermal evaporation with an evaporation current of 120 A and an evaporation rate of 0.1 nm / s. A mask was attached to the substrate surface and chromium and gold were deposited with thicknesses of 10 nm and 30 nm, respectively, to obtain an organic electrochemical transistor.
[0101] (3) Synthesis of Prussian blue-doped molecularly imprinted polymer (PBMIP) solution
[0102] 0.1 mmol cortisol was used as a template, 0.05 mmol azobisisobutyronitrile was used as an initiator, 1.6 mmol methacrylic acid was used as a functional monomer, 8 mmol methacrylate glycol was used as a cross-linking agent, and 0.2 mmol Prussian blue was added for doping; the above raw materials were dissolved in 4 mL dichloromethane to obtain a mixture, and then a polymerization reaction was carried out, and the polymerization reaction was continued at 0°C for 24 hours; the reaction vessel was a quartz round-bottom flask, and nitrogen was used to purge the reaction vessel before the start of the polymerization reaction to remove the air in the reaction vessel; at the beginning of the polymerization reaction, the quartz round-bottom flask containing the mixture was placed under ultraviolet light and the reaction vessel was cooled with an ice bath to avoid overheating; all operations and reaction processes were carried out under nitrogen protection; after the reaction, the generated block solid was ground into powder and washed three times with a methanol / acetic acid mixture (the volume ratio of methanol to acetic acid was 8:2); finally, the molecularly imprinted polymer (MIP) powder doped with Prussian blue (PB) was dried in a vacuum dryer (vacuum degree>0.8 kg / cm 3 ) for 12 h, and then the obtained powder was mixed with water in a mass ratio of 1:2 to obtain a PBMIP solution, which was sealed for later use.
[0103] (4) Preparation of Nafion solution
[0104] The commercially available Nafion solution was diluted with water to prepare a 5 wt % Nafion solution, which was sealed and stored for later use.
[0105] (5) Modification of organic electrochemical transistors
[0106] The PBMIP solution in step (3) and the Nafion solution in step (4) were mixed in a volume ratio of 1:1; 6 μL of the mixed solution was dropwise applied to the surface of the gate electrode and irradiated with an infrared lamp until the surface water evaporated to form a stable film, completing the modification and then sealing the film in a vacuum seal for storage.
[0107] (6) Preparation of hydrogel
[0108] Add 2 g of polyvinyl alcohol (PVA) with a weight-average molecular weight of 98,000 into a beaker, add 20 mL of water, and add 1.4 g of sucrose for pore formation. Stir at 80°C for 4 h, pour into a culture dish while hot, wait until it is completely dry, and soak it in distilled water for 24 h to completely dissolve the sucrose. Then cut the hydrogel into 1 cm*1 cm pieces and soak it in PBS buffer solution for later use.
[0109] (7) Construction of cortisol sensor
[0110] The electrode on the surface of the organic electrochemical transistor modified in step (5) is covered with a PE waterproof film, and then the hydrogel prepared in step (6) is covered on the surface of the transistor, and the hydrogel is bonded to the substrate using plastic glue to obtain a cortisol sensor.
[0111] (8) Integrated circuit design
[0112] A current and voltage measuring device is used to detect the signal current of the cortisol sensor, and the signal current is amplified based on the obtained data. The amplification circuit is used to eliminate the bias current; the heart pulse sensor uses the PPG heart rate measurement method and is directly integrated into the circuit board; the data collected by both sensors are transmitted to the microcontroller for analysis, and the results are sent to a mobile phone or computer.
[0113] Example 2
[0114] (1) Preparation of PEDOT:PSS mixed solution
[0115] 0.8 mL of ethylene glycol, 0.8 mL of 3-glycidoxypropyltrimethoxysilane, 10 mL of PEDOT:PSS solution (the volume ratio of PEDOT:PSS is 1:8, water is used as the dispersant, and the mass concentration is 1.5%), and 0.12 mL of dodecylbenzenesulfonic acid are stirred evenly and sealed and stored in a refrigerator at 4°C.
