Analog front-end system based on nano-enzyme microelectrode and detection method

Abstract

The invention discloses an analog front-end system based on a nano-enzyme microelectrode and a detection method. The system comprises a nano-enzyme microelectrode array, an electrophysiology acquisition module, an electrochemical acquisition module and a control module, the electrochemical acquisition module is used for acquiring electrochemical signals, and the control module is used for receiving and processing the electrochemical signals in an electrochemical acquisition mode; the nano-enzyme microelectrode array is used for being in contact with limbs of a detected object so as to collect electromyographic signals; the control module is used for receiving and processing the electromyographic signals in an electrophysiological acquisition mode, and determining the electrophysiological signals through the electromyographic signals; and the control module is also used for switching acquisition modes. According to the embodiment of the invention, the accuracy of the analog front-end circuit system in the aspect of neural signal acquisition can be improved; meanwhile, through a multi-module integration mode, the size of the system is reduced. The method can be widely applied to the technical field of electrochemical signal detection.

Description

Technical Field

[0001] The present invention relates to the technical field of electrochemical signal detection, and in particular to an analog front-end system and a detection method based on nanozyme microelectrodes. Background Art

[0002] Studying neuronal signals is the basis for our understanding of the functional regulation mechanism and disease mechanism of the nervous system. Since neurons communicate through complex chemical and electrical signal patterns and form a highly sophisticated information network, physiological or pathological events cannot be explained by a single signal communication method. In related technologies, electrochemical workstations have good signal acquisition accuracy and anti-interference capabilities, and support a variety of acquisition modes and electrochemical monitoring methods. These workstations collect single signals, which affects accuracy; and their internal hardware systems are composed of discrete devices, resulting in a larger circuit size. Summary of the invention

[0003] The purpose of the present invention is to solve one of the technical problems existing in the prior art to at least a certain extent.

[0004] To this end, the object of the present invention is to provide a comprehensive analog front-end system and detection method based on nanozyme microelectrodes.

[0005] In order to achieve the above technical objectives, the technical solutions adopted by the embodiments of the present invention include the following aspects:

[0006] On the one hand, the embodiment of the present invention provides an analog front-end system based on nanozyme microelectrodes, including: a nanozyme microelectrode array, an electrophysiological acquisition module, an electrochemical acquisition module and a control module; the electrochemical acquisition module is connected to the control module, and the electrochemical acquisition module is used to collect electrochemical signals by differential pulse voltammetry, square wave voltammetry, linear sweep voltammetry or conventional pulse voltammetry, and the control module is used to receive and process the electrochemical signals in the electrochemical acquisition mode; the nanozyme microelectrode array is connected to the control module through the electrophysiological acquisition module, and the nanozyme microelectrode array is used to contact the limbs of the object to collect electromyographic signals; the control module is used to receive and process the electromyographic signals in the electrophysiological acquisition mode, and determine the electrophysiological signals by the electromyographic signals; the control module is also used to switch the acquisition mode; the control module is also used to determine the detection results of the object's nervous system according to the electrochemical signals and the electrophysiological signals. The embodiment of the present application collects electrophysiological signals through the nanozyme microelectrode array, and can also collect electrochemical signals through a workstation, and the acquisition mode is switched by the control module. The embodiment of the present application realizes the collection of multiple signals, which is beneficial to improving the accuracy of the analog front-end circuit system in neural signal collection; at the same time, the volume of the system is reduced through multi-module integration.

[0007] In addition, the analog front-end system based on the nanozyme microelectrode according to the above embodiment of the present invention may also have the following additional technical features:

[0008] Furthermore, in the analog front-end system based on nanozyme microelectrodes of an embodiment of the present invention, the electrophysiological acquisition module includes an ADS1299 chip, and the input end of the ADS1299 chip is respectively connected to 8 nanozyme microelectrode arrays and 1 right leg drive circuit through an interface; the analog power supply end of the ADS1299 chip is grounded through a capacitor, and the analog ground end of the ADS1299 chip is connected to the analog bypass capacitor end of the ADS1299 chip through a capacitor.

[0009] Furthermore, in one embodiment of the present invention, the electrochemical acquisition module includes an AD5941 chip; the RE end, CE end and SE end of the AD5941 chip are respectively connected to three electrodes through interfaces for collecting current signals; the input end of the AD5941 chip is respectively connected to two electrodes through interfaces for collecting voltage signals.

[0010] Furthermore, in one embodiment of the present invention, the system also includes a power module, the power module includes a battery, the battery is connected to the input end of the LTC3200 chip; the output end of the LTC3200 chip is connected to the input end of the TPS73250 chip, and the output end of the TPS73250 chip supplies power to the electrophysiological acquisition module, the electrochemical acquisition module and the control module.

[0011] Furthermore, in one embodiment of the present invention, the system also includes a WiFi module, which is used to connect the control module and the host computer, and the control module is used to transmit the collected electrochemical signals and electrophysiological signals to the host computer through the WiFi module, and the host computer is used for signal processing and display.

[0012] Furthermore, in one embodiment of the present invention, the system also includes a USB module, the universal interface of the control module is connected to the RXD end and the TXD end of the CH340 chip, and the UD end of the CH340 chip is connected to the type-c interface.

[0013] Furthermore, in one embodiment of the present invention, the PCB board corresponding to the system is a four-layer board, and the structure of the four-layer board is a top signal layer, a ground layer, a power supply layer and a bottom signal layer in sequence, and the ground layer includes a digital ground and an analog ground.

