Cortisol combined with skin conductance psychophysiological stress monitoring device and experimental paradigm method

Abstract

The application discloses a cortisol combined skin conductance mental stress monitoring device and an experimental paradigm method. The device comprises a cortisol detection module, which is used for controlling the excitation voltage between a working electrode and a reference electrode; a skin conductance detection module, which is composed of a PWM driving circuit and realizes real-time monitoring of skin conductance by detecting a weak current signal flowing through the skin; a TIA module, which uses a dual power amplifier chip to realize detection of cortisol response current and skin conductance response current; a temperature correction module, which adopts a bridge-type voltage division circuit to detect the resistance value change of a thermistor caused by temperature change, reversely deduces the size of the temperature, and assists in correcting the detection result of the skin conductance; a heart rate detection module, which is completed by a blood oxygen heart rate chip MAX30102 chip and realizes real-time monitoring of a pulse wave by applying an optical detection principle to extract heart rate information; and a signal transmission module, which adopts a serial communication mode, connects a wireless Bluetooth module, and realizes wireless transmission of data.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of sensors, in particular to a cortisol combined skin conductance mental stress monitoring device and experimental paradigm method. BACKGROUND

[0002] Cortisol is a biomarker for detecting many psychological stress-related diseases and fatigue, stress monitoring, which can be detected in blood, saliva, sweat, interstitial fluid, tears, urine and hair. Studies by Kloet et al. show that when people are affected by stress, abnormal secretion of cortisol occurs. The secretion of cortisol varies from person to person and changes constantly, and the cortisol content in the blood changes at different times of the day, with the highest level in the morning and the lowest level at midnight. The intake of diet and metabolic imbalance can cause further fluctuations in the content of cortisol. Although detecting cortisol levels in the human body is considered the gold standard method for quantifying mental stress levels, the changes of cortisol in the human body are relatively slow, with a possible delay of up to fifteen minutes, and cannot be obtained in real time and continuously, and a single cortisol detection cannot meet the demand of people for real-time detection of mental stress.

[0003] When sensory stimulation occurs or emotions change, the autonomic nervous system activity of the human body causes the skin blood vessels to contract or dilate, and the corresponding decrease or activity of the sweat glands, and the secretion enters the skin surface through the pores, changes the positive and negative balance of the current, thereby causing changes in the skin conductance. Although the skin conductance has a high response speed, in addition to emotions, the skin conductance is generally affected by environmental temperature, skin condition, arousal level, stimulation nature, activity state and other factors, and motion artifacts are also prone to occur when making wearable devices.

[0004] Therefore, the measurement results of the skin conductance often have large individual differences, and long-term baseline correction is required when measuring, and other supplementary measures are also required to improve the rough diagnostic effect.

[0005] REFERENCES

[0006] [1]Kloet, E. R. d., M. Joels, and F. Holsboer, Stress and the brain: from adaptation to disease [J]. Nature Reviews Neuroscience, 2005, 6: 463-475.

[0007] [2] Sunwoo, S. H., et al., Chronic and acute stress monitoring by electrophysiological signals from adrenal gland [J]. Proceedings of the National Academy of Sciences, 2019, 116: 1146-1151.

[0008] [3] Sephton, S. E., et al., Diurnal cortisol rhythm as a predictor of breast cancer survival [J]. Journal of the National Cancer Institute, 2000, 92(12): 994-1000.

[0009] [4] Corbalan-Tutau, D., et al., Daily profile in two circadian markers“melatonin and cortisol”and associations with metabolic syndrome components [J]. Physiology & Behavior, 2014, 123: 231-235.

[0010] [5] Parlak, O., Portable and wearable real-time stress monitoring: A critical review [J]. Sensors and Actuators Reports, 2021, 3: 100036. SUMMARY

[0011] The present application provides a cortisol combined skin conductance mental stress monitoring device, the present application realizes the detection of cortisol through the cortisol molecularly imprinted detection electrode, realizes the real-time monitoring of mental stress by adopting the method of combining biomarkers with physical markers, and simultaneously calibrates the measured heart rate and temperature in real time, details of which are described below:

[0012] A cortisol combined skin conductance mental stress monitoring device, the device comprising:

[0013] A microcontroller module realizes the opening and closing of the functional module, the output of the excitation voltage, and the collection and transmission of the signal.

