Optical genetic calibration method and system based on special space research

By accurately adjusting the optical components and real-time calibration mechanism in the optical path regulation module, the limitations of existing optogenetic technologies in spatial resolution and accuracy are solved, and precise regulation of specific neurons or neural network areas is achieved, which significantly improves the application effect of optogenetic technologies.

CN119721155AActive Publication Date: 2025-03-28SHANGHAI JIAOTONG UNIV

Patent Information

Application Number
CN202411800650.4
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-09
Publication Date
2025-03-28
Estimated Expiration
2044-12-09

AI Technical Summary

Technical Problem

Existing optogenetic technologies have limitations in spatial resolution and accuracy, making it difficult to achieve precise regulation of specific neurons or neural networks. Especially in complex neural networks, existing methods are difficult to accurately locate and regulate neuronal activities in specific regions.

Method used

An optogenetic calibration method based on special space research is provided, and the precise projection of the light beam in a specific spatial area is achieved by accurately adjusting the optical elements in the optical path control module. The method includes initial calibration and real-time calibration, real-time monitoring of environmental changes and dynamically adjusting optical path parameters to ensure that the beam is always maintained at the center of the target area.

Benefits of technology

The spatial resolution and accuracy of optogenetic regulation are significantly improved, precise regulation of specific neurons or neural network areas is achieved, and the application effect of optogenetic technology and the stability and reliability of experiments are improved.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention provides an optical genetic calibration method and system based on special space research, and the method comprises the steps: determining a target and a performance index of system design, selecting a proper optical element according to the performance index, and carrying out the layout design and parameter calculation; performing initial calibration, determining a position reference point of each optical element, adjusting an optical path, and recording initial values of parameters; real-time calibration is carried out, and system parameters are adjusted according to environment changes; detecting the characteristics of the output light in real time, and calculating the deviation between an actual value and an expected value; adjusting the position or angle of the optical element through a control circuit according to the deviation size and direction; and carrying out system data feedback and optimization, collecting and analyzing data in a real-time calibration process, and adjusting system parameters according to a data analysis result. According to the invention, the spatial resolution and accuracy of optogenetic regulation are improved.
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Description

Technical Field

[0001] The present invention relates to the field of spectral analysis technology, and in particular to an optogenetic calibration method and system based on special space research. Background Art

[0002] Optogenetics is a method of precisely controlling neuronal activity through optical technology and has been widely used in neuroscience research. However, existing optogenetic techniques have certain limitations in spatial resolution and accuracy, making it difficult to achieve precise regulation of specific neurons or neural networks. Especially in complex neural networks, existing methods have difficulty accurately locating and regulating neuronal activity in specific areas. Therefore, there is an urgent need for an optogenetic calibration method based on special spatial research to improve the accuracy and spatial resolution of optogenetic regulation.

[0003] The shortcomings of the prior art are mainly in the following aspects:

[0004] Insufficient precision: Most existing technologies lack high-precision beam positioning and real-time adjustment capabilities, resulting in low spatial resolution of experimental results.

[0005] The real-time calibration function is not perfect: the real-time calibration and automatic calibration functions of the existing technology are weak, and it is difficult to deal with the problem of optical path deviation caused by environmental changes during the experiment.

[0006] Poor environmental adaptability: Lack of real-time monitoring and compensation mechanism for environmental parameters (such as temperature, humidity, vibration, etc.), which affects the stability and reliability of the experiment.

[0007] Complex operation: Many systems rely on manual adjustment of optical components, which is complex and error-prone, making it difficult to achieve efficient experimental operation.

[0008] High system cost: Some high-precision systems (such as holography) are expensive and complex, making them unsuitable for widespread use in conventional laboratories.

[0009] The academic paper High-resolution optogenetic control of cortical circuits using holography (Nature Methods, 2015) introduces a method of high-resolution optogenetic control using holography, which generates complex light patterns to achieve precise regulation of cerebral cortical circuits. The disadvantage is that the holographic system is complex and expensive, and it is difficult to popularize and apply it in conventional laboratories. It has poor adaptability to environmental changes during the experiment and lacks real-time dynamic adjustment and automatic calibration functions.

[0010] Optogenetics: precise tools for probing neural circuits (Neuron, 2011) This review article introduces the basic principles of optogenetics and its application in neuroscience research, and discusses the advantages and disadvantages of different optogenetic tools. The disadvantage is that it is a review article and lacks specific details on optical path control and calibration techniques. It mainly focuses on the biological applications of optogenetic tools and does not involve precise control and calibration techniques of optical systems. Summary of the invention

[0011] In view of the defects in the prior art, the object of the present invention is to provide an optogenetic calibration method and system based on special space research.

[0012] According to the present invention, an optogenetic calibration method based on special space research includes:

[0013] Step S1: clarify the goals and performance indicators of system design, select appropriate optical components according to the performance indicators, and perform layout design and parameter calculation;

[0014] Step S2: Perform initial calibration, determine the position reference points of each optical element, adjust the optical path, and record the initial values ​​of the parameters;

[0015] Step S3: perform real-time calibration and adjust system parameters according to environmental changes; detect the characteristics of the output light in real time and calculate the deviation between the actual value and the expected value; adjust the position or angle of the optical element through the control circuit according to the size and direction of the deviation;

[0016] Step S4: Perform system data feedback and optimization, collect and analyze data during the real-time calibration process, and adjust system parameters according to the data analysis results.

[0017] Preferably, in step S1:

[0018] Specific design of the optical path control module:

[0019] Light source module: Select a laser or LED light source with preset high stability to ensure the stability and uniformity of light output. The light source should have adjustable light intensity and wavelength to meet different experimental requirements.

[0020] Select a light source suitable for optogenetic excitation, including lasers or preset high-power LEDs. The light source operates within a specific wavelength range to activate different types of photosensitive proteins. Use an optical power control circuit to adjust the light intensity to achieve different stimulation intensities, and use pulse width modulation to generate precise sequences of light pulses.

[0021] Lenses and reflectors: Use preset high-quality lenses and reflectors to ensure preset high transmittance and preset low scattering of optical components; the lens group is designed to have a structure that can adjust the focal length to adapt to different working distances and target areas;

[0022] Optical fiber transmission: Select optical fiber with preset low loss and preset high transmission efficiency to ensure the quality of the light beam in the preset long-distance transmission. The optical fiber interface is designed as a structure with adjustable angle, which can flexibly position and guide the light beam;

[0023] Add a microlens or microwave guide at the end of the optical fiber to focus the light beam and accurately locate the light irradiation point;

[0024] Micro motor and adjustment device: A preset high-precision stepper motor or piezoelectric driver is used to ensure the preset micro-adjustment accuracy of the lens and reflector. The adjustment device has a feedback control function to monitor the adjustment status in real time and make corrections.

[0025] Use electro-optic modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective to achieve single-cell resolution light illumination;

[0026] Light pulse control is achieved using a preset high-frequency switching circuit and modulator; the illumination system is synchronized with the neural recording system to record the response of neurons to light stimulation, which is achieved through hardware trigger signals or software synchronization.

[0027] Preferably, in step S2:

[0028] Calibration plate preparation: Use an optical calibration plate with preset high-precision marks and place it on the experimental platform. The position of the calibration plate should be fixed and keep a preset distance from the optical path control module; Light source calibration: Use a spectrum analyzer to measure the wavelength and power density parameters of the light source to ensure that they are within the preset standard range;

[0029] Coarse adjustment of the optical path: Start the light source, adjust the lens and reflector in the optical path control module to align the light beam with the reference point on the calibration plate, and preliminarily correct the direction and position of the light beam through manual adjustment; observe the position of the light spot through a microscope to ensure that the center of the light beam is aligned with the mark on the calibration plate;

[0030] Calibration: Connect the optogenetic calibration system to the neuron recording system, detect the excitation effect of the light beam at the neuron position through the recording system, adjust the optical path parameters to ensure that the light beam can excite the target neurons, and record the optical path parameters at this time as a benchmark;

[0031] Precise alignment of the light beam: Start the sensor and data processing module to monitor the position of the light beam on the calibration board in real time; make fine adjustments through the micro motor to make the center of the light beam completely coincide with the reference point of the calibration board; record the initial position and parameters of the optical element.

