CN113144428A - Multichannel wireless optogenetic stimulation system and method - Google Patents

Multichannel wireless optogenetic stimulation system and method Download PDF

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Publication number
CN113144428A
CN113144428A CN202110081735.1A CN202110081735A CN113144428A CN 113144428 A CN113144428 A CN 113144428A CN 202110081735 A CN202110081735 A CN 202110081735A CN 113144428 A CN113144428 A CN 113144428A
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stimulation
optical
wireless
stimulator
module
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CN113144428B (en
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陈涛
苏良闯
赵宇
康博栋
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Beijing University of Technology
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Beijing University of Technology
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/0613Apparatus adapted for a specific treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N2005/065Light sources therefor
    • A61N2005/0651Diodes
    • A61N2005/0652Arrays of diodes
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02BCLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO BUILDINGS, e.g. HOUSING, HOUSE APPLIANCES OR RELATED END-USER APPLICATIONS
    • Y02B20/00Energy efficient lighting technologies, e.g. halogen lamps or gas discharge lamps
    • Y02B20/40Control techniques providing energy savings, e.g. smart controller or presence detection

Abstract

The invention provides a multichannel wireless optogenetic stimulation system and method, which comprises 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 wirelessly connected 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 enable independent selection of areas of stimulation.

Description

Multichannel wireless optogenetic stimulation system and method
Technical Field
The invention relates to the technical field of optical stimulation, in particular to a multi-channel wireless optical genetic stimulation system and a 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 using a light control mode. By introducing the photosensitive protein into a specific cell for expression by using a viral vector, the introduced photosensitive protein can be activated only by light with a specific wavelength, so that the function of the nerve cell can be accurately regulated by activating or inhibiting an ion channel by using light with a corresponding wavelength. The time accuracy can reach the millisecond range, and the accurate control of a single cell or even a subcellular range can be realized in space. In recent years, this technology has gained great popularity in neuroscience research and will lead the next generation of neuro-rehabilitation approaches and neuro-therapy.
In order to better understand brain networks and brain functions, researchers typically employ a way of constructing an in vitro neural network. In response to the need for optogenetic technology in vitro stimulation, researchers have generally adopted LEDs as light sources to develop photostimulators. At present, most of in vitro optogenetic stimulators adopt LEDs as light sources, the size of equipment is large, the illumination area provided by the equipment is large, and the stimulation precision provided by the equipment is limited. The regulation and control of the optical stimulator depend on wired connection, and the parameters for regulation and control are less, so that the stimulation area can not be independently selected. Because the power of the equipment is relatively high, the equipment can generate heat after being used for a long time, so that the activity of nerve cells is influenced, and the growth of the nerve cells is not facilitated.
Disclosure of Invention
In view of the above problems, it is an object of the present invention to provide a multi-channel wireless optogenetic stimulation system and method that can independently select a stimulation region.
In order to achieve the above object, the present invention provides a multichannel wireless optogenetic stimulation system, which includes an upper computer, an optical stimulator and an array type stimulation optode, wherein the optical stimulator includes a plurality of stimulation channels, different stimulation channels are in electrical communication with different areas of the array type stimulation optode, the upper computer is configured to set optical stimulation parameters, the optical stimulation parameters include pulse frequency, duty cycle, stimulation time and one or more stimulation channels, the upper computer is wirelessly connected to the optical stimulator, and the optical stimulator receives the optical stimulation parameters set by the upper computer and outputs electrical pulse signals to the area of the array type stimulation optode in which the stimulation channels are in electrical communication in the optical stimulation parameters.
Optionally, the optical stimulator further comprises a wireless sending module and a wireless receiving module, the wireless sending module is connected with the upper computer and the wireless receiving module, the wireless receiving module is connected with the wireless sending module and the optical stimulator, and the wireless sending module sends the optical stimulation parameters of the upper computer to the optical stimulator through the wireless receiving module.
Optionally, the wireless transmission module includes a radio frequency amplifier and a high gain antenna.
Optionally, the array-type stimulation optode includes an optode substrate and a plurality of optodes for emitting light to perform optical stimulation on nerve cells.