[0014] A cortisol detection module for controlling the excitation voltage between the working electrode and the reference electrode;

[0015] A skin conductance detection module, which is composed of a PWM driving circuit, realizes real-time monitoring of skin conductance by detecting weak current signals flowing through the skin;

[0016] A TIA module, which uses a dual power amplifier chip to detect cortisol response current and skin conductance response current;

[0017] A temperature correction module, which uses a bridge-type voltage dividing circuit to detect the resistance value change of the thermistor caused by temperature change, and inversely deduces the temperature to assist in correcting the detection result of skin conductance;

[0018] A heart rate detection module, which is built by a blood oxygen heart rate chip MAX30102 chip, applies optical detection principle to realize real-time monitoring of pulse wave and extract heart rate information;

[0019] A signal transmission module, which uses serial communication mode, sets communication interface, connects wired USB to TTL module to realize data transmission, and connects wireless Bluetooth module to realize wireless data transmission.

[0020] The device further comprises:

[0021] A power management module, which uses ±5V voltage as input voltage to power the dual power amplifier used in the cortisol detection module, skin conductance detection module and TIA module.

[0022] Further, the device realizes blood oxygen and heart rate detection based on the optical blood oxygen heart rate detection principle of Lambert-Beer law.

[0023] The device further comprises:

[0024] A heart rate correction flag is set, when the heart rate data increases significantly in a short time and the skin conductance data is abnormal, the heart rate correction flag is set to 1.

[0025] Based on the sensitivity of thermistors to temperature, a Wheatstone bridge circuit is designed to realize real-time temperature detection. Then, a linear relationship between temperature and skin conductance under calm state is established through experiments, and a linear formula is obtained through fitting to correct the skin conductance.

[0026] The cortisol detection module realizes electrochemical detection of cortisol, including:

[0027] (1) Gold nanoparticles modification step: 100 μL of 1% chloroauric acid solution was added to the effective area of the bare electrode, and a square wave voltammetry was set by using an electrochemical workstation instrument, with the specific parameters being a scanning range of -0.2 V to 2 V, an increment of 10 mV, an amplitude of 25 mV, a frequency of 30 Hz, and 5 scans, and after the scanning was completed, the remaining solution was washed away by using ultrapure water;

[0028] (2) Prussian blue modification step: a fresh Prussian blue solution was prepared, which contained 2.5 mM FeCl3, 2.5 mM K3[Fe(CN)6], 0.1 M KCl, and 0.01 M HCl, and then 100 μL of the freshly prepared Prussian blue solution was added to the effective area of the gold nanoparticle modified electrode, and a chronoamperometry was set by using an electrochemical workstation instrument, with the specific parameters being a constant current of 50 μA and a time length of 120 s; on the basis of the gold nanoparticle / Prussian blue modified electrode, a layer of polypyrrole wrapped with cortisol was modified by an electro-polymerization method to form a gold nanoparticle / Prussian blue / polypyrrole electrode, and the cortisol molecules were removed from the polypyrrole by an electro-dissolution method to form a gold nanoparticle / Prussian blue / polypyrrole electrode, which was the final gold nanoparticle and Prussian blue modified cortisol molecular imprinting detection electrode;

[0029] (3) Electro-polymerization of polypyrrole: a mixed solution containing 20 mM pyrrole and 100 μg / mL cortisol was prepared, 50 μL of the mixed solution was added to the electrode, and then 50 μL of PBS solution was added, and after the mixture was uniformly mixed, a cyclic voltammetry was set by using an electrochemical workstation instrument, and the pyrrole and cortisol were electro-polymerized to generate a polypyrrole film with cortisol as a template molecule, with the parameters being a voltage range of 0 V to 1.2 V, a scanning rate of 50 mV / s, and 10 cycles of cyclic scanning; after the scanning was completed, the remaining solution was washed away by using ultrapure water;

[0030] (4) Electro-dissolution of cortisol molecules: 100 μL of PBS solution was added to the electrode modified with gold nanoparticles, Prussian blue, and a polypyrrole film containing cortisol molecules, and a cyclic voltammetry was set by using an electrochemical workstation instrument, with the voltage range being -1 V to 1 V and the scanning rate being 50 mV / s, and 10 cycles of cyclic scanning were performed.

[0031] Further, the calculation method of the pressure monitoring of the device comprises the following steps:

[0032] (1) Firstly, the original signal collected is subjected to ideal band-pass filtering, with a frequency range of 99 Hz to 101 Hz, and then the data collected every 2 seconds is subjected to discrete Fourier transform, and the amplitude at 100 Hz is taken, and the absolute value of the amplitude is normalized to the range of 0 to 100 as the overall evaluation range of the skin conductance, so as to realize real-time monitoring of the skin conductance;

[0033] (2) In the heart rate correction procedure, when the heart rate correction flag is 1, the heart rate detection result within 2 seconds is added to 50% of the heart rate change in the previous 5 seconds to obtain the heart rate correction value of skin conductance at this time. This correction value is added to the current amplitude information to indicate measurement abnormalities and possible sudden pressure increase, and the heart rate correction of skin conductance is completed.