[0032] Preferably, in step S3:

[0033] Sensor monitoring: Install a preset high-precision position sensor or a preset high-resolution camera to monitor the position and intensity of the light beam in the target area in real time. The sensor data is transmitted to the data processing module in real time to perform beam position analysis;

[0034] Data processing and feedback: The data processing module calculates the deviation of the light beam relative to the target area based on the sensor data, optimizes and adjusts the parameters through an adaptive algorithm, and improves the system's response speed and adjustment accuracy;

[0035] Control unit adjustment: Based on the feedback from the data processing module, the control unit drives the micro-motor to make real-time adjustments to ensure that the light beam always remains in the center of the target area and compensates for the light path deviation caused by environmental changes;

[0036] Error compensation: The control unit receives sensor data, calculates the deviation between the current position of the light beam and the predetermined position, and uses motors or piezoelectric drive devices to adjust the position or angle of the optical element in real time to compensate for the optical path deviation and ensure that the light beam is repositioned to the predetermined position;

[0037] Dynamic optimization: According to the law of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance to further improve the calibration accuracy.

[0038] Preferably, in step S4:

[0039] Data acquisition: During the experiment, the beam position, light intensity, and neuron response data are continuously collected, and the data are recorded and stored using a preset high-precision data acquisition card and dedicated software;

[0040] Automated control system: Integrate automatic calibration and real-time adjustment functions to enable the system to run automatically without human intervention, design user interface, and provide experimental parameter setting, real-time monitoring and data recording functions;

[0041] Environmental compensation and maintenance: The sensor monitors environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjusts the optical path parameters for compensation; regularly conducts system self-inspections to check the working status of optical components and sensors, and performs maintenance and replacement in a timely manner;

[0042] Data analysis and storage: During the experiment, the system automatically records the data of optical path adjustment and environmental parameter changes, providing complete data support for subsequent analysis; through big data and machine learning algorithms, the optical path control parameters are continuously optimized; the collected data is analyzed through data processing software to find out the relationship between the change of beam position and neuronal response. Statistical methods and machine learning algorithms are used to analyze the factors affecting the stability of the optical path and extract parameters;

[0043] Optimization algorithm: Based on the data analysis results, the optical path control algorithm is optimized and an adaptive control algorithm is used to optimize the optical path in real time to ensure that the light beam can always be accurately positioned;

[0044] System update: According to the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data are continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.

[0045] According to the present invention, an optogenetic calibration system based on special space research is provided, comprising:

[0046] Module M1: Clarify the goals and performance indicators of system design, select appropriate optical components based on the performance indicators, and perform layout design and parameter calculation;

[0047] Module M2: Perform initial calibration, determine the position reference points of each optical element, adjust the optical path, and record the initial values ​​of the parameters;

[0048] Module M3: performs real-time calibration and adjusts system parameters according to environmental changes; detects the characteristics of output light in real time and calculates the deviation between the actual value and the expected value; adjusts the position or angle of the optical element through the control circuit according to the size and direction of the deviation;

[0049] Module M4: Perform system data feedback and optimization, collect and analyze data during real-time calibration, and adjust system parameters based on data analysis results.

[0050] Preferably, in the module M1:

[0051] Specific design of the optical path control module:

[0052] Light source module: Select a laser or LED light source with preset high stability to ensure the stability and uniformity of light output. The light source should have adjustable light intensity and wavelength to meet different experimental requirements.

[0053] Select a light source suitable for optogenetic excitation, including lasers or preset high-power LEDs. The light source operates within a specific wavelength range to activate different types of photosensitive proteins. Use an optical power control circuit to adjust the light intensity to achieve different stimulation intensities, and use pulse width modulation to generate precise sequences of light pulses.

[0054] Lenses and reflectors: Use preset high-quality lenses and reflectors to ensure preset high transmittance and preset low scattering of optical components; the lens group is designed to have a structure that can adjust the focal length to adapt to different working distances and target areas;

[0055] Optical fiber transmission: Select optical fiber with preset low loss and preset high transmission efficiency to ensure the quality of the light beam in the preset long-distance transmission. The optical fiber interface is designed as a structure with adjustable angle, which can flexibly position and guide the light beam;

[0056] Add a microlens or microwave guide at the end of the optical fiber to focus the light beam and accurately locate the light irradiation point;

[0057] Micro motor and adjustment device: A preset high-precision stepper motor or piezoelectric driver is used to ensure the preset micro-adjustment accuracy of the lens and reflector. The adjustment device has a feedback control function to monitor the adjustment status in real time and make corrections.

[0058] Use electro-optic modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective to achieve single-cell resolution light illumination;

[0059] Light pulse control is achieved using a preset high-frequency switching circuit and modulator; the illumination system is synchronized with the neural recording system to record the response of neurons to light stimulation, which is achieved through hardware trigger signals or software synchronization.

[0060] Preferably, in the module M2:

[0061] Calibration plate preparation: Use an optical calibration plate with preset high-precision marks and place it on the experimental platform. The position of the calibration plate should be fixed and keep a preset distance from the optical path control module; Light source calibration: Use a spectrum analyzer to measure the wavelength and power density parameters of the light source to ensure that they are within the preset standard range;

[0062] Coarse adjustment of the optical path: Start the light source, adjust the lens and reflector in the optical path control module to align the light beam with the reference point on the calibration plate, and preliminarily correct the direction and position of the light beam through manual adjustment; observe the position of the light spot through a microscope to ensure that the center of the light beam is aligned with the mark on the calibration plate;

[0063] Calibration: Connect the optogenetic calibration system to the neuron recording system, detect the excitation effect of the light beam at the neuron position through the recording system, adjust the optical path parameters to ensure that the light beam can excite the target neurons, and record the optical path parameters at this time as a benchmark;

[0064] Precise alignment of the light beam: Start the sensor and data processing module to monitor the position of the light beam on the calibration board in real time; make fine adjustments through the micro motor to make the center of the light beam completely coincide with the reference point of the calibration board; record the initial position and parameters of the optical element.

[0065] Preferably, in the module M3:

[0066] Sensor monitoring: Install a preset high-precision position sensor or a preset high-resolution camera to monitor the position and intensity of the light beam in the target area in real time. The sensor data is transmitted to the data processing module in real time to perform beam position analysis;

[0067] Data processing and feedback: The data processing module calculates the deviation of the light beam relative to the target area based on the sensor data, optimizes and adjusts the parameters through an adaptive algorithm, and improves the system's response speed and adjustment accuracy;

[0068] Control unit adjustment: Based on the feedback from the data processing module, the control unit drives the micro-motor to make real-time adjustments to ensure that the light beam always remains in the center of the target area and compensates for the light path deviation caused by environmental changes;

[0069] Error compensation: The control unit receives sensor data, calculates the deviation between the current position of the light beam and the predetermined position, and uses motors or piezoelectric drive devices to adjust the position or angle of the optical element in real time to compensate for the optical path deviation and ensure that the light beam is repositioned to the predetermined position;

[0070] Dynamic optimization: According to the law of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance to further improve the calibration accuracy.

[0071] Preferably, in the module M4:

[0072] Data acquisition: During the experiment, the beam position, light intensity, and neuron response data are continuously collected, and the data are recorded and stored using a preset high-precision data acquisition card and dedicated software;

[0073] Automated control system: Integrate automatic calibration and real-time adjustment functions to enable the system to run automatically without human intervention, design user interface, and provide experimental parameter setting, real-time monitoring and data recording functions;

[0074] Environmental compensation and maintenance: The sensor monitors environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjusts the optical path parameters for compensation; regularly conducts system self-inspections to check the working status of optical components and sensors, and performs maintenance and replacement in a timely manner;

[0075] Data analysis and storage: During the experiment, the system automatically records the data of optical path adjustment and environmental parameter changes, providing complete data support for subsequent analysis; through big data and machine learning algorithms, the optical path control parameters are continuously optimized; the collected data is analyzed through data processing software to find out the relationship between the change of beam position and neuronal response. Statistical methods and machine learning algorithms are used to analyze the factors affecting the stability of the optical path and extract parameters;

[0076] Optimization algorithm: Based on the data analysis results, the optical path control algorithm is optimized and an adaptive control algorithm is used to optimize the optical path in real time to ensure that the light beam can always be accurately positioned;

[0077] System update: According to the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data are continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.

[0078] Compared with the prior art, the present invention has the following beneficial effects:

[0079] 1. The present invention improves the spatial resolution and accuracy of optogenetic regulation. The present invention achieves accurate projection of light beams in a specific spatial region by accurately adjusting the optical elements in the optical path regulation module. By combining initial calibration with real-time calibration, the light beam can be accurately aligned with the target neuron or neural network region, significantly improving the spatial resolution of optogenetic technology and ensuring the accuracy and effectiveness of regulation.

