CN113144428B - Multichannel wireless optogenetic stimulation system and method - Google Patents
Multichannel wireless optogenetic stimulation system and method Download PDFInfo
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- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
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Abstract
The invention provides a multichannel wireless optogenetic stimulation system and method, comprising an upper computer, an optical stimulator and an array type stimulation optode, wherein the optical stimulator comprises a plurality of stimulation channels, different stimulation channels are electrically communicated with different areas of the array type stimulation optode, the upper computer is used for setting optical stimulation parameters, the optical stimulation parameters comprise pulse frequency, duty ratio, stimulation time and one or more stimulation channels, the upper computer is in wireless connection with the optical stimulator, the optical stimulator receives the optical stimulation parameters set by the upper computer, and outputs electric pulse signals to the areas of the array type stimulation optode, which are electrically communicated with the stimulation channels, in the optical stimulation parameters. The method and system described above allow for independent selection of the area of stimulation.
Description
Technical Field
The invention relates to the technical field of optical stimulation, in particular to a multichannel wireless optical genetic stimulation system and a multichannel wireless optical genetic stimulation method.
Background
The optogenetic technology is a new technology combining optics and genetics, and can accurately regulate and control the activity of specific neurons by utilizing a light control mode. By introducing the photosensitive protein into specific cells for expression by using the viral vector, the introduced photosensitive protein can only be activated by light with specific wavelength, so that the precise regulation and control of the nerve cell function can be realized by utilizing the illumination with corresponding wavelength to activate or inhibit ion channels. The time accuracy can reach millisecond range, and the accurate control of single cell and even subcellular range can be realized in space. In recent years, this technology has been very popular in neuroscience research and will lead to next generation neuro-repair methods and neurosurgery.
To better understand brain networks and brain functions, researchers have generally employed ways to construct neural networks in vitro. For the in vitro stimulation requirement of the optogenetic technology, researchers generally use LEDs as light sources to develop the optical stimulator. At present, most in-vitro optogenetic stimulators adopt LEDs as light sources, the equipment is large in size, the provided illumination area is large, and the provided stimulation precision is limited. The regulation and control of the optical stimulator are connected by wires, and the parameters for regulation and control are less, so that the stimulated region cannot be independently selected. Because the power of the device is relatively high, the device can be heated after long-time use, thereby affecting the activity of nerve cells and being unfavorable for the growth of the nerve cells.
Disclosure of Invention
In view of the foregoing, it is an object of the present invention to provide a multichannel wireless optogenetic stimulation system and method that enables independent selection of the areas of stimulation.
In order to achieve the above purpose, the invention provides a multi-channel wireless optogenetic stimulation system, which comprises a host computer, an optical stimulator and an array type stimulation optode, wherein the optical stimulator comprises a plurality of stimulation channels, different stimulation channels are electrically communicated with different areas of the array type stimulation optode, the host computer is used for setting optical stimulation parameters, the optical stimulation parameters comprise pulse frequency, duty ratio, stimulation time and one or more stimulation channels, the host computer is in wireless connection with the optical stimulator, the optical stimulator receives the optical stimulation parameters set by the host computer, and outputs electric pulse signals to the areas of the array type stimulation optode, which are electrically communicated with the stimulation channels, in the optical stimulation parameters.
Optionally, the system further comprises a wireless transmitting module and a wireless receiving module, wherein the wireless transmitting module is connected with the upper computer and the wireless receiving module, the wireless receiving module is connected with the wireless transmitting module and the optical stimulator, and the wireless transmitting module transmits the optical stimulation parameters of the upper computer to the optical stimulator through the wireless receiving module.
Optionally, the wireless transmitting module includes a radio frequency amplification and a high gain antenna.
Optionally, the array type laser-stimulating electrode comprises an electrode base plate and a plurality of electrodes, and the electrodes are used for emitting light rays to perform optical stimulation on nerve cells.
Optionally, the substrate material of the photoelectrode bottom plate adopts a silicon substrate, and the surface of the substrate material is plated with a layer of epoxy resin film.
Optionally, the light is a μled.
