CN103417205B - Neural information detecting system - Google Patents

Abstract

The invention discloses a nerve information detection system, comprising: an electrophysiological module, including N-channels of electrophysiological signal channels; a data acquisition module, connected with the electrophysiological signal module, and used for detecting N-channels of electrophysiological signals in the electrophysiological module The electrophysiological data collected by the channel is sampled and converted from analog to digital; the analog switch array includes N analog switch channels, and each analog switch channel in the N analog switch channels includes: an electrophysiological signal switch whose front end is connected to a The microelectrode is connected to one of the N electrophysiological signal channels at its rear end; the central processing module is connected to the analog switch array and the data acquisition module, and is used to control each of the N analog switch channels. Closing and opening of electrophysiological signal switches in switch channels. The nerve information detection system of the present invention solves the problem that the nerve information detection instrument with a fixed number of channels cannot be compatible with microelectrode arrays with various numbers of channels.

Description

A neural information detection system

technical field

The invention relates to the field of signal detection in the electronic industry, in particular to a neural information detection system.

Background technique

The pulse discharge of nerve cells and the release of neurotransmitters (chemical substances) are a fast and transient process. Nerve information detection captures the process of pulse discharge and neurotransmitter release synchronously at high speed and in real time, so as to study the pathogenesis of certain diseases It has important scientific significance and clinical value in terms of mechanism, nerve signal transmission, and drug response. At the same time, the response of organisms to external events and every process of information processing requires the joint action of many nerve cells. Therefore, it is a convenient method in neuroscience research to simultaneously detect the electrophysiological activities of multiple brain nerve cells. , Normal information acquisition method.

Since various microelectrode arrays with different channel numbers are often used when detecting electrophysiological information of multiple nerve cells, FIG. 1 is a schematic structural diagram of a nerve information detection system in the prior art. As shown in Figure 1, the nerve information detection system includes an electrophysiological module, a data acquisition module, a central processing module, a USB module, a cache, and the like. However, the number of information channels from the electrophysiological module to the microelectrode array is certain, so it can only be connected to the microelectrode array with a specific channel number, and is not compatible with the microelectrode array with other channel numbers, so that the instrument cannot be fully utilized. Use the potential to meet the needs of clinical and scientific research. Therefore, it is of great significance to design neural information detection instruments compatible with microelectrode arrays with various channel numbers to reduce the cost of neuroscience research and improve scientific research efficiency.

Contents of the invention

(1) Technical problems to be solved

In order to solve one or more of the above problems, the present invention provides a nerve information detection system to solve the problem that a nerve information detection instrument with a fixed number of channels cannot match a microelectrode array with various numbers of channels.

(2) Technical solution

The invention discloses a nerve information detection system, comprising: an electrophysiological module, including N-channels of electrophysiological signal channels; a data acquisition module, connected with the electrophysiological signal module, and used for detecting N-channels of electrophysiological signals in the electrophysiological module The electrophysiological data collected by the channel is sampled and converted from analog to digital; the analog switch array includes N analog switch channels, and each analog switch channel in the N analog switch channels includes: an electrophysiological signal switch whose front end is connected to a The microelectrode is connected to one of the N electrophysiological signal channels at its rear end; the central processing module is connected to the analog switch array and the data acquisition module, and is used to control each of the N analog switch channels. Closing and opening of electrophysiological signal switches in switch channels.

(3) Beneficial effects

It can be seen from the above technical solutions that the neural information detection system of the present invention has the following beneficial effects:

(1) In the neural information detection system of the present invention, the analog switch array is internally divided into four groups, and each group has 18 interfaces connected to the microelectrode array, and each group of analog switch arrays can be individually connected to the microelectrode array, so that the system It can be configured as 16, 32, 48 and 64 channels respectively, and can be used for different microelectrode arrays to ensure that the instrument is compatible with microelectrode arrays with various channel numbers;

(2) In the neural information detection system of the present invention, the electrophysiological module, the electrochemical module and the data acquisition module are included at the same time, and the analog switch array can be configured to connect each electrode to the instrument, so that the electrode array can be used to measure the electrophysiological Signal and electrochemical signal, to ensure that the instrument can capture pulse discharge and neurotransmitter release process synchronously at high speed and in real time.