Optionally, the substrate material of the optode baseplate is a silicon substrate, and the surface of the silicon substrate is plated with a layer of epoxy resin film.
Optionally, the light electrode is a μ LED.
Optionally, the array-type stimulation optode comprises 24 optodes, the optical stimulator comprises 6 optical stimulation channels, each four optodes are an area, and each area is controlled by one optical stimulation channel.
Optionally, the optical stimulator includes 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, the power driving circuit is configured to supply power, the switch is configured to turn on and off the optical stimulator, the clock circuit is configured to provide 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 configured to display the on and off status of the optical stimulator, and when the power indicator light is on, the optical stimulator indicates that the optical stimulator is working, the communication status indicator light is configured to display the communication status of the optical stimulator and the upper computer, when the optical stimulator successfully receives a signal sent by the upper computer, the communication status indicator light changes in brightness, the wireless communication interface is configured to connect the upper computer and the optical stimulator, the second microcontroller is configured to extract optical stimulation parameters, after being processed, the signals are transmitted to an output circuit in the form of electric pulse signals, the output circuit is used for connecting the optical stimulator and the array type stimulation optical pole and transmitting the electric pulse signals output by the second microcontroller to the optical pole, and the reset circuit is used for restoring the optical stimulator to an initialization state.
Optionally, the upper computer includes a parameter setting module, a state display module and an operation button, the parameter setting module is configured to set light stimulation parameters, the state display module is configured to display a frequency, a duty ratio and a remaining stimulation time of a current light stimulation, and the operation button includes a stimulation start button, a stimulation stop button and an on-off key; the on-off key is used for controlling the starting and stopping of the stimulation channel, the stimulation starting button is used for sending a stimulation starting instruction, and the stimulation stopping button is used for sending a stimulation stopping instruction.
In order to achieve the above object, the present invention also provides a multichannel wireless optogenetic stimulation method, including:
arranging an array type stimulating photoelectrode which comprises a plurality of areas for emitting light;
setting optical stimulation parameters, wherein the optical stimulation parameters comprise the frequency, duty cycle, stimulation time and one or more stimulation channels of pulses;
and generating an electric pulse signal through the optical stimulation parameters to the area of the array type stimulation optode electrically communicated with the stimulation channel in the optical stimulation parameters.
The multichannel wireless optogenetic stimulation system and the multichannel wireless optogenetic stimulation method adopt an array mode to carry out optical stimulation, have a larger area of stimulation range, and are more suitable for application places with cell culture and large-area illumination requirements; each channel of the array can be independently controlled to be opened and closed, and the array is suitable for the research of selective stimulation of multiple regions; the device can provide the setting of 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 are 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 fully described. 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. Further, the present invention is intended to include all such aspects and their equivalents.
Drawings
FIG. 1 is a schematic structural diagram of a multi-channel wireless optogenetic stimulation system according to the present invention;
FIG. 2 is a schematic view of the upper computer of the present invention;
fig. 3 is a schematic diagram of the structure of the array-type stimulation optode substrate according to the present invention.
The implementation, functional features and advantages of the objects of the present invention will be further described with reference to the accompanying drawings.
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 the multichannel wireless optogenetic stimulation system of the present invention, as shown in fig. 1, the multichannel wireless optogenetic stimulation system includes an upper computer 100, an optical stimulator 400 and an array type stimulation optode 500, the optical stimulator 400 includes a plurality of stimulation channels, different stimulation channels are electrically connected to different regions of the array type stimulation optode 500, the upper computer 100 is configured to set optical stimulation parameters, the optical stimulation parameters include a pulse frequency, a pulse duty cycle, a stimulation time and one or more stimulation channels, the upper computer 200 is wirelessly connected to the optical stimulator 400, the optical stimulator 400 receives the optical stimulation parameters set by the upper computer 100, and outputs an electrical pulse signal to a region of the array type stimulation optode 500 where the stimulation channels are electrically connected in the optical stimulation parameters.
In one embodiment, the multichannel wireless optogenetic stimulation system further comprises a wireless transmitting module 200 and a wireless receiving module 300, 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 transmission module 200 includes a radio frequency amplifier 205 and a high gain antenna 204.
