Optogenetic calibration method and system based on special space research
By using an optical path control module and a real-time calibration algorithm, the limitations of optogenetics in spatial resolution and environmental adaptability are solved, enabling precise control of specific neurons or neural networks, reducing system costs, and making it suitable for a wide range of neuroscience research.
Patent Information
- Application Number
- CN202411800650.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-09
- Publication Date
- 2025-10-21
- Estimated Expiration
- 2044-12-09
AI Technical Summary
Existing optogenetic technologies have limitations in spatial resolution and accuracy, making it difficult to achieve precise control of specific neurons or neural networks. They also lack real-time calibration and environmental adaptability, and are complex and costly to operate.
By designing an optical path control module, including a highly stable light source, precision lenses and mirrors, real-time sensor monitoring and data processing, and combining it with an adaptive algorithm for real-time beam calibration and environmental compensation, the precise positioning and stability of the beam can be achieved.
It significantly improves the spatial resolution and accuracy of optogenetic regulation, ensures precise beam projection in specific areas, reduces human error, adapts to complex environmental changes, lowers system costs, and is suitable for a wide range of neuroscience research.
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Figure CN119721155B_ABST
Abstract
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, a method that uses optical technology to precisely control neuronal activity, has been widely used in neuroscience research. However, existing optogenetic techniques have limitations in spatial resolution and accuracy, making it difficult to precisely control specific neurons or neural networks. In particular, in complex neural networks, existing methods struggle to accurately locate and control neuronal activity in specific regions. Therefore, there is an urgent need for optogenetic calibration methods based on specialized spatial studies to improve the precision and spatial resolution of optogenetic control.
[0003] The shortcomings of the existing technology 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] Imperfect real-time calibration function: The real-time calibration and automatic calibration functions of existing technologies 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 efficient experimental operation difficult.
[0008] High system cost: Some high-precision systems (such as holography) are expensive and have complex equipment, making them unsuitable for widespread application in conventional laboratories.
[0009] The academic paper "High-resolution optogenetic control of cortical circuits using holography" (Nature Methods, 2015) describes a method for high-resolution optogenetic control using holography. By generating complex light patterns, it achieves precise control of cortical circuits. However, the holographic system is complex and expensive, making it difficult to widely use in routine laboratories. It also has poor adaptability to environmental changes during experiments and lacks real-time dynamic adjustment and automatic calibration capabilities.
[0010] Optogenetics: Precision Tools for Probing Neural Circuits (Neuron, 2011) This review article introduces the basic principles of optogenetics and its applications in neuroscience research, discussing the advantages and disadvantages of various optogenetic tools. However, due to its nature as a review article, it lacks detailed information on optical path manipulation and calibration techniques. It primarily focuses on the biological applications of optogenetic tools and does not address the precise control and calibration of optical systems. Summary of the Invention
[0011] In view of the defects in the prior art, the purpose 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 is provided, comprising:
[0013] Step S1: Clarify the system design goals and performance indicators, select appropriate optical components based on 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 to 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; and 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 based on 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 light-sensitive 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 light pulse sequences.
[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 with a structure that can adjust the focal length to adapt to different working distances and target areas;
[0022] Fiber optic transmission: Select optical fibers with preset low loss and preset high transmission efficiency to ensure the quality of the light beam during preset long-distance transmission. The fiber optic interface is designed with an angle-adjustable structure to 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-optical modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective lens 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 markings and place it on the experimental platform. The calibration plate should be fixed in position and maintain a preset distance from the optical path control module. Light source calibration: Use an optical 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 optical path adjustment: Start the light source and adjust the lens and reflector in the optical path control module so that the light beam is aligned with the reference point on the calibration plate. Through manual adjustment, preliminarily correct the direction and position of the light beam; 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. Use the recording system to detect the excitation effect of the light beam at the neuron location, 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 plate in real time; use the micro motor to make fine adjustments so that the center of the light beam completely coincides with the reference point of the calibration plate; 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 for 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 sensor data, optimizes and adjusts parameters through adaptive algorithms, 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 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 actuators 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: Based on the patterns of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance and further improve calibration accuracy.
