Wireless transcranial direct current stimulator suitable for laboratory animals

Abstract

The invention discloses a wireless transcranial direct current stimulator suitable for laboratory animals. The wireless transcranial direct current stimulator comprises a power supply module, a wireless communication module, a main control chip, a current output module, an electrode assembly and fixing device, a data monitoring and transmission module and a control terminal. The wireless transcranial direct current stimulator is suitable for laboratory animals, can realize wireless transcranial direct current stimulation of laboratory animals such as rats and mice, meets treatment intervention in waking and active states, improves the naturalness of experiments, is used for dynamic experiments requiring free activities, has the functions of polarity transformation, stimulation data recording, real-time regulation and control and the like, and has wide application prospects. Therefore, hardware conditions are provided for exploring the curative effect and mechanism of wireless transcranial direct current stimulation.

Description

Technical Field

[0001] The present invention relates to the technical field of medical equipment, and in particular to a wireless transcranial direct current stimulator suitable for laboratory animals. Background Art

[0002] Transcranial direct current stimulation is a non-invasive brain stimulation technology that transmits low-intensity direct current (usually 1-2 mA) through electrodes on the surface of the scalp to specific areas of the brain to regulate neural activity. It can be used in the clinical treatment of depression, stroke and other diseases and in the field of sports training enhancement. At present, transcranial direct current stimulation is mostly wired: the electrode base is first fixed on the user's scalp, and an external power supply provides current through wires to the cranial brain tissue around the electrode. The electrode is connected to the control module by wire to ensure stable transmission and regulation of the current. In order to ensure the quality of electrical stimulation, a monitoring module for electrode contact quality is often included.

[0003] Wired connections often need to be fixed, which limits the user's range of motion, especially in experiments that require long-term use or movement. In addition, the presence of multiple cables may cause inconvenience in operation, increase the complexity of equipment layout, and affect the naturalness of the experiment. And wired connections cannot adapt to locations and environments that require flexible adjustment, especially in remote operations and non-laboratory environments, such as sports training. Although there are a small number of devices on the market that can be used for wireless transcranial direct current stimulation of the human body, in clinical applications, most patients are in a static sitting state, which is essentially an electrical stimulation intervention that restricts activity, and is not strictly true wireless transcranial direct current stimulation.

[0004] In addition, the existing transcranial direct current stimulation is relatively simple. Specifically, first of all, the stimulation polarity is single. Direct current stimulation can be divided into cathode direct current stimulation and anode direct current stimulation, each with a different mechanism of action. At present, during the stimulation process, the current polarity is pre-set and cannot be changed. Secondly, the current stimulation mode is mostly about 10-30 minutes in duration, relying on the accumulation of current to achieve a certain therapeutic effect, and the process is relatively vague. There are few schemes to record parameters such as current intensity and duration at specific times during the stimulation process for subsequent analysis, which is not conducive to accurately studying the efficacy and mechanism under specific stimulation conditions in a short period of time. In addition, most of the current stimulation schemes are set and fixed before the intervention, and cannot be adjusted in time during the stimulation process, and have low flexibility.

[0005] Wireless transcranial direct current stimulation has great research potential in motor enhancement and motor rehabilitation. However, the existing wireless direct current stimulators on the market are large in size and not lightweight enough. However, most animal research subjects are small animals such as mice and rats. It is difficult to conduct basic research related to movement under existing conditions. Animal experiments on transcranial direct current stimulation are all wired connections that restrain the body. This will have a great impact on the experimental results and is not conducive to the study of efficacy and mechanism. Therefore, there is an urgent need for a wireless transcranial electrical stimulation instrument suitable for small animals under laboratory conditions, which can be used for related research and has functions such as polarity conversion, stimulation data recording, and real-time regulation to promote the transformation of wireless transcranial direct current stimulation therapy to clinical practice. Summary of the invention

[0006] In order to solve the above technical problems, the present invention aims to design a wireless transcranial direct current stimulator suitable for laboratory animals, which can realize wireless transcranial direct current stimulation of laboratory animals such as rats and mice, meet the needs of therapeutic intervention in awake and active states, improve the naturalness of the experiment, and be used for dynamic experiments that require free movement. It also has functions such as polarity conversion, stimulation data recording, and real-time regulation, thereby providing hardware conditions for exploring the efficacy and mechanism of wireless transcranial direct current stimulation.

