Wireless wearable electrical stimulation microsystem for cell infection research

Abstract

The invention provides a wireless wearable electrical stimulation microsystem for cell infection research, and relates to the technical field of medical instruments. The system comprises a power supply module, a microprocessor module, a signal adjusting module, a wireless operation module, a load module and a signal monitoring module, the power supply module is connected with the signal adjusting module, and the power supply module supplies power to the wireless wearable electrical stimulation microsystem; the first output end of the microprocessor module is connected with the input end of the wireless operation module, the output end of the wireless operation module is connected with the first input end of the microprocessor module, and the second output end of the microprocessor module is connected with the second input end of the signal adjusting module. The output end of the signal adjusting module is connected with the input end of the load module. The output end of the load module is connected with the input end of the signal monitoring module. According to the invention, adjustable electrical stimulation signals can be provided for the electrode according to clinical requirements, the electrical stimulation process can be monitored in real time, and the safety and reliability of operation are ensured.

Description

Technical Field

[0001] The present disclosure relates to the technical field of medical devices, and in particular to a wireless wearable electrical stimulation microsystem for cell invasion research. Background Art

[0002] Wound healing is a complex process involving the close coordination of cell migration, proliferation, matrix deposition and remodeling, as well as inflammation and angiogenesis. When repair goes wrong during this process, it may lead to risks including inflammation, fibrosis, and even cancer. When the skin and biological barriers are damaged, open wounds are formed, and external pathogens and other microorganisms can easily invade, causing wound infection and inflammation. Effective skin healing is not only crucial for preventing infection and maintaining homeostasis, but microbial infection at the site of injury will also prolong the time and state of wound healing. Therefore, wound healing and wound infection occur synergistically and restrict each other, requiring synergistic treatment of wound healing and complications such as infection caused by gas to achieve optimal results.

[0003] Currently, wound healing and infection are primarily treated with medication and physical therapy. In the case of physical therapy, treatments that simulate or enhance human bioelectricity by applying electrical stimulation to the body have been applied to electrically active tissues and organs with intrinsically conductive properties, such as nerves, bones, and heart tissue, to achieve repair and regeneration. In skin tissue, external direct current stimulation of wounds can regulate the migration and proliferation of key cells at the wound site, helping to accelerate wound healing. Appropriate direct current helps accelerate the sustained migration of cells from the damaged area to the wound edge, generating traction that accelerates wound closure. Results showed that continuous treatment with a 1.03V / cm electric field stimulated fibroblasts to migrate toward the positive electrode and proliferate. Different electric field parameters produce different cellular stimulation results, with a typical electrophysiological range of 0.1-10V / cm. Electrical stimulation of human bone marrow mesenchymal stem cells for 60 minutes, after increasing the DC field strength to 2V / cm, was found to reduce the elastic modulus of the cells and separate the cell membrane and cytoskeleton. Applying 10V / cm and stimulating primary bovine osteoblasts and human osteosarcoma cells for 10-30 seconds changes the local intercellular traction force, affecting cell shape and cell alignment. Further using magnesium and molybdenum materials to form a primary cell and increase the electric field parameters to 0.9V (30V / cm) can accelerate intestinal wound healing. However, after reducing the voltage to 0.5V / cm and stimulating for 100 minutes, the local intercellular traction force and intercellular stress of human glial cells (HaCaT) changed, further affecting cell migration and alignment. With the further development of biomaterials, a degradable electromechanical suture composed of poly(lactic-co-glycolic acid), polycaprolactone, and magnesium can generate an electric field of 1V / cm in response to movement and stretching, thereby promoting tissue regeneration, extracellular matrix deposition, and angiogenesis, accelerating wound healing by 50%. Summary of the Invention

[0004] In view of this, the purpose of the present disclosure is to propose a wireless wearable electrical stimulation microsystem for cell invasion research, which can specifically solve the existing problems.

[0005] Based on the above objectives, the present disclosure proposes a wireless wearable electrical stimulation microsystem for cell invasion research, comprising: a power supply module, a microprocessor module, a signal conditioning module, a wireless operation module, a load module and a signal monitoring module; the first output end of the power supply module is connected to the first input end of the signal conditioning module, and the second output end of the power supply module supplies power to the wireless wearable electrical stimulation microsystem; the first output end of the microprocessor module is connected to the input end of the wireless operation module, the output end of the wireless operation module is connected to the first input end of the microprocessor module, and the second output end of the microprocessor module is connected to the second input end of the signal conditioning module; the output end of the signal conditioning module is connected to the input end of the load module, and the output end of the load module is connected to the input end of the signal monitoring module; the output end of the signal monitoring module is connected to the second input end of the microprocessor module.