[0116] (2) Construction of organic electrochemical transistors
[0117] The substrate is PET with a thickness of 0.1 mm. The substrate surface is rinsed with deionized water and ethanol for 5 times respectively, and then the entire surface is covered with photoresist. The standard photolithography process is used to expose the channel where PEDOT:PSS is to be spin-coated, and then the substrate is developed to obtain a substrate with exposed PEDOT:PSS channels. The developed substrate is then treated with a plasma cleaning machine for 60 seconds. After being taken out, the PEDOT:PSS mixed solution prepared in step 1 is filtered with a filter membrane and then drop-coated on the position of the exposed channel. The substrate is spin-coated at 3000 rpm for 10 seconds and then placed in an oven at 180°C for 20 minutes. After being taken out, the substrate is debonded with a debonding solution to obtain a substrate with a partially attached PEDOT:PSS film (such as Figure 2); then, electrodes were deposited using thermal evaporation with an evaporation current of 140 A and an evaporation rate of 0.1 nm / s. A mask was attached to the substrate surface and chromium and gold were deposited with thicknesses of 10 nm and 30 nm, respectively, to obtain an organic electrochemical transistor.
[0118] (3) Synthesis of Prussian blue-doped molecularly imprinted polymer (PBMIP) solution
[0119] 0.6 mmol of cortisol was used as a template, 0.09 mmol of azobisisobutyronitrile was used as an initiator, 2.8 mmol of methacrylic acid was used as a functional monomer, 14 mmol of methacrylic acid glycol was used as a cross-linking agent, and 0.8 mmol of Prussian blue was added for doping; the above raw materials were dissolved in 10 mL of dichloromethane to obtain a mixture, and then a polymerization reaction was carried out at 0°C for 24 hours; the reaction vessel was a quartz round-bottom flask, and nitrogen was used to purge the reaction vessel before the start of the polymerization reaction to remove the air in the reaction vessel; at the beginning of the polymerization reaction, the quartz round-bottom flask containing the mixture was placed under ultraviolet light and the reaction vessel was cooled with an ice bath to avoid overheating; all operations and reaction processes were carried out under nitrogen protection; after the reaction, the generated block solid was ground into powder and washed three times with a methanol / acetic acid mixture (the volume ratio of methanol to acetic acid was 8:2); finally, the molecularly imprinted polymer (MIP) powder doped with Prussian blue (PB) was dried in a vacuum dryer (vacuum degree>0.8 kg / cm 3 ) for 24 h, and then the obtained powder was mixed with water in a mass ratio of 1:8 to obtain a PBMIP solution, which was sealed for later use.
[0120] (4) Preparation of Nafion solution
[0121] The commercially available Nafion solution was diluted with water to prepare a 5 wt % Nafion solution, which was sealed and stored for later use.
[0122] (5) Modification of organic electrochemical transistors
[0123] The PBMIP solution in step (3) and the Nafion solution in step (4) were mixed in a volume ratio of 1:6; 6 μL of the mixed solution was dropwise applied to the surface of the gate electrode and irradiated with an infrared lamp until the surface water evaporated to form a stable film, completing the modification and then sealing the film in a vacuum seal.
[0124] (6) Preparation of hydrogel
[0125] Add 6 g of polyvinyl alcohol (PVA) with a weight-average molecular weight of 98,000 into a beaker, add 60 mL of water, and add 2.8 g of sucrose for pore formation. Stir at 120°C for 4 h, pour into a culture dish while hot, wait until it is completely dry, and soak it in distilled water for 24 h to completely dissolve the sucrose. Then cut the hydrogel into 1 cm*1 cm pieces and soak it in PBS buffer solution for later use.
[0126] (7) Construction of cortisol sensor
[0127] The electrode on the surface of the organic electrochemical transistor modified in step (5) is covered with a PVC waterproof film, and then the hydrogel prepared in step (6) is covered on the surface of the transistor, and the hydrogel is bonded to the substrate using plastic glue to obtain a cortisol sensor.
[0128] (8) Integrated circuit design
[0129] A current and voltage measuring device is used to detect the signal current of the cortisol sensor, and the signal current is amplified based on the obtained data. The amplification circuit is used to eliminate the bias current; the heart pulse sensor uses the PPG heart rate measurement method and is directly integrated into the circuit board; the data collected by both sensors are transmitted to the microcontroller for analysis, and the results are sent to a mobile phone or computer.