[0038] Preferably, in step S4:
[0039] Data acquisition: During the experiment, the beam position, light intensity, and neuronal response data are continuously collected and 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 operate automatically without human intervention. Design a user interface to provide experimental parameter setting, real-time monitoring and data recording functions;
[0041] Environmental compensation and maintenance: Sensors monitor environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjust optical path parameters for compensation; perform regular system self-tests to check the working status of optical components and sensors, and perform maintenance and replacement in a timely manner;
[0042] Data analysis and storage: During the experiment, the system automatically records data on optical path adjustments and environmental parameter changes, providing complete data support for subsequent analysis. Using big data and machine learning algorithms, the optical path control parameters are continuously optimized. Data processing software analyzes the collected data to identify the relationship between changes in beam position and neuronal responses. Statistical methods and machine learning algorithms are used to analyze factors affecting optical path stability 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: Based on the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data is 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: Define the system design objectives and performance indicators, select appropriate optical components based on the performance indicators, and perform layout design and parameter calculations;
[0047] Module M2: Perform initial calibration, determine the position reference points of each optical component, adjust the optical path, and record the initial values of the parameters;
[0048] Module M3: Performs real-time calibration and adjusts system parameters based on environmental changes. It detects the characteristics of the output light in real time and calculates the deviation between the actual value and the expected value. Based on the size and direction of the deviation, it adjusts the position or angle of the optical element through the control circuit.
[0049] Module M4: Perform system data feedback and optimization, collect and analyze data during the real-time calibration process, and adjust system parameters based on the 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 light-sensitive 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 light pulse sequences.
[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 with a structure that can adjust the focal length to adapt to different working distances and target areas;
[0055] Fiber optic transmission: Select optical fibers with preset low loss and preset high transmission efficiency to ensure the quality of the light beam during preset long-distance transmission. The fiber optic interface is designed with an angle-adjustable structure to 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-optical modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective lens 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 markings and place it on the experimental platform. The calibration plate should be fixed in position and maintain a preset distance from the optical path control module. Light source calibration: Use an optical 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 optical path adjustment: Start the light source and adjust the lens and reflector in the optical path control module so that the light beam is aligned with the reference point on the calibration plate. Through manual adjustment, preliminarily correct the direction and position of the light beam; 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. Use the recording system to detect the excitation effect of the light beam at the neuron location, 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 plate in real time; use the micro motor to make fine adjustments so that the center of the light beam completely coincides with the reference point of the calibration plate; 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 for 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 sensor data, optimizes and adjusts parameters through adaptive algorithms, 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 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 actuators 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: Based on the patterns of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance and further improve calibration accuracy.
[0071] Preferably, in the module M4:
[0072] Data acquisition: During the experiment, the beam position, light intensity, and neuronal response data are continuously collected and 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 operate automatically without human intervention. Design a user interface to provide experimental parameter setting, real-time monitoring and data recording functions;
[0074] Environmental compensation and maintenance: Sensors monitor environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjust optical path parameters for compensation; perform regular system self-tests to check the working status of optical components and sensors, and perform maintenance and replacement in a timely manner;
[0075] Data analysis and storage: During the experiment, the system automatically records data on optical path adjustments and environmental parameter changes, providing complete data support for subsequent analysis. Using big data and machine learning algorithms, the optical path control parameters are continuously optimized. Data processing software analyzes the collected data to identify the relationship between changes in beam position and neuronal responses. Statistical methods and machine learning algorithms are used to analyze factors affecting optical path stability 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: Based on the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data is 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. This invention improves the spatial resolution and precision of optogenetic regulation. By precisely adjusting the optical components in the optical path control module, this invention achieves precise projection of a light beam within a specific spatial region. By combining initial calibration with real-time calibration, the light beam can be precisely aligned with the target neuron or neural network region, significantly improving the spatial resolution of optogenetics and ensuring the accuracy and effectiveness of regulation.
[0080] 2. The present invention enables real-time dynamic adjustment of the optical path. This invention incorporates a real-time monitoring and feedback control mechanism. A sensor monitors the beam position in real time, a data processing module performs real-time analysis based on the monitoring data, and a control unit dynamically adjusts the optical path control module. This real-time calibration mechanism effectively compensates for optical path deviations caused by environmental changes (such as temperature fluctuations and mechanical vibrations), ensuring the stability and accuracy of the beam position during the experiment.
[0081] 3. This invention improves the reliability and stability of optogenetic experiments. Through an automated and intelligent calibration and adjustment process, this invention reduces human intervention and operational errors, significantly improving the reliability and stability of experiments. The system automatically identifies and corrects optical path deviations, ensuring that the 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 present invention's high-precision optical path control capability enables precise control of specific neurons or neural network regions within complex neural networks. By regulating the activity of neurons in specific spatial regions and studying their functional changes under different states, this technology provides powerful technical support for functional research on complex neural networks.
[0083] 5. This invention promotes the research and treatment of neurological diseases. This invention's breakthrough in optogenetic calibration and regulation technology provides a new approach for studying the pathogenic mechanisms and treating neurological diseases. By regulating the activity of neurons in specific regions, it is possible to study the pathological processes of neurological diseases (such as Parkinson's disease and Alzheimer's disease), explore new therapeutic targets and solutions, and promote the development of neurological disease treatment technologies.