[0080] 2. The present invention realizes real-time dynamic adjustment of the optical path. The present invention introduces a real-time monitoring and feedback control mechanism. The sensor monitors the position of the light beam in real time, the data processing module performs real-time analysis based on the monitoring data, and dynamically adjusts the light path control module through the control unit. The real-time calibration mechanism can effectively compensate for the light path deviation caused by environmental changes (such as temperature fluctuations, mechanical vibrations, etc.), ensuring the stability and accuracy of the light beam position during the experiment.

[0081] 3. The present invention improves the reliability and stability of optogenetic experiments. The present invention reduces human intervention and operational errors through an automated and intelligent calibration and adjustment process, significantly improving the reliability and stability of the experiment. The system can automatically identify and correct optical path deviations to ensure that the light beam is always accurately positioned in the target area, ensuring the stability and repeatability of optogenetic regulation.

[0082] 4. The present invention supports precise control of complex neural networks. The high-precision optical path control capability of the present invention enables precise control of specific neurons or neural network regions in complex neural networks. By regulating the activity of neurons in a specific spatial region and studying their functional changes under different states, it provides strong technical support for functional research on complex neural networks.

[0083] 5. The present invention promotes the research and treatment of neurological diseases. The present invention's breakthrough in optogenetic calibration and regulation technology provides a new method for the study and treatment of the pathogenic mechanism of neurological diseases. By regulating the neuronal activity in specific areas, the pathological process of neurological diseases (such as Parkinson's disease, Alzheimer's disease, etc.) can be studied, new therapeutic targets and schemes can be explored, and the development of neurological disease treatment technology can be promoted.

[0084] 6. The present invention enhances the breadth and depth of application of optogenetic technology. The system can be integrated into a variety of optogenetic experimental equipment and is suitable for different types of neuroscience research scenarios, including single-cell neuron regulation, complex neural network research, neurological disease mechanism research, etc. The modular design and high adaptability of the system enable it to be widely used in various optogenetic experiments. By improving the accuracy and stability of optogenetic experiments, the present invention provides more powerful technical tools for neuroscience research and promotes the in-depth development of neuronal function and network mechanism research. In particular, the high-precision control capabilities of the present invention will play an important role in studying the pathogenic mechanisms of neurological diseases and developing treatment plans.

[0085] 7. The present invention provides an integrated solution. The present invention provides an integrated optogenetic calibration and regulation solution that is easy to apply in existing neuroscience experimental equipment. The modular design of the system enables it to flexibly adapt to different types of optogenetic experimental requirements, and has broad application prospects and scientific research value.

[0086] 8. The present invention optimizes the design and performance of the optical system. By optimizing the design and calibration algorithm of the optical system, the present invention can effectively improve the performance of the optical system. The high-precision optical path control and real-time calibration mechanism ensure that the optical system always maintains the best performance under different experimental conditions, improving the overall effect of optogenetics.

[0087] 9. The present invention promotes innovation in scientific research and clinical applications. The technical effects of the present invention are not limited to basic research, but also have broad clinical application potential. By improving the accuracy and stability of optogenetics, the present invention provides a powerful tool for neuroscience research and clinical applications, and promotes the innovation and development of optogenetics in scientific research and clinical fields.

[0088] 10. The present invention provides efficient data analysis and processing. The data processing module has powerful data analysis capabilities, can process sensor monitoring data in real time, quickly calculate beam deviations and make corresponding adjustments. Through big data analysis and machine learning algorithms, the system can continuously optimize control parameters and improve the accuracy and stability of the experiment. The system can automatically record the optical path adjustment and environmental parameter changes during the experiment, providing complete data support for subsequent data analysis and result verification.

[0089] 11. The present invention is capable of high-precision optical path control. Through micro-motors and precision adjustment devices, it can achieve micron-level precise positioning and real-time adjustment of the light beam, significantly improving the spatial resolution and control accuracy of the experiment.

[0090] 12. The present invention can be calibrated dynamically in real time: the system has real-time monitoring by sensors and feedback control by data processing modules, which can compensate for optical path deviation in real time to ensure that the light beam always stays in the target area. The present invention can automatically calibrate and optimize in real time: the automatic calibration function is combined with an adaptive algorithm, which can make real-time adjustments according to changes in the experimental environment to maintain the stability and reliability of the optical path.

[0091] 13. The present invention is capable of real-time environmental compensation mechanism: the system can monitor environmental parameters in real time and automatically adjust optical path parameters for compensation, thereby improving the stability of the experiment.

[0092] 14. The present invention can be operated in real time and conveniently: it has a user-friendly interface and a high degree of automation, which reduces the complexity and error of manual operation and improves experimental efficiency. The present invention is cost-effective: compared with high-cost equipment such as holographic systems, the system design of the present invention is more economical and suitable for wide application in conventional laboratories. BRIEF DESCRIPTION OF THE DRAWINGS

[0093] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0094] Figure 1 A roadmap for calibrating methods for optogenetic systems based on special space research;

[0095] Figure 2 It is a system mode diagram under special space;

[0096] Figure 3 Design a schematic diagram for the overall block diagram and working mode of optogenetics;

[0097] Figure 4 is the system block diagram;

[0098] Figure 5 This is the laser driver block diagram;

[0099] Figure 6 is a schematic diagram of a DC conversion circuit;

[0100] Figure 7 Schematic diagram of the emission light path;

[0101] Figure 8 It is a pulse signal diagram;

[0102] Fig. 9 This is a schematic diagram for setting waveform signals. DETAILED DESCRIPTION

[0103] The present invention is described in detail below in conjunction with specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, several changes and improvements can also be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

[0104] Embodiment 1:

[0105] The purpose of the present invention is to provide an optogenetic calibration method based on special space research, which can achieve precise regulation of neuronal activity in a specific spatial area by optimizing the optical path design and calibration algorithm, thereby improving the application effect of optogenetic technology in neuroscience research.

[0106] By implementing the optogenetic calibration method of the present invention, the spatial resolution and control accuracy of optogenetic experiments can be significantly improved, precise control of specific neurons or neural network areas can be achieved, and the in-depth development of neuroscience research can be promoted. At the same time, the method has good stability and reliability, providing strong technical support for the study of the pathogenic mechanism of neurological diseases and the development of treatment plans.

[0107] The efficient operation of the system depends on the data entry and settings of the experimenter. Clarify the goals and performance indicators of the system design, such as light intensity stability, wavelength selectivity, etc.; select appropriate optical components (such as lenses, reflectors, polarizers) according to the performance indicators, and perform layout design and parameter calculation;

[0108] Design the mechanical structure that supports and fixes the optical components to ensure their stability and adjustability;

[0109] Design drive circuits for controlling the position of optical elements, and circuits for signal detection and processing;

[0110] Develop software algorithms for data processing and control strategies.

[0111] Under this premise, initial calibration should also be performed, which includes: determining the position reference points of each optical component; using tools such as laser pointers to assist in adjusting the optical path so that each component reaches the optimal alignment state; and recording the initial values ​​of all key parameters for subsequent comparison and reference.

[0112] After the initial calibration, the experimental requirements can be met. During the experimental operation, the system will perform real-time calibration, including: continuously monitoring environmental changes and adjusting system parameters according to the changes; the system's internal photoelectric detectors and other devices detect the characteristics of the output light (such as intensity, phase) in real time; the deviation between the actual value and the expected value is calculated through software algorithms; and the position or angle of the optical element is adjusted through the control circuit according to the size and direction of the deviation.

[0113] Throughout the experiment, the efficient operation of the system completely relies on system data feedback and optimization, including: collecting and analyzing data during the real-time calibration process to evaluate the stability and accuracy of the system; adjusting system parameters based on data analysis results to improve performance; identifying potential problems in the system and taking measures to prevent failures; and providing an intuitive operation interface for users to monitor system status and make manual adjustments.

[0114] It is important to note that this process is not linear, but may involve feedback and iteration. For example, problems discovered during real-time calibration may lead to returning to the preset stage for modification, or further optimization may be found after data analysis, leading to re-initial calibration and other steps.

[0115] According to an optogenetic calibration method based on special space research provided by the present invention, Figure 1 As shown, including:

[0116] Step S1: clarify the goals and performance indicators of system design, select appropriate optical components according to the performance indicators, and perform layout design and parameter calculation;

[0117] Specifically, in step S1:

[0118] Specific design of the optical path control module:

[0119] Light source module: Select a laser or LED light source with preset high stability to ensure the stability and uniformity of light output. The light source should have adjustable light intensity and wavelength to meet different experimental requirements.