[0006] In general, the present disclosure has at least the following beneficial effects: it can provide adjustable electrical stimulation signals to electrodes according to clinical needs, and it can monitor the electrical stimulation process in real time to ensure the safety and reliability of the operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] In the accompanying drawings, unless otherwise specified, the same reference numerals throughout the multiple drawings represent the same or similar components or elements. These drawings are not necessarily drawn to scale. It should be understood that these drawings only depict some embodiments according to the present disclosure and should not be regarded as limiting the scope of the present disclosure.

[0008] Figure 1 A schematic diagram of a wireless wearable electrical stimulation microsystem for cell invasion research according to an embodiment of the present disclosure is shown; Figure 2 A program control flow chart of a wireless wearable electrical stimulation microsystem for cell invasion research according to an embodiment of the present disclosure is shown; Figure 3 A schematic diagram of a voltage stabilization circuit of a wireless wearable electrical stimulation microsystem for cell invasion research according to an embodiment of the present disclosure is shown; Figure 4 A schematic diagram of a voltage boost circuit in a wireless wearable electrical stimulation microsystem for cell invasion research according to an embodiment of the present disclosure is shown; Figure 5FIG2 shows a schematic diagram of a signal monitoring module in a wireless wearable electrical stimulation microsystem for cell invasion research according to an embodiment of the present disclosure; Figure 6 1. A design diagram of a ring electrode in a wireless wearable electrical stimulation microsystem for cell invasion research according to an embodiment of the present disclosure is shown; Figure 7 A schematic diagram of the overall construction of a wireless wearable electrical stimulation microsystem for cell invasion research according to an embodiment of the present disclosure is shown; Figure 8 The system operation test results of the wireless wearable electrical stimulation microsystem for cell invasion research according to an embodiment of the present disclosure are shown. DETAILED DESCRIPTION

[0009] The present disclosure will be further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are intended only to illustrate the relevant invention and are not intended to limit the invention. It should also be noted that, for ease of description, only portions relevant to the relevant invention are shown in the accompanying drawings.

[0010] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments in the present disclosure may be combined with each other. The present disclosure will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0011] Figure 1 The present invention discloses a wireless wearable electrical stimulation microsystem for cell invasion research. In an embodiment of the present invention, the system includes: A power supply module, a microprocessor module, a signal conditioning module, a wireless operation module, a load module and a signal monitoring module; the first output end of the power supply module is connected to the first input end of the signal conditioning module, and the second output end of the power supply module supplies power to the wireless wearable electrical stimulation microsystem; the first output end of the microprocessor module is connected to the input end of the wireless operation module, the output end of the wireless operation module is connected to the first input end of the microprocessor module, and the second output end of the microprocessor module is connected to the second input end of the signal conditioning module; the output end of the signal conditioning module is connected to the input end of the load module, and the output end of the load module is connected to the input end of the signal monitoring module; the output end of the signal monitoring module is connected to the second input end of the microprocessor module.

[0012] In some optional implementations of any embodiment of the present disclosure, the power supply module is used to output an initial electrical stimulation signal, the signal conditioning module generates the electrical stimulation signal, and outputs the electrical stimulation signal to the load module; the load module is used to receive the electrical stimulation signal from the signal conditioning module, and output the electrical stimulation signal to the object to be stimulated in the load module; the microprocessor module is used to send an instruction to the signal conditioning module to generate an electrical stimulation signal; the signal monitoring module is used to monitor the status data of the load module and feed the status data back to the microprocessor module.

[0013] In some optional implementations of any embodiment of the present disclosure, the wireless operation module is a terminal device, and the wireless operation module is used to receive status data sent by the signal monitoring module, and to feed back the status data to the microprocessor module. The microprocessor module sends the status data to the wireless operation module, and the wireless operation module displays the status data.

[0014] In some optional implementations of any embodiment of the present disclosure, the operating capacity duration of the wireless operation module is greater than the target duration threshold; the wireless operation module has a digital-to-analog conversion function, a serial communication function, a serial asynchronous communication function and an integrated bus communication function.

