Monitoring device based on microneedle electrode array

Abstract

The invention discloses a microneedle electrode array-based monitoring device, which comprises a base, a plurality of microneedle electrodes, a top cover, a spring needle and a circuit module, and is characterized in that the bottom of the base comprises a plurality of holes, the microneedle electrodes are fixed through the holes, the spring needle corresponds to the microneedle electrodes in position, and the microneedle electrodes are fixed through the top cover. The spring needle is connected with the circuit module, the base and the top cover form a closed space, and the spring needle and the circuit module are arranged in the closed space. The embodiment of the invention can reduce crosstalk and improve the accuracy of a test result, and can be widely applied to the technical field of biological detection.

Description

Technical Field

[0001] The present invention relates to the field of biological detection technology, and in particular to a monitoring device based on a microneedle electrode array. Background Art

[0002] The detection of physiological signals (such as electrophysiological and biochemical signals) is of great significance in medicine and health monitoring. The detection and analysis of these signals can help doctors diagnose and monitor a variety of diseases at an early stage. At the same time, physiological signal detection can also evaluate the effectiveness of treatment and adjust treatment plans, such as evaluating the effectiveness of chemotherapy or radiotherapy by monitoring the changes in biomarkers during cancer treatment. By detecting physiological signals through wearable devices, real-time monitoring of individual health status can be achieved to prevent the occurrence of diseases. This type of detection also plays an important role in rehabilitation therapy and sports medicine, helping to formulate and adjust rehabilitation training plans and monitor the patient's rehabilitation progress. Physiological signal detection has also promoted the development of personalized medicine. Through the analysis of individual physiological signals, targeted health advice and treatment plans can be provided to improve the accuracy and effectiveness of medical services. In addition, physiological signal detection is an important tool for biomedical research. Through the study of these signals, we can gain a deep understanding of the physiological and pathological mechanisms of the human body and promote the development of new drugs, new technologies and new treatment methods.

[0003] Traditional detection methods for physiological signals usually require puncture or blood sampling, which may cause pain and discomfort. In recent years, microneedle transdermal technology has made significant progress in physiological signal detection, demonstrating its huge application potential. Microneedle transdermal technology uses tiny needles to penetrate the surface of the skin to achieve painless and minimally invasive physiological signal detection. Compared with traditional physiological signal detection methods, microneedle technology has many advantages. The current microneedle array monitoring has crosstalk problems, which affects the accuracy of the test results. Summary of the invention

[0004] In view of this, in order to solve one of the above problems, an object of an embodiment of the present invention is to provide a monitoring device based on a microneedle electrode array, which can reduce crosstalk and improve the accuracy of test results.

[0005] An embodiment of the present invention provides a monitoring device based on a microneedle electrode array, including a base, a plurality of microneedle electrodes, a top cover, a spring needle and a circuit module, wherein the bottom of the base comprises a plurality of holes, the microneedle electrodes are fixed by the holes, the spring needle corresponds to the position of the microneedle electrodes, the spring needle is connected to the circuit module, the base and the top cover form a closed space, and the spring needle and the circuit module are arranged in the closed space.

[0006] Optionally, the microneedle electrode comprises a thumbtack-type microneedle electrode, wherein the thumbtack-type microneedle electrode comprises a substrate and a microneedle, and the substrate is detachably connected to the microneedle.

[0007] Optionally, a modification layer is provided on the surface of the microneedle electrode.

[0008] Optionally, the side wall of the base is provided with a side hole, and the base and the top cover are fitted together through the side hole to form a closed space.

[0009] Optionally, the thickness of the bottom of the base is determined according to the length of the microneedle electrode leaking out of the bottom of the base and the length of the microneedle.

[0010] Optionally, the circuit module includes a power supply and a test circuit board, the test circuit board includes a first circuit board and a second circuit board, the power supply includes a battery, and the battery is arranged between the first circuit board and the second circuit board.

[0011] Optionally, the circuit module further includes a male connector and a female connector, and the first circuit board and the second circuit board are connected via the male connector and the female connector.

[0012] Optionally, the holes at the bottom of the base are arranged according to a preset array rule.