Optionally, the array type stimulation optodes comprise 24 optodes, the optical stimulator comprises 6 optical stimulation channels, each four optodes is a region, and each region is controlled by one optical stimulation channel.
Optionally, the optical stimulator includes power driving circuit, a switch, a clock circuit, the pilot lamp, a wireless communication interface, the second microcontroller, reset circuit and output circuit, power driving circuit is used for supplying power, the switch is used for opening and closing of optical stimulator, clock circuit is used for providing the clock signal for the second microcontroller, the pilot lamp includes power pilot lamp and communication status pilot lamp, power pilot lamp is used for showing the open and closed state of optical stimulator, light then indicates that optical stimulator is in work, communication status pilot lamp is used for showing the communication status of optical stimulator and host computer, after optical stimulator successfully receives the signal that the host computer sent, communication status pilot lamp will take place bright and dark change, wireless communication interface is used for connecting host computer and optical stimulator, the second microcontroller is used for retrieving optical stimulation parameter, after handling, transmit to output circuit with electric pulse signal form, output circuit is used for connecting optical stimulator and array type stimulation light pole, the electric pulse signal that will output by the second microcontroller resumes the light pole, reset circuit is used for with optical stimulator to initial state.
Optionally, the upper computer comprises a parameter setting module, a state display module and an operation button, wherein the parameter setting module is used for setting optical stimulation parameters, the state display module is used for displaying the frequency, the duty cycle and the residual stimulation time of the current optical stimulation, and the operation button comprises a start stimulation button, a stop stimulation button and a switch key; the on-off key is used for controlling the start and stop of the stimulation channel, the start stimulation button is used for sending a command for starting stimulation, and the stop stimulation button is used for sending a command for stopping stimulation.
In order to achieve the above object, the present invention further provides a multi-channel wireless optogenetic stimulation method, comprising:
setting an array type stimulating light pole which comprises a plurality of areas for emitting light;
setting optical stimulation parameters, wherein the optical stimulation parameters comprise the frequency, the duty cycle, the stimulation time and one or more stimulation channels of pulses;
and generating an electric pulse signal to the area of the array-type stimulating electrode, which is electrically communicated with the stimulating channel in the optical stimulation parameter, through the optical stimulation parameter.
The multichannel wireless optogenetic stimulation system and the multichannel wireless optogenetic stimulation method adopt an array mode to perform optical stimulation, have a larger stimulation range, and are more suitable for application places requiring cell culture and large-area illumination; each channel of the array can be independently controlled to be opened and closed, and the array is suitable for researching the selective stimulation of multiple areas; the device can provide a plurality of different stimulation parameters, and provides a reliable tool for the application of the optogenetic technology; the wireless communication technology is adopted, and the power enhancement and high gain antenna is matched, so that the wireless communication system has a longer transmission distance and more stable transmission signals.
To the accomplishment of the foregoing and related ends, one or more aspects of the invention comprise the features hereinafter particularly pointed out. The following description and the annexed drawings set forth in detail certain illustrative aspects of the invention. These aspects are indicative, however, of but a few of the various ways in which the principles of the invention may be employed. Furthermore, the invention is intended to include all such aspects and their equivalents.
Drawings
FIG. 1 is a schematic diagram of a multi-channel wireless optogenetic stimulation system according to the present invention;
FIG. 2 is a schematic diagram of the upper computer according to the present invention;
FIG. 3 is a schematic view of the structure of the bottom plate of the array-type stimulating light electrode according to the present invention.
The achievement of the objects, functional features and advantages of the present invention will be further described with reference to the accompanying drawings, in conjunction with the embodiments.
Detailed Description
Specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
Fig. 1 is a schematic structural diagram of a multi-channel wireless optogenetic stimulation system according to the present invention, as shown in fig. 1, where the multi-channel wireless optogenetic stimulation system includes a host computer 100, a photo-stimulator 400 and an array type stimulating electrode 500, the photo-stimulator 400 includes a plurality of stimulation channels, different stimulation channels are electrically connected with different areas of the array type stimulating electrode 500, the host computer 100 is used for setting photo-stimulation parameters, the photo-stimulation parameters include a frequency of a pulse, a duty cycle, a stimulation time and one or more stimulation channels, the host computer 200 is wirelessly connected with the photo-stimulator 400, the photo-stimulator 400 receives the photo-stimulation parameters set by the host computer 100, and outputs an electrical pulse signal to the area of the array type stimulating electrode 500 where the stimulation channels are electrically connected.