In one embodiment, the arrayed stimulation optrode 500 includes an optrode substrate 502 and a plurality of optrodes 501 for emitting light to optically stimulate nerve cells.
Optionally, the substrate material of the optode baseplate is a silicon substrate, and the surface of the silicon substrate is plated with a layer of epoxy resin film.
Optionally, the light electrode is a μ LED.
Optionally, the array-type stimulation optode comprises 24 optodes, the optical stimulator comprises 6 optical stimulation channels, each four optodes are an area, and each area 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 lamp 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 configured to supply power, the switch is configured to turn on and off the optical stimulator, the clock circuit is configured to provide a clock signal to the second microcontroller, the indicator lamp includes a power indicator lamp and a communication status indicator lamp, the power indicator lamp is configured to display the on and off status of the optical stimulator, and when the optical stimulator is successfully received by the upper computer, the light indicates that the optical stimulator is working, the communication status indicator lamp is configured to display the communication status between the optical stimulator and the upper computer, when the optical stimulator successfully receives a signal sent by the upper computer, the communication status indicator lamp will change in brightness, the wireless communication interface is configured to connect the upper computer and the optical stimulator, the second microcontroller is configured to extract optical stimulation parameters, after being processed, the signals are transmitted to an output circuit in the form of electric pulse signals, the output circuit is used for connecting the optical stimulator and the array type stimulation optical pole and transmitting the electric pulse signals output by the second microcontroller to the optical pole, and the reset circuit is used for restoring the optical stimulator to an initialization state.
In one embodiment, the upper computer comprises a parameter setting module, a state display module and operation buttons, wherein the parameter setting module is used for setting light stimulation parameters, the state display module is used for displaying the frequency, duty ratio and residual stimulation time of current light stimulation, and the operation buttons comprise a stimulation starting button, a stimulation stopping button and an on-off key; the on-off key is used for controlling the starting and stopping of the stimulation channel, the stimulation starting button is used for sending a stimulation starting instruction, and the stimulation stopping button is used for sending a stimulation stopping instruction.
In one embodiment, the multichannel wireless optogenetic stimulation system comprises an upper computer, a wireless transmitting module, a wireless receiving module, an optical stimulator and an array type stimulation optode, 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 stimulating optode is connected with an output circuit of the optical stimulator;
the upper computer is used for setting light stimulation parameters and comprises a parameter setting module, a state display module and an operation button;
the wireless sending module is used for sending 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 sending module and transmitting the signal to the optical stimulator;
the optical stimulator is used for processing stimulation information from an upper computer and then outputting corresponding electric pulse signals to the array type stimulation optodes;
the array type stimulation photoelectrode comprises a photoelectrode bottom plate and 24 mu LED chips, and is used for emitting light to perform optical stimulation on nerve cells.
Optionally, the adjustment range of the optical stimulation parameter frequency is 1-500Hz, the adjustment range of the duty ratio is 0-100%, the number of 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 purpose of selectively stimulating the nerve cell region is achieved.
Optionally, the optical stimulator is integrated with 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. The modules are connected with each other through a lead on a 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 stabilizer. The switch is used for controlling the stimulator to be switched on and off. 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, the power indicator lamp is used for displaying the on and off states of the stimulator, the stimulator works if the power indicator lamp is bright, the communication state indicator lamp is used for displaying the communication state of the stimulator and the upper computer, and the communication state indicator lamp changes brightness and darkness after the stimulator successfully receives a signal sent by the upper computer. 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 electric pulse signals after processing. The reset circuit includes a reset switch, a capacitor, and a resistor 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 end of the photostimulator is provided with a 3 multiplied by 3mm digging area, and two sides of the digging area are provided with 6 pairs of rectangular welding pads which are used for being connected with the array type stimulating optodes.
And 6 pairs of rectangular copper-plated bonding pads are arranged on two sides of the optode baseplate, and each pair of bonding pads is connected with 4 pairs of mu LED bonding pads through copper-plated wires.