[0120] Select a light source suitable for optogenetic excitation, including lasers or preset high-power LEDs. The light source operates within a specific wavelength range to activate different types of photosensitive proteins. Use an optical power control circuit to adjust the light intensity to achieve different stimulation intensities, and use pulse width modulation to generate precise sequences of light pulses.

[0121] Lenses and reflectors: Use preset high-quality lenses and reflectors to ensure preset high transmittance and preset low scattering of optical components; the lens group is designed to have a structure that can adjust the focal length to adapt to different working distances and target areas;

[0122] Optical fiber transmission: Select optical fiber with preset low loss and preset high transmission efficiency to ensure the quality of the light beam in the preset long-distance transmission. The optical fiber interface is designed as a structure with adjustable angle, which can flexibly position and guide the light beam;

[0123] Add a microlens or microwave guide at the end of the optical fiber to focus the light beam and accurately locate the light irradiation point;

[0124] Micro motor and adjustment device: A preset high-precision stepper motor or piezoelectric driver is used to ensure the preset micro-adjustment accuracy of the lens and reflector. The adjustment device has a feedback control function to monitor the adjustment status in real time and make corrections.

[0125] Use electro-optic modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective to achieve single-cell resolution light illumination;

[0126] Light pulse control is achieved using a preset high-frequency switching circuit and modulator; the illumination system is synchronized with the neural recording system to record the response of neurons to light stimulation, which is achieved through hardware trigger signals or software synchronization.

[0127] Step S2: Perform initial calibration, determine the position reference points of each optical element, adjust the optical path, and record the initial values ​​of the parameters;

[0128] Specifically, in step S2:

[0129] Calibration plate preparation: Use an optical calibration plate with preset high-precision marks and place it on the experimental platform. The position of the calibration plate should be fixed and keep a preset distance from the optical path control module; Light source calibration: Use a spectrum analyzer to measure the wavelength and power density parameters of the light source to ensure that they are within the preset standard range;

[0130] Coarse adjustment of the optical path: Start the light source, adjust the lens and reflector in the optical path control module to align the light beam with the reference point on the calibration plate, and preliminarily correct the direction and position of the light beam through manual adjustment; observe the position of the light spot through a microscope to ensure that the center of the light beam is aligned with the mark on the calibration plate;

[0131] Calibration: Connect the optogenetic calibration system to the neuron recording system, detect the excitation effect of the light beam at the neuron position through the recording system, adjust the optical path parameters to ensure that the light beam can excite the target neurons, and record the optical path parameters at this time as a benchmark;

[0132] Precise alignment of the light beam: Start the sensor and data processing module to monitor the position of the light beam on the calibration board in real time; make fine adjustments through the micro motor to make the center of the light beam completely coincide with the reference point of the calibration board; record the initial position and parameters of the optical element.

[0133] Step S3: perform real-time calibration and adjust system parameters according to environmental changes; detect the characteristics of the output light in real time and calculate the deviation between the actual value and the expected value; adjust the position or angle of the optical element through the control circuit according to the size and direction of the deviation;

[0134] Specifically, in step S3:

[0135] Sensor monitoring: Install a preset high-precision position sensor or a preset high-resolution camera to monitor the position and intensity of the light beam in the target area in real time. The sensor data is transmitted to the data processing module in real time to perform beam position analysis;

[0136] Data processing and feedback: The data processing module calculates the deviation of the light beam relative to the target area based on the sensor data, optimizes and adjusts the parameters through an adaptive algorithm, and improves the system's response speed and adjustment accuracy;

[0137] Control unit adjustment: Based on the feedback from the data processing module, the control unit drives the micro-motor to make real-time adjustments to ensure that the light beam always remains in the center of the target area and compensates for the light path deviation caused by environmental changes;

[0138] Error compensation: The control unit receives sensor data, calculates the deviation between the current position of the light beam and the predetermined position, and uses motors or piezoelectric drive devices to adjust the position or angle of the optical element in real time to compensate for the optical path deviation and ensure that the light beam is repositioned to the predetermined position;

[0139] Dynamic optimization: According to the law of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance to further improve the calibration accuracy.

[0140] Step S4: Perform system data feedback and optimization, collect and analyze data during the real-time calibration process, and adjust system parameters according to the data analysis results.

[0141] Specifically, in step S4:

[0142] Data acquisition: During the experiment, the beam position, light intensity, and neuron response data are continuously collected, and the data are recorded and stored using a preset high-precision data acquisition card and dedicated software;

[0143] Automated control system: Integrate automatic calibration and real-time adjustment functions to enable the system to run automatically without human intervention, design user interface, and provide experimental parameter setting, real-time monitoring and data recording functions;

[0144] Environmental compensation and maintenance: The sensor monitors environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjusts the optical path parameters for compensation; regularly conducts system self-inspections to check the working status of optical components and sensors, and performs maintenance and replacement in a timely manner;

[0145] Data analysis and storage: During the experiment, the system automatically records the data of optical path adjustment and environmental parameter changes, providing complete data support for subsequent analysis; through big data and machine learning algorithms, the optical path control parameters are continuously optimized; the collected data is analyzed through data processing software to find out the relationship between the change of beam position and neuronal response. Statistical methods and machine learning algorithms are used to analyze the factors affecting the stability of the optical path and extract parameters;

[0146] Optimization algorithm: Based on the data analysis results, the optical path control algorithm is optimized and an adaptive control algorithm is used to optimize the optical path in real time to ensure that the light beam can always be accurately positioned;

[0147] System update: According to the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data are continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.

[0148] Embodiment 2:

[0149] Embodiment 2 is a preferred example of Embodiment 1, and is used to illustrate the present invention in more detail.

[0150] The present invention also provides an optogenetic calibration system based on special space research, which can be implemented by executing the process steps of the optogenetic calibration method based on special space research, that is, those skilled in the art can understand the optogenetic calibration method based on special space research as a preferred implementation of the optogenetic calibration system based on special space research.

[0151] According to the present invention, an optogenetic calibration system based on special space research is provided, such as Figure 4 As shown, including:

[0152] Module M1: Clarify the goals and performance indicators of system design, select appropriate optical components based on the performance indicators, and perform layout design and parameter calculation;

[0153] Specifically, in the module M1:

[0154] Specific design of the optical path control module:

[0155] Light source module: Select a laser or LED light source with preset high stability to ensure the stability and uniformity of light output. The light source should have adjustable light intensity and wavelength to meet different experimental requirements.

[0156] Select a light source suitable for optogenetic excitation, including lasers or preset high-power LEDs. The light source operates within a specific wavelength range to activate different types of photosensitive proteins. Use an optical power control circuit to adjust the light intensity to achieve different stimulation intensities, and use pulse width modulation to generate precise sequences of light pulses.

[0157] Lenses and reflectors: Use preset high-quality lenses and reflectors to ensure preset high transmittance and preset low scattering of optical components; the lens group is designed to have a structure that can adjust the focal length to adapt to different working distances and target areas;

[0158] Optical fiber transmission: Select optical fiber with preset low loss and preset high transmission efficiency to ensure the quality of the light beam in the preset long-distance transmission. The optical fiber interface is designed as a structure with adjustable angle, which can flexibly position and guide the light beam;

[0159] Add a microlens or microwave guide at the end of the optical fiber to focus the light beam and accurately locate the light irradiation point;

[0160] Micro motor and adjustment device: A preset high-precision stepper motor or piezoelectric driver is used to ensure the preset micro-adjustment accuracy of the lens and reflector. The adjustment device has a feedback control function to monitor the adjustment status in real time and make corrections.

[0161] Use electro-optic modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective to achieve single-cell resolution light illumination;

[0162] Light pulse control is achieved using a preset high-frequency switching circuit and modulator; the illumination system is synchronized with the neural recording system to record the response of neurons to light stimulation, which is achieved through hardware trigger signals or software synchronization.

[0163] Module M2: Perform initial calibration, determine the position reference points of each optical element, adjust the optical path, and record the initial values ​​of the parameters;

[0164] Specifically, in the module M2:

[0165] Calibration plate preparation: Use an optical calibration plate with preset high-precision marks and place it on the experimental platform. The position of the calibration plate should be fixed and keep a preset distance from the optical path control module; Light source calibration: Use a spectrum analyzer to measure the wavelength and power density parameters of the light source to ensure that they are within the preset standard range;

[0166] Coarse adjustment of the optical path: Start the light source, adjust the lens and reflector in the optical path control module to align the light beam with the reference point on the calibration plate, and preliminarily correct the direction and position of the light beam through manual adjustment; observe the position of the light spot through a microscope to ensure that the center of the light beam is aligned with the mark on the calibration plate;

[0167] Calibration: Connect the optogenetic calibration system to the neuron recording system, detect the excitation effect of the light beam at the neuron position through the recording system, adjust the optical path parameters to ensure that the light beam can excite the target neurons, and record the optical path parameters at this time as a benchmark;

[0168] Precise alignment of the light beam: Start the sensor and data processing module to monitor the position of the light beam on the calibration board in real time; make fine adjustments through the micro motor to make the center of the light beam completely coincide with the reference point of the calibration board; record the initial position and parameters of the optical element.