In one embodiment, the multi-channel wireless optogenetic stimulation system further comprises a wireless transmission module 200 and a wireless receiving module 300, wherein the wireless transmission module is connected with the upper computer and the wireless receiving module, the wireless receiving module is connected with the wireless transmission module and the optical stimulator, and the wireless transmission module transmits the optical stimulation parameters of the upper computer to the optical stimulator through the wireless receiving module.
Optionally, the wireless transmission module 200 includes a radio frequency amplifier 205 and a high gain antenna 204.
In one embodiment, the array type stimulating optode 500 includes an optode base 502 and a plurality of optodes 501 for emitting light to stimulate nerve cells.
Optionally, the substrate material of the photoelectrode bottom plate adopts a silicon substrate, and the surface of the substrate material is plated with a layer of epoxy resin film.
Optionally, the light is a μled.
Optionally, the array type stimulation optodes comprise 24 optodes, the optical stimulator comprises 6 optical stimulation channels, each four optodes is a region, and each region is controlled by one optical stimulation channel.
In one embodiment, the optical stimulator 400 includes a power driving circuit 401, a switch 402, a clock circuit 403, an indicator light 404, a wireless communication interface 405, a second microcontroller 406, a reset circuit 407, and an output circuit 408, where the power driving circuit is used for supplying power, the switch is used for turning on and off the optical stimulator, the clock circuit is used for providing a clock signal for the second microcontroller, the indicator light includes a power indicator light and a communication status indicator light, the power indicator light is used for displaying on and off states of the optical stimulator, the light indicates that the optical stimulator is working, the communication status indicator light is used for displaying communication states of the optical stimulator and an upper computer, when the optical stimulator successfully receives signals sent by the upper computer, the communication status indicator light changes in brightness, the wireless communication interface is used for connecting the upper computer and the optical stimulator, the second microcontroller is used for extracting optical stimulation parameters, after processing, the optical stimulation parameters are transmitted to the output circuit in the form of electric pulse signals, the output circuit is used for connecting the optical stimulator and an array type stimulating light pole, the electric pulse signal output by the second microcontroller is transmitted to the optical pole, and the reset circuit is used for restoring the optical stimulator to an initial state.
In one embodiment, the upper computer comprises a parameter setting module, a state display module and an operation button, wherein the parameter setting module is used for setting optical stimulation parameters, the state display module is used for displaying the frequency, the duty cycle and the residual stimulation time of the current optical stimulation, and the operation button comprises a start stimulation button, a stop stimulation button and a switch key; the on-off key is used for controlling the start and stop of the stimulation channel, the start stimulation button is used for sending a command for starting stimulation, and the stop stimulation button is used for sending a command for stopping stimulation.
In one embodiment, the multi-channel wireless optogenetic stimulation system comprises a host computer, a wireless transmission module, a wireless receiving module, an optical stimulator and an array type stimulation optodes, wherein:
the upper computer is connected with the wireless transmitting module through a USB interface, the wireless receiving module is connected with a wireless communication interface of the optical stimulator, and the array type laser stimulating electrode is connected with an output circuit of the optical stimulator;
the upper computer is used for setting optical stimulation parameters and comprises a parameter setting module, a state display module and an operation button;
the wireless transmitting module is used for transmitting the optical stimulation parameters set by the upper computer to the optical stimulator in a 2.4G wireless transmission mode;
the wireless receiving module is used for receiving the signal from the wireless transmitting module and transmitting the signal to the optical stimulator;
the optical stimulator is used for processing the stimulation information from the upper computer and then outputting a corresponding electric pulse signal to the array type stimulating laser electrode;
the array type spining laser electrode comprises an optical electrode bottom plate and 24 mu LED chips, and the array type spining laser electrode is used for emitting light to perform optical stimulation on nerve cells.