[0015] In some optional implementations of any embodiment of the present disclosure, the power supply module includes a voltage stabilizing circuit and a voltage boosting circuit, the voltage stabilizing circuit is provided with a buck-boost converter, the voltage boosting circuit is provided with a switching power supply chip, and the power supply module is provided on an independent PCB board; the input and output ends of the buck-boost converter are both provided with bypass capacitors, and the buck-boost converter is used to output a DC voltage to power the wireless wearable electrical stimulation microsystem; the input pin of the switching power supply chip is connected to the battery, the enable pin of the switching power supply chip is connected to the input pin, the feedback pin of the switching power supply chip is connected to the output end through two feedback resistors, and another feedback resistor is connected to the ground end; a power inductor is connected between the output end and the switch pin of the switching power supply chip, the switch pin is connected to the anode of the unidirectional diode, and the cathode of the unidirectional diode serves as the output end of the boost circuit.

[0016] In some optional implementations of any embodiment of the present disclosure, the signal regulation module includes a voltage regulation submodule, a driving submodule and a signal modulation submodule; the voltage regulation submodule includes a digital potentiometer, based on the digital potentiometer being arranged in an adjustable boost circuit, the digital potentiometer adjusts the electrical stimulation voltage through a microprocessor; the driving submodule includes a follower circuit and a power amplifier circuit; the signal modulation submodule includes waveform modulation circuits of square wave, sine wave, triangle wave and sawtooth wave to generate electrical stimulation signals of multiple frequencies and waveforms.

[0017] In some optional implementations of any embodiment of the present disclosure, the signal monitoring module includes a current detection circuit and a voltage attenuation circuit; the current detection circuit is composed of a digital current detection amplifier, which is used to monitor the current flowing through the sensing resistor in real time, and transmit the collected status data to the microprocessor module through an interface; the voltage attenuation circuit includes a passive voltage attenuation module provided with a chip resistor, or includes an active voltage attenuation module provided with an operational amplifier, and the voltage attenuation circuit is used to feed back the voltage value of the object.

[0018] In some optional implementations of any embodiment of the present disclosure, the wireless operation module includes an antenna, and host computer software is installed on the wireless operation module, that is, the host computer. For example, the host computer software can be a mobile phone APP software, specifically software running on Android, MAC and Hongmeng systems. The microprocessor module has a built-in communication sub-module that can realize Bluetooth communication function; the wireless operation module uses the software to perform curve fitting on the changes in the electrical parameters of the object during the electrical stimulation process, and performs real-time feedback and dynamically adjusts the generation or output of the electrical stimulation signal.

[0019] In some optional implementations of any embodiment of the present disclosure, the load module includes a ring electrode, a lead, a wound sealing hydrogel and the object to be stimulated; the ring electrode includes an outer ring and an inner ring, the outer ring and the inner ring are eccentric rings, the outer ring and the inner ring are connected by a substrate, and are bent to form upper and lower concentric rings when in use; the outer ring and the inner ring form an electric field to stimulate the wound site, the radius of the outer ring electrode is 2-20 mm, and the width is 0.5-1 mm; the radius of the inner ring electrode is 1-19 mm, and the width is 0.5-1 mm, and the direction of the electric field is selected from the outer ring direction to the inner ring direction or from the inner ring direction to the outer ring direction according to the cell migration direction in the object; the electrode is connected to the control circuit through a gold finger, and the gold finger area is reinforced with PI material with a reinforcement thickness of 2-10 mm.

[0020] The object to be stimulated is a cell or wound tissue; the wound sealing hydrogel is formed by chemically cross-linking methacrylate gelatin and dissolved carboxymethyl chitosan using lithium phosphinate; and the wound sealing hydrogel is a drug-loaded hydrogel.

[0021] In some optional implementations of any embodiment of the present disclosure, the microprocessor module includes a low-power wireless microcontroller, an external clock and a download module; the standby current of the low-power wireless microcontroller is less than a preset current threshold; the external clock is composed of a crystal oscillator and a load capacitor, providing the required clock frequency for the operation of the microprocessor module.

[0022] The present invention can provide adjustable electrical stimulation signals to the electrodes according to clinical needs, and can also monitor the electrical stimulation process in real time to ensure the safety and reliability of the operation. It focuses on the field of bacterial interaction after cell electrical stimulation and the treatment of in vivo wound infection, and guides the rapid wound healing and anti-infection synergistic treatment strategies of clinical infections.

[0023] The present disclosure also provides a wireless wearable electrical stimulation microsystem, specifically, The power module includes a lithium polymer battery. The buck-boost converter is a high-efficiency step-down / boost converter suitable for applications where the input voltage may be higher, lower, or equal to the output voltage. It features a 1.5 MHz switching frequency, allowing the use of small external components. Bypass capacitors are included on the input and output terminals, and the converter outputs a stable DC voltage to power the entire system.