[0169] Module M3: performs real-time calibration and adjusts system parameters according to environmental changes; detects the characteristics of output light in real time and calculates the deviation between the actual value and the expected value; adjusts the position or angle of the optical element through the control circuit according to the size and direction of the deviation;

[0170] Specifically, in the module M3:

[0171] Sensor monitoring: Install a preset high-precision position sensor or a preset high-resolution camera to monitor the position and intensity of the light beam in the target area in real time. The sensor data is transmitted to the data processing module in real time to perform beam position analysis;

[0172] Data processing and feedback: The data processing module calculates the deviation of the light beam relative to the target area based on the sensor data, optimizes and adjusts the parameters through an adaptive algorithm, and improves the system's response speed and adjustment accuracy;

[0173] Control unit adjustment: Based on the feedback from the data processing module, the control unit drives the micro-motor to make real-time adjustments to ensure that the light beam always remains in the center of the target area and compensates for the light path deviation caused by environmental changes;

[0174] Error compensation: The control unit receives sensor data, calculates the deviation between the current position of the light beam and the predetermined position, and uses motors or piezoelectric drive devices to adjust the position or angle of the optical element in real time to compensate for the optical path deviation and ensure that the light beam is repositioned to the predetermined position;

[0175] Dynamic optimization: According to the law of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance to further improve the calibration accuracy.

[0176] Module M4: Perform system data feedback and optimization, collect and analyze data during real-time calibration, and adjust system parameters based on data analysis results.

[0177] Specifically, in the module M4:

[0178] Data acquisition: During the experiment, the beam position, light intensity, and neuron response data are continuously collected, and the data are recorded and stored using a preset high-precision data acquisition card and dedicated software;

[0179] Automated control system: Integrate automatic calibration and real-time adjustment functions to enable the system to run automatically without human intervention, design user interface, and provide experimental parameter setting, real-time monitoring and data recording functions;

[0180] Environmental compensation and maintenance: The sensor monitors environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjusts the optical path parameters for compensation; regularly conducts system self-inspections to check the working status of optical components and sensors, and performs maintenance and replacement in a timely manner;

[0181] Data analysis and storage: During the experiment, the system automatically records the data of optical path adjustment and environmental parameter changes, providing complete data support for subsequent analysis; through big data and machine learning algorithms, the optical path control parameters are continuously optimized; the collected data is analyzed through data processing software to find out the relationship between the change of beam position and neuronal response. Statistical methods and machine learning algorithms are used to analyze the factors affecting the stability of the optical path and extract parameters;

[0182] Optimization algorithm: Based on the data analysis results, the optical path control algorithm is optimized and an adaptive control algorithm is used to optimize the optical path in real time to ensure that the light beam can always be accurately positioned;

[0183] System update: According to the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data are continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.

[0184] Embodiment 3:

[0185] Embodiment 3 is a preferred example of Embodiment 1, and is used to illustrate the present invention in more detail.

[0186] The integrated control software developed using the MATLAB platform can accurately control the light intensity, pulse sequence, scanning path and other parameters of the light source. The specific lighting scheme is designed according to the experimental requirements, including the time sequence, spatial distribution and intensity change of light stimulation.

[0187] Setting process when performing control operation:

[0188] Step 1: Light source selection and modulation: Select a light source suitable for optogenetic excitation, such as a laser or high-power LED. These light sources need to operate in a specific wavelength range, usually blue light (~470nm) or red light (~630nm) to activate different types of light-sensitive proteins (such as ChR2 or Jaws); use an optical power control circuit to adjust the light intensity to achieve different stimulation intensities. Use pulse width modulation (PWM) to generate precise sequences of light pulses.

[0189] Step 2: Optical fiber and waveguide operation: Select optical fiber with high numerical aperture (NA) and low loss to ensure that the light is lost as little as possible during transmission; add microlenses or microwave guides at the end of the optical fiber to focus the light beam and accurately locate the light irradiation point. This design can greatly improve the spatial resolution of light.

[0190] Step 3: Spatial control operation: Use an electro-optical modulator (EOM) to quickly change the direction of the light beam to achieve high-resolution spatial positioning; it can also be combined with a confocal microscope to use a high numerical aperture objective to further focus the light beam and achieve single-cell resolution light irradiation.

[0191] Step 4: Time-controlled operation: Use high-frequency switching circuits and modulators (such as AOM or EOM) to achieve millisecond or even microsecond light pulse control; synchronize the illumination system with the neural recording system to accurately record the response of neurons to light stimulation. This can be achieved through hardware trigger signals or software synchronization.

[0192] The optogenetic calibration method is a key step to ensure that optogenetic technology can accurately control neuronal activity in neuroscience research. The optogenetic calibration method of the present invention mainly includes the following core links that need to be completed before the control operation: initial calibration, real-time calibration, and data feedback and optimization.

[0193] 1. Initial calibration

[0194] Initial calibration is the basic calibration performed before the system is put into use, the purpose is to ensure the basic accuracy and stability of the optical path. Initial calibration mainly includes the following steps:

[0195] Light source calibration: Select a suitable light source, such as laser or LED, and ensure that its wavelength matches the optogenetic protein used. Use a spectrum analyzer to measure the wavelength, power density and other parameters of the light source to ensure that they are within the standard range.

[0196] Optical path alignment: Use a standard optical calibration plate to project the light beam onto the calibration plate, and ensure that the light beam is accurately focused at the predetermined position on the calibration plate by adjusting optical elements such as lenses and reflectors. Observe the light spot position through a microscope to ensure that the center of the light beam is aligned with the mark on the calibration plate.

[0197] Calibration: Connect the optogenetic calibration system to the neuron recording system, and use the recording system to detect the excitation effect of the light beam at the neuron position. Adjust the optical path parameters to ensure that the light beam can accurately excite the target neurons, and record the optical path parameters at this time as a benchmark.

[0198] 2. Real-time calibration

[0199] Real-time calibration is a dynamic adjustment of the optical path during the experiment to compensate for the optical path deviation caused by environmental changes or other factors, ensuring that the light beam can always be accurately positioned. Real-time calibration mainly includes the following steps:

[0200] Real-time monitoring: Integrate high-precision sensors (such as photodetectors or position-sensitive detectors) in the optical path system to monitor the position and intensity of the light beam in real time. The monitoring system collects data on the position changes of the light beam during the experiment, and records and analyzes the data.

[0201] Error compensation: The control unit receives sensor data and calculates the deviation between the current position of the light beam and the predetermined position. Using devices such as precision motors or piezoelectric actuators, the position or angle of the optical element is adjusted in real time to compensate for the optical path deviation and ensure that the light beam is repositioned to the predetermined position.

[0202] Dynamic optimization: Feedback the real-time monitoring data to the data processing module, and optimize the optical path parameters through adaptive algorithms. According to the law of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance to further improve the calibration accuracy.

[0203] 3. Data Feedback and Optimization

[0204] Data feedback and optimization are key steps in improving the accuracy and stability of the optogenetic calibration method. The optimal control of the optical path can be achieved through continuous accumulation and analysis of data. Data feedback and optimization mainly include the following steps:

[0205] Data acquisition: During the experiment, the data such as beam position, light intensity, neuron response, etc. are continuously collected. High-precision data acquisition cards and dedicated software are used to record and store data.

[0206] Data analysis: Analyze the collected data through data processing software to find out the relationship between the change of beam position and neuronal response. Use statistical methods and machine learning algorithms to analyze the main factors affecting the stability of the optical path and extract key parameters.

[0207] Optimization algorithm: Based on the data analysis results, the optical path control algorithm is optimized to improve the response speed and accuracy of the system. Adaptive control algorithm is used to optimize the optical path in real time to ensure that the light beam can always be accurately positioned.

[0208] System update: According to the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance. Continuously accumulate experimental data, update the optimization model, and gradually improve the intelligence level of the system.

[0209] Embodiment 4:

[0210] Embodiment 4 is a preferred example of Embodiment 1, and is used to illustrate the present invention in more detail.