[0014] Furthermore, in one embodiment of the present invention, the PCB board adopts a front and back layout, wherein the electrophysiological acquisition module, the electrochemical acquisition module and the control module are arranged on the front side, and the WiFi module and the power module are arranged on the back side.

[0015] On the other hand, an embodiment of the present invention proposes a detection method of a nanozyme microelectrode-based analog front-end system, which is applied to the above-mentioned nanozyme microelectrode-based analog front-end system, and the method includes:

[0016] In the electrochemical signal acquisition mode, the electrochemical signals are acquired by differential pulse voltammetry, square wave voltammetry, linear sweep voltammetry or conventional pulse voltammetry;

[0017] Alternatively, in an electrophysiological acquisition mode, receiving an electromyographic signal acquired by a nanozyme microelectrode array, and determining an electrophysiological signal through the electromyographic signal;

[0018] A detection result of the subject's nervous system is determined based on the electrochemical signal and the electrophysiological signal.

[0019] Furthermore, the detection method of the analog front-end system based on the nanozyme microelectrode of the embodiment of the present invention further includes:

[0020] The WiFi module of the circuit is turned on, and the WiFi network of the circuit and the host computer are kept consistent, the working mode is switched to the electrochemical acquisition mode, electrochemical characterization is performed through three electrodes, and the characterization results are displayed through the host computer.

[0021] The system provided by the embodiment of the present invention includes a nanozyme microelectrode array, an electrophysiological acquisition module, an electrochemical acquisition module and a control module; the electrochemical acquisition module is connected to the control module, and the electrochemical acquisition module is used to collect electrochemical signals by differential pulse voltammetry, square wave voltammetry, linear sweep voltammetry or conventional pulse voltammetry, and the control module is used to receive and process the electrochemical signals in the electrochemical acquisition mode; the nanozyme microelectrode array is connected to the control module through the electrophysiological acquisition module, and the nanozyme microelectrode array is used to contact the limbs of the object to collect electromyographic signals; the control module is used to receive and process the electromyographic signals in the electrophysiological acquisition mode, and determine the electrophysiological signals by the electromyographic signals; the control module is also used to switch the acquisition mode; the control module is also used to determine the detection results of the object's nervous system according to the electrochemical signals and the electrophysiological signals. The embodiment of the present application collects electrophysiological signals by the nanozyme microelectrode array, and can also collect electrochemical signals by a workstation, and the acquisition mode is switched by the control module. The embodiment of the present application realizes the collection of multiple signals, which is beneficial to improving the accuracy of the analog front-end circuit system in neural signal collection; at the same time, the volume of the system is reduced through multi-module integration. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the embodiments of the present invention or the drawings of related technical solutions in the prior art are introduced below. It should be understood that the drawings introduced below are only for the convenience of clearly describing some embodiments of the technical solutions of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0023] Figure 1 A schematic structural diagram of an embodiment of a nanozyme microelectrode-based analog front-end system provided by the present invention;

[0024] Figure 2 A schematic structural diagram of an embodiment of a nanozyme microelectrode-based analog front-end system provided by the present invention;

[0025] Figure 3 An electrical schematic diagram of an embodiment of an electrophysiological acquisition module provided by the present invention;

[0026] Figure 4 An electrical schematic diagram of an embodiment of the electrochemical collection module provided by the present invention;

[0027] Figure 5 An electrical schematic diagram of an embodiment of a power module provided by the present invention;

[0028] Figure 6 An electrical schematic diagram of an embodiment of the WiFi module provided by the present invention;

[0029] Figure 7 An electrical schematic diagram of an embodiment of the USB module provided by the present invention;

[0030] Figure 8 An electrical schematic diagram of an embodiment of a control module provided by the present invention;

[0031] Fig. 9 A front 3D simulation diagram of an embodiment of the system hardware provided by the present invention;

[0032] Fig.10 A 3D simulation diagram of the reverse side of an embodiment of the system hardware provided by the present invention;

[0033] Fig.11 A schematic diagram of the results of electrochemical signal detection by the system provided by the present invention;

[0034] Fig.12 A schematic diagram of the results of electrochemical signal detection in AA solution by the system provided by the present invention;

[0035] Fig.13 This is a signal display diagram for the 8-channel electrophysiological signal acquisition provided by the present invention. DETAILED DESCRIPTION

[0036] The embodiments of the present invention are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and are not to be construed as limitations of the present invention. For the step numbers in the following embodiments, they are only provided for the convenience of explanation, and the order between the steps is not limited in any way, and the execution order of each step in the embodiment can be adaptively adjusted according to the understanding of those skilled in the art.

[0037] Studying neuronal signals is the basis for understanding the functional regulation mechanisms and disease mechanisms of the nervous system. Since neurons communicate through complex chemical and electrical signal patterns and form highly sophisticated information networks, physiological or pathological events cannot be explained by a single signal communication method alone. In order to study the complex collaborative activity mechanisms of neuronal populations behind different brain activities, multi-channel microelectrode arrays are needed to record neuronal electrical signals in different regions. At the same time, studying the distribution and activity patterns of neurotransmitters can reveal the neural basis behind specific behaviors, emotions, and cognitive processes in different brain regions. Therefore, the preparation and system construction of electrodes for monitoring multi-channel electrophysiological and electrochemical neural signals are of great significance for in-depth research on the intrinsic mechanisms of neurology.