Description of drawings

FIG. 1 is a schematic structural diagram of a neural information detection system in the prior art;

2 is a schematic structural diagram of a neural information detection system according to an embodiment of the present invention;

3 is a schematic structural diagram of an analog switch channel in the analog switch array of the neural information detection system according to an embodiment of the present invention;

4 is a circuit diagram of an electrophysiological module in a neural information detection system according to an embodiment of the present invention;

Fig. 5 is the circuit diagram of the electrochemical module in the neural information detection system of the embodiment of the present invention;

Fig. 6 is a schematic structural diagram of a data acquisition module in a neural information detection system according to an embodiment of the present invention.

Detailed ways

In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be described in further detail below in conjunction with specific embodiments and with reference to the accompanying drawings.

It should be noted that, in the drawings or descriptions of the specification, similar or identical parts all use the same figure numbers. And in the drawings, the embodiments are marked for simplification or convenience. Furthermore, elements or implementations not shown or described in the drawings are forms known to those of ordinary skill in the art. Additionally, while illustrations of parameters comprising particular values may be provided herein, the parameters need not be exactly equal to the corresponding values, but rather may approximate the corresponding values within acceptable error margins or design constraints.

In an exemplary embodiment of the present invention, a neural information detection system is proposed. FIG. 2 is a schematic structural diagram of a neural information detection system according to an embodiment of the present invention. As shown in Figure 2, the neural information detection system of this embodiment includes: a central processing module, an analog switch array, an electrical stimulation module, an electrophysiological module, an electrochemical module, a data acquisition module, a cache module, a USB transmission module and a host computer module. Each component will be described in detail below. Each hollow arrow with a slash in the figure represents a bus, and the number below the slash represents the number of data lines contained in the bus.

The central processing module is used to control the state of each analog switch channel in the analog switch array, and at the same time receive the data collected by the data acquisition module, and encode the data and transmit it to the buffer module through the USB interface.

The upper computer module belongs to the upper computer software, which realizes the configuration of the analog switch array, data acquisition module, electrical stimulation module, etc. through the central processing module; it can realize synchronous marking of the electrophysiological signals and electrochemical signals stored in the cache module , synchronous storage; at the same time, the measured signal can be selectively stored to reduce the amount of data storage.

The analog switch array, whose control terminal is connected to the central processing module, includes 64 analog switch channels, for each analog switch channel, its front end is connected to a microelectrode in the microelectrode array, and its rear end is connected to the following circuit One of: an electrophysiological signal channel of the electrophysiological module, an electrochemical signal channel of the electrochemical module, an electrical stimulation channel of the electrical stimulation module, or ground, the analog switch array is used to configure the way the microelectrode is connected to the instrument . Here, 64 channels are just a common setting method, and those skilled in the art can set the number of analog switch channels included in the analog switch array according to their needs.

For some of the analog switch channels, it may include four switches, and their connections with electrodes and circuits are shown in FIG. 3 . By setting the analog switch through the central processing module, each electrode can be selected for different purposes, so that it can be connected to the electrophysiological signal channel, electrochemical signal channel, electrical stimulation circuit, reference or ground respectively, so that it can be used according to the specific According to the experimental requirements, the arrangement of the microelectrode array can be changed as one likes. In particular, it cooperates with the electrophysiological module, electrochemical module and data acquisition module to realize the synchronous detection of electrochemical signals and electrophysiological signals with configurable detection sites. Controlling the state of each switch through the central processing module can also realize the interconnection between the circuits, especially when the electrical stimulation is performed, the electrophysiological signal channel and the electrochemical signal channel are connected to the ground, which can avoid the electrophysiological signal channel and electrochemical amplification. The circuit enters a saturated state under the influence of electrical stimulation, thereby avoiding mutual interference between circuits when electrodes are multiplexed, and greatly improving the performance of the system.

Here, for ease of description, an analog switch branch includes an electrophysiological signal switch, an electrochemical signal switch, an electrical stimulation signal switch, and a reference/ground switch. However, those skilled in the art should understand that for another part of the analog switch channel, it may also include three switches, such as an electrophysiological signal switch, an electrochemical signal switch, and an electrical stimulation signal switch, etc.; it may also include two switches, such as An electrophysiological signal switch and an electrical stimulation signal switch, or an electrophysiological signal switch and a reference/ground, etc.; of course, only point physiological signal switches may be included.