[0034] (3) In the temperature correction procedure, a direct assignment and accumulation strategy is adopted. The temperature detection result within 2 seconds is substituted into the equation of the temperature-conductivity curve and then multiplied by a weight of 0.1 to obtain the temperature correction value of skin conductance at this time. This value is directly accumulated into the current amplitude information to complete the temperature correction of skin conductance.

[0035] A paradigm for experimental monitoring of cortisol combined with skin conductance under stress, wherein the experimental paradigm is as follows:

[0036] (1) Color Text Task: The text and font colors are randomly combined and refreshed every 4 seconds. Participants need to eliminate text interference and correctly select the font color. The correctness is judged based on the user's click event.

[0037] (2) Mental arithmetic task: refreshes every 6 seconds, randomly generates addition and subtraction equations within ten, and judges the correctness based on the user's click "submit";

[0038] (3) Directional task: refreshes every 3 seconds, randomly appears up, down, left and right arrows, corresponding to the keyboard direction keys, and judges the correctness based on the direction entered by the user.

[0039] The beneficial effects of the technical solution provided by this invention are:

[0040] 1. This invention employs a combined detection method of biomarkers (cortisol) and physical markers (skin conductance) to achieve real-time monitoring of mental stress. Heart rate and temperature are also included as calibration parameters. Skin conductance can compensate for the lack of real-time and continuous detection in cortisol detection, while cortisol detection can supplement the lack of accuracy and reliability in skin conductance detection. Each has its advantages and complements the other, working together to comprehensively assess the real-time mental stress state of the individual. This invention provides a relatively systematic and scientific solution for individual mental stress monitoring.

[0041] 2. This invention proposes for the first time a cortisol combined with skin conductance mental stress monitoring device. This device realizes the electrochemical detection of salivary cortisol and the physical detection of skin conductance, heart rate and temperature. After data statistical analysis, it finally realizes the real-time monitoring of personal mental stress. This device has the advantages of miniaturization, wearability, multi-parameter measurement and real-time analysis, and has great market application potential. Attached Figure Description

[0042] Figure 1A structural schematic diagram of a cortisol combined with skin conductance mental stress monitoring device;

[0043] Figure 2 A schematic diagram of a cortisol molecularly imprinted electrode;

[0044] Figure 3 A principle diagram of cortisol molecularly imprinted detection;

[0045] Figure 4 A characterization diagram of cortisol molecularly imprinted electrode modification CV;

[0046] Figure 5 A cortisol molecularly imprinted electrode detection result diagram, wherein the cortisol concentration from top to bottom is 0 ng / mL, 1 ng / mL, 10 ng / mL, 100 ng / mL, 1 μg / mL;

[0047] Figure 6 An interface diagram of a cortisol combined with skin conductance mental stress monitoring experiment paradigm;

[0048] Figure 7 A skin conductance actual detection result diagram under the experiment paradigm. DETAILED DESCRIPTION

[0049] In order to make the purpose, technical scheme and advantages of the present application more clear, the embodiments of the present application are further described in detail below.

[0050] In order to solve the problems in the background art, the present application embodiment introduces a cortisol biochemical detection index to quantize and accurately measure stress, and realizes complementary advantages. Skin conductance as a physical quantity related to mental stress can make up for the real-time and continuity deficiency of cortisol detection, while cortisol detection can make up for the accuracy and reliability deficiency of skin conductance detection. Both have their own advantages and complement each other, and the combination of the two can comprehensively judge the real-time mental stress state of the human body.

[0051] A cortisol combined with skin conductance mental stress monitoring device, as shown in Figure 1 The device includes a microcontroller module, a cortisol detection module, a heart rate detection module, a skin conductance detection module, a temperature correction module, a TIA (transimpedance amplifier) module, a power management module, a signal transmission module, etc. Through the device, electrochemical detection of saliva cortisol, real-time monitoring of skin conductance and heart rate are realized, and through data analysis, the monitoring of personal mental stress is finally realized. The specific design is as follows:

[0052] The power management module part uses ±5V voltage as input voltage to directly power the dual power amplifier (used in cortisol detection module, skin conductance detection module, TIA module) ; AMS1117-3.3 chip is used to convert 5V voltage into stable 3.3V to provide stable and suitable working voltage for microcontroller module; AMS1117-1.8 chip is used to convert 3.3V voltage into stable 1.8V voltage to power heart rate detection module; AZ431 chip is used to generate accurate 1.24V reference source voltage to realize the function of processing negative voltage in TIA module. The microcontroller module uses STM32F103RCT6 chip to realize the opening and closing of the function module, the output of excitation voltage and the collection and transmission of signal, mainly through the chip IO (input output) port PWM (pulse width modulation) output, chip integrated DAC (digital analog converter) output and ADC (analog to digital converter) collection function. The cortisol detection module is mainly composed of dual power amplifier chip AD8674, which realizes the accurate control of the excitation voltage between the working electrode and the reference electrode, so that it is not affected by the polarization voltage and current. The skin conductance detection module is mainly composed of PWM drive circuit, which realizes 100Hz frequency voltage output, and realizes real-time monitoring of skin conductance by detecting weak current signals flowing through the skin. The TIA module, i.e. trans-impedance amplifier module, uses the same dual power amplifier chip to realize current to voltage conversion with little current loss, so as to realize the detection of cortisol response current and skin conductance response current, and achieve the purpose of cortisol and skin conductance detection. The temperature correction module adopts bridge type voltage division circuit to accurately detect the resistance value change of thermistor caused by temperature change, so as to inversely deduce the size of temperature and assist in correcting the detection result of skin conductance. The heart rate detection module is mainly composed of blood oxygen heart rate chip MAX30102 chip, which applies optical detection principle to realize real-time monitoring of pulse wave, so as to extract heart rate information. The signal transmission module adopts serial communication mode, sets communication interface, can connect wired USB to TTL (transistor-transistor logic level) module to realize data transmission, or can connect wireless Bluetooth module to realize wireless transmission of data.

[0053] A cortisol combined skin conductance mental stress monitoring device adopts an alternating current detection impedance method to measure skin conductance, that is, an alternating current voltage source is used as an excitation source to measure the current passing through the body to determine the skin conductivity. Compared with a direct current signal, the alternating current signal can eliminate electrode polarization and avoid single sweat gland high pressure, thereby avoiding possible skin damage to the user. Specifically, a microcontroller (MCU) outputs an adjustable pulse width modulation (PWM) square wave with an output frequency of 100 Hz, and a field effect transistor is used to build a level conversion circuit to realize voltage driving, and finally reaches a flexible electrode made of conductive gel. After the skin receives the alternating current signal, a weak current feedback signal is generated, which is converted from current to voltage through a transimpedance amplifier (TIA), and then the signal is collected through an analog-to-digital conversion (ADC) chip with a sampling frequency of 500 Hz.

[0054] The skin conductance detection result is assisted and corrected by using two physical parameters of heart rate and temperature:

[0055] (1) When most people face temporary sudden stress, the heart rate tends to accelerate, and the measurement of skin conductance is easily affected by external factors such as action. The addition of the heart rate parameter can assist in judging the changes in mental stress and improve the accuracy of mental stress monitoring. Based on the optical blood oxygen heart rate detection principle of Lambert-Beer's law, red light and near-infrared light are used as light sources, and a photosensitive probe is used to detect the intensity of red light and near-infrared light reflected by the skin, to realize blood oxygen and heart rate detection.

[0056] The specific correction method is as follows: when the heart rate data increases significantly in a short time, and the skin conductance data is abnormal (the gel electrode piece is not in close contact with the skin), the heart rate correction flag bit is set to 1, and the heart rate data is taken as an important parameter and brought into the processing steps of the synchronous detection of the conductance data, to correct the conductance data. When the heart rate changes are within the normal range, the heart rate correction flag bit is reset.

[0057] (2) Early studies of skin conductance have shown that environmental temperature can affect skin conductance, so it is necessary to combine temperature sensor measurement to fit the linear relationship between temperature and skin conductance in a calm state to eliminate unnecessary signal fluctuations caused by changes in skin temperature and further correct the conductance data. Based on the sensitivity of the thermistor to temperature, a Wheatstone bridge circuit is designed to realize real-time detection of temperature; then the linear relationship between temperature and skin conductance in a calm state is established through experiments, and a linear formula is obtained through fitting, and the skin conductance is corrected according to the formula.

[0058] The specific correction method is: after fitting the linear relationship between temperature and skin conductance, the current temperature is brought into the linear formula (y=1.622x+3.036, wherein x is temperature, unit: Celsius), to obtain the objective fixed value of skin conductance, and the fixed value is brought into the processing step of the current conductance data as a calibration parameter, to achieve the purpose of correcting the conductance data.