[0130] Example 3
[0131] (1) Preparation of PEDOT:PSS mixed solution
[0132] 0.6 mL of ethylene glycol, 0.3 mL of 3-glycidoxypropyltrimethoxysilane, 9 mL of PEDOT:PSS solution (the volume ratio of PEDOT:PSS is 1:5, water is used as the dispersant, and the mass concentration is 1.5%), and 0.12 mL of dodecylbenzenesulfonic acid are stirred evenly and sealed and stored in a refrigerator at 4°C.
[0133] (2) Construction of organic electrochemical transistors
[0134] The substrate is a silicon wafer with a 300nm silicon oxide surface layer and a thickness of 0.1mm; the substrate surface is rinsed with deionized water and ethanol respectively for 5 times, and then the surface is completely covered with photoresist. The standard photolithography process is used to expose the channel where PEDOT:PSS is to be spin-coated, and then the substrate is developed to obtain a substrate with a channel exposed with PEDOT:PSS; then, the developed substrate is treated with a plasma plasma cleaning machine for 40s, and after being taken out, the PEDOT:PSS mixed solution prepared in step 1 is filtered with a filter membrane, and then drop-coated on the position of the exposed channel, spin-coated at 2000rpm for 30s, and then placed in an oven at 100°C and heated for 30min. After being taken out, the substrate is debonded with a debonding solution to obtain a substrate with a partially attached PEDOT:PSS film (such as Figure 2 ); then, electrodes were deposited using thermal evaporation with an evaporation current of 130 A and an evaporation rate of 0.1 nm / s. A mask was attached to the substrate surface and chromium and gold were deposited with thicknesses of 10 nm and 30 nm, respectively, to obtain an organic electrochemical transistor.
[0135] (3) Synthesis of Prussian blue-doped molecularly imprinted polymer (PBMIP) solution
[0136] 0.4 mmol of cortisol was used as a template, 0.07 mmol of azobisisobutyronitrile was used as an initiator, 1.8 mmol of methacrylic acid was used as a functional monomer, 10 mmol of methacrylate glycol was used as a cross-linking agent, and 0.4 mmol of Prussian blue was added for doping; the above raw materials were dissolved in 6 mL of dichloromethane to obtain a mixture, and then a polymerization reaction was carried out, and the polymerization reaction was continued at 0°C for 24 hours; the reaction vessel was a quartz round-bottom flask, and nitrogen was used to purge the reaction vessel before the start of the polymerization reaction to remove the air in the reaction vessel; at the beginning of the polymerization reaction, the quartz round-bottom flask containing the mixture was placed under ultraviolet light and the reaction vessel was cooled with an ice bath to avoid overheating; all operations and reaction processes were carried out under nitrogen protection; after the reaction, the generated block solid was ground into powder and washed three times with a methanol / acetic acid mixture (the volume ratio of methanol to acetic acid was 8:2); finally, the molecularly imprinted polymer (MIP) powder doped with Prussian blue (PB) was dried in a vacuum dryer (vacuum degree>0.8 kg / cm 3 ) for 20 h, and then the obtained powder was mixed with water in a mass ratio of 1:2 to obtain a PBMIP solution, which was sealed for later use.
[0137] (4) Preparation of Nafion solution
[0138] The commercially available Nafion solution was diluted with water to prepare a 5 wt % Nafion solution, which was sealed and stored for later use.
[0139] (5) Modification of organic electrochemical transistors
[0140] The PBMIP solution in step (3) and the Nafion solution in step (4) were mixed in a volume ratio of 1:2; 6 μL of the mixed solution was dropwise applied to the surface of the gate electrode and irradiated with an infrared lamp until the surface water evaporated to form a stable film, completing the modification and then sealing in a vacuum seal for storage.
[0141] (6) Preparation of hydrogel
[0142] Add 2 g of polyvinyl alcohol (PVA) with a weight-average molecular weight of 98,000 into a beaker, add 20 mL of water, and add 2 g of sucrose for pore formation. Stir at 100°C for 3 h, pour into a culture dish while hot, wait until it is completely dry, and soak it in distilled water for 24 h to completely dissolve the sucrose. Then cut the hydrogel into 1 cm*1 cm pieces and soak them in PBS buffer solution for later use.