[0013] Optionally, the circuit module includes a voltage conversion circuit, a filtering circuit, an amplifying circuit, an analog-to-digital conversion circuit, a microcontroller and a communication circuit.

[0014] Optionally, the communication circuit includes a wireless communication circuit, and the wireless communication circuit includes any one of a WIFI communication circuit, a millimeter wave communication circuit or an ultra-wideband communication circuit.

[0015] The implementation of the embodiment of the present invention includes the following beneficial effects: a monitoring device based on a microneedle electrode array includes a base, a plurality of microneedle electrodes, a top cover, a spring needle and a circuit module, the bottom of the base includes a plurality of holes, the microneedle electrodes are fixed through the holes, the spring needles correspond to the positions of the microneedle electrodes, the spring needles are connected to the circuit module, the base and the top cover form a closed space, the spring needles and the circuit module are arranged in the closed space, and before being fixed to the holes, each microneedle electrode is independent, achieving a detection resolution at the level of a single microneedle, effectively reducing crosstalk between microneedle arrays, and improving the accuracy of test results; in addition, by replacing the microneedle electrodes, it is possible to quickly adapt to different application scenarios and improve applicability; the microneedle electrodes are connected to the circuit module via spring needles, which can improve the stability and reliability of the monitoring device and further improve the accuracy of the test results. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is a cross-sectional view of a monitoring device based on a microneedle electrode array provided in an embodiment of the present invention;

[0017] Figure 2is a three-dimensional diagram of a base provided by an embodiment of the present invention;

[0018] Figure 3 is a three-dimensional diagram of a top cover provided by an embodiment of the present invention;

[0019] Figure 4 is a schematic structural diagram of a thumbtack-type microneedle electrode provided by an embodiment of the present invention;

[0020] Figure 5 is a circuit schematic diagram of a pad provided by an embodiment of the present invention;

[0021] Figure 6 is a circuit schematic diagram of an electromyography simulation front end provided by an embodiment of the present invention;

[0022] Figure 7 is a circuit schematic diagram of an electrochemical simulation front end provided by an embodiment of the present invention;

[0023] Figure 8 is a circuit schematic diagram of a microcontroller provided by an embodiment of the present invention;

[0024] Fig. 9 is a circuit schematic diagram of a low voltage dropout linear regulator provided by an embodiment of the present invention;

[0025] Fig.10 is a circuit schematic diagram of a positive and negative output charge pump provided by an embodiment of the present invention;

[0026] Fig.11 The present invention provides a circuit diagram of a WIFI communication module. DETAILED DESCRIPTION

[0027] The present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments. The step numbers in the following embodiments are only provided for the convenience of explanation and description, and the order between the steps is not limited in any way. The execution order of each step in the embodiment can be adaptively adjusted according to the understanding of those skilled in the art.

[0028] See also Figures 1 to 3 , Figure 1 A cross-sectional view showing a monitoring device based on a microneedle electrode array, Figure 2 A perspective view showing the base, Figure 3A three-dimensional diagram showing a top cover, an embodiment of the present invention provides a monitoring device based on a microneedle electrode array, including a base 1-1, a plurality of microneedle electrodes 1-5, a top cover 1-2, a spring needle 1-4 and a circuit module 1-3, the bottom of the base 1-1 includes a plurality of holes, the microneedle electrodes 1-5 are fixed through the holes, the spring needle 1-4 corresponds to the position of the microneedle electrode 1-5, the spring needle 1-4 is connected to the circuit module 1-3, the base 1-1 and the top cover 1-2 form a closed space, and the spring needle 1-4 and the circuit module 1-3 are arranged in the closed space.

[0029] After the monitoring device based on the microneedle electrode array is assembled, the microneedle electrodes are connected to the circuit module through spring needles. During the test, after the microneedle electrodes penetrate the skin, the microneedle electrodes collect physiological signals under the skin, and the physiological signals are transmitted to the circuit module through the spring needles. The circuit module processes the physiological signals and sends the processed data to the host computer.