[0038] In the construction of neural signal monitoring systems, two key parts are usually included: the front-end signal acquisition sensor module and the back-end signal transmission and processing hardware circuit system. The front-end sensor module has weak neural signal strength and is easily interfered by the outside world. Implantable biosensors have become the focus of research because they can stably detect neural signals and are less susceptible to interference. However, these sensors usually face the challenges of high inherent impedance and poor biocompatibility, which makes it difficult to effectively detect weak signals during long-term implantation and may cause chronic neuroinflammation. For the back-end hardware circuit system, traditional electrochemical workstations have good signal acquisition accuracy and anti-interference ability, and support a variety of acquisition modes and electrochemical monitoring methods. However, these workstations usually rely on wired connections for signal transmission, and their internal hardware systems are composed of discrete devices, resulting in a large circuit size. Therefore, the circuit scheme of traditional electrochemical workstations is not suitable for long-term in vivo monitoring.

[0039] Traditional metal neural electrodes have high stability when recording neural signals. However, due to their inherent high impedance characteristics, weak signals cannot be detected during long-term implantation. At the same time, due to the large difference between the surface properties of traditional metal electrodes and the poor biocompatibility of the materials, the peripheral nerve tissue may reject foreign bodies, thereby inducing chronic neuroinflammation. Due to its many limitations, traditional electrochemical workstations cannot meet the needs of long-term monitoring of living bodies. First, these devices are usually large in size, heavy in weight, lack portability, and are difficult to use in application scenarios that need to be carried or implanted in the body. Secondly, these workstations usually rely on external power supplies and cannot provide continuous energy support, making it difficult to meet the needs of long-term continuous monitoring. In addition, the data transmission method of these devices mainly relies on wired connections, which limits their application in dynamic or mobile environments. For all the above reasons, it is difficult for traditional electrochemical workstations to play a role in long-term monitoring of living bodies.

[0040] The following is a detailed description of the analog front-end system and detection method based on nanozyme microelectrode according to an embodiment of the present invention with reference to the accompanying drawings. The analog front-end system based on nanozyme microelectrode provided by the present invention specifically includes:

[0041] Nanozyme microelectrode array, electrophysiological acquisition module, electrochemical acquisition module and control module;

[0042] The electrochemical acquisition module is connected to the control module, the electrochemical acquisition module is used to collect electrochemical signals by differential pulse voltammetry, square wave voltammetry, linear sweep voltammetry or conventional pulse voltammetry, and the control module is used to receive and process the electrochemical signals in the electrochemical acquisition mode;

[0043] The nanozyme microelectrode array is connected to the control module through the electrophysiological acquisition module, and the nanozyme microelectrode array is used to contact the limbs of the object to be tested to collect electromyographic signals; the control module is used to receive and process the electromyographic signals in the electrophysiological acquisition mode, and determine the electrophysiological signals through the electromyographic signals; the control module is also used to switch the acquisition mode; the control module is also used to determine the detection results of the object's nervous system based on the electrochemical signals and the electrophysiological signals.

[0044] The present invention mainly develops a complete set of analog front-end circuit systems for collecting electrochemical and electrophysiological signals for nanozyme microelectrodes. Figure 1 As shown, the hardware circuit development of this system is based on the STM32 single-chip microcomputer platform, which can cooperate with nanozyme electrodes to realize four electrochemical detection methods: differential pulse voltammetry (DPV), square wave voltammetry (SWV), linear sweep voltammetry (LSV) and normal pulse voltammetry (NPV) to perform high-quality detection of electrochemical signals. At the same time, the circuit system can also switch to the electrophysiological signal acquisition mode. For the collection of electrophysiological signals, the maximum supported sampling rate is 2kHz. The circuit system of the present invention adopts a four-layer board design, and the signal acquisition modules all use highly integrated analog front-end chips, so that this circuit has excellent wearable potential.

[0045] The embodiment of the present application selects a nanozyme microelectrode as the front-end sensor module of the system. The nanozyme electrode obtained by modifying the electrode surface using artificial nanozymes by electrodeposition method shows the advantages of significant impedance reduction and increased cathode charge storage capacity. The electrode has sufficient sensitivity and reliability for the detection of weak neural signals.

[0046] At the same time, a hardware circuit system was developed for nanozyme microelectrodes. The system uses analog front-end chips to replace traditional discrete devices, which greatly improves the hardware integration of the entire system and enables it to collect signals with minimal space occupancy. Figure 2 As shown in the figure, the development of this system is a complete system development from sensors to lower computers and then to upper computers. This circuit solution transmits signals wirelessly via WIFI and also uses a battery-powered solution, so it has excellent wearable potential.

[0047] Optionally, in the analog front-end system based on nanozyme microelectrodes in an embodiment of the present invention, the electrophysiological acquisition module includes an ADS1299 chip, and the input end of the ADS1299 chip is respectively connected to 8 nanozyme microelectrode arrays and 1 right leg drive circuit through an interface; the analog power supply end of the ADS1299 chip is grounded through a capacitor, and the analog ground end of the ADS1299 chip is connected to the analog bypass capacitor end of the ADS1299 chip through a capacitor.