Optionally, the adjusting range of the frequency of the optical stimulation parameter is 1-500Hz, the adjusting range of the duty ratio is 0-100%, the number of the adjustable stimulation channels is 6, and each stimulation channel can be independently controlled to be opened and closed by an upper computer, so that the aim of selectively stimulating the nerve cell area is fulfilled.
Optionally, the optical stimulator is integrated with a power drive circuit, a switch, a clock circuit, an indicator light, a wireless communication interface, a second microcontroller, a reset circuit, and an output circuit. The modules are connected with each other through wires on the PCB, and the power supply driving circuit is used for supplying power to the stimulator and the wireless communication module and comprises a 3.7V lithium battery and an RT9193-33GB low-dropout linear voltage regulator. The switch is used for controlling the opening and closing of the stimulator. The clock circuit comprises an 8M active crystal oscillator and a decoupling capacitor, and is used for providing a clock signal for the second microcontroller. The indicator lamp comprises a power indicator lamp and a communication state indicator lamp, wherein the power indicator lamp is used for displaying the on-off state of the stimulator, the on state indicates that the stimulator is working, the communication state indicator lamp is used for displaying the communication state of the stimulator and the upper computer, and when the stimulator successfully receives a signal sent by the upper computer, the communication state indicator lamp is changed in brightness. The wireless communication interface is used for connecting the wireless receiving module and the stimulator. The second microcontroller is used for extracting the wireless instruction information received by the wireless receiving module, and transmitting the wireless instruction information to the output circuit in the form of an electric pulse signal after processing. The reset circuit comprises a reset switch, a capacitor and a resistor and is used for restoring the stimulator to an initialized state. The output circuit is used for connecting the stimulator and the optode and transmitting the electric pulse signal output by the second microcontroller to the optode.
The top of the optical stimulator is provided with a hole digging area with the diameter of 3 multiplied by 3mm, and 6 pairs of rectangular bonding pads are arranged on two sides of the hole digging area and are used for being connected with the array type stimulating optodes.
And 6 pairs of rectangular copper plating pads are arranged on two sides of the photoelectrode bottom plate, and each pair of copper plating pads is connected with 4 pairs of mu LED pads through copper plating wires.
The 6 pairs of rectangular copper plated pads were set as positive electrodes on one side and as negative electrodes on the other side, and the dimensions were 500 μm×300 μm.
The shape of the mu LED bonding pad is circular, and the diameter of the mu LED bonding pad is 70 mu m.
The substrate material of the photoelectrode bottom plate adopts a silicon substrate, and the surface of the substrate material is plated with a layer of epoxy resin film.
The wavelength of the mu LED is 470nm.
The optical stimulator 400 receives the stimulation command from the upper computer 100 through the wireless receiving module 300 and transmits the processed stimulation signal to the array type stimulation optode 500, thereby completing the optical stimulation of the nerve cells.
The upper computer 100 is a control program running on a PC, and can be used by a user to adjust the frequency, duty cycle and switching of the array channels of the optical stimulus.
The wireless transmitting module 200 is composed of a USB-to-serial interface connector 201, a USB-to-serial interface chip 202, a first microcontroller 203, a high gain antenna 204, a radio frequency amplifier 205, a wireless chip 206, and an LDO regulator chip 207. The wireless transmitting module 200 is connected with the upper computer 100 through the USB serial port connector 201, so as to realize the communication of the stimulation signals. The LDO voltage stabilizing chip 207 stabilizes the voltage provided by the USB-to-serial interface connector 201 and provides power for the first microcontroller 203 and the wireless chip 206. The USB-to-serial chip 202 converts the optical stimulus instruction from the host computer and transmits the converted optical stimulus instruction to the first microcontroller 203, the first microcontroller 203 converts the serial data received from the USB-to-serial chip 202 into a data packet and transmits the data packet to the wireless chip 206, and the instruction is sent to the wireless receiving module 300, so that the distance of wireless communication and the stability of signal transmission can be improved by matching the high-gain antenna 204 and the radio frequency amplifier 205.
The wireless receiving module comprises a 2×4 pin header 301, a wireless chip 302, and an antenna 303. When the wireless receiving module 300 receives the stimulation command transmitted from the wireless transmitting module 200, the received command information is transmitted to the stimulator 400 through the 2×4 pin header 301.