[0030] The type and quantity of the microneedle electrodes are determined according to the actual application, and are not specifically limited in this embodiment. For example, the microneedle electrodes include electromyography monitoring electrodes, pH monitoring electrodes, and ROS monitoring electrodes. The microneedle electrodes are fixed through the holes to ensure that the microneedles can be firmly inserted and firmly stuck, and are not easy to shift, thereby improving the stability of the monitoring device.

[0031] Optionally, the side wall of the base is provided with a side hole, and the base and the top cover are fitted together through the side hole to form a closed space.

[0032] See also Figure 2 and Figure 3 The side wall of the base is provided with side holes, and the base and the top cover fit more stably through the side holes, while saving space for the monitoring device.

[0033] Optionally, the thickness of the bottom of the base is determined according to the length of the microneedle electrode protruding from the bottom of the base and the length of the microneedle.

[0034] The length of the microneedle electrode protruding from the bottom of the base is determined according to the test requirements. The lengths of the microneedles for different tests may vary. The thickness of the bottom of the base is determined based on the length of the microneedle electrode protruding from the bottom of the base and the length of the microneedle.

[0035] Optionally, the microneedle electrode comprises a thumbtack-type microneedle electrode, which comprises a substrate and a microneedle, and the substrate and the microneedle are detachably connected.

[0036] The specific shape of the microneedle electrode is determined according to the actual application, and this embodiment does not impose any specific restrictions, such as a pin-shaped microneedle electrode or a columnar electrode. Figure 1 The pushpin-type microneedle (TSMN) electrode can be better fixed to the hole at the bottom of the base. The specific method of detachable connection between the substrate and the microneedle is determined according to the actual application, and this embodiment does not make specific restrictions. Figure 4 The substrate and the microneedle are detachably connected by size matching. The thumbtack-type microneedle electrode includes a substrate and a microneedle, and the substrate and the microneedle are detachably connected. To test different physiological signals, the microneedle can be directly replaced without replacing the entire monitoring device, thereby improving the applicability of the monitoring device.

[0037] In a specific embodiment, CNC processing technology is used to perform engraving, grinding, polishing and other process steps on the acrylic sheet to complete the manufacture of the base. The top cover ring is made of SLA photosensitive resin material and manufactured using 3D printing technology. The 3M medical tape is processed by laser processing technology, and then the processed tape is accurately attached to the base to ensure a tight fit. Next, the microneedle array is accurately placed on the base one by one according to its corresponding position; then, the circuit module is placed inside the base, and it is ensured that the spring needle and the corresponding microneedle electrode can be accurately aligned; finally, the top cover is placed on the base, and it is ensured that it is correctly engaged to complete the assembly process of the entire prototype.

[0038] Optionally, a modification layer is provided on the surface of the microneedle electrode.

[0039] Setting a modification layer on the surface of the microneedle electrode can significantly improve the signal sensing ability and electrochemical performance of the electrode, such as electrodeposition of a PEDOT:PSS modification layer on the surface of the microneedle electrode. PEDOT:PSS is an aqueous solution of a high molecular polymer with high conductivity. Different aqueous solutions with different conductivity can be obtained according to different formulations.

[0040] The preparation, testing and simulation process of the microneedle electrode are described below.

[0041] The preparation process of various microneedle electrodes is as follows:

[0042] In a specific embodiment, the microneedle electrode is a PEDOT:PSS / Au electrode as an example. The preparation process of the TSMN microneedle adopts CNC processing technology and laser welding technology. The TSMN uses an acidic detergent to remove the oxide layer on the surface of the TSMN, and then it is washed with deionized water and dried; then, it is placed in a gold sulfite solution, and an electrochemical workstation is used to perform an electroplating reaction at a constant current of -2mA for 600s to deposit an Au layer on the microneedle; then, the microneedle is immersed in a mixed solution of 0.01M ethylenedioxythiophene monomer (EDOT) and 0.1M sodium polystyrene sulfonate (NaPSS), and electrochemical polymerization is performed by applying a constant current of 10uA for 400s, and PEDOT:PSS is deposited on the Au electrode to prepare a PEDOT:PSS / Au electrode. The electropolymerized film is washed with deionized water at room temperature and dried with N2 spray.