[0007] In view of this, the present invention provides a wireless transcranial direct current stimulator suitable for laboratory animals, comprising: a power module, a wireless communication module, a main control chip, a current output module, an electrode assembly and a fixing device, a data monitoring and transmission module and a control terminal.

[0008] Furthermore, the power module is a miniature lithium polymer battery (Li-Po) for providing current stimulation and circuit power supply.

[0009] Furthermore, the communication protocol of the wireless communication module is low-power Bluetooth; the integrated chip adopts NordicnRF52810, with a size of 2.5mm x 2.5mm, and the antenna is a PCB integrated antenna designed on the main control board to reduce the volume.

[0010] Furthermore, the main control chip includes a microcontroller Nordic nRF52810, and a CPU of ARM Cortex-M4, which is used for data recording and stimulation regulation.

[0011] Furthermore, the current output module realizes dynamic switching of the anode and cathode through a micro H-bridge circuit to adapt to different stimulation requirements and can realize dynamic polarity conversion during electrical stimulation.

[0012] Furthermore, the electrode assembly and the fixing device are composed of a silver-plated copper metal electrode and a polylactic acid base.

[0013] Furthermore, the polylactic acid base is designed to be in a cap shape that fits the skull, and is provided with an electrode hole at the bottom.

[0014] Furthermore, the data monitoring and transmission module measures the current value between the electrode and the skin through the monitoring chip INA219 to determine whether the skin is correctly contacted. The stimulation data is stored in the ultra-small EEPROM storage chip for reading and analysis after the experiment.

[0015] Furthermore, the wireless transcranial direct current stimulator includes a backpack-type integrated module, an electrode assembly and a fixing device, and a control terminal. The backpack-type integrated module integrates the power module, the wireless communication module, the main control chip, the current output module, and the data monitoring and transmission module of the wireless transcranial direct current stimulator into a backpack-type integrated module, which is fixed to the back of a laboratory animal by an elastic band.

[0016] The present invention also provides a method for performing direct current stimulation on laboratory animals using the wireless transcranial direct current stimulator:

[0017] 1) installing the electrode assembly and the fixing device on the skull surface of a laboratory animal;

[0018] 2) Using an elastic band, the backpack-type integrated module is mounted on the back of the laboratory animal and the electrode assembly is connected to the fixture;

[0019] 3) Wireless direct current stimulation and regulation of laboratory animals through control terminals;

[0020] 4) During the stimulation process, the control terminal monitors the electrode contact and current changes in real time to determine the state of electrical stimulation;

[0021] 5) After the stimulation is completed, the stimulation data stored in the data monitoring and transmission module is read, and a comprehensive experimental analysis is performed in combination with the behavioral changes of the laboratory animals corresponding to the changes in the stimulation mode during the experiment.

[0022] Compared with the prior art, the present invention has the following advantages:

[0023] As a wireless transcranial direct current stimulator designed for laboratory animals, the present invention can apply electrical stimulation intervention in awake and active states, has a high degree of freedom of movement, and breaks the activity limitations of previous wired stimulation. It can be used for dynamic treatment research on rats, mice and other animals in diseases such as stroke, Alzheimer's disease, and depression, allowing researchers to observe more realistic behaviors and movement patterns, thereby obtaining data with greater ecological validity.

[0024] The present invention can reduce the impact of anesthesia and restricted activities on the therapeutic effect of transcranial direct current stimulation in animals. Animals can explore, forage, socialize and other behaviors in complex experimental scenes, better simulate the movement and behavior patterns in the natural environment, and explore the real impact of electrical stimulation on motor behavior. These behaviors may not be manifested in traditional restricted activity environments. The present invention makes the conditions of basic experiments closer to the actual clinical situation and promotes the transformation to clinical practice.

[0025] The invention can also be used in the fields of sports training, sports physiology, sports rehabilitation, etc. The wireless design allows animals to receive transcranial direct current stimulation while performing dynamic tasks (such as running, jumping, climbing). This stimulation study under complex tasks helps to reveal the potential mechanism of transcranial direct current stimulation in motor learning, motor planning and neural control.