[0048] In some possible implementations, reference Figure 3 As shown in the figure, the peripheral circuit designed based on the ADS1299 chip includes a chip filter circuit, an interface use or disable circuit, and an interface and filter circuit for the 8-channel working electrode and the counter electrode. Among them, the input structure of the 8-channel electrophysiological signal analog front end (ADS1299) is 8 differential inputs (one positive and one negative), and a right leg drive circuit is also designed. The right leg drive circuit (RLD) is a circuit used in a biomedical signal acquisition system. Its main function is to reduce common-mode interference, especially power frequency interference (such as 50 / 60Hz power supply noise) during the measurement of bioelectric signals. By feeding back the common-mode signal to the patient's right leg, the right leg drive circuit can effectively reduce the common-mode voltage induced on the measuring electrode, thereby improving the signal-to-noise ratio of the signal and ensuring more accurate bioelectric signal acquisition. This circuit is often used in bioelectric signal measurement equipment such as electrocardiograms (ECGs). The 8-channel electrophysiological signal analog front end (ADS1299) first fans out 17 low-pass filters at its input end (8 pairs of positive and negative inputs and one input for the right leg drive circuit) to further eliminate the low-frequency noise often encountered when collecting signals. Finally, it is connected to the FPC interface. This FPC interface supports up to 18 channels of output while ensuring a small footprint.

[0049] Optionally, in the analog front-end system based on nanozyme microelectrodes in an embodiment of the present invention, the electrochemical acquisition module includes an AD5941 chip; the RE end, CE end and SE end of the AD5941 chip are respectively connected to three electrodes through interfaces for collecting current signals; the input end of the AD5941 chip is respectively connected to two electrodes through interfaces for collecting voltage signals.

[0050] In some possible implementations, reference Figure 4The peripheral circuits shown in the figure are designed based on the AD5940 chip, including chip filtering circuits, interface use or disable circuits, and current and voltage signal acquisition interfaces. The input structure of the electrochemical signal analog front end (AD5941) is a dual-electrode input to realize voltage signal acquisition; and a three-electrode input to realize current signal acquisition. For the interface selection of the two-electrode system or the three-electrode system, users can customize the connection according to their needs. That is, any two of the five interfaces can be used as dual-electrode inputs, and any three can be used as three-electrode inputs.

[0051] Optionally, in the analog front-end system based on nanozyme microelectrodes in an embodiment of the present invention, the system also includes a power module, the power module includes a battery, and the battery is connected to the input end of the LTC3200 chip; the output end of the LTC3200 chip is connected to the input end of the TPS73250 chip, and the output end of the TPS73250 chip supplies power to the electrophysiological acquisition module, the electrochemical acquisition module and the control module.

[0052] In some possible implementations, reference Figure 5 As shown in the figure, the boost and voltage regulation are realized by LTC3200 chip and TPS73250 chip. At the same time, the voltage conversion is realized by TPS73633.

[0053] Optionally, in the analog front-end system based on nanozyme microelectrodes in an embodiment of the present invention, the system also includes a WiFi module, which is used to connect the control module and the host computer, and the control module is used to transmit the collected electrochemical signals and the electrophysiological signals to the host computer through the WiFi module, and the host computer is used for signal processing and display.

[0054] In some possible implementations, reference Figure 6 The device connection diagram of the WiFi module shown in the figure shows that the first to seventh and ninth pins are connected to the control module to realize data transmission.

[0055] Optionally, the analog front-end system based on nanozyme microelectrodes in an embodiment of the present invention further comprises a USB module, the universal interface of the control module is connected to the RXD and TXD ends of the CH340 chip, and the UD end of the CH340 chip is connected to the type-c interface.

[0056] Reference Figure 7 The connection relationship diagram of an embodiment of the USB module shown in FIG. 1 is used to realize data transmission of the USB interface. Figure 8 In one embodiment of the control module shown, the connection relationship of the hardware circuit provided by the present application can be known through the representation of the pins.

[0057] Optionally, in the analog front-end system based on nanozyme microelectrodes in the embodiment of the present invention, the PCB board corresponding to the system is a four-layer board, and the structure of the four-layer board is a top signal layer, a ground layer, a power supply layer and a bottom signal layer in sequence, and the ground layer includes a digital ground and an analog ground.

[0058] Optionally, in the analog front-end system based on nanozyme microelectrodes in the embodiment of the present invention, the PCB board adopts a front and back layout, wherein the electrophysiological acquisition module, the electrochemical acquisition module and the control module are arranged on the front side, and the WiFi module and the power module are arranged on the back side.

[0059] In the drawing of the PCB layout in the embodiment of the present application, a 4-layer board process is selected, which can ensure that the routing of the communication signals between the two analog front-end chips and the MCU is as short and straight as possible, thereby reducing the interference that may be coupled during the signal transmission process. The stacked structure of the PCB version is the top signal layer-inner electrical layer (ground layer)-inner electrical layer (power layer)-bottom signal layer. The inner electrical layer (ground layer) is divided into digital ground and analog ground; the inner electrical layer (power layer) is divided into 3.3V power supply and 5V power supply. The advantage of this is that it can ensure the integrity of the power supply and reduce the impact of power supply noise on the signal.

[0060] The PCB area is minimized by laying out the front and back sides of the PCB. In addition, the use of 0402 packaged resistors and capacitors can further reduce the PCB area while maintaining good signal integrity. The MCU (ST, STM32F411CCU6TR) and the electrochemical signal analog front end (AD5941) are also selected with the smallest package area. Fig. 9 The front 3D simulation image and Fig.10 The reverse 3D simulation diagram shown in the figure shows that the position design of different modules achieves the effect of occupying a smaller area. Of course, the above design is an illustrative example and is not specifically limited in this application.