[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, and neurological disease mechanism research. 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 a more powerful technical tool for neuroscience research and promotes the in-depth development of neuronal function and network mechanism research. In particular, the high-precision control capability of the present invention will play an important role in studying the pathogenic mechanisms of neurological diseases and developing treatment plans.
[0085] 7. This invention provides an integrated optogenetic calibration and control solution, easily adaptable to existing neuroscience experimental equipment. The system's modular design allows for flexible adaptation to diverse optogenetic experimental requirements, offering broad application prospects and scientific research value.
[0086] 8. This invention optimizes optical system design and performance. By optimizing the optical system design and calibration algorithm, the present invention effectively improves optical system performance. High-precision optical path control and real-time calibration mechanisms ensure that the optical system consistently maintains optimal performance under varying experimental conditions, enhancing the overall effectiveness of optogenetics.
[0087] 9. This invention promotes innovation in scientific research and clinical applications. The technical benefits of this invention are not limited to basic research but also have broad clinical potential. By improving the precision and stability of optogenetics, this invention provides a powerful tool for neuroscience research and clinical applications, promoting innovation and development of optogenetics in both scientific research and clinical practice.
[0088] 10. This invention provides efficient data analysis and processing. The data processing module possesses powerful data analysis capabilities, capable of processing sensor data in real time, rapidly calculating beam deviation, and making corresponding adjustments. Through big data analysis and machine learning algorithms, the system continuously optimizes control parameters, improving experimental accuracy and stability. The system automatically records optical path adjustments and environmental parameter changes during the experiment, providing comprehensive 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 enables real-time dynamic calibration: The system utilizes real-time sensor monitoring and feedback control from a data processing module, enabling real-time compensation for optical path deviations to ensure the beam remains within the target area. The present invention also enables real-time automatic calibration and optimization: The automatic calibration function, combined with an adaptive algorithm, enables real-time adjustments based on changes in the experimental environment, maintaining 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 is user-friendly and easy to operate in real time: its user-friendly interface and high degree of automation reduce the complexity and errors of manual operations, thereby improving experimental efficiency. The present invention is cost-effective: compared to high-cost equipment such as holographic systems, the system design of the present invention is more economical and suitable for widespread application in conventional laboratories. BRIEF DESCRIPTION OF THE DRAWINGS
[0093] Other features, objects and advantages of the present invention will become more apparent upon reading the detailed description of non-limiting embodiments with reference to the following drawings:
[0094] Figure 1 A roadmap for calibrating optogenetic systems based on specialized space research;
[0095] Figure 2 It is a system pattern diagram under special space;
[0096] Figure 3 Design a schematic diagram for the overall framework 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] Figure 9 Schematic diagram for setting waveform signal. DETAILED DESCRIPTION
[0103] The present invention will be described in detail below with reference to specific embodiments. The following examples 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 skilled in the art, several changes and improvements can be made without departing from the scope of the present invention. These all fall within the scope of protection of the present invention.
[0104] Example 1:
[0105] The purpose of this invention is to provide an optogenetic calibration method based on special space research. By optimizing the optical path design and calibration algorithm, it can achieve precise regulation of neuronal activity in a specific spatial area and improve the application effect of optogenetic technology in neuroscience research.
[0106] By implementing the optogenetic calibration method of this invention, the spatial resolution and control accuracy of optogenetic experiments can be significantly improved, enabling precise control of specific neurons or neural network regions, and promoting the in-depth development of neuroscience research. Furthermore, the method exhibits excellent stability and reliability, providing strong technical support for the study of the pathogenic mechanisms of neurological diseases and the development of treatment options.
[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 and wavelength selectivity; select appropriate optical components (such as lenses, reflectors, polarizers) based on 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, as well as 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 specifically 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; using internal photodetectors and other devices in the system to detect the characteristics of the output light (such as intensity and phase) in real time; calculating the deviation between the actual value and the expected value through software algorithms; and adjusting the position or angle of the optical element through the control circuit according to the size and direction of the deviation.
[0113] Throughout the experiment, the system's efficient operation relies entirely on system data feedback and optimization. This includes: collecting and analyzing data from the real-time calibration process to evaluate the system's stability and accuracy; adjusting system parameters based on data analysis results to improve performance; identifying potential problems in the system and taking measures to prevent them; and providing an intuitive operating interface to facilitate user monitoring of system status and 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 data analysis may reveal areas that require further optimization, leading to re-initial calibration and other steps.
[0115] According to the present invention, an optogenetic calibration method based on special space research is provided, such as Figure 1 Shown, including:
[0116] Step S1: Clarify the system design goals and performance indicators, select appropriate optical components based on 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 light-sensitive 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 light pulse sequences.