[0211] Specific design of the optical path control module:

[0212] Light source module: Choose a highly stable laser or LED light source to ensure the stability and uniformity of the light output. The light source should have adjustable light intensity and wavelength to meet different experimental requirements.

[0213] Lenses and reflectors: Use high-quality lenses and reflectors to ensure high transmittance and low scattering of optical components. The lens group should be designed with an adjustable focal length to adapt to different working distances and target areas.

[0214] Fiber optic transmission: Choose low-loss, high-transmission-efficiency optical fibers to ensure the quality of the light beam during long-distance transmission. The fiber optic interface should be designed as an angle-adjustable structure to flexibly position and guide the light beam.

[0215] Micro motors and adjustment devices: Use high-precision stepper motors or piezoelectric drivers to ensure the fine adjustment accuracy of lenses and reflectors. The adjustment device should have feedback control function to monitor the adjustment status in real time and make corrections.

[0216] Initial calibration:

[0217] Calibration plate preparation: Use an optical calibration plate with high-precision markings and place it on the experimental platform. The position of the calibration plate should be fixed and keep an appropriate distance from the optical path control module.

[0218] Coarse adjustment of the optical path: Start the light source and adjust the lens and reflector in the optical path control module so that the light beam is roughly aligned with the reference point on the calibration board. Through manual adjustment, the direction and position of the light beam are preliminarily corrected.

[0219] Precise beam alignment: Start the sensor and data processing module to monitor the position of the beam on the calibration board in real time. Use the micro motor to make fine adjustments so that the center of the beam completely coincides with the reference point of the calibration board. Record the initial position and parameters of the optical element as a reference for subsequent calibration.

[0220] Real-time calibration:

[0221] Sensor monitoring: Install high-precision position sensors or high-resolution cameras to monitor the exact position of the beam in the target area in real time. The sensor data is transmitted to the data processing module in real time for beam position analysis.

[0222] Data processing and feedback: The data processing module calculates the deviation of the light beam relative to the target area based on the sensor data. The adaptive algorithm optimizes the adjustment parameters to improve the system's response speed and adjustment accuracy.

[0223] Control unit adjustment: Based on the feedback from the data processing module, the control unit drives the micro motor to make real-time adjustments, ensuring that the light beam always remains in the center of the target area and compensating for the light path deviation caused by environmental changes.

[0224] System Integration and Optimization:

[0225] Automatic control system: integrated automatic calibration and real-time adjustment functions, enabling the system to run automatically without human intervention. Designed with a user-friendly interface, it provides experimental parameter setting, real-time monitoring and data recording functions.

[0226] Environmental compensation and maintenance: The sensor monitors environmental parameters in real time, such as temperature, humidity, vibration, etc., and automatically adjusts the optical path parameters for compensation. Regularly perform system self-tests to check the working status of optical components and sensors, and perform maintenance and replacement in a timely manner.

[0227] Data analysis and storage: During the experiment, the system automatically records the data of optical path adjustment and environmental parameter changes, providing complete data support for subsequent analysis. The data processing module has powerful data analysis capabilities, and continuously optimizes the optical path control parameters through big data and machine learning algorithms.

[0228] The optogenetic system based on special space research has the following characteristics:

[0229] The optogenetic device uses a post-information transmission mode, and the device directly generates data files. The multi-function card reader reads the data file to the computer host and transmits it to the ground through the space station communication network. After the experiment, the astronauts turn off the device, remove the memory card, and use the card reader to transfer the recorded data file to the ground, where the ground analysis software performs data analysis and processing. Figure 2 )

[0230] The optogenetic neural regulation system is mainly composed of a master control unit, a laser drive unit, a light source unit, a power supply unit, and a display interface. The workflow after power-on is as follows: the master control unit is notified through the display interface to control the laser light source of the optional band, and a light source with adjustable laser power and stable output is emitted. The laser light source is then collimated by the optical module, and the collimated light source is transmitted to the experimental subject through the optical fiber. At the same time, the system enters the working state through a hard trigger. Use light to activate or inhibit the activity of specific neurons, regulate and record the response of cell subpopulations, and then let the cells reproduce this response, so as to clarify the functional role of this type of cell on behavior. ( Figure 3 )

[0231] The appearance of the miniaturized radiation damage biodosimeter is a cube structure (32cm×22cm×12cm), weighing less than 6kg, including a load-bearing structure (duraluminum shell), a master control circuit board, a laser driver board, and a power board. The box body of the device adopts an integral wall plate structure, the integral wall plate is formed by mechanical milling, and the joint surface of the box body is chamfered. The end faces of the cover plates on both sides are sealed by fastening bolts; the surface treatment of the structure uses aluminum oxidation coloring.

[0232] Central Processing Unit: The core processor chip of the master control unit is Xilinx's Zynq-7000X series chip, model XC7Z020. Its advantages are that it has many memory control interfaces, can realize multi-channel input / output, embedded ARM, saves costs, and the system can operate in multiple tasks and multiple threads, greatly shortening the development cycle. It achieves unparalleled system performance, flexibility, and scalability with advantages such as low power consumption, high stability, and low cost.

[0233] Communication interface circuit: Through the display interface design, the parameters to be transmitted are sent to the master control unit through the serial port RS232, and the master control unit performs the corresponding action after the interface command. The serial port level is the RS232 standard level and is protected according to the specification.

[0234] The optogenetic neural regulation system needs to provide a 28VDC power supply, and the power supply interface is a designated model socket. Figure 6 ) shows a DC conversion circuit. In the power supply circuit, multiple groups of filters are used to suppress ripples and filter noise.

[0235] Laser drive design: Since the injection current of the laser is directly proportional to the optical power of the laser, when the optical power output by the laser is greater than a certain set value, the injection current needs to be reduced to reduce the optical power. Conversely, when the optical power is less than a certain set value, the injection current needs to be increased to increase the optical power. Based on the closed-loop negative feedback principle, a constant current drive mode is adopted, that is, the output power of the semiconductor laser is adjusted by controlling the injection current of the semiconductor laser.

[0236] ( Figure 5 )

[0237] Light source unit design: The laser is used as the emission light source. The two divergence angles of the laser are different, so consider using a cylindrical mirror group to collimate the light source. The emission light path design diagram is as follows Figure 7 As shown, collimating lenses 1 and 2 compress the light beam in the direction of the fast axis, and collimating lens 3 compresses the light beam in the direction of the slow axis to obtain parallel light emission, the purpose of which is to obtain a light source with better spot uniformity.

[0238] Grounding design: to ensure its conductive performance. When designing the ground wire, the ground wire is classified into power ground, analog ground, digital ground, power ground and chassis ground, etc. Different grounds are handled separately, and the design ensures that other grounds are insulated from the chassis ground, making the chassis a floating ground. At the same time, a double-layer board is used in the circuit board design, one of which is a large-area ground to meet the electromagnetic compatibility design requirements.

[0239] Storage unit design: To meet the system's requirements for data storage, a 128M-byte FLASH is selected as the storage unit. It communicates with the master control unit via the SPI interface. The communication rate is set to 2M / S. It is a commonly used board-level high-speed, full-duplex communication bus that can achieve 1 master and multiple slaves. The interface standard should be designed in accordance with the specifications.

[0240] Embedded Software Design

[0241] The embedded software is mainly responsible for output channel parameter settings, including waveform parameters, string parameters, sequence parameters, output mode settings and trigger association settings.

[0242] Pulse parameters

[0243] Set the waveform parameters to adjust the characteristics of the output waveform within a single cycle. The following parameters mainly determine the characteristics of the waveform within a cycle.

[0244] isBiphasic: waveform form, On-turn on biphasic pulse; Off-select monophasic pulse.

[0245] Phase1Voltage: Set the waveform voltage value (-10~10V).

[0246] Phase1Duration: Set the signal duty cycle (high level time, 0 to 3600s).

[0247] Phase Interval: Set the signal duty cycle (low level time, 0 to 3600s).

[0248] The Phase1Duration and Phase Interval parameters determine the frequency characteristics of the signal.

[0249] When isBiphasic is selected as ON, the system can output biphasic pulse waves, and the following additional parameters will appear in the menu.

[0250] Inter Phase Interval: Set the internal pulse interval of the biphasic wave (0~3600s).

[0251] Phase2Voltage: Set the second phase pulse voltage (-10~10V, accuracy 0.078V).

[0252] Phase2Duration: Set the second phase pulse time (0~3600s). Each corresponding channel can set a reference voltage, which defines the voltage between phases, pulses and pulse trains. The default is 0V.