6 pairs of rectangular copper-plated pads, each having a size of 500. mu. m.times.300. mu.m, were provided as a positive electrode on one side and a negative electrode on the other side.
The mu LED pad is circular in shape and has a diameter of 70 mu m.
The photoelectrode bottom plate substrate material adopts a silicon substrate, and a layer of epoxy resin film is plated on the surface of the silicon substrate.
The wavelength of the mu LED is 470 nm.
The optical stimulator 400 receives the stimulation command from the upper computer 100 through the wireless receiving module 300 and sent through the wireless sending module 200, and then transmits the processed stimulation signal to the array type stimulation optode 500, so as to complete the optical stimulation on 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 and duty ratio of light stimulation and the switching of an array channel.
The wireless transmitting module 200 is composed of a USB to serial port connector 201, a USB to serial port 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 to the upper computer 100 through the USB to serial port connector 201, so as to realize communication of the stimulation signal. The LDO regulator chip 207 regulates the voltage provided by the USB to serial port connector 201, and then provides power to the first microcontroller 203 and the wireless chip 206. The USB serial-to-serial port chip 202 converts the optical stimulation instruction from the upper computer and transmits the converted optical stimulation instruction to the first microcontroller 203, the first microcontroller 203 converts the received serial data from the USB serial-to-port 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 wireless communication distance and the signal transmission stability can be improved by matching with the high-gain antenna 204 and the radio frequency amplifier 205.
The wireless receiving module comprises a 2 x 4 pin connector 301, a wireless chip 302 and an antenna 303. When the wireless receiving module 300 receives the stimulation instruction sent by the wireless sending module 200, the received instruction information is transmitted to the stimulator 400 through the 2 × 4 pin header 301.
The stimulator 400 includes a power source 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 source 401 supplies power to the second microcontroller 406 and the wireless receiving module 300. When the second microcontroller 406 receives the stimulation command from the wireless receiving module 300 through the wireless communication interface 405, the second microcontroller 406 first checks whether the received command information is correct, if so, extracts the stimulation information in the command, if not, continues to wait for receiving new command information, the extracted stimulation information includes a stimulation starting command or a stimulation stopping command, wherein the stimulation starting command further includes an opened channel, a stimulation frequency and a stimulation duty cycle, and the second microcontroller 406 configures an output electric pulse of the channel according to the command 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 stimulation optode 500 is composed of a mu LED501 and an optode substrate 502. The optode substrate 502 is connected to the output circuit 408, and transmits the output electrical signal from the optical stimulator 400 to the μ LED501 through a copper wire, thereby completing optical stimulation of nerve cells.
As shown in fig. 2, the upper computer 100 includes a parameter setting module, a status display module 104 and operation buttons, the parameter setting module includes 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; the operation buttons include a channel selection switch button 105 and a start end button 106. The stimulation time setting module 101 is used for setting the stimulation time. The stimulation mode configuration module 102 is used for selecting stimulation modes, including a free stimulation mode and a timing mode, the free stimulation mode is that a user freely determines stimulation duration through a stimulation start button and a stimulation end button, the timing mode is that the optical stimulator performs optical stimulation with duration set by the user, the stimulation modes can be selected, and a control interface is simple. 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 remaining stimulation time in the timing mode. The channel selection switch button 105 is a switch of the photostimulation array, and a user can select switches of different arrays through the channel selection switch button 105 on the upper computer 100, so that the purpose of selective stimulation of different areas is achieved. The start/end button 106 is used to control the start and end of the optical stimulation, and when the start stimulation button is clicked, the optical stimulation is started, and when the end stimulation is clicked, the optical stimulation is stopped. The stimulation parameter setting module 107 includes modifications of stimulation frequency and duty cycle, and the user can modify the stimulation parameters directly by entering values in a box.
As shown in FIG. 3, the optode base plate 502 is comprised of a rectangular pad 5021, a μ LED pad 5022, and a copper plated wire 5023. The rectangular pads 5021 are distributed on two sides of the photo-electrode substrate 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-plated wires 5023, the anodes of the mu LEDs are connected with the LED pads connected with the rectangular pads of the anodes, every four mu LEDs share one rectangular pad of the anodes and the cathodes to form a 4 x 1 mu LED array, 6 groups of positive and negative pads form a 1 x 6 array, each group is independently connected with the output port of the optical stimulator 400, and the selective stimulation to nerve cells in a larger 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 fastest 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 employs STM32F103RCT 6.