[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 with a structure that can adjust the focal length to adapt to different working distances and target areas;
[0122] Fiber optic transmission: Select optical fibers with preset low loss and preset high transmission efficiency to ensure the quality of the light beam during preset long-distance transmission. The fiber optic interface is designed with an angle-adjustable structure to 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-optical modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective lens 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 markings and place it on the experimental platform. The calibration plate should be fixed in position and maintain a preset distance from the optical path control module. Light source calibration: Use an optical 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 optical path adjustment: Start the light source and adjust the lens and reflector in the optical path control module so that the light beam is aligned with the reference point on the calibration plate. Through manual adjustment, preliminarily correct the direction and position of the light beam; 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. Use the recording system to detect the excitation effect of the light beam at the neuron location, 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 plate in real time; use the micro motor to make fine adjustments so that the center of the light beam completely coincides with the reference point of the calibration plate; record the initial position and parameters of the optical element.
[0133] Step S3: Perform real-time calibration to 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; and 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 for 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 sensor data, optimizes and adjusts parameters through adaptive algorithms, 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 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 actuators 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: Based on the patterns of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance and further improve 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 based on the data analysis results.
[0141] Specifically, in step S4:
[0142] Data acquisition: During the experiment, the beam position, light intensity, and neuronal response data are continuously collected and 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 operate automatically without human intervention. Design a user interface to provide experimental parameter setting, real-time monitoring and data recording functions;
[0144] Environmental compensation and maintenance: Sensors monitor environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjust optical path parameters for compensation; perform regular system self-tests to check the working status of optical components and sensors, and perform maintenance and replacement in a timely manner;
[0145] Data analysis and storage: During the experiment, the system automatically records data on optical path adjustments and environmental parameter changes, providing complete data support for subsequent analysis. Using big data and machine learning algorithms, the optical path control parameters are continuously optimized. Data processing software analyzes the collected data to identify the relationship between changes in beam position and neuronal responses. Statistical methods and machine learning algorithms are used to analyze factors affecting optical path stability 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: Based on the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data is continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.
[0148] Example 2:
[0149] Example 2 is a preferred example of Example 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 Shown, including:
[0152] Module M1: Define the system design objectives and performance indicators, select appropriate optical components based on the performance indicators, and perform layout design and parameter calculations;
[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 light-sensitive 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 light pulse sequences.
[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 with a structure that can adjust the focal length to adapt to different working distances and target areas;
[0158] Fiber optic transmission: Select optical fibers with preset low loss and preset high transmission efficiency to ensure the quality of the light beam during preset long-distance transmission. The fiber optic interface is designed with an angle-adjustable structure to 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-optical modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective lens 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 component, 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 markings and place it on the experimental platform. The calibration plate should be fixed in position and maintain a preset distance from the optical path control module. Light source calibration: Use an optical 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 optical path adjustment: Start the light source and adjust the lens and reflector in the optical path control module so that the light beam is aligned with the reference point on the calibration plate. Through manual adjustment, preliminarily correct the direction and position of the light beam; 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. Use the recording system to detect the excitation effect of the light beam at the neuron location, 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 plate in real time; use the micro motor to make fine adjustments so that the center of the light beam completely coincides with the reference point of the calibration plate; record the initial position and parameters of the optical element.
[0169] Module M3: Performs real-time calibration and adjusts system parameters based on environmental changes. It detects the characteristics of the output light in real time and calculates the deviation between the actual value and the expected value. Based on the size and direction of the deviation, it adjusts the position or angle of the optical element through the control circuit.
[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 for 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 sensor data, optimizes and adjusts parameters through adaptive algorithms, 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 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 actuators 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: Based on the patterns of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance and further improve calibration accuracy.
[0176] Module M4: Perform system data feedback and optimization, collect and analyze data during the real-time calibration process, and adjust system parameters based on the data analysis results.
[0177] Specifically, in the module M4:
[0178] Data acquisition: During the experiment, the beam position, light intensity, and neuronal response data are continuously collected and 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 operate automatically without human intervention. Design a user interface to provide experimental parameter setting, real-time monitoring and data recording functions;
[0180] Environmental compensation and maintenance: Sensors monitor environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjust optical path parameters for compensation; perform regular system self-tests to check the working status of optical components and sensors, and perform maintenance and replacement in a timely manner;
[0181] Data analysis and storage: During the experiment, the system automatically records data on optical path adjustments and environmental parameter changes, providing complete data support for subsequent analysis. Using big data and machine learning algorithms, the optical path control parameters are continuously optimized. Data processing software analyzes the collected data to identify the relationship between changes in beam position and neuronal responses. Statistical methods and machine learning algorithms are used to analyze factors affecting optical path stability 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: Based on the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data is continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.
[0184] Example 3:
[0185] Example 3 is a preferred example of Example 1 and is used to illustrate the present invention in more detail.