[0253] Resting Voltage: Static reference voltage (-10~10V).

[0254] Through the above settings, we define the characteristic parameters of one cycle of the output signal, and we define this signal as a pulse signal (Pulse). Figure 8 )

[0255] Burst parameters

[0256] Use string parameters to set a single pulse signal to generate a series of regular, periodic signals, which we call waveform string signals.

[0257] Burst Duration: The duration of each set of waveform train output (0~3600s). When this parameter is set to 0, the pulse train setting is turned off.

[0258] Inter Burst Interval: Waveform burst interval (0 to 3600s)

[0259] The signal obtained after the string parameter modulation is called a waveform string signal. Fig. 9 )

[0260] Train parameters

[0261] Define sequence parameters to control the delay and duration of the waveform train signal to form the final modulated waveform signal.

[0262] Pulse Train Delay: Output delay time (0~3600s).

[0263] Pulse Train Duration: Output duration (0~3600s).

[0264] Output mode setting: By setting the above parameters, we have completed the modulation of the waveform signal. At this time, we can use the options under the Trigger Now menu to test and output the modulated signal.

[0265] Click Single Train to immediately output the modulated waveform signal in the current channel, and click Single Pulse to output a pulse signal of one cycle. Click again at any time to stop the current output task. If the Continuous parameter is set to On, the output duration (Pulse TrainDuration) in the sequence parameters (Train parameters) setting will be set to positive infinity, that is, the output signal is not controlled by the output duration and is continuously output. At this time, the output delay time (Pulse Train Delay) parameter is still valid.

[0266] Trigger association settings: In addition to single-channel output, you can also link multiple channels to up to 2 trigger input channels to achieve synchronous output or set waveform output. Use Link Trigger 1 and LinkTrigger 2 in the menu to connect the channel output to the trigger channel.

[0267] Interface design

[0268] Power supply interface: The power supply interface of the optogenetic neural regulation system is a two-core flat male socket, which needs to be powered by 28VDC. At the same time, a boat-type switch, model KCD2-23N-FA4A-BR-57, is configured at the power supply interface to control power supply / power off.

[0269] Stimulation signal interface: The optogenetic neuromodulation system is equipped with two optional light source output interfaces, which are coaxial cable female interfaces. The mechanical coupling method uses a bayonet connection and is used for 50-ohm coaxial cable connection. It provides two channels for sending stimulation signals to the experimental subjects.

[0270] Communication interface: The optogenetic neural regulation system is equipped with two USB interfaces for connecting to a computer. After the experiment is completed, the experimental data can be exported and the device parameter information can be changed online.

[0271] Trigger interface: external trigger interface, connected to electrophysiology and behavior software, to achieve closed-loop optogenetic experiments. This interface is a high-level trigger signal, and the interface is usually pulled low by default.

[0272] Reserved signal interface: The optogenetic neural regulation system has reserved two light source input interfaces in the hardware design. The interface is a coaxial cable female interface. The mechanical coupling method uses a bayonet connection for 50-ohm coaxial cable connection. It provides two channels for recording the behavior of experimental subjects after light stimulation. After the main function development is completed in the early stage, software programming will be enabled to improve the interface function.

[0273] System remote update interface: The system remote update interface is also a reserved interface for system equipment. It is designed with an RJ45 interface, supports Gigabit network transmission, and is used for system remote update.

[0274] Security Design and Analysis

[0275] (1) The optogenetic neuromodulation materials are tested on animals in accordance with GB / T-16886-10:2017 "Biological Evaluation of Medical Devices" to ensure that the materials have no irritation or allergic reaction to the experimental animals; at the same time, the formaldehyde content, banned azo dye content, pH value, odor, etc. in the materials are tested to ensure that they meet the requirements of relevant industry standards;

[0276] (2) The optogenetic neural regulation system must be tested for harmful gas spills in accordance with the “Medical Requirements and Evaluation Methods for Non-metallic Materials in Manned Vehicle Crew Cabins” and must meet relevant medical requirements;

[0277] (3) All modules of the optogenetic neural regulation system are powered by wires, and the power supply connectors are specially reinforced and insulated to avoid any impact on the safety of staff.

[0278] (4) Optimize the interface fixation method of the optogenetic neural regulation system, fully protect the wound, and formulate a response strategy to prevent the optical fiber and interface from falling off or brain damage;

[0279] (5) No sticky or falling consumables are used during the operation of the project equipment, and no waste is generated during the experiment;

[0280] (6) The equipment noise of this project is very small, and it does not contain strong vibration sources such as pumps, centrifuges, motors, fans, etc., and will not generate loud noise and mechanical vibration;

[0281] (7) The equipment is easy to operate after modification;

[0282] (8) The equipment in this project will not generate radio frequency radiation leakage and ultraviolet leakage.

[0283] Those skilled in the art know that, in addition to realizing the system and its various devices, modules, and units provided by the present invention in a purely computer-readable program code, it is entirely possible to realize the same functions in the form of logic gates, switches, application-specific integrated circuits, programmable logic controllers, and embedded microcontrollers by logically programming the method steps. Therefore, the system and its various devices, modules, and units provided by the present invention can be considered as a hardware component, and the devices, modules, and units included therein for realizing various functions can also be regarded as structures within the hardware component; the devices, modules, and units for realizing various functions can also be regarded as both software modules for realizing the method and structures within the hardware component.

[0284] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various changes or modifications within the scope of the claims, which does not affect the essence of the present invention. In the absence of conflict, the embodiments of the present application and the features in the embodiments can be combined with each other arbitrarily.

Claims

1. An optogenetic calibration method based on special space research, characterized in that: include: Step S1: clarify the goals and performance indicators of system design, select appropriate optical components according to the performance indicators, and perform layout design and parameter calculation; Step S2: Perform initial calibration, determine the position reference points of each optical element, adjust the optical path, and record the initial values ​​of the parameters; Step S3: perform real-time calibration and adjust system parameters according to environmental changes; detect the characteristics of the output light in real time and calculate the deviation between the actual value and the expected value; adjust the position or angle of the optical element through the control circuit according to the size and direction of the deviation; Step S4: Perform system data feedback and optimization, collect and analyze data during the real-time calibration process, and adjust system parameters according to the data analysis results.

2. The optogenetic calibration method based on special space research according to claim 1, characterized in that: In step S1: Specific design of the optical path control module: Light source module: Select a laser or LED light source with preset high stability to ensure the stability and uniformity of light output. The light source should have adjustable light intensity and wavelength to meet different experimental requirements. Select a light source suitable for optogenetic excitation, including lasers or preset high-power LEDs. The light source operates within a specific wavelength range to activate different types of photosensitive proteins. Use an optical power control circuit to adjust the light intensity to achieve different stimulation intensities, and use pulse width modulation to generate precise sequences of light pulses. Lenses and reflectors: Use preset high-quality lenses and reflectors to ensure preset high transmittance and preset low scattering of optical components; The lens group is designed to have an adjustable focal length to suit different working distances and target areas; Optical fiber transmission: Select optical fiber with preset low loss and preset high transmission efficiency to ensure the quality of the light beam in the preset long-distance transmission. The optical fiber interface is designed as a structure with adjustable angle, which can flexibly position and guide the light beam; Add a microlens or microwave guide at the end of the optical fiber to focus the light beam and accurately locate the light irradiation point; Micro motor and adjustment device: Use preset high-precision stepper motor or piezoelectric driver to ensure the preset micro-adjustment accuracy of lens and reflector. The adjustment device has feedback control function to monitor the adjustment status in real time and make corrections; Use electro-optic modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective to achieve single-cell resolution light illumination; Light pulse control is achieved using a preset high-frequency switching circuit and modulator; the illumination system is synchronized with the neural recording system to record the response of neurons to light stimulation, which is achieved through hardware trigger signals or software synchronization.

3. The optogenetic calibration method based on special space research according to claim 1, characterized in that: In step S2: Calibration plate preparation: Use an optical calibration plate with preset high-precision marks and place it on the experimental platform. The position of the calibration plate should be fixed and keep a preset distance from the optical path control module; Light source calibration: Use a spectrum analyzer to measure the wavelength and power density parameters of the light source to ensure that they are within the preset standard range; Coarse adjustment of the optical path: Start the light source, adjust the lens and reflector in the optical path control module to align the light beam with the reference point on the calibration plate, and preliminarily correct the direction and position of the light beam through manual adjustment; observe the position of the light spot through a microscope to ensure that the center of the light beam is aligned with the mark on the calibration plate; Calibration: Connect the optogenetic calibration system to the neuron recording system, detect the excitation effect of the light beam at the neuron position through the recording system, adjust the optical path parameters to ensure that the light beam can excite the target neurons, and record the optical path parameters at this time as a benchmark; Precise alignment of the light beam: Start the sensor and data processing module to monitor the position of the light beam on the calibration board in real time; make fine adjustments through the micro motor to make the center of the light beam completely coincide with the reference point of the calibration board; record the initial position and parameters of the optical element.