[0061] The following is a detailed description of the analog front-end system based on nanozyme microelectrode provided in the embodiment of the present application by a specific embodiment, specifically:

[0062] Regarding the design of the circuit, the hardware circuit module of this system mainly includes five parts, namely, the microprocessor, the electrophysiological signal acquisition module, the electrochemical signal acquisition module, the WiFi communication module, and the power module. Among them, the electrophysiological signal acquisition module and the electrochemical signal acquisition module can be classified as data acquisition modules. After the sensor performs data acquisition, the data is sent to the microprocessor through the SPI protocol. After the microprocessor receives the data, it packages the data and sends it to the WiFi communication module through the SPI protocol. Finally, the signal is sent to the host computer through WiFi. The drawing of the hardware circuit PCB adopts the domestic software Lichuang EDA, which has the advantages of simple interactive logic, complete device library package library, and cloud storage of data, so it has attracted the attention of a large number of hardware engineers. In the layout of the circuit board, a four-layer board design structure is selected. The two inner layers in the middle are the ground layer and the power layer, respectively. In this way, the wiring can be replaced by a large area of ​​copper plating, saving the cumbersome power line routing space. At the same time, a double-sided layout design is also used to further reduce the area of ​​the circuit board diagram.

[0063] The microprocessor selected is STM32F411CCU6TR. STM32F411CCU6TR uses the ARM Cortex-M4 core, which has high-performance 32-bit processing capabilities and a highly efficient instruction set, supporting single-cycle multiplication and hardware division. This core also provides a floating-point unit (FPU) that can perform complex floating-point operations. STM32F411CCU6TR supports multiple clock sources and power modes, and can be flexibly configured according to application requirements. It has a high-precision internal clock source and supports external clock input. The microprocessor has 64KB of Flash memory for program code and data storage, and 128KB of SRAM for data storage, which can meet our needs for simultaneous acquisition of multi-channel signal data without data congestion. The most important thing is that the STM32F411CCU6TR chip uses the QFN-48 package model, which ensures a small size and minimizes the number of pins, while also meeting the system's needs for low power consumption, high performance, and sufficient peripherals for the microprocessor.

[0064] Electrophysiological signal acquisition module: Currently, most of the synchronous acquisition of multi-channel electrophysiology on the market uses discrete devices. Since most electrophysiological signals are low-frequency and weak signals, they are extremely susceptible to interference from power frequency noise. Therefore, they need to go through a series of amplification and filtering operations such as a first-level acquisition amplifier circuit, a first-level filter circuit, a notch filter, a second-level amplifier circuit, and a second-level filter circuit to obtain a true and clear physiological electrical waveform. However, the disadvantage of this solution is that the circuit area will increase significantly with the increase in the number of channels, and the difficulty of circuit layout and wiring will also increase accordingly. Therefore, in order to minimize the circuit area as much as possible and ensure the quality of simultaneously acquiring multi-channel electrophysiological signals, this study selected the ADS1299 analog front-end chip. ADS1299 is a high-precision, low-power biological signal analog front-end chip launched by Texas Instruments (TI). It is an integrated circuit specially used for amplification and digital processing of bioelectric signals, and is widely used in medical equipment, biomedical research, brain-computer interface and other fields. A single ADS1299 chip can realize 8-channel acquisition and amplification of tiny bioelectric signals and digitize the signals. It has the characteristics of high input impedance, low noise, low power consumption, high dynamic range and high common mode rejection ratio. The chip has a programmable amplification gain of up to 24 times and different filter settings. It uses a 24-bit analog-to-digital converter (ADC), so it can provide high-quality bioelectric signal acquisition and meet the needs of this study for physiological electrical signal acquisition.

[0065] Electrochemical signal acquisition module: As mentioned above, in order to reduce the circuit area, a more integrated analog front-end chip can be used to replace the complicated discrete device circuit in circuit design. In order to collect electrochemical voltage signals and electrochemical current signals, this study uses the AD5941 chip. AD5941 is an integrated biosensor analog front-end chip launched by ADI (Analog Devices). It is designed for biosensor and biosensor array applications and can provide highly accurate measurements and flexible configuration options. Its functional features include: integrated 24-bit ADC for high-precision, low-power analog signal conversion; built-in low-noise preamplifier, which can amplify weak biological signals to improve measurement accuracy; provides a programmable current driver suitable for the measurement of electrochemical sensors and electrodes; equipped with an analog-to-digital synthesizer, which can be used to generate the required control signals, such as AC signals or pulse identification signals; supports two commonly used communication interfaces, SPI and I2C, which facilitates data exchange and configuration with the main control device. In general, AD5941 is an integrated biosensor analog front-end chip with the characteristics of high precision, multi-function and flexible configuration. It is an ideal choice for biosensor and array applications, enabling highly accurate bio-measurement and multi-channel measurement requirements. This study designed the corresponding peripheral circuits for this chip, such as Figure 4 As shown, it is possible to collect two current signals and two voltage signals, and the resistance value of the transimpedance can be customized to adjust the amplification factor of the collected signal according to different types of current signals.