[0026] The present invention can reduce the physiological and psychological stress of animals caused by factors such as restraining the body during the experiment, and improve the accuracy and repeatability of data. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 It is a schematic structural diagram of an embodiment of the wireless transcranial direct current stimulator of the present invention.

[0028] Figure 2 It is a schematic diagram of the wireless transcranial direct current stimulator of the present invention applied to laboratory animals.

[0029] In the figure: 1-backpack integrated module; 2-electrode assembly and fixing device; 3-electrode wire; 4-elastic band; 5-control terminal. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solutions and advantages of the invention clearer, the present invention will be described in more detail below with reference to the accompanying drawings, but the present invention is not limited thereto.

[0031] The present invention will be further described in detail below through specific embodiments in conjunction with the accompanying drawings.

[0032] The present invention provides a wireless transcranial direct current stimulator suitable for laboratory animals, which includes a power module, a wireless communication module, a main control chip, a current output module, an electrode assembly and a fixing device, a data monitoring and transmission module and a control terminal. Figure 1 As shown, in a specific embodiment, the wireless transcranial direct current stimulator suitable for laboratory animals of the present invention comprises:

[0033] The power module is used to provide current stimulation and circuit power supply. It is a miniature lithium polymer battery (Li-Po), model: PD651723, weighing about 4 grams, with dimensions of 6.5mm x 17mm x 25mm, capacity of 200mAh, and voltage of 3.7V. While ensuring sufficient stimulation intensity and duration, it is lightweight enough to reduce the burden on experimental animals.

[0034] The main control chip includes a microcontroller Nordic nRF52810, and a CPU of ARM Cortex-M4, 64MHz. The memory is 192KB flash memory and 24KB RAM for data recording. The built-in DAC is used to achieve precise current output control (0.1mA to 2mA, resolution 0.01mA), real-time monitoring of battery power and electrode contact status to ensure the safe operation of the device, and store key information such as stimulation parameters and time of each experiment for subsequent analysis.

[0035] The wireless communication module uses Bluetooth Low Energy (BLE5.0) as the communication protocol, with a transmission distance of up to 10 meters, which is suitable for experimental environments. The integrated chip uses Nordic nRF52810, with a size of 2.5mm x 2.5mm, and the antenna is a PCB integrated antenna designed on the main control board to reduce the volume. Through this module, two-way data communication with a handheld wireless controller can be achieved, and the current stimulation parameters can be adjusted in real time to observe the effects of different stimulation modes, intensities, durations, and cycles on animal behavior.

[0036] Current output module, DC current output range: 0.1mA-2mA, using ultra-small digital-to-analog converter Texas Instruments DAC60501, size 2.9mm x 2.8mm x 1.1mm, to achieve high-precision current output and accurately adjust the current, suitable for different experimental needs. The stability of the current output is ensured by an operational amplifier and a precision resistor network. The dynamic switching of the anode and cathode is achieved through a micro H-bridge circuit to adapt to different stimulation needs, thereby achieving dynamic polarity conversion during electrical stimulation.

[0037] The electrode assembly and fixture consist of a silver-plated copper metal electrode and a polylactic acid (PLA) base. The silver-plated copper metal electrode is needle-shaped, providing good conductivity and corrosion resistance. The wire led out from the stimulation power module is parallel to the back of the animal's neck and obliquely inserted into the hole between the electrode base and the skull. The polylactic acid base has good biocompatibility and is designed to fit the skull cover. It is 2-4 mm thick (depending on the animal's body shape and skull size), and has an electrode hole with a diameter of 1-2 mm at the bottom for the electrode to be inserted. The electrode base is adhered to the skull and electrode surface with dental cement to protect the electrode and prevent it from falling off due to scratching by the animal.

[0038] The data monitoring module measures the current value between the electrode and the skin through the monitoring chip INA219 to determine whether the electrode is in correct contact with the skin and ensure that the stimulation current is effectively transmitted to the target area. If the electrode is in poor contact, the system can issue an alarm. The stimulation data is stored in an ultra-small EEPROM storage chip and can be read and analyzed after the experiment.