[0043] In a specific embodiment, microneedle electrodes are used as ROS and pH electrodes as an example. For the ROS sensor, the previously prepared PEDOT:PSS / Au electrode is immersed in a platinum sulfite solution, platinum nanoparticles are electroplated to the electrode surface using an electrochemical workstation, and electrochemical polymerization is performed for 400s by applying a constant current of 10uA to deposit Pt on the PEDOT:PSS / Au electrode to prepare a Pt / PEDOT:PSS / Au electrode. For the pH potential sensor, the previously prepared PEDOT:PSS / Au electrode is immersed in a mixed solution of 0.25M aniline and 0.5M H2SO4. Then, PANI is deposited on the Au electrode to prepare a PANI / PEDOT:PSS / Au electrode by CV between 0 and 0.95V at a rate of 100mV / s for 20 cycles of deposition in a dispersed solution.

[0044] In a specific embodiment, take the microneedle electrode as the counter electrode. Take the microneedle that has completed the electrochemical deposition of gold, connect the electrochemical workstation, use the microneedle as the working electrode, the platinum sheet electrode as the counter electrode, and the Ag / AgCl electrode as the reference electrode. Add 20mL of 2mmol / L sodium platinum sulfite aqueous solution to a 50mL beaker, immerse the three electrodes in the solution, and use a multi-step constant current method to electrochemically deposit platinum on the microneedle in the sodium platinum sulfite solution. The parameters are as follows: the first stage: 0.00005A, 15s; the second stage: -0.00005A, 15s; the third stage: -0.015A, 500s. After deposition, put it in ultrasound for cleaning for 20min, and take it out and dry it naturally.

[0045] In a specific embodiment, a microneedle electrode is used as a reference electrode. A microneedle that has been electrochemically gold plated is coated with Ag / AgCl ink and dried in an oven at 100°C. After drying, it is taken out and immersed in a methanol solution of 2% polyvinyl butyral (methanol solution of PVB) by mass for coating, and dried at room temperature for more than 20 hours.

[0046] The characterization process of various microneedle electrodes is as follows: take the prepared metal microneedle electrode, sputter it in a gold sputtering instrument at 80% power for 100s, so that a layer of gold material is evenly coated on the surface of the electrode, and then observe the morphology under a scanning electron microscope.

[0047] Electrochemical tests of various microneedle electrodes are as follows:

[0048] In a specific embodiment, the microneedle electrode is a PEDOT:PSS / Au electrode as an example. The in vitro electrochemical performance test of the sensing electrode is performed using an electrochemical workstation, and the test methods include CV and electrochemical impedance spectroscopy (EIS). A three-electrode configuration is used for detection, with platinum wire and Ag / AgCl electrodes serving as control electrode and reference electrode, respectively. For electrochemical impedance spectroscopy detection, the electrolyte is a 10mM PBS solution (pH 7.4), which is performed by applying a 10mV sinusoidal disturbance to a DC potential fixed at 0V and a range of 1Hz–1MHz. For CV detection, the electrolyte is a mixed solution containing 5mM potassium ferrocyanide and 0.1mM KCl, and the potential is 100mV s -1 The scan rate was swept from -0.3 V to +0.3 V. In the first cycle, the current was integrated in the potential range from -0.3 to 0.3 V to calculate CSCc.

[0049] In a specific embodiment, a microneedle electrode is used as an example of a ROS electrode. The ROS electrode was tested for in vitro electrochemical performance using an electrochemical workstation, and four electrochemical techniques, CV, DPV, SWV and it, were used for comprehensive analysis. The test used a standard three-electrode configuration, using a Pt / PEDOT:PSS / Au electrode as a working electrode, a platinum electrode as a counter electrode, and an Ag / AgCl electrode as a reference electrode, and H2O2 was detected by gradually increasing the concentration of H2O2 in the solution from 0 to 2, 4, 6, 8 and 10 mmol / L. In the CV test, the potential range was set to -0.2V to +0.6V, and a cyclic scan was performed at a scan rate of 100mV / s. In the DPV test, the potential range was set to -0.4V to +0.4V, the pulse amplitude was 50mV, the pulse width was 50ms, and each pulse period was 500ms. In the SWV test, the potential range was set to -0.6V to +0.6V, the voltage increment was 4mV, the amplitude was 30mV, and the frequency was set to 50Hz. In the it test, a constant potential was applied at -0.1V close to the H2O2 reduction peak potential, and the current was recorded over time. The test was performed by adding interferents to the PBS solution to analyze the effects of different interferents on H2O2 detection.

