Multicolor fiber optic stimulation and recording coupled drive system and fiber optic stimulation and recording system

Abstract

This invention discloses a multi-color fiber optic stimulation and recording coupled driving system and a fiber optic stimulation and recording system, belonging to the field of neural signal recording technology. The driving system is used in a fiber optic stimulation and recording system including a light source and a digital camera. The system includes a controller and a driving module. The driving module includes high / low power driving circuits, which drive the corresponding light sources as a stimulation light source emitting stimulation light and an excitation light source emitting excitation light, respectively. The controller controls the low-power driving circuit and the digital camera, ensuring that the excitation light source is activated earlier than the digital camera. Furthermore, the controller controls the driving module so that the stimulation light is at the same frequency or an integer division of the excitation light, and that the two are in different phases, achieving time-division multiplexing of the stimulation and excitation light. This invention achieves physical isolation between optogenetic stimulation light and multiple fluorescent excitation light within the same fiber, introducing an advance amount to the activation of the excitation light to stabilize the light source and ensure the accuracy and scientific validity of the recorded signal.

Description

Technical Field

[0001] This utility model relates to the field of neural signal recording technology, and more specifically, to a multi-color fiber optic stimulation and recording combined drive system and a fiber optic stimulation and recording system. Background Technology

[0002] Cutting-edge life science research frequently uses fluorescence signals to record physiological processes. For example, neural activity can be reflected by the fluorescence intensity of fluorescent proteins sensitive to cell membrane potential, calcium ion concentration, or neurotransmitter concentration. These fluorescence signals are characterized by wavelength variations depending on the specific fluorescent protein, rapid transmission, easy bleaching, and non-uniform spatial distribution. Fiber photometry is one of the commonly used methods for recording such signals. It guides excitation light into the sample via optical fiber and measures the fluorescence intensity returning to the device. The synchronization of the light emission and fluorescence acquisition processes is crucial. Optogenetics refers to various methods that influence biological processes through light stimulation and artificially modified photosensitive proteins. For example, photosensitive cation channels can be used to artificially activate neurons and are an important experimental tool for studying biological processes.

[0003] However, existing fiber optic recording equipment has the following drawbacks: 1. It does not support simultaneous optogenetic stimulation and fluorescence recording through a single optical fiber. Therefore, optogenetic operations must be performed through another optical fiber, which means that the scope of optogenetic operations and the scope of fluorescence signal recording cannot strictly overlap. For a few devices that integrate optogenetic and fluorescence signal recording, the high-intensity optogenetic light and fluorescence excitation light may be emitted simultaneously and ultimately separated by lock-in amplifier demodulation rather than physical isolation. This may cause the optogenetic light to mix into the recorded fluorescence signal, affecting the recording quality.

[0004] 2. Generally, it only supports simultaneous sampling of one to three fluorescence bands, and cannot cover the wide spectrum of various fluorescent protein probes.

[0005] 3. Many fiber optic photometric recording devices that use camera sampling have low upper limits for sampling rates, sometimes even fixed at tens of hertz. However, some fluorescence signals, such as those reflecting cell membrane potential, may vary on a millisecond scale, thus requiring controllers that support high-speed sampling. For controllers using photomultiplier tubes (PMTs) and supporting high sampling rates, the start-up of the light source and the exposure of the acquisition device are often completely synchronized. This cannot guarantee the scientific accuracy of the recorded signal, as LED and laser light sources commonly used in fiber optic photometry require a settling time from startup to peak power.

[0006] 4. Existing equipment has a limited number and functionality of electrical interfaces, while experiments involving multiple devices often require perfect time alignment between them. The current common method is to record the start time of each device and then perform software alignment during subsequent data processing. However, this method cannot eliminate the effects of timing errors between devices and inconsistent sampling phases between devices. Utility Model Content

[0007] To address the problems in existing fiber optic recording devices where the range of optogenetic operations and the range of fluorescence signal recording cannot strictly overlap during optogenetic stimulation and fluorescence recording, or where optogenetic light is mixed with the recorded fluorescence signal, affecting recording quality, this invention proposes a multicolor fiber optic stimulation and recording combined drive system to overcome these problems.