[0039] The control terminal is a handheld wireless controller. The microcontroller is ARM Cortex-M4, frequency 60MHz, memory: 256KB Flash, 64KB RAM. 0.96-inch OLED display, resolution: 128x64 pixels, real-time display of the device's working status, including current intensity, battery power, connection status, etc. Physical buttons are used to adjust the current (increase / decrease), mode switching, power switch, confirmation and other functions. The communication module is BLE 5.0 (Nordic nRF52810), which is used for two-way communication with the transcranial direct current stimulation device, sending control instructions and receiving status information connection mode. A built-in 500mAh rechargeable lithium polymer battery is used as a power source.

[0040] In a preferred embodiment, the wireless transcranial direct current stimulator includes a backpack-type integrated module, an electrode assembly and a fixing device, and a control terminal. The backpack-type integrated module integrates a power module, a wireless communication module, a main control chip, a current output module, and a data monitoring and transmission module into a backpack-type integrated module, which is fixed to the back of a laboratory animal by an elastic band.

[0041] When using the wireless transcranial direct current stimulator including the backpack integrated module, the electrode assembly and the fixing device and the control terminal to perform direct current stimulation on laboratory animals, taking SD rats, which are commonly used research subjects in the laboratory, as an example, the process is as follows:

[0042] 1) Installation of electrode assembly and fixture. After the rat was anesthetized, the hair on the surface of the rat skull was removed with a shaver, and the epidermis was disinfected with iodine. The rat scalp and subcutaneous tissue were opened and removed using medical surgical scissors and tweezers, and the periosteum on the surface of the skull was oxidized with hydrogen peroxide to completely expose the skull. After locating the brain area to be studied through bony landmarks such as the skull fontanelle and lambdoid suture, dental cement was used to adhere the cap-shaped polylactic acid base that fits the skull to the skull surface.

[0043] 2) Fixing of backpack integrated module. After the electrode base is installed on the skull, the backpack integrated module is installed on the rat's back using an elastic band. The elastic band is wrapped around the rat's chest to the rat's back, and the restraint on the rat's activities is reduced as much as possible while ensuring stability. Lead out the wire to connect the silver-plated copper metal electrode, insert it into the electrode hole between the electrode base and the skull, and inject conductive paste or saline to increase conductivity if necessary.

[0044] 3) Wireless stimulation control. Set the starting DC stimulation intensity, stimulation time and other parameters through the handheld wireless controller. Wait for the rat to wake up from the anesthesia and move freely. According to different experimental purposes and actual conditions, use the handheld wireless controller to wirelessly control the DC stimulation of the active rats, such as changing the current polarity, to explore the efficacy and mechanism of electrical stimulation in the active state. And record the stimulation parameters during the experiment through the ultra-small EEPROM storage chip.

[0045] 4) Monitoring of the stimulation process. During the stimulation process, use the handheld wireless controller to constantly observe the electrode contact and current changes to determine the state of electrical stimulation. If problems such as electrode detachment or poor contact occur, pause and make adjustments in time.

[0046] 5) Stimulation data analysis: After the stimulation is completed, the stimulation data stored in the ultra-small EEPROM storage chip is read and combined with the behavioral changes of the rats corresponding to the changes in the stimulation mode during the experiment, as well as other physiological indicators such as the level of related proteins in brain tissue for comprehensive analysis.

[0047] 6) Module maintenance. After the experiment, remove the backpack integrated module and stimulation electrodes in time to restore the rats' daily life to the greatest extent possible, replenish the power supply in time, and check the working status of each module.

[0048] The wireless transcranial direct current stimulator of the present invention can be specifically applied to:

[0049] 1) Neurorehabilitation research. In stroke or nerve injury model animals, the present invention enables experimental animals to receive brain stimulation in a free-moving state. This kind of rehabilitation research in a free-moving state is closer to the natural environment, which is helpful to study the real effect of transcranial direct current stimulation on neural plasticity and functional recovery, and increases the ecological validity and external validity of the experimental results.

[0050] 2) Research on emotion regulation and mental illness models. In laboratory animal models for studying mental illnesses (such as anxiety and depression), the present invention can avoid interference of wires on animal behavior, making behavioral testing more accurate. Researchers can evaluate the effects of transcranial direct current stimulation on animal behavior in open fields or complex environments without worrying about equipment connection issues, and obtain reliable behavioral data.