[0050] In a specific embodiment, the microneedle electrode is used as a pH electrode as an example. The in vitro electrochemical performance of the pH electrode is tested using an electrochemical workstation, and the test is performed using an open circuit potential method. A buffer solution with a pH range of 5-8 is prepared. Before use, the pH of each solution is measured using a commercial pH meter as a reference. The test is performed by adding interfering substances to deionized water to analyze the effects of different interfering substances on pH detection.

[0051] The electrical simulation process of microneedles is as follows:

[0052] Two microneedle electrodes with a spacing of 5 mm were accurately inserted into the rabbit's epidermis at a depth of 800 um, ensuring that the insertion depth of the electrodes remained consistent, and an impedance spectrum test was performed using an electrochemical workstation in the frequency range of 1 Hz to 100 kHz. During the test, special attention was paid to ensure that the microneedle electrodes were stably inserted into the epidermis and in full contact with the skin to ensure the accuracy and reliability of the test. In order to reduce experimental errors, each test was repeated three times, and the results were recorded and averaged. According to the actual measurement data of the microneedle-skin, it was imported into the ZView fitting software for data fitting to further obtain the specific parameters of the equivalent circuit of the microneedle-skin model.

[0053] Optionally, the circuit module includes a power supply and a test circuit board, the test circuit board includes a first circuit board and a second circuit board, and the power supply includes a battery, which is arranged between the first circuit board and the second circuit board.

[0054] To ensure the compactness of the entire monitoring device, the circuit module is divided into two upper and lower circuit boards (a first circuit board and a second circuit board). At the same time, to save space, the battery is arranged between the first circuit board and the second circuit board.

[0055] Optionally, the circuit module further includes a male connector and a female connector, and the first circuit board is connected to the second circuit board via the male connector and the female connector.

[0056] To ensure accuracy during docking, each circuit board is equipped with a male connector and a female connector. One circuit board uses a male connector, while the other circuit board uses a corresponding female connector. This design ensures that when two circuit boards are stacked and docked, the male and female connectors can be accurately matched, thus avoiding the possibility of wrong connection.

[0057] Optionally, the holes at the bottom of the base are arranged according to a preset array rule.

[0058] The specific arrangement of the preset array is determined according to the actual application, and this embodiment does not impose any specific restrictions, including but not limited to a matrix arrangement or a ring arrangement.

[0059] Optionally, the circuit module includes a voltage conversion circuit, a filtering circuit, an amplifying circuit, an analog-to-digital conversion circuit, a microcontroller and a communication circuit.

[0060] Optionally, the communication circuit includes a wireless communication circuit, and the wireless communication circuit includes any one of a WIFI communication circuit, a millimeter wave communication circuit or an ultra-wideband communication circuit.