4. The optogenetic calibration method based on special space research according to claim 1, characterized in that: In step S3: Sensor monitoring: Install a preset high-precision position sensor or a preset high-resolution camera to monitor the position and intensity of the light beam in the target area in real time. The sensor data is transmitted to the data processing module in real time to perform beam position analysis; Data processing and feedback: The data processing module calculates the deviation of the light beam relative to the target area based on the sensor data, optimizes and adjusts the parameters through an adaptive algorithm, and improves the system's response speed and adjustment accuracy; Control unit adjustment: Based on the feedback from the data processing module, the control unit drives the micro-motor to make real-time adjustments to ensure that the light beam always remains in the center of the target area and compensates for the light path deviation caused by environmental changes; Error compensation: The control unit receives sensor data, calculates the deviation between the current position of the light beam and the predetermined position, and uses motors or piezoelectric drive devices to adjust the position or angle of the optical element in real time to compensate for the optical path deviation and ensure that the light beam is repositioned to the predetermined position; Dynamic optimization: According to the law of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance to further improve the calibration accuracy.

5. The optogenetic calibration method based on special space research according to claim 1, characterized in that: In step S4: Data acquisition: During the experiment, the beam position, light intensity, and neuron response data are continuously collected, and the data are recorded and stored using a preset high-precision data acquisition card and dedicated software; Automated control system: Integrate automatic calibration and real-time adjustment functions to enable the system to run automatically without human intervention, design user interface, and provide experimental parameter setting, real-time monitoring and data recording functions; Environmental compensation and maintenance: The sensor monitors environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjusts the optical path parameters for compensation; regularly conducts system self-inspections to check the working status of optical components and sensors, and performs maintenance and replacement in a timely manner; Data analysis and storage: During the experiment, the system automatically records the data of optical path adjustment and environmental parameter changes, providing complete data support for subsequent analysis; through big data and machine learning algorithms, the optical path control parameters are continuously optimized; the collected data is analyzed through data processing software to find out the relationship between the change of beam position and neuronal response; statistical methods and machine learning algorithms are used to analyze the factors affecting the stability of the optical path and extract parameters; Optimization algorithm: Based on the data analysis results, the optical path control algorithm is optimized and an adaptive control algorithm is used to optimize the optical path in real time to ensure that the light beam can always be accurately positioned; System update: According to the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data are continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.

6. An optogenetic calibration system based on special space research, characterized in that: include: Module M1: Clarify the goals and performance indicators of system design, select appropriate optical components based on the performance indicators, and perform layout design and parameter calculation; Module M2: Perform initial calibration, determine the position reference points of each optical element, adjust the optical path, and record the initial values ​​of the parameters; Module M3: performs real-time calibration and adjusts system parameters according to environmental changes; detects the characteristics of output light in real time and calculates the deviation between the actual value and the expected value; adjusts the position or angle of the optical element through the control circuit according to the size and direction of the deviation; Module M4: Perform system data feedback and optimization, collect and analyze data during real-time calibration, and adjust system parameters based on data analysis results.

7. The optogenetic calibration system based on special space research according to claim 6, characterized in that: In the module M1: Specific design of the optical path control module: Light source module: Select a laser or LED light source with preset high stability to ensure the stability and uniformity of light output. The light source should have adjustable light intensity and wavelength to meet different experimental requirements. Select a light source suitable for optogenetic excitation, including lasers or preset high-power LEDs. The light source operates within a specific wavelength range to activate different types of photosensitive proteins. Use an optical power control circuit to adjust the light intensity to achieve different stimulation intensities, and use pulse width modulation to generate precise sequences of light pulses. Lenses and reflectors: Use preset high-quality lenses and reflectors to ensure preset high transmittance and preset low scattering of optical components; The lens group is designed to have an adjustable focal length to suit different working distances and target areas; Optical fiber transmission: Select optical fiber with preset low loss and preset high transmission efficiency to ensure the quality of the light beam in the preset long-distance transmission. The optical fiber interface is designed as a structure with adjustable angle, which can flexibly position and guide the light beam; Add a microlens or microwave guide at the end of the optical fiber to focus the light beam and accurately locate the light irradiation point; Micro motor and adjustment device: Use preset high-precision stepper motor or piezoelectric driver to ensure the preset micro-adjustment accuracy of lens and reflector. The adjustment device has feedback control function to monitor the adjustment status in real time and make corrections; Use electro-optic modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective to achieve single-cell resolution light illumination; Light pulse control is achieved using a preset high-frequency switching circuit and modulator; the illumination system is synchronized with the neural recording system to record the response of neurons to light stimulation, which is achieved through hardware trigger signals or software synchronization.

8. The optogenetic calibration system based on special space research according to claim 6, characterized in that: In the module M2: Calibration plate preparation: Use an optical calibration plate with preset high-precision marks and place it on the experimental platform. The position of the calibration plate should be fixed and keep a preset distance from the optical path control module; Light source calibration: Use a spectrum analyzer to measure the wavelength and power density parameters of the light source to ensure that they are within the preset standard range; Coarse adjustment of the optical path: Start the light source, adjust the lens and reflector in the optical path control module to align the light beam with the reference point on the calibration plate, and preliminarily correct the direction and position of the light beam through manual adjustment; observe the position of the light spot through a microscope to ensure that the center of the light beam is aligned with the mark on the calibration plate; Calibration: Connect the optogenetic calibration system to the neuron recording system, detect the excitation effect of the light beam at the neuron position through the recording system, adjust the light path parameters to ensure that the light beam can excite the target neurons, and record the light path parameters at this time as a benchmark; Precise alignment of the light beam: Start the sensor and data processing module to monitor the position of the light beam on the calibration board in real time; make fine adjustments through the micro motor to make the center of the light beam completely coincide with the reference point of the calibration board; record the initial position and parameters of the optical element.

9. The optogenetic calibration system based on special space research according to claim 6, characterized in that: In the module M3: Sensor monitoring: Install a preset high-precision position sensor or a preset high-resolution camera to monitor the position and intensity of the light beam in the target area in real time. The sensor data is transmitted to the data processing module in real time to perform beam position analysis; Data processing and feedback: The data processing module calculates the deviation of the light beam relative to the target area based on the sensor data, optimizes and adjusts the parameters through adaptive algorithms, and improves the response speed and adjustment accuracy of the system; Control unit adjustment: Based on the feedback from the data processing module, the control unit drives the micro-motor to make real-time adjustments to ensure that the light beam always remains in the center of the target area and compensates for the light path deviation caused by environmental changes; Error compensation: The control unit receives sensor data, calculates the deviation between the current position of the light beam and the predetermined position, and uses motors or piezoelectric drive devices to adjust the position or angle of the optical element in real time to compensate for the optical path deviation and ensure that the light beam is repositioned to the predetermined position; Dynamic optimization: According to the law of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance to further improve the calibration accuracy.

10. The optogenetic calibration system based on special space research according to claim 6, characterized in that: In the module M4: Data acquisition: During the experiment, the beam position, light intensity, and neuron response data are continuously collected, and the data are recorded and stored using a preset high-precision data acquisition card and dedicated software; Automated control system: Integrate automatic calibration and real-time adjustment functions to enable the system to run automatically without human intervention, design user interface, and provide experimental parameter setting, real-time monitoring and data recording functions; Environmental compensation and maintenance: The sensor monitors environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjusts the optical path parameters for compensation; regularly conducts system self-inspections to check the working status of optical components and sensors, and performs maintenance and replacement in a timely manner; Data analysis and storage: During the experiment, the system automatically records the data of optical path adjustment and environmental parameter changes, providing complete data support for subsequent analysis; through big data and machine learning algorithms, the optical path control parameters are continuously optimized; the collected data is analyzed through data processing software to find out the relationship between the change of beam position and neuronal response; statistical methods and machine learning algorithms are used to analyze the factors affecting the stability of the optical path and extract parameters; Optimization algorithm: Based on the data analysis results, the optical path control algorithm is optimized and an adaptive control algorithm is used to optimize the optical path in real time to ensure that the light beam can always be accurately positioned; System update: According to the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data are continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.

Citation Information

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