The power supply of the photostimulator adopts a 3.7V lithium battery for power supply.
The adjustable range of the photostimulation 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 470 nm.
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:
arranging an array type stimulating photoelectrode which comprises a plurality of areas for emitting light;
setting optical stimulation parameters, wherein the optical stimulation parameters comprise the frequency, duty cycle, stimulation time and one or more stimulation channels of pulses;
and generating an electric pulse signal through the optical stimulation parameters to the area of the array type stimulation optode electrically communicated with the stimulation channel in the optical stimulation parameters.
In one embodiment, the second microcontroller constructs a neural network structure model, the input of the neural network structure model is 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 may also include proportions of different cell states in total cells), the output is light stimulation parameters, the brain CT and the light stimulation parameters of a plurality of clients with the cell activation effect meeting requirements are collected to train the neural network structure model, and the second microcontroller obtains output light stimulation parameters of a new brain CT through the trained neural network structure model as a reference and transmits the output light stimulation parameters to the upper computer.
Optionally, the second microcontroller determines whether the cell activation effect meets the requirement according to cation inflow outside the cell membrane, and the frequency, duty cycle, stimulation time and the like of the pulse in the activation region or/and the non-activation region can be obtained through the trained neural network structure model.
In one embodiment, a method for performing photostimulation by using a multichannel wireless optogenetic stimulation system comprises the following steps:
inserting the wireless receiving module into the stimulator according to the identification direction, and turning on 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 sending module into a USB port of a computer, opening upper computer software, and performing wireless module parameter configuration;
selecting a stimulation mode, wherein the optical stimulation system provides two stimulation modes, one mode is a free stimulation mode, a user freely determines stimulation time by clicking a stimulation starting button and a stimulation ending button, and the other mode is a timing stimulation mode, namely optical stimulation with set duration is generated according to the set time of the user;
selecting a stimulation channel to be opened, and opening a switch of the corresponding stimulation channel to represent that the stimulation channel is opened by stimulation;
stimulation parameters are configured, and a user can input stimulation parameters such as frequency and duty ratio on an upper computer to configure the parameters;
and clicking to start stimulation to wirelessly transmit the stimulation parameters, and starting corresponding light stimulation by the light stimulator after receiving the configuration parameters. If the parameters need to be modified, the modification of the stimulation parameters can be completed only by clicking to start stimulation after the modified stimulation parameters are input on an upper computer interface;
and after the stimulation is finished, the stimulator switch is closed, and the wireless receiving module and the wireless transmitting module are taken down.
In one embodiment, the upper computer sends the set stimulation parameters to a light stimulator connected with the wireless receiving module through the wireless sending module, the light stimulator outputs corresponding electric pulse signals after receiving the stimulation instruction and processing the electric pulse signals by the second micro-processor, and the electric pulse signals are transmitted to the array type stimulation optodes through the output circuit to complete stimulation on nerve cells. The user can realize the selective stimulation of different areas on the upper computer by selecting the opening or closing of multiple channels according to the regulation and control requirements, the value is modified at the frequency and duty ratio input window to realize the modification of the light stimulation parameters, 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 for performing photostimulation by using the multichannel 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 injury, necrosis, apoptosis and the like, and can also comprise the proportion of different cell states in total cells), and the output is light stimulation parameters;
collecting brain CT and light stimulation parameters of a plurality of clients with cell activation effects meeting requirements to train a neural network structure model;
and obtaining a new output light stimulation parameter of the brain CT through the trained neural network structure model.
Optionally, comprising: and determining whether the cell activation effect meets the requirement or not according to the cation inflow outside the cell membrane, and obtaining the frequency, duty ratio, stimulation time and the like of the pulse in the activation region or/and the pulse not passing through the activation region through the trained neural network structure model.