[0061] In a specific embodiment, the microcontroller uses the chip STM32F411CCU6, and is programmed on-board through the ST-LINK downloader. The microcontroller is the core of the system and coordinates the work of each functional module. The electrochemical analog front end uses the chip AD5940 to process electrochemical-related signals, which can adapt to various electrochemical measurement requirements in multiple measurement types and resolution modes. In addition, the multiplexer flexibly connects the microneedle array sensor to the appropriate channel. Ensure that the conditioned voltage value is always within the detectable limit of the ADC. In the circuit board, electrical isolation is provided between the analog ground (AGND) and the conventional ground (GND) pins. The power management module ensures stable power supply for the system. The low-dropout regulator uses the chip TPS7A2133 to adjust the lithium battery voltage to a stable 3.3V to power the MCU, wireless communication and analog front-end chips; the low-noise positive and negative output charge pump uses the chip LM27762 to convert 3.3V to ±2.5V, thereby providing the required analog power supply for the analog front-end chip. The WIFI communication module is used to wirelessly transmit data and commands between the host computer and the monitoring device, and uses the ALK8266 high-speed WIFI module. The circuit board below is mainly used to place the electromyography analog front end using the chip ADS1299, which is responsible for processing the collected EMG. In order to effectively suppress baseline drift, a first-order RC low-pass filter (cut-off frequency 1Hz) is added before the analog front end. The analog front end realizes the functions of differential input, signal amplification (24 times) and analog-to-digital conversion of EMG, and samples the input signal at a rate of 2kHz. In order to achieve a stable and reliable connection with the microneedle electrode array sensor at the bottom, gold-plated spring pins are specially designed at the bottom of the circuit board. This design not only ensures the stability of the connection, but also improves the durability of the system. The 3.7V lithium-ion lithium battery is placed between the two circuit boards as the power input of the system. See Figure 5 and Figure 6 , Figure 5 The circuit diagram of one of the pads is shown. The pad is used to solder the spring pin. E12 represents the pad. C25 and R1 form a first-order high-pass filter. The electromyographic signal passes through the first-order high-pass filter (IN1P, IN1N) and then connects to ADS1299. The same goes for the signals collected by other pads. Figure 6 It represents the schematic diagram of the electromyography analog front end (AFE), which is used to realize the processing and conversion of electromyography signals.

[0062] See also Figure 7 , Figure 7It represents the electrochemical AFE schematic diagram, realizing electrochemical signal processing and conversion. AD594X-SCLK, AD594X-MOSI, AD594X-MISO, and AD594X-CS are all pins of the SPI communication bus protocol, and AD594X-RESET is reset, all of which are connected to the microcontroller (STM32). AD594X-RE0 is the reference electrode in ROS detection, AD594X-CE0 is the counter electrode in ROS detection, AD594X-SE0 is the working electrode 1 in ROS detection, AD594X-DE0 is the working electrode 2 in ROS detection, AIN0 is the reference electrode in pH detection, AIN1 is the working electrode 1 in pH detection, and AIN2 is the working electrode 2 in pH detection. R22 is the isolation resistor between analog ground and digital ground, L6 is the power supply bead, and GPIO0 is the interrupt output pin.

[0063] See also Figure 8 , Figure 8 The circuit diagram of the microcontroller is shown. The microcontroller is the core of the system and coordinates the work of each functional module. LED6, LED7, and LED8 are lithium battery power indicators. ADC-BAT collects the voltage of the lithium battery. TXD and RXD are serial port debugging. SWCLK and SWDIO are ST-LINK download ports.

[0064] See also Fig. 9 , Fig. 9 The schematic diagram of the circuit of the low dropout linear regulator (LDO) converts the 3.7V voltage to 3.3V. CN2 is used to connect the lithium battery, SW4 is the switch, and F2 is the fuse. D2 is a diode to prevent the lithium battery from being connected reversely. R24 and R26 are series voltage divider resistors, so that the voltage detected by ADC-BAT is half of the lithium battery. U7 is an LDO, which converts the lithium battery voltage 3.7V to DVDD (3.3V).

[0065] See also Fig.10 , Fig.10 The schematic diagram of the positive and negative output charge pump converts the 3.3V voltage into ±2.5V to power the analog pins of the ADS1299.

[0066] See also Fig.11 , Fig.11 The schematic diagram of the WIFI communication module is used to transmit data and commands wirelessly. WIFI-SCK, WIFI-MOSI, WIFI-MISO, and WIFI-CS are all pins of the SPI communication bus protocol, and WIFI-RST is reset, all of which are connected to the STM32.