[0024] The wireless wearable electrical stimulation microsystem supports a 0-28 V output voltage. A lithium battery is connected to the input pin, while the enable pin is connected to the input pin. One feedback pin is connected to two feedback resistors, which are connected to the output terminal, and the other feedback resistor is connected to ground. A power inductor is connected between the output terminal and the switch pin. The anode of a single-phase diode is connected to the switch pin, while the cathode serves as the output terminal of the boost circuit.

[0025] The power module is designed as an independent module on an independent PCB board. The PCB is a circular structure with a radius of 1CM. The substrate includes a flexible circuit board and a hard circuit board made of FR4 material.

[0026] Optionally, the power module includes a 3.3 V regulated output circuit based on a buck-boost converter design to provide operating voltage for the entire system, and a boost circuit based on a switching power supply chip design as an initial electrical stimulation signal.

[0027] Optionally, the power management circuit uses a 3.7 V polymer lithium battery as the system power supply, which is connected to the input ends of the voltage stabilizing circuit and the voltage boosting circuit through a miniature no-load fluctuation switch.

[0028] The voltage stabilizing circuit is composed of a buck-boost converter, a bypass capacitor, and a power inductor.

[0029] The voltage stabilization circuit integrates both boost and buck functions, and can convert a supply voltage in the range of 1.2 V to 5.5 V into a fixed voltage output of 3.3 V, ensuring system stability when the lithium battery power supply decreases during use.

[0030] The bypass capacitors in the voltage stabilizing circuit are non-polarized capacitors, and two bypass capacitors are placed at the input and output ends of the buck-boost converter to filter out interference signals in the environment.

[0031] The boost circuit is composed of a switching power supply chip, a power inductor, a power diode, a self-recovery fuse, and a bypass capacitor.

[0032] The switching power supply chip has a conversion efficiency of 97% (greater than the conversion efficiency threshold), and the lower power loss (less than the power loss threshold) can provide a longer battery life for the electrical stimulation device.

[0033] The self-resetting fuse is connected to the back side of the switch, and automatically cuts off the circuit when the current exceeds 100mA, preventing short circuits caused by possible misoperation during the electrical stimulation process from damaging the circuit.

[0034] In some optional implementations, the microprocessor module includes a low-power wireless microcontroller, an external clock, and a download module.

[0035] The low-power wireless microprocessor module has a built-in low-power Bluetooth module and establishes a wireless connection with other devices (such as wireless operation modules) through a radio frequency antenna.

[0036] The low-power wireless microcontroller has 24 pins, an ultra-low standby current of less than 0.71 μA, a built-in 12-bit resolution analog-to-digital conversion module, an asynchronous receiver and transmitter module, and supports a serial peripheral interface and an integrated circuit bus interface.

[0037] The external clock is composed of an 8M passive crystal oscillator, a 32.768 kHz crystal oscillator and its load capacitors, which provide the required clock frequency for the operation of the microprocessor module.

[0038] The download module is connected to the external download module using a small board-to-board connector, which effectively saves PCB layout space.

[0039] In some optional implementations, the signal conditioning module includes a digital potentiometer and a voltage follower designed based on a low-power operational amplifier.

[0040] The digital potentiometer has a selection resolution of 256 positions, receives instructions from a microprocessor through a serial peripheral interface, changes the tap position on the internal resistance ladder of the digital potentiometer according to the instructions, determines the resistance ratio of the digital potentiometer, and realizes voltage adjustment from 0 to 30V by changing the resistance divider value.

[0041] The voltage follower supports a wide voltage range of 0 to 40V, and has a maximum output current of 80mA. The voltage input terminal of the digital potentiometer is connected to the non-inverting input terminal of the subsequent voltage follower.

[0042] The low-power operational amplifier provides rail-to-rail input and output capabilities and has excellent DC precision and AC performance.

[0043] Optionally, a MOS tube switching circuit is connected to the back end of the digital potentiometer to realize pulse adjustment of the electrical stimulation signal. By adjusting the switching frequency of the MOS tube, the frequency and duty cycle of the pulse signal are changed, thereby changing the intensity of the electrical stimulation signal.

[0044] Optionally, a digital potentiometer may be connected as a feedback resistor to the feedback pin of the boost converter to achieve control of the voltage amplitude of the electrical stimulation signal.

[0045] In some optional implementations, the signal monitoring module includes a digital current detector, namely a current detection circuit, and a voltage attenuation circuit.