The stimulator 400 includes a power supply 401, a switch 402, a clock circuit 403, an indicator light 404, a wireless communication interface 405, a second microcontroller 406, a reset circuit 407, and an output circuit 408. The power supply 401 powers the second microcontroller 406 and the wireless receiving module 300. When the second microcontroller 406 receives the stimulation instruction from the wireless receiving module 300 through the wireless communication interface 405, the second microcontroller 406 firstly checks whether the received instruction information is correct, extracts the stimulation information in the instruction if the received instruction information is correct, and continues to wait for receiving new instruction information if the received instruction information is wrong, wherein the extracted stimulation information comprises a start stimulation instruction or a stop stimulation instruction, the start stimulation instruction further comprises an opened channel, a stimulation frequency and a stimulation duty ratio, the second microcontroller 406 configures an output electric pulse of the channel according to the instruction information, and then transmits the output electric pulse to the optode through an output circuit to complete the update of the stimulation signal output.
The array-type stimulating optode 500 is composed of a mu LED501 and an optode base 502. The photoelectrode substrate 502 is connected to the output circuit 408, and the output electric signal from the optical stimulator 400 is transmitted to the μled501 via a copper wire, thereby completing optical stimulation of nerve cells.
As shown in fig. 2, the upper computer 100 includes a parameter setting module including a stimulation time setting module 101, a stimulation mode configuration module 102, a wireless communication parameter configuration module 103, and a stimulation parameter setting module 107, a status display module 104, and operation buttons; the operation buttons include a channel selection switch button 105 and a start end button 106. The stimulation time setting module 101 is configured to set a stimulation time period. The stimulation mode configuration module 102 is configured to select a stimulation mode, including a free stimulation mode and a timing mode, where the free stimulation mode is that a user freely decides a stimulation duration through a start stimulation button and an end stimulation button, the timing mode is that the optical stimulator performs optical stimulation with a duration set by the user, the stimulation mode is selectable, and the control interface is concise. The wireless communication parameter configuration module 103 is configured to configure relevant parameters of the wireless transmission module 200, including port selection, baud rate setting, data bit length, and check bit setting. The wireless communication parameter configuration module 103 is configured to display the current stimulation parameters and the stimulation remaining time in the timed mode. The channel selection switch button 105 is a switch of the optical stimulation array, and a user can select different arrays of switches through the channel selection switch button 105 on the upper computer 100, so that the aim of selectively stimulating different areas is fulfilled. The start/end button 106 is used to control the start and end of the optical stimulus, and clicking the start/end button starts the optical stimulus, and clicking the start/end button stops the optical stimulus. The stimulation parameter setting module 107 includes modifications of the stimulation frequency and the duty cycle, and the user can directly modify the stimulation parameters by inputting values in the boxes.
As shown in fig. 3, the photoelectrode substrate 502 is composed of a rectangular pad 5021, a μled pad 5022, and copper plated wires 5023. The rectangular pads 5021 are distributed on two sides of the photoelectrode base plate 502, and one side is a positive electrode, and the other side is a negative electrode. Every four mu LED pads 5022 are connected with the rectangular pads 5021 through copper plating wires 5023, the positive electrode of each mu LED is connected with the LED pad connected with the positive rectangular pad, every four mu LEDs share one positive electrode and one negative rectangular pad to form a 4X 1 mu LED array, 6 groups of positive and negative pads form a 1X 6 array, each group is independently connected with the output port of the optical stimulator 400, and the selective stimulation of nerve cells in a large area can be realized by controlling the switch of each array through the second microcontroller 406 of the optical stimulator 400.
The wireless chip in the invention can adopt NRF24L01+, the working frequency band of the chip is 2.4 GHz-2.5 GHz, the data transmission rate can reach 2Mbps at the highest speed, and the wireless chip can be directly connected with the first microcontroller 203 through an SPI interface.
The second microcontroller of the optical stimulator in the present invention adopts STM32F103RCT6.
The power supply of the light stimulator is powered by a 3.7V lithium battery.