[0059] The calculation method of the above pressure monitoring includes the following steps:

[0060] (1) Firstly, the ideal band-pass filtering is performed on the collected original signal, the frequency range is 99Hz-101Hz, only the frequency band signal close to the 100Hz PWM excitation signal in the signal is reserved; then the discrete Fourier transform (DFT) is performed on the data collected every 2 seconds (1000 data), the amplitude at 100Hz is taken, the amplitude information contains the skin conductivity information, the greater the amplitude, the greater the skin conductance, and vice versa; the absolute value of the amplitude is normalized to the range of 0-100, as the overall evaluation range of the skin conductance, to realize the real-time monitoring of the skin conductance;

[0061] (2) In the heart rate correction program, the integral assignment strategy is adopted, when the heart rate correction flag is 1, the heart rate detection result within 2s is added by 50% of the heart rate change amount within the previous 5s, to obtain the heart rate correction value of the skin conductance at this time, the correction value is accumulated to the current amplitude information, to prompt the measurement abnormality and possible pressure sudden increase phenomenon, and the heart rate correction of the skin conductance is completed;

[0062] (3) In the temperature correction program, the direct assignment accumulation strategy is adopted, the temperature detection result within 2s is brought into the equation of the temperature-conductivity linear curve, and then multiplied by the weight 0.1, to obtain the temperature correction additional value of the skin conductance at this time, the additional value is directly accumulated to the current amplitude information, to complete the temperature correction of the skin conductance.

[0063] The cortisol detection module is used to realize the electrochemical detection of cortisol:

[0064] A cortisol molecular imprinting detection electrode modified by gold nanoparticles and Prussian blue, adopts PET material as the electrode substrate, conductive carbon paste and conductive silver paste as the printing materials, uses a self-designed screen printing plate as the printing template, and adopts the screen printing process to print the three-electrode basic sensor device layer by layer, from bottom to top, which are PET substrate, conductive silver paste, conductive carbon paste and waterproof layer. The unmodified three-electrode basic sensor device (bare electrode) can be mass-produced by the above process, and the cost is low.

[0065] Wherein, on the basis of the bare electrode, gold nanoparticles and Prussian blue materials are modified on the working electrode layer by layer through a specific electrodeposition process, to form a gold nanoparticle / Prussian blue modified electrode.

[0066] (1) Gold nanoparticles modification step: 100 μL of 1% chloroauric acid solution was added to the effective area of the bare electrode, so that the three electrodes were completely immersed in the solution, and the square wave voltammetry (SWV) was set using the electrochemical workstation instrument, with the specific parameters being a scanning range of -0.2V~2V, an increment of 10mV, an amplitude of 25mV, a frequency of 30Hz, and 5 scans. During the deposition process, the color of the working electrode area gradually became golden, indicating the successful modification of gold nanoparticles. After the scanning was completed, the remaining solution was washed away with ultrapure water. The electrical characteristics were characterized using cyclic voltammetry (CV), and the specific operation was as follows: 100 μL of Fe 2+ / Fe 3+ redox pair solution was added to the electrode, and the cyclic voltammetry was set, with the parameters being a voltage range of -0.4V~0.6V and a scanning rate of 50mV / s. As shown in Figure 4 , compared with the bare electrode, the absolute value of the oxidation-reduction peak current increased significantly, proving that the modification of gold nanoparticles significantly increased the conductivity of the electrode.

[0067] (2) Prussian blue modification step: On the basis of gold nanoparticle modification, a fresh Prussian blue solution was first prepared, which contained 2.5mM FeCl3, 2.5mM K3[Fe(CN)6], 0.1M KCl, and 0.01M HCl. Then, 100 μL of the freshly prepared Prussian blue solution was added to the effective area of the gold nanoparticle modified electrode, so that the three electrodes were completely immersed in the solution. The chronoamperometry (CP) was set using the electrochemical workstation instrument, with the specific parameters being a constant current of 50μA and a time length of 120s. During the deposition process, the color of the working electrode area gradually became dull, indicating the successful modification of Prussian blue. After the electrodeposition was completed, the remaining solution was washed away with ultrapure water. The modification of Prussian blue increased the redox properties of the electrode itself, which served as a redox probe to help the effective transfer of electrons from the upper layer of substances.

[0068] As shown in the detection principle Figure 3 , on the basis of the gold nanoparticle / Prussian blue modified electrode, a layer of polypyrrole wrapped with cortisol was modified by the method of electro-polymerization to form a gold nanoparticle / Prussian blue / polypyrrole (cortisol) electrode. Then, on the basis of this, the cortisol molecules were removed from the polypyrrole by the method of electro-dissolution to form a gold nanoparticle / Prussian blue / polypyrrole (cortisol-removed) electrode, which was the final gold nanoparticle and Prussian blue modified cortisol molecular imprinting detection electrode. After the removal of the cortisol molecules, the polypyrrole film formed a large number of cavities, i.e., molecular imprints. When the cortisol molecules were filled into the cavities by voltage-driven means, the electrical resistance value of the film was changed, and the sensitive detection of cortisol was realized by detecting the current change thus generated.