[0046] The digital circuit detector can be used as a current, voltage, and power monitor, and is set as a high-side sensing application in the electrical stimulation system to transmit data to a microprocessor module such as a Bluetooth chip such as CC2430, CC2530, etc. through an integrated circuit bus interface.

[0047] The digital circuit detector is composed of a digital current detection amplifier, which can monitor the current flowing through the sensing resistor in real time, transmit the collected data to the wireless microcontroller through an interface, and report the current, bus voltage and power values.

[0048] The voltage attenuation circuit uses resistor division to attenuate the measured voltage to a range that can be processed by the microprocessor module and transmits it to the microprocessor's analog-to-digital conversion pin. The voltage attenuation circuit can include a passive voltage attenuation module designed with chip resistors or an active voltage attenuation module designed with an operational amplifier, which is used to provide feedback on the voltage value at a specific location on the wound.

[0049] In some optional implementations, the wireless operation module has a built-in Bluetooth module, an antenna circuit, and host computer software.

[0050] The antenna circuit is pre-installed with a passive LC low-pass filter to filter out clutter interference during wireless communication. The antenna chip operates in a frequency range of 2.4 to 2.5 GHz.

[0051] The functions of the host computer software include the setting of the amplitude, frequency and waveform of the electrical stimulation signal, and the dynamic curve display of the voltage state of the electrical stimulation signal.

[0052] The electrical stimulation amplitude ranges from 0 to 30V, and the waveforms include DC signal, sine wave, square wave (adjustable pulse signal), triangle wave, and sawtooth wave.

[0053] The voltage dynamic curve display can reflect the real-time changes of the stimulation voltage during the electrical stimulation process.

[0054] In some optional implementations, the wireless microprocessor module supports multiple wireless protocols for receiving status data and sending control commands.

[0055] The microprocessor module consumes very low power of only a few microamperes in sleep mode, making it very suitable for battery-powered applications. It can maintain efficient operation for a long time during the implementation of electrical stimulation without the need for frequent charging or battery replacement.

[0056] The built-in communication module in the microprocessor module communicates with the host computer through an antenna with an operating frequency range of 2.4~2.5GHz.

[0057] The wireless microcontroller supports wireless downloading function.

[0058] The wireless microcontroller has built-in functions such as digital-to-analog conversion, serial communication, serial port asynchronous communication, and integrated bus communication.

[0059] In some optional implementations, the microprocessor module, signal conditioning module, and signal monitoring module are integrated on a PCB with a diameter of 0.8-1.2 cm and a circular shape. The materials include aluminum substrate material, FR4 material, ordinary PI material, and transparent PI material.

[0060] According to an embodiment of the present disclosure, the load module includes a ring electrode, a lead, a wound sealing hydrogel and an object to be stimulated, and the object to be stimulated is a cell or a wound tissue.

[0061] The annular electrode includes an outer ring and an inner ring. The inner ring and outer ring electrodes are eccentric rings. The inner ring and outer ring are connected by a substrate and can be bent to form upper and lower concentric rings when in use. The inner ring and outer ring form an electric field to stimulate the wound site. The radius of the outer ring electrode is 2-20mm and the width is 0.5-1mm; the radius of the inner ring electrode is 1-19mm and the width is 0.5-1mm. The direction of the electric field is selected from the outer ring direction to the inner ring direction or from the inner ring direction to the outer ring direction according to the direction of cell migration.

[0062] The ring electrode material includes silver, gold, copper, chromium, platinum and the like.

[0063] The flexible electrode substrate material includes ordinary PI material and transparent PI material, with a thickness of 1mm~2mm.

[0064] The electrodes are connected to the control circuit via gold fingers, and the gold finger area is reinforced with PI material with a thickness of 2-10 mm.

[0065] The wound sealing hydrogel is made of gelatin methacrylate (GelMA) and dissolved carboxymethyl chitosan (CMCS) chemically cross-linked with lithium phosphinate (LAP), and is prepared in a ratio of 1:1-1:5 according to swelling requirements.

[0066] The wound closure hydrogel contains drug-loaded hydrogel, and the drugs include ibrutinib, melaleucain, enoxacin, sodium butyrate, and edranib.

[0067] The electrically stimulated cells are rat crypt intestinal epithelial cells, human breast cancer cells, non-small cell lung cancer cells, human immortalized keratinocytes, etc., and the bacteria used for infection are Staphylococcus aureus and Escherichia coli, etc.