The adjustable range of the optical stimulation frequency is 1-500Hz, and the setting range of the duty ratio is 0-100%.
The wavelength of the mu LED adopted by the invention is 470nm.
The multi-channel wireless optogenetic stimulation system has the advantages of simple structure, low cost and easy production.
The invention also provides a multichannel wireless optogenetic stimulation method, which comprises the following steps:
setting an array type stimulating light pole which comprises a plurality of areas for emitting light;
setting optical stimulation parameters, wherein the optical stimulation parameters comprise the frequency, the duty cycle, the stimulation time and one or more stimulation channels of pulses;
and generating an electric pulse signal to the area of the array-type stimulating electrode, which is electrically communicated with the stimulating channel in the optical stimulation parameter, through the optical stimulation parameter.
In one embodiment, the second microcontroller constructs a neural network structure model, the input of the neural network structure model is the image characteristics of brain CT (the image characteristics include cell states and coordinates, the cell states include cell damage, necrosis, apoptosis and the like, and the cell states can also include the proportion of different cell states to total cells), the output is a light stimulation parameter, the brain CT and the light stimulation parameters of a plurality of clients with the cell activation effect reaching the requirement are collected to train the neural network structure model, and the second microcontroller obtains the new output light stimulation parameter of the brain CT through the trained neural network structure model and transmits the new output light stimulation parameter to the upper computer as a reference.
Optionally, the second microcontroller determines whether the cell activation effect meets the requirement according to the cation inflow outside the cell membrane, and the frequency, the duty ratio, the stimulation time and the like of the pulse of the activation region or/and the pulse not passing through the activation region can be obtained through the trained neural network structure model.
In one embodiment, a method of optical stimulation using a multi-channel wireless optogenetic stimulation system includes:
inserting the wireless receiving module into the stimulator according to the identification direction, and opening a switch on the stimulator, wherein the light stimulation frequency is 0, the duty ratio is 0%, and no stimulation signal exists;
inserting the wireless transmission module into a computer USB port, opening upper computer software, and configuring parameters of the wireless module;
selecting a stimulation mode, wherein the optical stimulation system provides two stimulation modes, one is a free stimulation mode, the user freely decides the stimulation time by clicking a start stimulation button and an end stimulation button, and the other is a timing stimulation mode, namely, the optical stimulation with the set time length is generated according to the set time of the user;
selecting a stimulation channel to be opened, and opening a switch corresponding to the stimulation channel to represent that the stimulation channel is stimulated to be opened;
configuring stimulation parameters, wherein a user can perform parameter configuration by inputting stimulation parameters such as frequency, duty cycle and the like on an upper computer;
clicking on the start stimulus initiates wireless transmission of the stimulus parameters, and the optical stimulator will initiate corresponding optical stimulus after receiving the configuration parameters. If the parameters need to be modified, the modification of the stimulation parameters can be completed by clicking to start stimulation after the modified stimulation parameters are input into the upper computer interface;
and after the stimulation is finished, closing a stimulator switch, and taking down the wireless receiving module and the wireless transmitting module.
In one embodiment, the upper computer sends the set stimulation parameters to the optical stimulator connected with the wireless receiving module through the wireless sending module, and after the optical stimulator receives the stimulation instruction, the optical stimulator outputs corresponding electric pulse signals after processing by the second micro processor, and the electric pulse signals are transmitted to the array type stimulation optodes through the output circuit to finish the stimulation on nerve cells. The user can realize the selective stimulation of different areas by selecting the opening or closing of the multiple channels on the upper computer according to the regulation and control requirements, the modification of the optical stimulation parameters is realized by modifying the numerical values in the frequency and duty ratio input window, and the modified stimulation information is transmitted to the stimulator in a 2.4G wireless transmission mode, so that the real-time modification of the stimulator is completed.
In one embodiment, the method of optical stimulation using a multi-channel wireless optogenetic stimulation system further comprises:
constructing a neural network structure model, wherein the input of the neural network structure model is the image characteristics of brain CT (the image characteristics comprise cell states and coordinates, the cell states comprise cell damage, necrosis, apoptosis and the like, and the ratio of different cell states to total cells can be also included), and the output is a light stimulation parameter;
collecting brain CT and optical stimulation parameters of a plurality of clients with cell activation effect reaching requirements, and training a neural network structure model;
and obtaining the new output light stimulation parameters of the brain CT through the trained neural network structure model.