At the same time, the analog switch array is internally divided into four groups, and each group contains 16 analog switch channels. There are 16 analog switch channels in each group, together with 1 reference interface and 1 ground interface, a total of 18 interfaces are connected to the microelectrode array, as shown in FIG. 2 . Each group of analog switches can be individually connected to the microelectrode array, so that the system can be configured as 16, 32, 48 and 64 channels for different microelectrode arrays. In this embodiment, by simulating the switch array, the system can be configured as 16, 32, 48, and 64 channels for use, and at the same time, the use of each electrode can be configured, so that the electrode array can be used to measure electrophysiological signals at the same time And electrochemical signals, therefore, it can be realized that the system can measure electrophysiological signals and electrochemical signals at the same time, and solve the problem that the nerve information detection instrument with a fixed channel number cannot capture the pulse discharge and neurotransmitter release process simultaneously at high speed and in real time, and the fixed channel The problem that the number of nerve information detection instruments cannot be compatible with microelectrode arrays with various channel numbers.

As shown in Figure 2, for each analog switch in the analog switch array, it may also include: a preamplifier circuit, located at the front end of the analog switch, used to achieve impedance matching with the microelectrode array, to prevent the signal from being transmitted during transmission. Excessive attenuation. The pre-amplification circuit is realized by an emitter follower, and those skilled in the art should understand the design of the relevant emitter follower, and details will not be repeated here.

The electrophysiological module, whose control end is connected with the central processing module, and whose input end is connected with the analog switch array, is used for amplifying and filtering the electrophysiological signal to improve the signal-to-noise ratio. The electrophysiological module includes 64 electrophysiological signal channels. The block diagram of each channel is shown in Figure 4. It consists of three parts. According to the flow direction of the signal, it is a differential amplifier circuit, a low-pass filter (LFP) and a high-pass filter ( HFP). The differential amplification circuit differentially amplifies the input electrophysiological signal and the reference signal (REF), and passes the signal to the next stage while suppressing common-mode noise. The resistor R in the figure determines the magnification of the circuit. When R is set to 5.1K, the magnification of the circuit is 10 times. The instrumentation amplifier AD620R is the core device of this circuit. Its input impedance is 10GΩ. When the magnification is 10, the total The mode rejection ratio is 110db, and the input noise is Various parameters can meet the detection needs of weak neuroelectric signals. The low-pass filter (LFP) realizes the second-stage amplification of the signal (magnification by 5 times), and at the same time filters out high-frequency noise in the circuit. The high-pass filter (HFP) realizes the third-stage amplification of the signal (magnification by 4 times), and at the same time filters out the low-frequency noise in the circuit, and passes the signal to the data acquisition module. The entire electrophysiological signal channel can amplify microvolt-level signals by 1000 times, making them into millivolt-level signals that can be easily collected by the data acquisition module, and suppress various noises in the circuit, greatly improving the signal-to-noise ratio. It should be noted that the 64 electrophysiological signal channels are also a common setting, which does not constitute a limitation to the present invention. In addition, the control function of the central processing module on the electrophysiological module is mainly reflected in the size of the adjustable resistance in the control circuit, thereby controlling the amplification factor and passband of the circuit.