[0051] 3) Learning and memory research. In learning and memory experiments on mice or rats, the present invention allows animals to move freely in dynamic environments such as mazes and runways while receiving stimulation of specific areas of the brain. This research method can better simulate the learning and memory process in reality. No longer limited to fixed scenes or restrictions on animal movement, the impact of stimulation on learning and memory can be tested in more complex and changeable environments, improving the comprehensiveness and authenticity of the research.

[0052] 4) Research on brain network and functional connectivity. The present invention can be used to synchronously or asynchronously stimulate different brain regions to study the dynamic changes of brain networks. Since there is no restriction of wires, experimental animals can move freely in a wider space, and researchers can observe the effects of direct current stimulation on brain network connectivity under different environments.

[0053] 5) Motor training enhancement. In motor training enhancement research, the present invention can intervene when laboratory animals perform complex motor tasks, such as running, climbing stairs, balance training, etc., to continuously or intermittently stimulate the motor-related areas of the brain (such as the primary motor cortex), thereby observing the effects of transcranial direct current stimulation on motor performance at different stages of exercise.

[0054] It should be noted that the above-described embodiments are only preferred embodiments of the present invention. For those skilled in the art, without departing from the principles of the present invention, the present invention may be modified, improved and replaced with equivalents, and these modifications, improvements and equivalent replacements are also considered to fall within the scope of protection of the claims of the present invention.

Claims

1. A wireless transcranial direct current stimulator suitable for laboratory animals, comprising: Power module, wireless communication module, main control chip, current output module, electrode assembly and fixture, data monitoring and transmission module and control terminal.

2. The wireless transcranial direct current stimulator according to claim 1, characterized in that: The power module is a miniature lithium polymer battery (Li-Po) for providing current stimulation and circuit power supply.

3. The wireless transcranial direct current stimulator according to claim 1, characterized in that: The communication protocol of the wireless communication module is low-power Bluetooth; the integrated chip adopts Nordic nRF52810, with a size of 2.5mm x 2.5mm, and the antenna is a PCB integrated antenna designed on the main control board to reduce the volume.

4. The wireless transcranial direct current stimulator according to claim 1, characterized in that: The main control chip includes a microcontroller Nordic nRF52810, and a CPU of ARM Cortex-M4, which is used for data recording and stimulation regulation.

5. The wireless transcranial direct current stimulator according to claim 1, characterized in that: The current output module realizes dynamic switching of the anode and cathode through a micro H-bridge circuit to adapt to different stimulation requirements and can realize dynamic polarity conversion during electrical stimulation.

6. The wireless transcranial direct current stimulator according to claim 1, characterized in that: The electrode assembly and the fixing device are composed of a silver-plated copper metal electrode and a polylactic acid base.

7. The wireless transcranial direct current stimulator according to claim 6, characterized in that: The polylactic acid base is designed to be in a cap shape that fits the skull, and is provided with electrode holes at the bottom.

8. The wireless transcranial direct current stimulator according to claim 1, characterized in that: The data monitoring and transmission module measures the current value between the electrode and the skin through the monitoring chip INA219 to determine whether the skin is correctly contacted. The stimulation data is stored in the ultra-small EEPROM storage chip for reading and analysis after the experiment.

9. The wireless transcranial direct current stimulator according to claim 1, characterized in that: The backpack-type integrated module comprises an electrode assembly and a fixing device and a control terminal. The backpack-type integrated module integrates the power module, the wireless communication module, the main control chip, the current output module, and the data monitoring and transmission module into a backpack-type integrated module, which is fixed on the back of the laboratory animal by an elastic band.

10. A method for performing direct current stimulation on laboratory animals using the wireless transcranial direct current stimulator according to claim 9, comprising: 1) installing the electrode assembly and the fixing device on the skull surface of the laboratory animal; 2) using an elastic band to mount the backpack-type integrated module on the back of the laboratory animal and connect the electrode assembly to a fixing device; 3) performing wireless direct current stimulation and regulation on the laboratory animals through the control terminal; 4) During the stimulation process, the control terminal is used to monitor the electrode contact and current changes in real time, thereby determining the state of electrical stimulation; 5) After the stimulation is completed, the stimulation data stored in the data monitoring and transmission module is read, and a comprehensive experimental analysis is performed in combination with the behavioral changes of the laboratory animals corresponding to the changes in the stimulation mode during the experiment.

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