[0069] (1) The electropolymerization of polypyrrole is as follows: a mixed solution containing 20 mM pyrrole (diluted in ethanol) and 100 μg / mL cortisol (dissolved in ethanol) is prepared, 50 μL of the mixed solution is dropped onto an electrode, and then 50 μL of a PBS solution (pH = 7.4, serving as a conductive matrix) is dropped. After mixing, an electrochemical workstation instrument is used to set a cyclic voltammetry method, and pyrrole is electropolymerized with cortisol to generate a polypyrrole film with cortisol as a template molecule. The specific parameters are as follows: a voltage range of 0 V to 1.2 V, a scanning rate of 50 mV / s, and 10 cycles of cyclic scanning. After scanning, the remaining solution is washed away with ultrapure water. The polypyrrole film-modified electrode is characterized using a cyclic voltammetry method. Specifically, 100 μL of a Fe 2+ / Fe 3+ redox pair solution is dropped onto the electrode, a cyclic voltammetry method is used, a voltage range of -0.4 V to 0.6 V is set, and a scanning rate of 50 mV / s is set. As shown in Figure 4 , compared with the electrode modified with gold nanoparticles and Prussian blue, the absolute value of the current of the redox peak decreases significantly, which is caused by the poor conductivity of polypyrrole, and proves the successful modification of the polypyrrole film.

[0070] (2) The electro-dissolution of cortisol molecules is as follows: 100 μL of a PBS solution (pH = 7.4) is dropped onto the electrode modified with gold nanoparticles, Prussian blue, and a polypyrrole film containing cortisol molecules. An electrochemical workstation instrument is used to set a cyclic voltammetry method, a voltage range of -1 V to 1 V is set, a scanning rate of 50 mV / s is set, and 10 cycles of cyclic scanning are performed. The cortisol molecules in the film are removed by using the electro-dissolution characteristics under a wide voltage, and the cortisol molecule-imprinted detection electrode modified with gold nanoparticles and Prussian blue is prepared. As shown in Figure 4 , compared with the electrode without removing cortisol molecules, the absolute value of the current of the CV redox peak increases significantly.

[0071] The cortisol detection module uses differential pulse voltammetry (DPV) to detect cortisol. The scanning voltage range is set to 0.2 V to 0.65 V, the increment is 10 mV, the amplitude is 50 mV, the pulse width is 0.05 s, and the cycle is 0.5 s. Anhydrous ethanol is used to prepare a 100 μg / mL cortisol solution, which is then diluted with a PBS buffer to 10 μg / mL, 1 μg / mL, 100 ng / mL, 10 ng / mL, and 1 ng / mL, respectively, as cortisol standard solutions. The prepared cortisol molecule-imprinted detection electrode modified with gold nanoparticles and Prussian blue is sequentially dropped with 100 μL of the above-mentioned 10 μg / mL, 1 μg / mL, 100 ng / mL, 10 ng / mL, and 1 ng / mL cortisol standard solutions, respectively, as shown in Figure 5As shown, using the DPV method for detection, different DPV current response curves are obtained, and the peak current shows a downward trend as the cortisol concentration increases. Through repeated experiments, a linear relationship curve of the peak current and the cortisol concentration is obtained through linear fitting, which is used as the standard curve for cortisol detection. When an unknown concentration of cortisol to be tested is added to the electrode, the peak current data is obtained through DPV scanning, which is brought into the standard curve to obtain the cortisol concentration information of the unknown liquid through calculation, realizing the detection of cortisol.

[0072] A cortisol combined skin conductance mental stress monitoring experiment paradigm method is provided to verify the effectiveness of the cortisol combined skin conductance mental stress monitoring device for mental stress monitoring, as shown in Figure 6 As shown, MATLAB is used to design a relaxation guide and task stress experiment paradigm. The overall experiment consists of 5 minutes of guided relaxation and 5 minutes of task stress stimulation. The stress stimulation degree is changed by adjusting the number and difficulty of the tasks. Skin conductance data of the subjects are collected during the experiment, and fingertip pulse rate is measured as real-time heart rate data to assist in judgment. Temperature is collected for data correction. The experiment uses continuous measurement, and 10 minutes of data (5 minutes of relaxation state and 5 minutes of stress state) are recorded for each experiment. Saliva samples of the subjects are collected before and after the experiment for biochemical index (salivary cortisol content) detection. Mixed white noise classical music is used for calm guidance in the relaxation state; the stress stimulation experiment consists of color text tasks, addition and subtraction mental arithmetic tasks within 10, and direction key selection tasks that can effectively increase stress in psychology. The three tasks have different independent automatic refresh times, and real-time correct and false feedback is provided through color change of the indicator light according to user clicks. The subjects need to plan the time independently and complete the tasks as many times as possible with a correct rate of more than 50%.