[0066] Communication module and power module: This system uses the ESP8266 chip for WiFi communication, which is used to send the data received and processed by the microprocessor to the host computer for real-time waveform display. ESP8266 is a highly integrated, low-cost Wi-Fi module chip launched by Espressif Systems. It has become one of the widely used chips in the field of Internet of Things applications, providing reliable wireless connection and network communication functions. This system designs a serial communication module, firstly to facilitate the early debugging of the prototype; secondly, to use AT commands for the microprocessor to edit the connection mode and connection information of the WiFi module. This study uses the CH340E serial chip for USB serial communication. CH340E is a high-performance, low-power USB to serial chip with wide compatibility and simple use. It plays the role of a bridge for serial communication in various application scenarios, providing convenience and reliability for data transmission between computers and other serial devices. This system uses a 3.7V lithium battery as the main power supply. According to the different power requirements of different chip models, the 3.7V power supply voltage needs to be boosted to 5V through the LTC3200ES6 boost chip and then stabilized through the TPS73250DBVR voltage regulator chip to provide a stable analog voltage for the chip; the 3.7V power supply voltage also needs to be obtained through the TPS73633DBVR power chip to obtain a 3.3V digital voltage. The combination of these two voltages realizes the power supply of the entire system.

[0067] For firmware program design, the firmware program of this system is written using the Keil 5 integrated development environment. Keil 5 (Keil MDK) is an embedded software development tool suite launched by Arm. It is a powerful, easy-to-use and reliable embedded software development tool suite. It has a built-in industry-renowned ARM compiler (armcc), which supports C and C++ languages ​​and can optimize compilation for a variety of Arm architecture processors. In addition, a complete set of tool chains, including assemblers, linkers and library files, is also provided. It supports the development of various Arm architecture microcontrollers. Keil 5 can help developers develop embedded software more efficiently, and has a wide range of applications and support, making it the preferred tool for many embedded system developers. The following is a brief description of the program writing logic: First, perform initialization configuration, that is, configure the corresponding general input / output IO port. Next, configure SPI and serial port communication modes, where SPI is an interface standard for fast and reliable serial communication. It supports flexible hardware connections through full-duplex data transmission between master and slave devices, and is widely used in various digital systems. SPI is particularly common in embedded systems and is used to exchange data with peripheral devices, providing a convenient and effective solution for communication between devices; serial communication is a communication method that transmits data serially, using a pair of data lines to send and receive data. It is simple, reliable and widely supported, and is suitable for data transmission between various systems and devices. Serial communication is commonly used in embedded systems, industrial automation, medical equipment and other fields, and plays an important role in digital systems. Finally, configure the working mode of each peripheral chip, and package the received data into data packets in a specific format and send them through the WiFi transmission protocol.

[0068] Secondly, the detection method of the analog front-end system based on nanozyme microelectrode proposed according to an embodiment of the present invention will be described with reference to the accompanying drawings.

[0069] The detection method of the analog front-end system based on the nanozyme microelectrode in the embodiment of the present invention is applied to the analog front-end system based on the nanozyme microelectrode described above, and mainly includes the following steps:

[0070] In the electrochemical signal acquisition mode, the electrochemical signals are acquired by differential pulse voltammetry, square wave voltammetry, linear sweep voltammetry or conventional pulse voltammetry;

[0071] Alternatively, in an electrophysiological acquisition mode, receiving an electromyographic signal acquired by a nanozyme microelectrode array, and determining an electrophysiological signal through the electromyographic signal;

[0072] A detection result of the subject's nervous system is determined based on the electrochemical signal and the electrophysiological signal.

[0073] Optionally, the detection method of the analog front-end system based on the nanozyme microelectrode in the embodiment of the present invention also includes: turning on the WiFi module of the circuit, keeping the circuit consistent with the WiFi network of the host computer, switching the working mode to the electrochemical acquisition mode, performing electrochemical characterization through three electrodes, and displaying the characterization results through the host computer.

[0074] The following is a detailed introduction to the simulation front-end system and detection method based on nanozyme microelectrode provided by the present application with specific embodiments:

[0075] Embodiment 1:

[0076] Electrochemical signal detection.

[0077] (1) Hardware preparation: Connect the test electrode, reference electrode, counter electrode to the analog front-end circuit, and control the analog front-end circuit through code to put it in the electrochemical signal detection state. At this time, the WIFI module of the circuit is turned on, and the WIFI network of the host computer needs to be manually adjusted to be consistent with the WIFI network of the circuit board. At this point, the circuit has completed the WIFI connection with the host computer and is in the electrochemical signal detection state.

[0078] (2) Prepare the test solution: Prepare DA and AA solutions of certain density and volume as required.

[0079] (3) Conducting electrochemical tests: This experiment uses a three-electrode system for electrochemical characterization, with Ag / AgCl as the reference electrode, a platinum electrode as the counter electrode, and a nanozyme microelectrode as the test electrode. When testing DA solutions of different concentrations by DPV, SWV, NPV, and LSV methods, DA solutions in the concentration range of 1μM to 200uM are tested respectively. DA solutions in the concentration range of 1μM to 200uM are prepared by adding 10mM, 1mM, and 100μM DA solutions to 10mL of PBS solution, respectively, so that the DA solution varies in the concentration range of 5uM to 50uM. Similarly, when testing AA solutions of different concentrations by DPV, SWV, NPV, and LSV methods, AA solutions in the concentration range of 200μM to 1200uM are tested respectively. The test results, such as Fig.11 As shown in Figures (a) to (d), the electrochemical gradient signals detected in DA solution using four electrochemical methods: DPV, SWV, NPV, and LSV. Fig.12 As shown, Figures (a) to (d) show the electrochemical gradient signals detected in AA solution using four electrochemical methods: DPV, SWV, NPV, and LSV.