[0008] In one aspect of this invention, a multi-color fiber optic stimulation and recording coupled driving system is proposed for use in a fiber optic stimulation and recording system. The fiber optic stimulation and recording system includes a light source and a digital camera. The light source includes multiple light sources emitting light of different wavelengths, and the light of different wavelengths is transmitted through the same optical fiber. The system is characterized by including a controller and a driving module. The driving module includes multiple driving modules, each driving module driving one of the multiple light sources. Each driving module includes a high-power driving circuit and a low-power driving circuit. The high-power driving circuit drives the light source as a stimulation light source emitting stimulation light, and the low-power driving circuit drives the light source as an excitation light source emitting excitation light. The controller is configured to control the driving module and the digital camera.

[0009] In the above aspects, as a more specific embodiment, both the high-power drive circuit and the low-power drive circuit include a power supply, a current-limiting resistor, and a field-effect transistor (FET). The power supply is connected to a light source via the current-limiting resistor, the light source is connected to the drain of the FET, the source of the FET is grounded, and the gate of the FET is connected to a controller. The FET is a metal-oxide-semiconductor field-effect transistor (MOSFET).

[0010] In the above aspects, as a more specific solution, the resistance value of the current-limiting resistor in the high-power drive circuit is smaller than the resistance value of the current-limiting resistor in the low-power drive circuit.

[0011] As a further improvement, an adjustable resistor is connected in series in both the high-power drive circuit and the low-power drive circuit.

[0012] In a further embodiment of the above, the multicolor fiber optic stimulation and recording combined drive system further includes an input component and an output component, wherein the controller receives signals from an external device via the input component and sends signals to an external device via the output component, wherein the external device includes a laser light source.

[0013] In addition to the above, as a further embodiment, the multicolor fiber optic stimulation and recording combined drive system also includes a host computer that communicates with the controller to send instructions to the controller and receive feedback from the controller.

[0014] In the above aspects, as a more specific embodiment, the controller is configured to control the drive module and the digital camera via digital signals, such that the excitation light source is turned on earlier than the digital camera, and the controller is configured to control the drive module via digital or analog signals, such that the frequency at which the stimulation light source turns on is the same frequency or an integer division of the frequency at which the excitation light source turns on, and the phases at which the stimulation light source and the excitation light source turn on are different.

[0015] In the above aspects, as a more specific embodiment, the light source is an LED light source, the digital signal is a square wave sequence, and the analog signal is an analog signal of at least 8 bits.

[0016] In another aspect of this invention, an optical fiber stimulation and recording system is proposed, which includes the multicolor optical fiber stimulation and recording combined drive system described above.

[0017] The beneficial effects of this utility model are as follows: 1. According to the multi-color fiber optic stimulation and recording drive system of this utility model, the optogenetic stimulation light and the fluorescence recording excitation light can be emitted from the same light source, introduced into the same optical fiber, and finally act on the same area of ​​the sample. Combined with high-precision timing control, the range of optogenetic operation and the range of fluorescence signal recording can be strictly overlapped. Furthermore, the stimulation light used for optogenetics and the fluorescence excitation light are physically isolated by time-division multiplexing, which helps to improve the recording quality.

[0018] 2. This utility model uses a controller to precisely control the drive module and digital camera, with a dead time as short as 10 microseconds between two exposures. It can support high-speed sampling of multiple fluorescence bands and simultaneously cover a wide spectrum of various fluorescent protein probes.

[0019] 3. The controller of this utility model can adjust the phase of the excitation light source to turn on in advance, leaving enough time for stabilization, so as to ensure that the power of the light source has reached a stable peak when the camera is exposed, thereby ensuring the accuracy and scientific nature of the recorded signal.

[0020] 4. The controller of this utility model controls external devices through input / output components. It can achieve unified scheduling of internal and external light sources, digital cameras and other external devices at the hardware circuit level, thereby realizing functions such as sampling sequence synchronization, sampling frame synchronization, stimulus sequence synchronization, stimulus pulse synchronization, sampling frame synchronous output, and sampling channel synchronous output. This allows the phase of the recorded signals from different devices to be aligned on a 10-microsecond scale when using fiber optic recording equipment and other external devices simultaneously, enhancing the scientific nature of the recorded signals.