[0067] To verify the EMG measurement performance of the circuit module, a waveform generator was connected to the input of the EMG acquisition of the circuit module to generate a sine wave with a frequency ranging from 0.1 Hz to 100 Hz and an amplitude of 16 mV. Subsequently, the host computer was used to record the data. During the recording process, the signal component with the largest amplitude in the acquired signal was extracted using LabVIEW's "Extract Single Frequency Information.vi". Then, the ratio of this signal component to the preset 16 mV amplitude was calculated to evaluate the voltage gain of the circuit at different frequencies. An RC filter circuit model similar to the circuit module was constructed in Multisim, and a frequency response simulation analysis was performed. The frequency response results obtained by simulation were compared with the voltage gain at different frequencies in the actual test. In addition, the "SINAD Analysis.vi" module in LabVIEW was used to analyze the signal-to-noise ratio of the eight channels. To verify the electrochemical measurement performance of the circuit module, the circuit module was compared with an electrochemical workstation (CHI760E). The measurement results of the circuit module and the electrochemical workstation were compared under the open circuit voltage method and the chronoamperometry method. In terms of system power consumption, a power analyzer is used to characterize the power consumption of the circuit module. By collecting power consumption data at a sampling rate of 1 Hz, the power consumption curve of the circuit module under different working conditions is obtained.

[0068] The application of the monitoring device based on the microneedle electrode array in the embodiment of the present invention is described below.

[0069] Example 1: Muscle fatigue model detection

[0070] An opening of about 3-4 cm was made along the path of the sciatic nerve on the back of the leg, and then the sciatic nerve was carefully exposed using a blunt dissection technique. Subsequently, the sciatic nerve was gently hooked using a double-hook electrode to ensure that the electrode was in close contact with the sciatic nerve, but excessive pulling was avoided to prevent damage to the nerve. At the same time, contact with surrounding muscle tissue was avoided. Then, the electrical stimulator was connected to the double-hook electrode, and the biphasic square wave electrical stimulation parameters with a half-phase period of 200us were set to electrically stimulate the sciatic nerve to induce leg tremors. The monitoring device was placed on the hair removal area to ensure that the monitoring device was in close contact with the skin and penetrated the stratum corneum. After applying a 32mA, 5Hz current stimulation for one hour to induce a contraction response in the leg muscles, the induced CMAP signal was recorded using the monitoring device. After completing the CMAP recording, the current stimulation was stopped immediately to avoid interference of the electrical stimulation signal with the subsequent detection of reactive oxygen and pH signals. Reactive oxygen and pH signals were recorded separately without interference from electrical stimulation, and each recording lasted for 5 minutes. To obtain the pH and reactive oxygen species concentration in the blood as reference values, blood samples were collected from the leg vein at 0, 2, and 5 hours. The results measured by the monitoring device were calibrated with the blood reference data at hour 0 to eliminate the differences between in vitro and in vivo experiments.

[0071] Example 2: Sciatic nerve injury model detection

[0072] The sciatic nerve of the rabbit was exposed surgically and gently separated with forceps. The exposed sciatic nerve was gently clamped with a double hook electrode and electrical stimulation was applied to induce CMAP. CMAP was recorded by a monitoring device, and the reactive oxygen level and pH value of the relevant muscles were recorded as control data. Blood samples were collected from the leg veins to measure the pH and reactive oxygen concentration in the blood to provide baseline and calibration data. To simulate nerve injury, three ligatures were made on the sciatic nerve using sutures, ensuring that the tightness of the sutures was moderate and that a slight twitch of the calf muscles or toes could be seen when ligating. In the initial test after modeling, electrical pulse stimulation was applied to obtain CMAP. Then, the double hook electrode and monitoring device were removed. When handling the surgical area, it was rinsed with normal saline, and then the muscle layer, subcutaneous tissue and skin layer were sutured in sequence, and the wound was disinfected with alcohol. On the second and third days after surgery, the sutures of the surgical wound were removed, and the monitoring device was reapplied to the leg muscle position. The sciatic nerve was clamped again with a double hook electrode, and the EMG test and electrochemical test were repeated. During each test, blood samples were collected from the leg vein at the same time, and the pH and reactive oxygen concentration in the blood were measured to refer to the various measurement data. The results measured by the monitoring device were calibrated with the blood reference data on the first day to eliminate the difference between in vitro and in vivo experiments. After each test, the monitoring device was removed, and the wound was cleaned, re-sutured and disinfected. After the experiment, the New Zealand rabbit was euthanized by injecting an overdose of anesthetic. Subsequently, the sciatic nerve tissue at the injury site was removed along the original surgical path, with a length of about 1 cm, and these nerve samples were immersed in 4% paraformaldehyde for fixation. After the nerve samples were dehydrated by various levels of alcohol, they were transparent, paraffin-impregnated and embedded to make longitudinal sections with a thickness of about 5 μm. Finally, the sections were dewaxed with xylene and dehydrated with different levels of ethanol before being stained with HE (hematoxylin-eosin), and the damage and recovery of the neural tissue were observed and recorded under an optical microscope.