Optionally, the method comprises: and determining whether the cell activation effect meets the requirement according to the cation inflow outside the cell membrane, and obtaining the frequency, the duty ratio, the stimulation time and the like of the pulse of the activation region or/and the pulse not passing through the activation region through the trained neural network structure model.
When the independently-controllable multichannel wireless optogenetic stimulation system is used, the upper computer sends the set stimulation parameters to the optical stimulation module connected with the wireless receiving module through the wireless sending module, and the corresponding electric signals are output to the array type stimulation optodes after being processed by the microprocessor, so that the mu LED outputs optical stimulation signals with certain frequency and duty ratio. The modification of the stimulation signal and the selection of the stimulation area can be completed in real time through the arrangement of the upper computer, so that the area selective stimulation of the large-area nerve cells is completed. The independently-controllable multichannel wireless light genetic stimulation system designed by the invention can provide effective support for the research of the action mechanism of light genetic in vitro nerves, and promote the application and development of light genetic in future.
The above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the technical solution of the present invention.
Claims (9)
1. A multi-channel wireless optogenetic stimulation system is characterized by comprising an upper computer, an optical stimulator and an array type stimulation optode, wherein the optical stimulator comprises a plurality of stimulation channels, different stimulation channels are electrically communicated with different areas of the array type stimulation optode, the upper computer is used for setting optical stimulation parameters, the optical stimulation parameters comprise pulse frequency, duty ratio, stimulation time and one or more stimulation channels, the upper computer is in wireless connection with the optical stimulator, the optical stimulator receives the optical stimulation parameters set by the upper computer and outputs electric pulse signals to the areas of the array type stimulation optode, which are electrically communicated with the stimulation channels, in the optical stimulation parameters,
the light is a mu LED and,
each four light poles in the array type laser-emitting pole are areas, each area is controlled by a light stimulation channel, the light pole base plate is composed of rectangular bonding pads, mu LED bonding pads and copper-plated wires, the rectangular bonding pads are distributed on two sides of the light pole base plate, one side of each rectangular bonding pad is a positive electrode, the other side of each rectangular bonding pad is a negative electrode, and each four mu LEDs share one positive electrode and each negative electrode rectangular bonding pad to form a 4 multiplied by 1 mu LED array;
the optical stimulator comprises a second microcontroller, the second microcontroller is used for extracting optical stimulation parameters, the optical stimulation parameters are transmitted to an output circuit in the form of electric pulse signals after being processed, the output circuit is used for connecting the optical stimulator and an array type stimulation optode, the electric pulse signals output by the second microcontroller are transmitted to the optode,
the second microcontroller builds a neural network structure model, the input of the neural network structure model is the image characteristic of brain CT, the output is the optical stimulation parameter, the brain CT and the optical stimulation parameters of a plurality of clients with the cell activation effect reaching the requirement are collected to train the neural network structure model, the second microcontroller obtains the output optical stimulation parameter of the new brain CT through the trained neural network structure model and transmits the output optical stimulation parameter to the upper computer as a reference,
and the second microcontroller determines whether the cell activation effect meets the requirement according to the cation inflow outside the cell membrane, and the trained neural network structure model is used for obtaining the frequency, the duty ratio and the stimulation time of the pulse of the activation region or/and the pulse which does not pass through the activation region.
2. The multi-channel wireless optogenetic stimulation system of claim 1, further comprising a wireless transmitting module and a wireless receiving module, wherein the wireless transmitting module is connected with the upper computer and the wireless receiving module, the wireless receiving module is connected with the wireless transmitting module and the optical stimulator, and the wireless transmitting module transmits the optical stimulation parameters of the upper computer to the optical stimulator through the wireless receiving module.
3. The multi-channel wireless optogenetic stimulation system of claim 2 wherein the wireless transmission module comprises a radio frequency amplification and high gain antenna.