[0021] 5. This utility model uses a power supply, resistor, and metal-oxide-semiconductor field-effect transistor (MOSFET) driving structure to enable the controller to quickly switch the light source through the gate of the MOSFET, minimizing circuit delay. While supporting flexible programmable stimulation sequences, it can also meet the stringent timing accuracy requirements of optogenetic stimulation and fluorescence recording.

[0022] 6. The present invention employs an adjustable resistor in the driving structure, enabling the driving system to achieve stepless fine adjustment of the output power, adapting to different sample sensitivity requirements, and mitigating the quenching of fluorescence signals during long-term recording on the hourly scale. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of an embodiment of the multicolor fiber optic stimulation and recording combined drive system of this utility model.

[0024] Figure 2 This is a flowchart of the controller operation in the multicolor fiber optic stimulation and recording combined drive system of this utility model. Detailed Implementation

[0025] like Figure 1As shown, the fiber optic stimulation and recording system of this invention includes a light source and a digital camera. In one embodiment, a multi-color fiber optic stimulation and recording combined driving system is provided, including a controller and a driving module. The light source includes multiple light sources emitting light of different wavelengths in multiple colors, and the light of different wavelengths is transmitted through the same optical fiber. The driving module includes multiple driving modules, each driving module for driving one of the multiple light sources. Each driving module includes a high-power driving circuit and a low-power driving circuit. The high-power driving circuit drives the light source as a stimulation light source emitting stimulation light, and the low-power driving circuit drives the light source as an excitation light source emitting excitation light. The controller is configured to control the low-power driving circuit and the digital camera, such that the excitation light source is turned on earlier than the digital camera. The controller is also configured to control the driving module, such that the frequency of the stimulation light is the same as or an integer division of the frequency of the excitation light, and the phase of the stimulation light is different from the phase of the excitation light. Thus, the controller can indirectly control the turning on and off of the light source in a time-division multiplexing manner. The number of driving modules is set according to the number of light sources, generally 1-5 channels. Each light source is electrically connected to a high-power (e.g., 5 W) drive circuit and a low-power (e.g., 0.5 W) drive circuit, suitable for both optogenetic stimulation and fluorescence signal recording functions, respectively. The light source is, for example, an LED light source.

[0026] According to the multi-color fiber optic stimulation and recording combined driving system of this invention, the optogenetic stimulation light and the fluorescence recording excitation light can be emitted from the same light source, guided into the same optical fiber, and ultimately act on the same area of ​​the sample. Combined with high-precision timing control, the range of optogenetic operation and the range of fluorescence signal recording can be strictly overlapped. Furthermore, the time-division multiplexing method physically isolates the stimulation light used for optogenetics from the fluorescence excitation light, which helps to improve the recording quality. By adjusting the phase of the excitation light source, the light source is turned on in advance, allowing sufficient stabilization time to ensure that the light source power has reached a stable peak when the camera is exposed, thereby ensuring the accuracy and scientific nature of the recorded signal.

[0027] In one embodiment of this invention, both the high-power driving circuit and the low-power driving circuit include a power supply, a resistor, and a field-effect transistor (FET). The power supply is, for example, a 5V power supply suitable for a single LED, connected to the light source via the resistor. The light source is connected to the drain of the FET, the source of the FET is grounded, and the gate of the FET is connected to a controller. The controller uses the gate of the FET to achieve rapid switching of the light source, meeting the stringent timing accuracy requirements of optogenetic stimulation and fluorescence recording. Specifically, the resistance value of the current-limiting resistor in the high-power driving circuit is smaller than that in the low-power driving circuit. This allows a larger current to pass through the high-power driving circuit, ultimately achieving higher output power to meet the high-power light source requirements of optogenetic stimulation, while limiting the current in the low-power driving circuit, ultimately achieving lower output power to meet the low-power light source requirements of fluorescence signal recording.