[0073] The implementation of the embodiment of the present invention includes the following beneficial effects: a monitoring device based on a microneedle electrode array includes a base, a plurality of microneedle electrodes, a top cover, a spring needle and a circuit module, the bottom of the base includes a plurality of holes, the microneedle electrodes are fixed through the holes, the spring needles correspond to the positions of the microneedle electrodes, the spring needles are connected to the circuit module, the base and the top cover form a closed space, the spring needles and the circuit module are arranged in the closed space, and before being fixed to the holes, each microneedle electrode is independent, achieving a detection resolution at the level of a single microneedle, effectively reducing crosstalk between microneedle arrays, and improving the accuracy of test results; in addition, by replacing the microneedle electrodes, it is possible to quickly adapt to different application scenarios and improve applicability; the microneedle electrodes are connected to the circuit module via spring needles, which can improve the stability and reliability of the monitoring device and further improve the accuracy of the test results.

[0074] The above is a specific description of the preferred implementation of the present invention, but the invention is not limited to the embodiments. Those skilled in the art may make various equivalent modifications or substitutions without violating the spirit of the present invention. These equivalent modifications or substitutions are all included in the scope defined by the claims of this application.

Claims

1. A monitoring device based on a microneedle electrode array, characterized in that: It includes a base, a plurality of microneedle electrodes, a top cover, a spring needle and a circuit module. The bottom of the base contains a plurality of holes. The microneedle electrodes are fixed through the holes. The spring needle corresponds to the position of the microneedle electrode. The spring needle is connected to the circuit module. The base and the top cover form a closed space. The spring needle and the circuit module are arranged in the closed space.

2. The monitoring device according to claim 1, characterized in that: The microneedle electrode comprises a thumbtack-type microneedle electrode, and the thumbtack-type microneedle electrode comprises a substrate and a microneedle, wherein the substrate is detachably connected to the microneedle.

3. The monitoring device according to claim 1, characterized in that: A modification layer is provided on the surface of the microneedle electrode.

4. The monitoring device according to claim 1, characterized in that: The side wall of the base is provided with a side hole, and the base and the top cover are fitted together through the side hole to form a closed space.

5. The monitoring device according to claim 1, characterized in that: The thickness of the bottom of the base is determined according to the length of the microneedle electrode protruding from the bottom of the base and the length of the microneedle.

6. The monitoring device according to claim 1, characterized in that: The circuit module includes a power supply and a test circuit board, the test circuit board includes a first circuit board and a second circuit board, the power supply includes a battery, and the battery is arranged between the first circuit board and the second circuit board.

7. The monitoring device according to claim 6, characterized in that: The circuit module further includes a male connector and a female connector, and the first circuit board and the second circuit board are connected via the male connector and the female connector.

8. The monitoring device according to claim 1, characterized in that: The holes at the bottom of the base are arranged according to a preset array rule.

9. The monitoring device according to any one of claims 1 to 8, characterized in that: The circuit module includes a voltage conversion circuit, a filtering circuit, an amplifying circuit, an analog-to-digital conversion circuit, a microcontroller and a communication circuit.

10. The monitoring device according to claim 9, characterized in that: The communication circuit includes a wireless communication circuit, and the wireless communication circuit includes any one of a WIFI communication circuit, a millimeter wave communication circuit or an ultra-wideband communication circuit.

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