[0186] Develop integrated control software using the MATLAB platform to precisely control light source parameters such as light intensity, pulse sequence, and scanning path. Design a specific lighting plan based on experimental requirements, including the time sequence, spatial distribution, and intensity variation of light stimulation.
[0187] Setting process for 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 must operate within a specific wavelength range, typically blue light (~470 nm) or red light (~630 nm), to activate different types of light-sensitive proteins (such as ChR2 or Jaws). Light intensity is adjusted using an optical power control circuit to achieve varying stimulation intensities. Pulse-width modulation (PWM) is used to generate precise sequences of light pulses.
[0189] Step 2: Fiber and waveguide manipulation: Select high numerical aperture (NA) and low-loss optical fibers to minimize light loss during transmission. Add microlenses or microwave guides to the ends of the fibers to focus the light beam and precisely locate the light impingement point. This design can significantly 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 lens to further focus the light beam and achieve single-cell resolution light illumination.
[0191] Step 4: Temporal Control: Use high-frequency switching circuits and modulators (such as AOMs or EOMs) to achieve millisecond or even microsecond control of light pulses. Synchronize the illumination system with the neural recording system to accurately record the neuronal response to light stimulation. This can be achieved through hardware trigger signals or software synchronization.
[0192] Optogenetic calibration is a key step in ensuring that optogenetics can precisely control neuronal activity in neuroscience research. The optogenetic calibration method of the present invention primarily includes the following core steps that must be completed prior to control: initial calibration, real-time calibration, and data feedback and optimization.
[0193] 1. Initial calibration
[0194] Initial calibration is a basic calibration performed before the system is put into use. Its 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 an appropriate light source, such as a laser or LED, and ensure its wavelength matches the optogenetic protein being used. Measure the wavelength, power density, and other parameters of the light source using a spectrum analyzer to ensure they are within the standard range.
[0196] Optical alignment: Use a standard optical calibration target to project a light beam onto the target. Adjust optical components such as lenses and reflectors to ensure the beam is precisely focused at the desired location on the target. Observe the beam spot through a microscope to ensure the center of the beam is aligned with the mark on the target.
[0197] Calibration: Connect the optogenetic calibration system to the neuronal recording system, and use the recording system to detect the excitation effect of the light beam on the neuronal location. Adjust the optical path parameters to ensure that the beam can accurately stimulate 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 optical path deviations caused by environmental changes or other factors, ensuring that the 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) into the optical path system to monitor the position and intensity of the beam in real time. The monitoring system collects data on the position changes of the beam during the experiment, records it, and analyzes it.
[0201] Error compensation: The control unit receives sensor data and calculates the deviation between the beam's current position and the desired position. Using devices such as precision motors or piezoelectric actuators, the position or angle of optical components is adjusted in real time to compensate for optical path deviations and ensure the beam is repositioned to the desired location.
[0202] Dynamic Optimization: Real-time monitoring data is fed back to the data processing module, which uses adaptive algorithms to optimize optical path parameters. Based on the patterns of beam deviation during the experiment, a predictive model is established to enable advance optical path adjustments, further improving calibration accuracy.
[0203] 3. Data Feedback and Optimization
[0204] Data feedback and optimization are key steps in improving system accuracy and stability in optogenetic calibration methods. By continuously accumulating and analyzing data, optimal control of the optical path is achieved. Data feedback and optimization mainly include the following steps:
[0205] Data Acquisition: During the experiment, data such as beam position, light intensity, and neuronal responses are continuously collected. High-precision data acquisition cards and dedicated software are used to record and store data.
[0206] Data Analysis: Data processing software analyzes the collected data to identify the relationship between changes in beam position and neuronal responses. Statistical methods and machine learning algorithms are used to analyze the main factors affecting optical path stability and extract key parameters.
[0207] Optimization Algorithm: Based on data analysis results, the optical path control algorithm is optimized to improve the system's response speed and accuracy. Adaptive control algorithms are used to optimize the optical path in real time to ensure that the beam is always accurately positioned.
[0208] System Update: Based on the results of the optimization algorithm, the optogenetic calibration system hardware and software will be upgraded to improve system performance. Continuously accumulate experimental data, update the optimization model, and gradually enhance the system's intelligence level.
[0209] Example 4:
[0210] Example 4 is a preferred example of Example 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 stable and uniform light output. The light source should have adjustable light intensity and wavelength to suit different experimental needs.
[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 accommodate different working distances and target areas.
[0214] Fiber optic transmission: Choose low-loss, high-transmission-efficiency optical fibers to ensure beam quality over long distances. Fiber optic interfaces should be designed with adjustable angles for flexible positioning and beam guidance.