[0028] As a further improvement, an adjustable resistor is connected in series in both the high-power drive circuit and the low-power drive circuit, enabling the drive system to achieve stepless fine-tuning of the output power, adapt to different sample sensitivity requirements, and mitigate the quenching of fluorescence signals under prolonged illumination.

[0029] In one embodiment of this invention, the multicolor fiber optic stimulation and recording combined drive system further includes an input / output component. The controller receives signals from or sends signals to an external device via this component. The external device is, for example, an external laser light source, which the controller can control in the same way. The excitation light emitted by the external light source can also be introduced into the optical path of the fiber optic stimulation and recording system and replace the function of the internal light source during optogenetic stimulation. The controller controls the external device at the hardware circuit level through the input / output component, enabling unified scheduling of internal and external light sources, digital cameras, and external devices. This allows for functions such as sampling sequence synchronization, sampling frame synchronization, stimulation sequence synchronization, stimulation pulse synchronization, sampling frame synchronous output, and sampling channel synchronous output, ensuring that the recorded signals are aligned on a microsecond scale when using fiber optic recording equipment and other devices simultaneously.

[0030] In one embodiment of this invention, for optogenetic stimulation, the controller controls the drive module and the external device using digital or analog signals, such as square wave sequences. The time interval of each pulse in the square wave sequence and the waveform of the analog signal can both be controlled by the controller, with a time resolution of at least 10 μs. The analog signal is at least 8 bits. The controller's cycle rate is higher than 100 kHz. When optogenetic stimulation pulses and fluorescence sampling require timing coordination of the same frequency but different phases, the controller can precisely control the interval between the two, thereby ensuring physical isolation. Furthermore, the fluorescence signal or neural activity of biological samples may change rapidly; a time resolution of 10 μs can meet the recording requirements of such high-speed processes, avoiding signal distortion or omissions due to insufficient time accuracy. The 8-bit analog signal can generate... =256 different level values. Specifically, if the analog signal corresponds to a voltage output of 0-5V when controlling the power of the light source, the 8-bit analog signal can achieve an adjustment accuracy of about 0.02V (5V / 255), thus enabling continuous and smooth changes in the brightness of the light source or the intensity of the stimulus.

[0031] In one embodiment of this utility model, the multicolor fiber optic stimulation and recording combined driving system of this utility model further includes a host computer, which communicates with the controller and is used to send instructions to the controller and receive feedback from the controller. The instructions include task start / stop instructions and parameter configuration instructions, and the feedback includes time information feedback, task progress feedback and running status feedback.

[0032] The host computer controls the start and stop of the digital camera via a controller, and configures the camera's parameters, including exposure time and exposure period. The controller is configured to control the digital camera via digital signals such as square wave sequences, and to control the camera's exposure time and exposure period via the pulse width and frequency of the digital signals, wherein the time resolution of the control is at least 10 μs. For example, for fluorescence signal recording, the controller can drive the module and the digital camera to operate via two square wave sequence commands on each fluorescence channel.

[0033] like Figure 2 As shown, this is the operation flow of the controller of this utility model. The controller starts after being powered on and executes the pre-set operation flow in a loop.

[0034] First, the controller handles communication with the host computer and input / output components, and updates and feeds back various variables accordingly based on the progress of the sampling and stimulation tasks, including whether the exposure and stimulation tasks need to be performed, exposure time, stimulation time, and operating status.

[0035] Then, based on the instructions from the host computer and the historical execution status, the controller calculates the current fluorescence sampling channel and the amount of sampling already completed, and decides whether to continue the sampling function. If not, it disconnects the drive circuit and stops the digital camera's exposure. If so, the controller iterates one step within the available excitation light band, and based on the operating status of the corresponding drive circuit and the digital camera, and the target working time, decides whether to start the drive circuit and begin the digital camera's exposure; the controller also decides whether to terminate the already started exposure program accordingly.