[0073] (1) Color text task: refresh every 4s, randomly combine text and font color, subjects need to exclude text interference to correctly select font color, and judge true or false according to user click event; (2) Mental arithmetic task: refresh every 6s, randomly generate addition and subtraction equations within 10, and judge true or false according to user click "submit"; (3) Direction task: refresh every 3s, randomly appear up, down, left and right arrows, corresponding to the keyboard direction keys, and judge true or false according to user key input direction. As shown in Figure 7 As shown, the experimental results of the cortisol combined skin conductance mental stress monitoring experiment paradigm show that the detection results of the stress state and the relaxation state have very obvious differences, showing a very effective mental stress monitoring effect.

[0074] A cortisol combined skin conductance mental stress monitoring smart phone software, through connecting a Bluetooth module, realizes cortisol detection, skin conductance detection, mobile phone wireless control of heart rate detection and body temperature detection, realizes wireless transmission, storage and intelligent analysis of detection data, realizes mental stress abnormal event reminding, online consultation and offline consultation service. Mainly divided into the following three parts:

[0075] (1) detection control part, the main page includes: skin conductance, cortisol, heart rate, body temperature correction four function buttons and history record button, click to enter the corresponding secondary detail page. In the secondary page of skin conductance, cortisol, heart rate, body temperature correction, the upper part shows the real-time drawing of the received data, the middle part shows the detection result, and the lower part shows the prompt information. The secondary page of history record displays the previously measured data results in the form of a list, and the topmost part displays a pressure report button. The software will generate a report on the recent pressure change situation after automatically analyzing the historical data.

[0076] (2) health service part, including online consultation module and offline consultation module, when the user appears mental stress abnormal condition, can choose corresponding expert according to need and make psychological consultation or make an appointment offline doctor. The online consultation interface includes the suggestions and some pressure relieving skills given by the system according to the pressure detection situation, and the online consultation service, click the online consultation to enter the secondary interface, the left side displays the chat box mark, and the right side displays the online doctor list, click any doctor to view its information and dialogue. In the offline consultation page, the nearby hospital list and distance information are displayed, the user can sort according to the distance or sort according to the remaining number of conditions, click to enter the secondary page, display the information and the reservation condition of the related doctors, click the reservation button to make a reservation.

[0077] (3) personal information part, the personal information includes name, gender, age, ID number, current position, contact number, also has historical detection record, and medical treatment reminding, drug reminding, pressure abnormality reminding, realizes the individualization and intelligent service of mental stress monitoring.

[0078] The model of each device in the embodiment of the application is not limited unless otherwise specified, and any device capable of achieving the above functions can be used.

[0079] Those skilled in the art can understand that the drawings are only schematic diagrams of a preferred embodiment, and the above embodiment numbers are only for description, not representing the advantages and disadvantages of the embodiments.

[0080] The above description is only a preferred embodiment of the application, and does not limit the application, and any modification, equivalent replacement, improvement, etc. within the spirit and principle of the application should be included in the protection scope of the application.