[0068] like Figure 1 As shown in the figure, the wireless wearable electrical stimulation microsystem includes a power module, a microprocessor module, a signal conditioning module, a wireless operation module, a load module, and a signal monitoring module. The microprocessor module, signal conditioning module, load module, and signal monitoring module within the dotted box can serve as the wireless wearable electrical stimulation chip, and the power module provides power to these modules.

[0069] like Figure 2 As shown, when the program is running, first the wireless operation module, such as the host computer, sends instructions to the microprocessor module; The microprocessor module controls the signal conditioning module to output the set electrical stimulation signal to the electrode according to the instruction; At the same time, the load-side electrical parameters are fed back to the host computer through the signal monitoring module. The user can use this feedback information to determine whether to make further adjustments to the electrical stimulation signal. The host computer can be a terminal device such as a mobile phone.

[0070] like Figure 3 As shown in FIG, the buck-boost converter has a total of 11 pins, a power inductor is connected between L1 and L2, and the enable port is connected to the input pin.

[0071] At the same time, the output pin 1 is connected to the feedback pin 10, and a stable voltage of 3.3V is output.

[0072] The package capacitors filter the input and output ports.

[0073] like Figure 4 As shown in the figure, the boost converter has a total of six pins, and the power inductor L2 is connected between the switch pin and the input pin.

[0074] The anode of the single diode D1 is connected to the switch pin, and the cathode serves as the output end of the boost circuit.

[0075] R266 and R268 are connected as feedback resistors to the FEEDBACK pin and the output, while R265 is connected as a feedback resistor to the FEEDBACK pin and ground.

[0076] The output port of the switching power supply is connected to the input port of the digital potentiometer.

[0077] The microprocessor module includes a low-power microprocessor, a reset circuit, and a crystal oscillator.

[0078] The microprocessor module has a total of 24 pins, which provide download pins for connecting to external download chips. The pins used by the electrical stimulation system include reset pins, analog-to-digital conversion input pins, serial communication input pins, clock pins, chip select pins, and integrated circuit bus data input and output pins.

[0079] The microprocessor module uses an external passive crystal oscillator, which is connected to pins 21 and 22 of the microprocessor to provide a 48M system clock for the microprocessor.

[0080] Five filter capacitors are connected to the front end of the microprocessor module power output to ensure the stability of the microprocessor's working state and prevent the sharp current from damaging the chip.

[0081] The signal conditioning module consists of a digital potentiometer and a voltage follower based on an operational amplifier design.

[0082] The A port of the digital potentiometer is connected to the initial voltage of electrical stimulation, the B port is connected to the ground, the voltage between the A and B ports is 28V, and the W port is connected to the operational amplifier as the voltage output terminal.

[0083] The digital potentiometer receives microprocessor command information through a serial communication protocol, and the user can adjust the output voltage of the digital potentiometer W port through the program.

[0084] The post-stage follower is designed based on an operational amplifier. The operational amplifier is powered by a single power supply, and the input signal of the pre-stage digital potentiometer W is connected to the non-inverting input terminal of the operational amplifier.

[0085] After the follower enhances the driving capability of the electrical stimulation signal, it is provided to the electrode as an electrical stimulation signal and connected to the attenuation circuit to collect the electrical stimulation voltage.

[0086] like Figure 5 As shown in Figure 1, the signal monitoring circuit consists of a digital current detection amplifier and an attenuation circuit. The digital current is transmitted to the main controller via the integrated circuit bus protocol.

[0087] In the electrical stimulation system, the digital current detector is configured as a high-side detection circuit, with IN+ connected to the bus voltage side of the sensing resistor R9, IN- connected to the load side of the sensing resistor, and the external electrode signal to be measured connected between the IN- pin and GND.

[0088] The digital current detector can monitor the current flowing through the sensing resistor R9 in real time and transmit the collected data to the main controller through the integrated circuit bus protocol interface.

[0089] The attenuation circuit is composed of R13 and R14, which attenuates the electrical stimulation voltage by 1 / 11 times and sends it to the analog-to-digital conversion pin of the microprocessor.

[0090] like Figure 6 As shown, the electrode substrate uses flexible circuit board technology. This material is not only light and thin but also has good flexibility. It can better adapt to surfaces of different shapes and ensure a close fit.

[0091] The pluggable gold finger located on the left side of the electrode substrate is designed and reinforced to ensure a fast and reliable connection between the electrode substrate and the drive circuit. This feature simplifies the assembly process and improves the convenience of maintenance and replacement.