4. The multi-channel wireless optogenetic stimulation system of claim 1 wherein the array of optogenetic electrodes comprises an optobase plate and a plurality of optogenetic electrodes for emitting light to optically stimulate the nerve cells.
5. The multi-channel wireless optogenetic stimulation system of claim 4 wherein the optobase substrate material is a silicon substrate and the surface is coated with a thin film of epoxy.
6. The multi-channel wireless optogenetic stimulation system of claim 4 wherein the array of stimulating optodes comprises 24 optodes and the optical stimulator comprises 6 optical stimulation channels.
7. The multi-channel wireless optogenetic stimulation system of claim 1, wherein the optical stimulator comprises a power driving circuit, a switch, a clock circuit, an indicator light, a wireless communication interface, a second microcontroller, a reset circuit and an output circuit, wherein the power driving circuit is used for supplying power, the switch is used for switching on and off the optical stimulator, the clock circuit is used for providing clock signals for the second microcontroller, the indicator light comprises a power indicator light and a communication state indicator light, the power indicator light is used for displaying the on and off states of the optical stimulator, the light indicates that the optical stimulator is working, the communication state indicator light is used for displaying the communication state of the optical stimulator and the upper computer, the communication state indicator light changes in brightness after the optical stimulator successfully receives signals sent by the upper computer, the wireless communication interface is used for connecting the upper computer and the optical stimulator, and the reset circuit is used for recovering the optical stimulator to an initialized state.
8. The multi-channel wireless optogenetic stimulation system of claim 1, wherein the host computer comprises a parameter setting module for setting the optical stimulation parameters, a status display module for displaying the frequency, duty cycle and remaining stimulation time of the current optical stimulation, and an operation button comprising a start stimulation button, a stop stimulation button and a switch key; the on-off key is used for controlling the start and stop of the stimulation channel, the start stimulation button is used for sending a command for starting stimulation, and the stop stimulation button is used for sending a command for stopping stimulation.
9. A method of multi-channel wireless optogenetic stimulation comprising:
setting an array type stimulation light pole, wherein the array type stimulation light pole comprises a plurality of areas for emitting light, the light stimulator comprises a plurality of stimulation channels, and different stimulation channels are electrically communicated with different areas of the array type stimulation light pole;
setting optical stimulation parameters, wherein the optical stimulation parameters comprise the frequency, the duty cycle, the stimulation time and one or more stimulation channels of pulses;
generating an electric pulse signal to the area of the array-type stimulating laser electrode which is electrically communicated with the stimulating channel in the optical stimulation parameter through the optical stimulation parameter,
the light is a mu LED and,
each four light poles in the array type laser-emitting pole are areas, each area is controlled by a light stimulation channel, the light pole base plate is composed of rectangular bonding pads, mu LED bonding pads and copper-plated wires, the rectangular bonding pads are distributed on two sides of the light pole base plate, one side of each rectangular bonding pad is a positive electrode, the other side of each rectangular bonding pad is a negative electrode, and each four mu LEDs share one positive electrode and each negative electrode rectangular bonding pad to form a 4 multiplied by 1 mu LED array;
the optical stimulator comprises a second microcontroller, the second microcontroller is used for extracting optical stimulation parameters, the optical stimulation parameters are transmitted to an output circuit in the form of electric pulse signals after being processed, the output circuit is used for connecting the optical stimulator and an array type stimulation optode, the electric pulse signals output by the second microcontroller are transmitted to the optode, the reset circuit is used for recovering the optical stimulator to an initialized state,
the second microcontroller builds a neural network structure model, the input of the neural network structure model is the image characteristic of brain CT, the output is the optical stimulation parameter, the brain CT and the optical stimulation parameters of a plurality of clients with the cell activation effect reaching the requirement are collected to train the neural network structure model, the second microcontroller obtains the output optical stimulation parameter of the new brain CT through the trained neural network structure model and transmits the output optical stimulation parameter to the upper computer as a reference,
and the second microcontroller determines whether the cell activation effect meets the requirement according to the cation inflow outside the cell membrane, and the trained neural network structure model is used for obtaining the frequency, the duty ratio and the stimulation time of the pulse of the activation region or/and the pulse which does not pass through the activation region.
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