[0036] Next, based on the instructions from the host computer and the historical execution status, the controller calculates the completion rate of the stimulation task and decides whether to execute optogenetic stimulation or external device synchronization. If not, the corresponding drive circuit is disconnected. If yes, the controller iterates through each available stimulation channel, calculates when the next stimulus should be given, and decides whether to start outputting the stimulation waveform accordingly. If yes, the controller records the current time for later feedback to the host computer and simultaneously starts the stimulation program for the corresponding channel. The controller also calculates the duration of the current stimulus on this channel and decides whether to terminate the already started stimulation program.

[0037] After completing the stimulation channel traversal, the controller's operation flow enters the next loop. This operation flow iterates through the sampling channels between loops, and under the instructions of the host computer, it can physically isolate sampling and stimulation according to the principle of time-division multiplexing, thus ensuring high-quality multicolor fluorescence recording while achieving optogenetic stimulation.

[0038] The above description is merely a selection of preferred embodiments of this disclosure and an explanation of the technical principles employed. Those skilled in the art should understand that the scope of the invention involved in the embodiments of this disclosure is not limited to technical solutions formed by specific combinations of the above-described technical features, but should also cover other technical solutions formed by arbitrary combinations of the above-described technical features or their equivalents without departing from the above-described inventive concept. For example, technical solutions formed by substituting the above-described features with (but not limited to) technical features with similar functions disclosed in the embodiments of this disclosure.

Claims

1. A multi-color fiber optic stimulation and recording coupled driving system, used in a fiber optic stimulation and recording system, the fiber optic stimulation and recording system comprising a light source and a digital camera, the light source comprising multiple light sources emitting light of different wavelengths, the light of different wavelengths being transmitted through the same optical fiber; characterized in that, Includes a controller and a drive module, wherein, The driving module includes multiple driving modules, each driving module being used to drive one of the multiple light sources. Each driving module includes a high-power driving circuit and a low-power driving circuit. The high-power driving circuit is used to drive the light source as a stimulation light source that emits stimulation light, and the low-power driving circuit is used to drive the light source as an excitation light source that emits excitation light. The controller is configured to control the drive module and the digital camera.

2. The multicolor fiber optic stimulation and recording coupled driving system according to claim 1, characterized in that, Both the high-power drive circuit and the low-power drive circuit include a power supply, a current-limiting resistor, and a field-effect transistor (FET). The power supply is connected to the light source via the current-limiting resistor, the light source is connected to the drain of the FET, the source of the FET is grounded, and the gate of the FET is connected to the controller.

3. The multicolor fiber optic stimulation and recording coupled driving system according to claim 2, characterized in that, The resistance value of the current-limiting resistor in a high-power drive circuit is less than that in a low-power drive circuit.

4. The multicolor fiber optic stimulation and recording coupled driving system according to claim 2, characterized in that, An adjustable resistor is also connected in series in both the high-power drive circuit and the low-power drive circuit.

5. The multicolor fiber optic stimulation and recording coupled driving system according to claim 1, characterized in that, It also includes an input component and an output component, wherein the controller receives signals from an external device via the input component and sends signals to an external device via the output component, wherein the external device includes a laser light source.

6. The multicolor fiber optic stimulation and recording coupled driving system according to claim 1, characterized in that, It also includes a host computer that communicates with the controller to send instructions to the controller and receive feedback from the controller.

7. The multicolor fiber optic stimulation and recording coupled driving system according to claim 1, characterized in that, The controller is configured to control the drive module and the digital camera via digital signals, such that the excitation light source is turned on earlier than the digital camera. The controller is also configured to control the drive module via digital or analog signals, such that the frequency at which the stimulus light source turns on is the same frequency or an integer division of the frequency at which the excitation light source turns on, and that the phases at which the stimulus light source and the excitation light source turn on are different.

8. The multicolor fiber optic stimulation and recording coupled driving system according to claim 7, characterized in that, The light source is an LED light source, the digital signal is a square wave sequence, and the analog signal is an analog signal of at least 8 bits.

9. A fiber optic stimulation and recording system, characterized in that, It includes a multicolor fiber optic stimulation and recording coupled drive system according to any one of claims 1 to 8.

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