[0080] Embodiment 2:

[0081] Electrophysiological signal detection.

[0082] (1) Hardware preparation: Connect the electrodes to be tested to the 8-channel electrophysiological acquisition interface of the circuit. And control the analog front-end circuit through code to put it in the electrophysiological signal detection state. At this time, the WIFI module of the circuit is turned on. We need to manually adjust the WIFI network of the host computer to be consistent with the WIFI network of the circuit board. At this point, the circuit has completed the WIFI connection with the host computer and is in the electrophysiological signal detection state.

[0083] (2) Software preparation: Set the sampling rate of this acquisition through the software code (such as setting it to 1 kHz), run the firmware code, and then start continuous and simultaneous sampling of electrophysiological signals of 8 channels.

[0084] (3) Collect electrophysiological signals: Place the multi-channel microelectrode close to the arm. Contract the arm muscles rhythmically so that the collected waveforms show regular stimulation signals. Continuously collect electromyographic signals and save the signal data to the host computer. Fig.13 The 8-channel analog front-end circuit electrophysiological signal acquisition shown shows the electromyographic time domain signals collected simultaneously by 8 channels.

[0085] It can be seen that the contents of the above system embodiments are all applicable to the present method embodiments, the functions specifically implemented by the present method embodiments are the same as those of the above system embodiments, and the beneficial effects achieved are also the same as those achieved by the above system embodiments.

[0086] The embodiment of the present invention provides an analog front-end device based on nanozyme microelectrode, comprising:

[0087] at least one processor;

[0088] at least one memory for storing at least one program;

[0089] When the at least one program is executed by the at least one processor, the at least one processor implements the detection method of the simulated front-end system based on the nanozyme microelectrode.

[0090] Similarly, the contents of the above method embodiments are all applicable to the present device embodiments. The functions specifically implemented by the present device embodiments are the same as those of the above method embodiments, and the beneficial effects achieved are also the same as those achieved by the above method embodiments.

[0091] An embodiment of the present invention also provides a computer-readable storage medium, which stores a program executable by a processor. When the program executable by the processor is executed by the processor, it is used to execute the above-mentioned detection method of the simulated front-end system based on the nanozyme microelectrode.

[0092] Similarly, the contents of the above method embodiments are all applicable to the present storage medium embodiments. The functions specifically implemented by the present storage medium embodiments are the same as those of the above method embodiments, and the beneficial effects achieved are also the same as those achieved by the above method embodiments.

[0093] In some selectable embodiments, the function / operation mentioned in the block diagram may not occur in the order mentioned in the operation diagram. For example, depending on the function / operation involved, the two boxes shown in succession can actually be executed substantially simultaneously or the boxes can sometimes be executed in reverse order. In addition, the embodiment presented and described in the flow chart of the present invention is provided by way of example, for the purpose of providing a more comprehensive understanding of technology. The disclosed method is not limited to the operation and logic flow presented herein. Selectable embodiments are expected, wherein the order of various operations is changed and the sub-operation of a part for which is described as a larger operation is performed independently.

[0094] In addition, although the present invention is described in the context of functional modules, it should be understood that, unless otherwise specified, one or more of the functions and / or features can be integrated into a single physical device and / or software module, or one or more functions and / or features can be implemented in a separate physical device or software module. It is also understood that a detailed discussion of the actual implementation of each module is unnecessary for understanding the present invention. More specifically, in view of the properties, functions and internal relationships of the various functional modules in the device disclosed herein, the actual implementation of the module will be understood within the conventional skills of the engineer. Therefore, those skilled in the art can implement the present invention set forth in the claims without excessive experimentation using ordinary techniques. It is also understood that the specific concepts disclosed are merely illustrative and are not intended to limit the scope of the present invention, which is determined by the full scope of the appended claims and their equivalents.

[0095] If the functions are implemented in the form of software functional units and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present invention, or the part that contributes to the prior art or the part of the technical solution, can be embodied in the form of a software product. The computer software product is stored in a storage medium, including several programs to enable a computer device (which can be a personal computer, a server, or a network device, etc.) to perform all or part of the steps of the methods described in each embodiment of the present invention. The aforementioned storage medium includes: U disk, mobile hard disk, read-only memory (ROM, Read-Only Memory), random access memory (RAM, Random Access Memory), disk or optical disk, etc., which can store program codes.

[0096] The logic and / or steps represented in the flowchart or otherwise described herein, for example, may be considered as an ordered list of executable programs for implementing the logical functions, and may be embodied in any computer-readable medium for use by a program execution system, device or apparatus (such as a computer-based system, a system including a processor, or other system that can fetch and execute a program from a program execution system, device or apparatus), or in conjunction with such program execution systems, devices or apparatuses. For purposes of this specification, a "computer-readable medium" may be any device that can contain, store, communicate, propagate or transmit a program for use by a program execution system, device or apparatus, or in conjunction with such program execution systems, devices or apparatuses.

[0097] More specific examples of computer-readable media (a non-exhaustive list) include the following: an electrical connection with one or more wires (electronic device), a portable computer disk case (magnetic device), a random access memory (RAM), a read-only memory (ROM), an erasable and programmable read-only memory (EPROM or flash memory), an optical fiber device, and a portable compact disk read-only memory (CDROM). In addition, the computer-readable medium may even be a paper or other suitable medium on which the program is printed, since the program may be obtained electronically, for example, by optically scanning the paper or other medium, followed by editing, deciphering or, if necessary, processing in another suitable manner, and then stored in a computer memory.