[0215] Micro-motors and adjustment devices: Use high-precision stepper motors or piezoelectric actuators to ensure the fine adjustment accuracy of lenses and mirrors. The adjustment device should have feedback control capabilities 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 calibration plate should be fixed and maintain an appropriate distance from the optical path control module.
[0218] Coarse optical path adjustment: 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 plate. Through manual adjustment, the direction and position of the light beam are preliminarily corrected.
[0219] Precise beam alignment: Sensors and data processing modules are activated to monitor the beam's position on the calibration plate in real time. Micromotors are used to finely adjust the beam's center so that it perfectly aligns with the calibration plate's reference point. The initial position and parameters of the optical components are recorded and used as a benchmark for subsequent calibration.
[0220] Real-time calibration:
[0221] Sensor monitoring: Install a high-precision position sensor or high-resolution camera to monitor the precise 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 sensor data. It optimizes and adjusts parameters through adaptive algorithms to improve the system's response speed and adjustment accuracy.
[0223] Control unit adjustment: Based on 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 optical path deviations caused by environmental changes.
[0224] System integration and optimization:
[0225] Automated control system: Integrated automatic calibration and real-time adjustment functions enable the system to operate automatically without human intervention. A user-friendly interface provides experimental parameter setting, real-time monitoring, and data logging functions.
[0226] Environmental compensation and maintenance: Sensors monitor environmental parameters such as temperature, humidity, and vibration in real time and automatically adjust optical path parameters to compensate. Regular system self-tests are performed to check the working status of optical components and sensors, allowing for timely maintenance and replacement.
[0227] Data Analysis and Storage: During the experiment, the system automatically records data on optical path adjustments and environmental parameter changes, providing comprehensive data support for subsequent analysis. The data processing module possesses powerful data analysis capabilities, continuously optimizing 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 optogenetics device uses a post-information transmission mode, with the device generating data files directly. The data files are read by a multi-function card reader and transferred to a host computer, which is then transmitted to the ground via the space station communication network. After the experiment is completed, the astronauts shut down the device, remove the memory card, and use the card reader to transfer the recorded data files to the ground, where they are analyzed and processed by ground-based analysis software. Figure 2 )
[0230] The optogenetic neuromodulation 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 emits a light source with adjustable laser power and stable output. 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 miniaturized radiation damage biodosimeter is a cubic structure (32cm × 22cm × 12cm) weighing less than 6kg. It comprises a load-bearing structure (duraluminum housing), a master control circuit board, a laser driver board, and a power supply board. The enclosure utilizes a monolithic wall panel structure, machine-cut to form the panels, with chamfered joints. The two side covers are sealed with bolts, and the surface treatment is aluminum oxide coloring.
[0232] Central Processing Unit: The core processor chip used for the master control unit is the Xilinx Zynq-7000X series chip, model XC7Z020. Its advantages include numerous memory control interfaces, enabling multi-channel input / output, an embedded ARM processor, cost savings, and system multitasking and multi-threading capabilities, significantly shortening development cycles. Its low power consumption, high stability, and low cost deliver unparalleled system performance, flexibility, and scalability.
[0233] Communication interface circuit: Through the display interface design, the parameters to be transmitted are sent to the master control unit via the RS232 serial port. The master control unit executes 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 requires a 28VDC power supply, and the power supply interface is a designated socket. Figure 6 ) shows a DC conversion circuit. The power supply circuit uses multiple filters to suppress ripple and filter noise.
[0235] Laser drive design: Since the laser's injection current is directly proportional to the laser's optical power, when the laser's output optical power exceeds a certain set value, the injection current needs to be reduced, thereby reducing the optical power. Conversely, when the optical power is less than a certain set value, the injection current needs to be increased, thereby increasing the optical power. Based on the closed-loop negative feedback principle, a constant current drive method 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 it is considered to use a cylindrical lens group to collimate the light source. The emission light path design diagram is as follows Figure 7 Collimating lenses 1 and 2 compress the light beam in the fast axis direction, while collimating lens 3 compresses the light beam in the slow axis direction to obtain parallel light output, so as to obtain a light source with better spot uniformity.
[0238] Grounding design: To ensure conductivity, ground lines are categorized into power ground, analog ground, digital ground, power ground, and chassis ground. Different grounds are handled separately, and the design ensures insulation between other grounds and the chassis ground, ensuring the chassis is floating. A double-layer circuit board is used, with one layer serving as a large ground surface, to meet electromagnetic compatibility requirements.
[0239] Storage unit design: To meet the system's data storage requirements, a 128M-byte FLASH memory was selected as the storage unit. It communicates with the master control unit via an SPI interface, with a communication rate set to 2 Mbps. This is a commonly used board-level high-speed, full-duplex communication bus that supports one master and multiple slaves. Interface standards should be adhered to during design.