[0143] (7) Construction of cortisol sensor
[0144] The electrode on the surface of the organic electrochemical transistor modified in step (5) is covered with a PET waterproof film, and then the hydrogel prepared in step (6) is covered on the surface of the transistor, and the hydrogel is bonded to the substrate using plastic glue to obtain a cortisol sensor.
[0145] (8) Integrated circuit design
[0146] A current and voltage measuring device is used to detect the signal current of the cortisol sensor, and the signal current is amplified based on the obtained data. The amplification circuit is used to eliminate the bias current; the heart pulse sensor uses the PPG heart rate measurement method and is directly integrated into the circuit board; the data collected by both sensors are transmitted to the microcontroller for analysis, and the results are sent to a mobile phone or computer.
[0147] The wearable device prepared in Example 1 was used to test the current changes of different concentrations of cortisol in artificial sweat, as well as the linear relationship between the current size and the cortisol concentration. The results are as follows: Figure 6 As shown. Figure 6 It can be seen that the concentration of cortisol is positively correlated with the current, and the linear relationship is good, which proves that the wearable device provided by the present invention can accurately detect cortisol data.
[0148] The wearable device prepared in Example 1 was used to test the current change of the sweat sensor (organic electrochemical transistor) and the concentration change of cortisol during the dynamic cycling exercise. The results are as follows: Figure 7 As shown. Figure 7 It can be seen that the current changes of the wearable device provided by the present invention are highly consistent with the changes in cortisol concentration, and cortisol data can be accurately detected.
[0149] As can be seen from the above embodiments, the wearable device provided by the present invention can more accurately detect and record changes in psychological stress, assess mental stress in a non-invasive manner, and can provide continuous monitoring for a long time.
[0150] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.
Claims
1. A cortisol sensor, characterized in that The organic electrochemical transistor comprises an organic electrochemical transistor, wherein the organic electrochemical transistor comprises a substrate, and a gate electrode, a source electrode, a drain electrode and a channel covering a surface of the substrate; The surface of the channel is poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid); The grid is made of gold-chromium alloy; the surface of the grid is modified with a Prussian blue-doped cortisol molecular imprinted methacrylic acid polymer.
2. The cortisol sensor according to claim 1, wherein The width of the channel is 0.5 to 2 mm, the length is 3 to 8 mm, and the distance from the gate is 0.5 to 2 cm.
3. The cortisol sensor according to claim 1 or 2, characterized in that The gold-chromium alloy comprises a superimposed chromium layer and a gold layer; the thickness of the chromium layer is 1 to 10 nm; the thickness of the gold layer is 10 to 50 nm.
4. The cortisol sensor according to claim 1, wherein A sweat absorbing layer is also provided on the surface of the Prussian blue-doped cortisol molecularly imprinted methacrylic acid polymer.
5. The cortisol sensor according to claim 1 or 4, characterized in that The surfaces of the gate, source and drain are also provided with a waterproof film.
6. The cortisol sensor according to claim 1, wherein The substrate is a silicon wafer or a flexible material; the thickness of the substrate is 0.01-1 mm.
7. The method for preparing the cortisol sensor according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) coating a substrate surface with photoresist and then performing photolithography and development processes in sequence to obtain a substrate with exposed channels; (2) coating a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) mixed solution on the exposed channel surface of the substrate, and then sequentially performing curing, debonding, and electrode evaporation to obtain a basic transistor, wherein the electrodes include a gate, a drain, and a source; (3) A Prussian blue-doped cortisol molecularly imprinted methacrylic acid polymer solution and a perfluorinated resin solution were coated on the gate surface and then dried to obtain a cortisol sensor.
8. A wearable device, characterized in that: including a circuit board, a cortisol sensor connected to the circuit board, and a heart pulse sensor connected to the circuit board; The circuit board is provided with a signal amplification module; The cortisol sensor is the cortisol sensor according to any one of claims 1 to 6 or the cortisol sensor obtained by the preparation method according to claim 7.
9. The wearable device according to claim 8, wherein: The wearable device is a wearable watch.
10. Use of the wearable device according to claim 8 or the wearable device obtained by the preparation method according to claim 9 in obtaining heart rate and cortisol concentration data.
Citation Information
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