[0092] The electrode base is connected to the driving circuit through the pluggable gold finger at the left end. The positive end of the electrical stimulation signal is connected to the outer pad through the gold finger, and the negative end is connected to the inner pad. At the same time, the pad is in direct contact with the skin or other parts to be measured, thereby accurately measuring the voltage changes at that part, ensuring the accuracy and reliability of the measurement results.

[0093] like Figure 7 As shown, in in vivo tissue validation, we used this system in combination with ring electrodes and drug-loaded hydrogel to effectively treat a wound model.

[0094] The system and the electrode are connected by pluggable gold fingers, so that the electrode model can be adjusted at any time as the wound width changes during use without replacing the entire system.

[0095] The host computer and the MCU in the system circuit communicate bidirectionally via a Bluetooth module, and the flexible electrodes are connected to the circuit via a printed circuit (FPC) interface. When the device is operating, commands from the host computer are transmitted to the MCU via the Bluetooth module. The MCU then generates an electrical stimulation signal of a set amplitude. This signal is then transmitted to the electrodes via a follower, creating an electric field in the target area to therapeutically stimulate the wound. Simultaneously, the MCU collects electrical signal status data via a current monitor, processes it, and feeds it back to the host computer.

[0096] Through the Bluetooth module in the controller and the radio frequency antenna, wireless interaction between the wearable electrical stimulation device and external communication equipment is completed, enabling users to intuitively view the signals and fully control the input signals.

[0097] like Figure 8 As shown in Figure 2, during the in vitro system operation test, we conducted life and stability tests on the system under a fixed load.

[0098] The system power supply uses a lithium manganese button battery as the system power supply, and uses a boost converter to increase the voltage to the maximum operating voltage of 30 V.

[0099] The system was tested for lifespan and stability using a no-load (0Ω) and a load close to tissue conductivity (1kΩ). The battery life reached 23.5 hours with a no-load (0Ω), representing at least 47 cycles of normal operation. The battery life reached 180 minutes with a 1kΩ load, representing at least 6 cycles of normal operation. In practice, lower tissue conductivity reduces the current drawn during operation, extending normal operation time. Therefore, the system can achieve long-term stable output as a wearable electrical stimulation device.

[0100] It should be noted that: In the above text, the terms "comprises", "comprising" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, an element defined by the statement "comprising a ..." does not exclude the presence of other identical elements in the process, method, article or device comprising the element. In addition, it should be noted that the scope of the methods and devices in the embodiments of the present disclosure is not limited to performing functions in the order shown or discussed, and may also include performing functions in a substantially simultaneous manner or in the opposite order according to the functions involved. For example, the described method may be performed in an order different from that described, and various steps may also be added, omitted, or combined. In addition, the features described with reference to certain examples may be combined in other examples.

[0101] Through the description of the above embodiments, those skilled in the art can clearly understand that the above-mentioned embodiment methods can be implemented by means of software plus the necessary general hardware platform. Of course, hardware can also be used, but in many cases the former is a more preferred embodiment. Based on this understanding, the technical solution of the present disclosure, or the part that contributes to the existing technology, can be embodied in the form of a software product. This computer software product is stored in a storage medium (such as ROM / RAM, magnetic disk, optical disk), and includes a number of instructions for enabling a terminal (which can be a mobile phone, computer, server, air conditioner, or network device, etc.) to execute the methods described in the various embodiments of the present disclosure.

[0102] The embodiments of the present disclosure are described above in conjunction with the accompanying drawings, which are only specific implementation methods of the present disclosure. However, the present disclosure is not limited to the above-mentioned specific implementation methods. The above-mentioned specific implementation methods are merely illustrative and not restrictive. Under the guidance of the present disclosure, ordinary technicians in this field can also make many forms without departing from the scope of protection of the purpose of the present disclosure and the claims, which are all within the protection of the present disclosure.

Claims

1. A wireless wearable electrical stimulation microsystem for cell invasion research, characterized in that: include: Power supply module, microprocessor module, signal conditioning module, wireless operation module, load module and signal monitoring module; The first output end of the power supply module is connected to the first input end of the signal conditioning module, and the second output end of the power supply module supplies power to the wireless wearable electrical stimulation microsystem; The first output end of the microprocessor module is connected to the input end of the wireless operation module, the output end of the wireless operation module is connected to the first input end of the microprocessor module, and the second output end of the microprocessor module is connected to the second input end of the signal conditioning module; The output end of the signal conditioning module is connected to the input end of the load module, and the output end of the load module is connected to the input end of the signal monitoring module; The output end of the signal monitoring module is connected to the second input end of the microprocessor module.

2. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that The power supply module is used to output an initial electrical stimulation signal, the signal conditioning module generates the electrical stimulation signal, and outputs the electrical stimulation signal to the load module; The load module is used to receive the electrical stimulation signal from the signal conditioning module and output the electrical stimulation signal to the object to be stimulated in the load module; The microprocessor module is used to send an instruction to the signal conditioning module to generate an electrical stimulation signal; The signal monitoring module is used to monitor the status data of the load module and feed the status data back to the microprocessor module.

3. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that The wireless operation module is a terminal device, which is used to receive status data sent by the signal monitoring module and feed the status data back to the microprocessor module. The microprocessor module sends the status data to the wireless operation module, and the wireless operation module displays the status data.

4. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that The operating time of the wireless operation module is greater than the target time threshold; The wireless operation module has digital-to-analog conversion function, serial communication function, serial port asynchronous communication function and integrated bus communication function.

5. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that The power module includes a voltage stabilizing circuit and a voltage boosting circuit. The voltage stabilizing circuit is provided with a buck-boost converter, and the voltage boosting circuit is provided with a switching power supply chip. The power module is provided on an independent PCB board. The input and output ends of the buck-boost converter are both provided with bypass capacitors, and the buck-boost converter is used to output a DC voltage to power the wireless wearable electrical stimulation microsystem; The input pin of the switching power supply chip is connected to a battery, the enable pin of the switching power supply chip is connected to the input pin, the feedback pin of the switching power supply chip is connected to the output end through two feedback resistors, and another feedback resistor is connected to the ground end; a power inductor is connected between the output end and the switch pin of the switching power supply chip, the switch pin is connected to the anode of a single diode, and the cathode of the single diode serves as the output end of the boost circuit.

6. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that The signal adjustment module includes a voltage adjustment submodule, a driving submodule and a signal modulation submodule; The voltage regulation submodule includes a digital potentiometer, which is arranged in an adjustable boost circuit and adjusts the electrical stimulation voltage through a microprocessor; The driving submodule includes a follower circuit and a power amplifier circuit; The signal modulation submodule includes waveform modulation circuits for square waves, sine waves, triangle waves and sawtooth waves, and generates electrical stimulation signals with a variety of different frequencies and waveforms.

7. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that The signal monitoring module includes a current detection circuit and a voltage attenuation circuit; The current detection circuit is composed of a digital current detection amplifier, which is used to monitor the current flowing through the sensing resistor in real time and transmit the collected status data to the microprocessor module through an interface; The voltage attenuation circuit includes a passive voltage attenuation module provided with a chip resistor, or includes an active voltage attenuation module provided with an operational amplifier, and the voltage attenuation circuit is used to feed back the voltage value of the object.

8. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that The wireless operation module includes an antenna, a host computer software is installed on the wireless operation module, and the microprocessor module has a built-in communication submodule; The wireless operation module performs curve fitting on the changes in the electrical parameters of the object during the electrical stimulation process through the host computer software, and performs real-time feedback and dynamic adjustment on the generation or output of the electrical stimulation signal.

9. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that: The microprocessor module includes a low-power wireless microcontroller, an external clock and a download module; The standby current of the low-power wireless microcontroller is less than a preset current threshold; The external clock is composed of a crystal oscillator and a load capacitor, and provides the required clock frequency for the operation of the microprocessor module.

10. The wireless wearable electrical stimulation microsystem according to claim 1, characterized in that: The load module includes a ring electrode, a lead, a wound sealing hydrogel, and an object to be stimulated; The annular electrode includes an outer ring and an inner ring, the outer ring and the inner ring are eccentric rings, the outer ring and the inner ring are connected by a substrate, and are bent to form upper and lower concentric rings when in use; the outer ring and the inner ring form an electric field to stimulate the wound site, the outer ring electrode has a radius of 2-20 mm and a width of 0.5-1 mm; the inner ring electrode has a radius of 1-19 mm and a width of 0.5-1 mm, and the direction of the electric field is selected from the outer ring direction to the inner ring direction or from the inner ring direction to the outer ring direction according to the cell migration direction in the subject; The electrode is connected to the control circuit through a gold finger, and the gold finger area is reinforced with PI material with a thickness of 2-10mm; The object to be stimulated is a cell or wound tissue; The wound sealing hydrogel is formed by chemically cross-linking methacrylate gelatin and dissolved carboxymethyl chitosan using lithium phosphinate, and the wound sealing hydrogel is a drug-loaded hydrogel.

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