[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 type, 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 wave, and the following additional parameters will appear in the menu.
[0250] Inter Phase Interval: Set the internal pulse interval of the biphasic wave (0 to 3600s).
[0251] Phase2Voltage: Set the second phase pulse voltage (-10~10V, accuracy 0.078V).
[0252] Phase2Duration: Set the second phase pulse time (0 to 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 waveform train output (0 to 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 string parameter modulation is called waveform string signal. Figure 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 Settings: By setting the above parameters, we have completed the modulation of the waveform signal. Now you can use the options under the Trigger Now menu to test and output the modulated signal.
[0265] Clicking Single Train immediately outputs the modulated waveform signal on the current channel, while clicking Single Pulse outputs a single-cycle pulse signal. Click again at any time to stop the current output task. If the Continuous parameter is set to On, the Pulse Train Duration in the Train parameters will be set to positive infinity, meaning the output signal continues to output regardless of the output duration. The Pulse Train Delay parameter remains in effect.
[0266] Trigger Link Settings: In addition to single-channel output, you can also link multiple channels to up to two trigger input channels for synchronized output or programmed waveform output. Use Link Trigger 1 and Link Trigger 2 in the menu to link the channel output to the trigger channel.
[0267] Interface design
[0268] Power Supply: The optogenetic neural modulation system uses a two-pin flat male connector and requires 28VDC. A rocker switch, model KCD2-23N-FA4A-BR-57, is located at the power supply port to control power on and off.
[0269] Stimulation signal interface: The optogenetic neuromodulation system is equipped with two optional light source output interfaces. These interfaces are coaxial cable female interfaces with a bayonet connection for mechanical coupling. They are used for 50-ohm coaxial cable connection and provide two channels for sending stimulation signals to experimental subjects.
[0270] Communication interface: The optogenetic neuromodulation system is equipped with two USB ports for connecting to a computer. After the experiment is completed, the experimental data can be exported and the device parameters can be modified online.
[0271] Trigger port: This port is used for external triggering, connecting to electrophysiology and behavioral software to implement closed-loop optogenetic experiments. This port is a high-level trigger signal and is normally pulled low by default.
[0272] Reserved signal interface: The optogenetic neuromodulation system's hardware design includes two reserved light source input interfaces. These interfaces are female coaxial cable connectors with a bayonet-type mechanical coupling for connection to 50-ohm coaxial cables. These interfaces provide two channels for recording subject behavior after light stimulation. Software programming will be implemented to enhance these interfaces once the initial core functionality is developed.
[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) Materials for optogenetic neuromodulation are tested on animals in accordance with GB / T-16886-10:2017 “Biological Evaluation of Medical Devices” to ensure that the materials do not cause irritation or allergic reactions in 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 hazardous gas leakage in accordance with the “Medical Requirements and Evaluation Methods for Non-metallic Materials in Manned Spacecraft 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 neuromodulation system, fully protect the wound, and develop a response strategy to prevent the optical fiber and interface from falling off or causing brain damage;
[0279] (5) No sticky or drop-off 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 low, 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 will appreciate that, in addition to implementing the system and its various devices, modules, and units provided by the present invention in purely computer-readable program code, it is entirely possible to implement the same functions of the system and its various devices, modules, and units provided by the present invention 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 a hardware component, and the devices, modules, and units included therein for implementing various functions can also be considered as structures within the hardware component; the devices, modules, and units for implementing various functions can also be considered as both software modules implementing the method and structures within the hardware component.
[0284] The above describes specific embodiments of the present invention. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art may make various changes or modifications within the scope of the claims, which do not affect the essence of the present invention. The embodiments of this application and the features in the embodiments may be combined with each other in any manner unless there is a conflict.
Claims
1. An optogenetic calibration method based on special space research, characterized in that: include: Step S1: Clarify the system design goals and performance indicators, select appropriate optical components based on 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 to 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; and 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 from the real-time calibration process, and adjust system parameters based on the data analysis results; 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 light-sensitive 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 light pulse sequences. Lenses and reflectors: Use preset high-quality lenses and reflectors to ensure the 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; Fiber optic transmission: Select optical fibers with preset low loss and preset high transmission efficiency to ensure the quality of the light beam during preset long-distance transmission. The fiber optic interface is designed with an angle-adjustable structure to 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 a preset high-precision stepper motor or piezoelectric driver 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; Use electro-optical modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective lens 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.