[0098] It should be understood that the various parts of the present invention can be implemented by hardware, software, firmware or a combination thereof. In the above-mentioned embodiments, a plurality of steps or methods can be implemented by software or firmware stored in a memory and executed by a suitable program execution system. For example, if implemented by hardware, as in another embodiment, it can be implemented by any one of the following technologies known in the art or their combination: a discrete logic circuit having a logic gate circuit for implementing a logic function for a data signal, a dedicated integrated circuit having a suitable combination of logic gate circuits, a programmable gate array (PGA), a field programmable gate array (FPGA), etc.

[0099] In the above description of this specification, the description with reference to the terms "one embodiment / example", "another embodiment / example" or "certain embodiments / examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0100] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

[0101] The above is a specific description of the preferred implementation of the present invention, but the present 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 the present invention.

Claims

1. An analog front-end system based on nanozyme microelectrodes, characterized in that: The system comprises: a nanozyme microelectrode array, an electrophysiological acquisition module, an electrochemical acquisition module and a control module; The electrochemical acquisition module is connected to the control module, the electrochemical acquisition module is used to collect electrochemical signals by differential pulse voltammetry, square wave voltammetry, linear sweep voltammetry or conventional pulse voltammetry, and the control module is used to receive and process the electrochemical signals in the electrochemical acquisition mode; The nanozyme microelectrode array is connected to the control module through the electrophysiological acquisition module, and the nanozyme microelectrode array is used to contact the limbs of the object to be tested to collect electromyographic signals; the control module is used to receive and process the electromyographic signals in the electrophysiological acquisition mode, and determine the electrophysiological signals through the electromyographic signals; the control module is also used to switch the acquisition mode; the control module is also used to determine the detection results of the object's nervous system based on the electrochemical signals and the electrophysiological signals.

2. The analog front-end system based on nanozyme microelectrode according to claim 1, characterized in that: The electrophysiological acquisition module includes an ADS1299 chip, the input end of the ADS1299 chip is respectively connected to 8-way nanozyme microelectrode arrays and 1-way right leg driving circuit through an interface; the analog power supply end of the ADS1299 chip is grounded through a capacitor, and the analog ground end of the ADS1299 chip is connected to the analog bypass capacitor end of the ADS1299 chip through a capacitor.

3. The analog front-end system based on nanozyme microelectrode according to claim 2, characterized in that: The electrochemical acquisition module includes an AD5941 chip; the RE end, CE end and SE end of the AD5941 chip are respectively connected to three electrodes through interfaces for collecting current signals; the input end of the AD5941 chip is respectively connected to two electrodes through interfaces for collecting voltage signals.

4. The analog front-end system based on nanozyme microelectrode according to claim 1, characterized in that: The system also includes a power module, which includes a battery, and the battery is connected to the input end of the LTC3200 chip; the output end of the LTC3200 chip is connected to the input end of the TPS73250 chip, and the output end of the TPS73250 chip supplies power to the electrophysiological acquisition module, the electrochemical acquisition module and the control module.

5. The analog front-end system based on nanozyme microelectrode according to claim 1, characterized in that: The system also includes a WiFi module, which is used to connect the control module and the host computer. The control module is used to transmit the collected electrochemical signals and electrophysiological signals to the host computer through the WiFi module, and the host computer is used to process and display the signals.

6. The analog front-end system based on nanozyme microelectrode according to claim 1, characterized in that: The system also includes a USB module, the universal interface of the control module is connected to the RXD end and the TXD end of the CH340 chip, and the UD end of the CH340 chip is connected to the type-c interface.

7. The analog front-end system based on nanozyme microelectrode according to claim 1, characterized in that: The PCB board corresponding to the system is a four-layer board, and the structure of the four-layer board is a top signal layer, a ground layer, a power supply layer and a bottom signal layer in sequence, and the ground layer includes a digital ground and an analog ground.

8. The analog front-end system based on nanozyme microelectrode according to claim 7, characterized in that: The PCB board adopts a front and back layout, wherein the electrophysiological acquisition module, the electrochemical acquisition module and the control module are arranged on the front side, and the WiFi module and the power module are arranged on the back side.

9. A detection method based on a nanozyme microelectrode analog front-end system, characterized in that: Applied to the analog front-end system based on nanozyme microelectrode as claimed in claim 1, the method comprises: In the electrochemical signal acquisition mode, the electrochemical signals are acquired by differential pulse voltammetry, square wave voltammetry, linear sweep voltammetry or conventional pulse voltammetry; Alternatively, in an electrophysiological acquisition mode, receiving an electromyographic signal acquired by a nanozyme microelectrode array, and determining an electrophysiological signal through the electromyographic signal; A detection result of the subject's nervous system is determined based on the electrochemical signal and the electrophysiological signal.

10. The detection method of the nanozyme microelectrode-based analog front-end system according to claim 6, characterized in that: The method further comprises: The WiFi module of the circuit is turned on, and the WiFi network of the circuit and the host computer are kept consistent, the working mode is switched to the electrochemical acquisition mode, electrochemical characterization is performed through three electrodes, and the characterization results are displayed through the host computer.

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