When the independently adjustable multi-channel 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 optical stimulation module outputs corresponding electric signals 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 stimulation signals and the selection of stimulation areas can be completed in real time through the setting of the upper computer, so that the area selective stimulation of large-area nerve cells is completed. The independently adjustable multi-channel wireless optogenetic stimulation system designed by the invention provides effective support for the research of the in-vitro nerve action mechanism of optogenetic and promotes the application and development of optogenetic in the future.
Although the present invention has been described in detail with reference to the preferred embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the spirit and scope of the present invention.

Claims (10)

1. The utility model provides a wireless optogenetic stimulation system of multichannel, its characterized in that, includes host computer, photostimulator and array stimulation optode, the photostimulator includes a plurality of stimulation passageways, and different stimulation passageways and array stimulation optode's different regional electricity communicate, the host computer is used for setting up the photostimulation parameter, the photostimulation parameter includes frequency, duty cycle, the stimulation time and one or more stimulation passageway of pulse, host computer and photostimulator wireless connection, the photostimulator receives the photostimulation parameter that the host computer set up, and the regional of array stimulation optode that the stimulation passageway electricity communicated in the output electric pulse signal gave the photostimulation parameter.
2. The multichannel 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 to the upper computer and the wireless receiving module, the wireless receiving module is connected to the wireless transmitting module and the optical stimulator, and the wireless transmitting module transmits 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 radio frequency amplification and a high gain antenna.
4. The multi-channel wireless optogenetic stimulation system of claim 1, wherein the arrayed stimulation optode comprises an optode substrate and a plurality of optodes for emitting light to photostimulate nerve cells.
5. The multi-channel wireless optogenetic stimulation system of claim 4, wherein the optode substrate is made of a silicon substrate and is coated with a layer of epoxy resin film.
6. The multi-channel wireless optogenetic stimulation system of claim 4, wherein the light is a μ LED.
7. The multi-channel wireless optogenetic stimulation system of claim 4, wherein the arrayed stimulation optodes comprise 24 optodes, and the optical stimulator comprises 6 optical stimulation channels, each four optodes being a zone, each zone being controlled by one optical stimulation channel.
8. The multi-channel wireless optogenetic stimulation system of claim 1, wherein the optostimulator 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, the power driving circuit is configured to supply power, the switch is configured to turn on and off the optostimulator, the clock circuit is configured to provide a clock signal to the second microcontroller, the indicator light comprises a power indicator light and a communication status indicator light, the power indicator light is configured to display the on and off status of the optostimulator, the light indicates that the optostimulator is working, the communication status indicator light is configured to display the communication status between the optostimulator and the host computer, the communication status indicator light changes brightness when the optostimulator successfully receives a signal sent by the host computer, the wireless communication interface is configured to connect the host computer and the optostimulator, the second microcontroller is used for extracting optical stimulation parameters, the optical stimulation parameters are transmitted to the output circuit in the form of electric pulse signals after being processed, the output circuit is used for connecting the optical stimulator and the array type stimulation optical pole and transmitting the electric pulse signals output by the second microcontroller to the optical pole, and the reset circuit is used for restoring the optical stimulator to an initialization state.
9. The multichannel wireless optogenetic stimulation system of claim 1, wherein the upper computer comprises a parameter setting module, a state display module and operation buttons, the parameter setting module is used for setting optical stimulation parameters, the state display module is used for displaying the frequency, duty ratio and residual stimulation time of current optical stimulation, and the operation buttons comprise a stimulation start button, a stimulation stop button and an on-off key; the switch key is used for controlling the starting and stopping of the stimulation channel, the stimulation starting button is used for sending a stimulation starting instruction, and the stimulation stopping button is used for sending a stimulation stopping instruction.
10. A multi-channel wireless optogenetic stimulation method, comprising:
arranging an array type stimulating photoelectrode which comprises a plurality of areas for emitting light;
setting optical stimulation parameters, wherein the optical stimulation parameters comprise the frequency, duty cycle, stimulation time and one or more stimulation channels of pulses;
and generating an electric pulse signal to the area of the array type stimulation photoelectrode electrically communicated with the stimulation channel in the optical stimulation parameters through the optical stimulation parameters.
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