2. 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 markings and place it on the experimental platform. The calibration plate should be fixed in position and maintain a preset distance from the optical path control module. Light source calibration: Use an optical 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 optical path adjustment: Start the light source and adjust the lens and reflector in the optical path control module so that the light beam is aligned with the reference point on the calibration plate. Through manual adjustment, preliminarily correct the direction and position of the light beam; 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 neuromodulation system to the neuron recording system. Use the recording system to detect the excitation effect of the light beam at the neuron location, 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 plate in real time; use the micro motor to make fine adjustments so that the center of the light beam completely coincides with the reference point of the calibration plate; record the initial position and parameters of the optical element.
3. 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 for 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 sensor data, optimizes and adjusts parameters through adaptive algorithms, 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 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 actuators 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: Based on the patterns of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance and further improve calibration accuracy.
4. 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 neuronal response data are continuously collected and 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 operate automatically without human intervention. Design a user interface to provide experimental parameter setting, real-time monitoring and data recording functions; Environmental compensation and maintenance: Sensors monitor environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjust optical path parameters for compensation; perform regular system self-tests to check the working status of optical components and sensors, and perform maintenance and replacement in a timely manner; Data Analysis and Storage: During the experiment, the system automatically records data on optical path adjustments and environmental parameter changes, providing complete data support for subsequent analysis. Using big data and machine learning algorithms, the optical path control parameters are continuously optimized. Data processing software analyzes the collected data to identify the relationship between changes in beam position and neuronal responses. Statistical methods and machine learning algorithms are used to analyze factors affecting optical path stability 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: Based on the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data is continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.
5. An optogenetic calibration system based on special space research, characterized in that: include: Module M1: Define the system design objectives and performance indicators, select appropriate optical components based on the performance indicators, and perform layout design and parameter calculations; Module M2: Perform initial calibration, determine the position reference points of each optical component, adjust the optical path, and record the initial values of the parameters; Module M3: Performs real-time calibration and adjusts system parameters based on environmental changes. It detects the characteristics of the output light in real time and calculates the deviation between the actual value and the expected value. Based on the size and direction of the deviation, it adjusts the position or angle of the optical element through the control circuit. 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; 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 light-sensitive 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 light pulse sequences. Lenses and reflectors: Use preset high-quality lenses and reflectors to ensure the 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; Fiber optic transmission: Select optical fibers with preset low loss and preset high transmission efficiency to ensure the quality of the light beam during preset long-distance transmission. The fiber optic interface is designed with an angle-adjustable structure to 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 a preset high-precision stepper motor or piezoelectric driver 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; Use electro-optical modulators to achieve high-resolution spatial positioning; or combine with confocal microscopy to further focus the beam using a preset high numerical aperture objective lens 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.
6. The optogenetic calibration system based on special space research according to claim 5, characterized in that: In the module M2: Calibration plate preparation: Use an optical calibration plate with preset high-precision markings and place it on the experimental platform. The calibration plate should be fixed in position and maintain a preset distance from the optical path control module. Light source calibration: Use an optical 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 optical path adjustment: Start the light source and adjust the lens and reflector in the optical path control module so that the light beam is aligned with the reference point on the calibration plate. Through manual adjustment, preliminarily correct the direction and position of the light beam; 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 neuromodulation system to the neuron recording system. Use the recording system to detect the excitation effect of the light beam at the neuron location, 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 plate in real time; use the micro motor to make fine adjustments so that the center of the light beam completely coincides with the reference point of the calibration plate; record the initial position and parameters of the optical element.
7. The optogenetic calibration system based on special space research according to claim 5, 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 for 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 sensor data, optimizes and adjusts parameters through adaptive algorithms, 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 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 actuators 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: Based on the patterns of beam deviation during the experiment, a prediction model is established to adjust the optical path in advance and further improve calibration accuracy.
8. The optogenetic calibration system based on special space research according to claim 5, characterized in that: In the module M4: Data acquisition: During the experiment, the beam position, light intensity, and neuronal response data are continuously collected and 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 operate automatically without human intervention. Design a user interface to provide experimental parameter setting, real-time monitoring and data recording functions; Environmental compensation and maintenance: Sensors monitor environmental parameters in real time, including temperature, humidity, and vibration, and automatically adjust optical path parameters for compensation; perform regular system self-tests to check the working status of optical components and sensors, and perform maintenance and replacement in a timely manner; Data Analysis and Storage: During the experiment, the system automatically records data on optical path adjustments and environmental parameter changes, providing complete data support for subsequent analysis. Using big data and machine learning algorithms, the optical path control parameters are continuously optimized. Data processing software analyzes the collected data to identify the relationship between changes in beam position and neuronal responses. Statistical methods and machine learning algorithms are used to analyze factors affecting optical path stability 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: Based on the results of the optimization algorithm, the hardware and software of the optogenetic calibration system are upgraded to improve system performance; experimental data is continuously accumulated, the optimization model is updated, and the intelligence level of the system is gradually improved.
Citation Information
Patent Citations
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