Claims

1. A cortisol combined skin conductance mental stress monitoring device, characterized in that, The device comprises: a microcontroller module, which realizes the opening and closing of the functional module, the output of the excitation voltage, and the collection and transmission of signals; a cortisol detection module for controlling the excitation voltage between the working electrode and the reference electrode; a skin conductance detection module composed of a PWM driving circuit, which realizes real-time monitoring of skin conductance by detecting weak current signals flowing through the skin; a TIA module, which uses a dual power amplifier chip to detect cortisol response current and skin conductance response current; a temperature correction module, which adopts a bridge-type voltage dividing circuit to detect the resistance value change of the thermistor caused by temperature change, reversely deduces the size of the temperature, and assists in correcting the detection results of the skin conductance; a heart rate detection module, which is built with a blood oxygen heart rate chip MAX30102 chip, applies the principle of optical detection, realizes real-time monitoring of the pulse wave, and extracts heart rate information; a signal transmission module, which adopts a serial communication mode, sets a communication interface, connects a wired USB-to-TTL module to realize data transmission, and connects a wireless Bluetooth module to realize wireless data transmission; The device further comprises: a heart rate correction flag bit is set to 1 when the heart rate data increases significantly in a short time and the skin conductance data is abnormal; based on the sensitivity of the thermistor to temperature, a Wheatstone bridge circuit is designed to realize real-time detection of temperature; then a linear relationship between temperature and skin conductance under calm state is established through experiments, and a linear formula is obtained through fitting to correct the skin conductance; The calculation method of the pressure monitoring of the device comprises the following steps: (1) First, the collected original signal is band-pass filtered, and the frequency range is 99Hz~101Hz; then the discrete Fourier transform is performed on the data collected every 2 seconds, and the amplitude at 100Hz is taken, which contains the skin conductivity information; the absolute value of the amplitude is normalized to the range of 0~100 as the overall evaluation range of the skin conductance, realizing real-time monitoring of the skin conductance; (2) In the heart rate correction program, when the heart rate correction flag bit is 1, the heart rate detection results within 2s are added to 50% of the heart rate change within the previous 5s to obtain the heart rate correction value of the skin conductance at this time, and the correction value is added to the current amplitude information to complete the heart rate correction of the skin conductance; (3) In the temperature correction program, a direct assignment accumulation strategy is adopted, the temperature detection results within 2s are brought into the equation of the temperature-conductivity linear formula, and then multiplied by the weight 0.1 to obtain the temperature correction additional value of the skin conductance at this time, which is directly added to the current amplitude information to complete the temperature correction of the skin conductance; The cortisol detection module realizes electrochemical detection of cortisol, including: 1) Gold nanoparticle modification step: 100μL of 1% chloroauric acid solution is added to the effective area of the bare electrode, and an electrochemical workstation instrument is used, and the parameters of square wave voltammetry are set as follows: scan range-0.2V~2V, increment 10mV, amplitude 25mV, frequency 30Hz, scan 5 times, and then the remaining solution is washed away with ultrapure water; 2) The modification step of Prussian blue is: preparing a fresh Prussian blue solution containing 2.5mM FeCl3, 2.5mM K3[Fe(CN)6], 0.1M KCl, 0.01M HCl, then adding 100μL of the freshly prepared Prussian blue solution to the effective area of the gold nanoparticle modified electrode, using an electrochemical workstation instrument, setting a chronovoltammetry method, the specific parameters are constant current 50μA, time length 120s; on the basis of the gold nanoparticle / Prussian blue modified electrode, a layer of polypyrrole wrapped with cortisol is modified by an electro-polymerization method to form a gold nanoparticle / Prussian blue / polypyrrole electrode, and the cortisol molecules are removed from the polypyrrole by an electro-dissolution method to form a gold nanoparticle / Prussian blue / polypyrrole electrode, which is the final gold nanoparticle and Prussian blue modified cortisol molecular imprinting detection electrode; 3) The electro-polymerization of polypyrrole is: preparing a mixed solution containing 20mM pyrrole and 100μg / mL cortisol, adding 50μL of the mixed solution to the electrode, then adding 50μL of PBS solution, mixing uniformly, and then using an electrochemical workstation instrument, setting a cyclic voltammetry method, and electro-polymerizing pyrrole and cortisol to generate a polypyrrole film with cortisol as the template molecule, the parameters are voltage range 0V~1.2V, scan rate 50mV / s, and cyclic scanning 10 times; after scanning, the remaining solution is washed away with ultrapure water; 4) The electro-dissolution of cortisol molecules is: adding 100μL of PBS solution to the electrode modified with gold nanoparticles, Prussian blue, and a polypyrrole film containing cortisol molecules, using an electrochemical workstation instrument, using a cyclic voltammetry method, setting the voltage range-1V~1V, the scan rate 50mV / s, and cyclic scanning 10 times.

2. The cortisol combined with skin conductance mental stress monitoring device according to claim 1, characterized in that, The device also includes: A power management module uses ±5V voltage as input voltage to power the dual power amplifier used in the cortisol detection module, skin conductance detection module, and TIA module.

3. The cortisol combined skin conductance mental stress monitoring device according to claim 1, characterized in that, The device realizes blood oxygen and heart rate detection based on the optical blood oxygen heart rate detection principle of Lambert-Beer's law.

4. A method of experimental paradigm based on the cortisol combined with skin conductance mental stress monitoring device according to any one of claims 1-3, characterized in that, The experimental paradigm method is: (1) Color text task: refresh every 4s, randomly combine text and font color, subjects need to exclude text interference to correctly select font color, judge true or false according to user click event; (2) Mental calculation task: refresh every 6s, randomly generate addition and subtraction equations within ten, judge true or false according to user click "submit"; (3) Direction task: refresh every 3s, randomly appear up, down, left and right arrows, corresponding to keyboard direction keys, judge true or false according to user key input direction.

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