The electrochemical module, whose control terminal is connected to the central processing module, and whose input terminal (i.e., the working electrode W) is connected to the analog switch array, is used to generate the constant potential required for electrochemical detection, and convert the electrochemical current signal into a voltage signal and amplify the signal. The electrochemical module includes 4 electrochemical signal channels. The block diagram of each electrochemical signal channel is shown in Figure 5. It is an electrochemical signal detection circuit with a three-electrode system, and its three electrodes are reference electrodes (R) , the counter electrode (C) and the working electrode (W). The circuit consists of three parts, a potentiostat, a current-voltage conversion circuit and a signal amplification circuit. The potentiostat part generates the voltage waveform required for electrochemical detection through the DAC chip MAX504, and this voltage is connected to the nerve cells or tissues to be measured through an operational amplifier U7A of AD8606, the reference electrode (R), and the counter electrode (C) , and form a current loop with the working electrode (W); the current-voltage conversion circuit converts the current signal detected by the working electrode (W) into a voltage signal through another operational amplifier U7B of AD8606 and a 100M sampling resistor R16, and the 1000P in the circuit The capacitor C40 is used to offset the parasitic capacitance in the circuit and improve the response speed of the system; the signal amplifier circuit differentially amplifies the input voltage signal through the instrument operational amplifier AD620R, and sends the signal to the data acquisition module, and the resistor R8 in the circuit determines the amplification Multiple, when R is set to 510 ohms, the magnification of the circuit is 100 times. The core circuit of the electrochemical signal detection circuit is a current-voltage conversion circuit. Since the detected electrochemical signal is at the pA level, the requirements for the required operational amplifier are high, so it is necessary to choose a chip with low bias current and low current noise density when selecting the type. The operational amplifier selected in this embodiment is AD8606, which has a bias current of only 0.2pA and a current noise density of only The FET operational amplifier with low noise and high open-loop gain can meet the needs of this instrument. It should be noted that the 4-way electrochemical signal channel is also a common setting, which does not constitute a limitation to the present invention. In addition, the control function of the central processing module on the electrochemical module is mainly reflected in the control of the electrochemical scanning method and the size of the scanning voltage: the scanning method can be electrochemical CV method, electrochemical IT method or fast CV method, etc.; the scanning voltage setting range Between -4V and 4V.

In addition, in order to realize the electrical stimulation function, the nerve information detection system of this embodiment further includes: an electrical stimulation module, used to realize the function of stimulating nerve cells and tissues, and at this time: a central processing module, which is also used to configure the electrical stimulation module.

The electrical stimulation module includes 4 electrical stimulation signal generation circuits. Each signal generation circuit uses a high-precision AD conversion chip powered by dual power supplies, which can generate bipolar voltage or current waveforms with adjustable amplitude and frequency and customized waveforms. This bipolar waveform can make the net charge on the electrode after stimulation zero, which can reduce the damage to nerve cells and tissues, and at the same time avoid the electrolysis of the electrode by the remaining charge, prolonging the service life of the electrode. It can be controlled by the central processing module to realize the function of selecting bipolar voltage or current waveform by using an alternative switch. It combines an analog switch array and an electrophysiological module to realize bidirectional (detection and stimulation) function switching of electrodes.

At the same time, in order to realize high-speed data collection, the neural information detection system also includes: a data collection module for collecting electrophysiological signals and electrochemical signals processed by the electrophysiological module and the electrochemical module. As shown in Fig. 6, the data acquisition module includes two parts: an I/O interface, a multi-way switch, a sampling parameter configuration sub-module and an analog-to-digital conversion control (ADC) sub-module. The sampling parameter configuration sub-module, whose control terminal is connected with the central processing module, is used to configure the input connection mode, sampling rate and measurement range during measurement. The I/O interface is connected with the electrophysiological module and the electrochemical module, and receives 64 electrophysiological signals and 4 electrochemical signals transmitted. The multi-channel switch is used to transmit the 64 channels of electrophysiological signals and 4 channels of electrochemical signals to the analog-to-digital conversion module one by one, so as to realize time-division multiplexing of the analog-to-digital conversion module. The analog-to-digital conversion module, its control end is connected with the sampling parameter configuration module, its input end is connected with the multi-way switch, and its output end is connected with the central processing module, which is used to realize the data acquisition of electrophysiological signals and electrochemical signals. The precision of the ADC module reaches 16 bits, and the total sampling speed is as high as 1.25MS/s. The total speed of any number of analog inputs can be configured as high as 1.25MS/s. In particular, the time resolution of electrochemical signal detection can be configured to reach more than 0.1ms to realize the detection of cell neurotransmitter release.

In addition, in this embodiment, the cache module is connected to the central processing module for caching the collected data; the USB transmission circuit is connected to the central processing module and connected to the upper computer module through the USB port for storing the data in the cache module. The data of the upper computer module is transmitted to the upper computer module, and the instructions of the upper computer module are transmitted to the central processing module to realize the control of the upper computer module on the instrument. In addition, the upper computer module is also used to display, store, process and analyze the measured signals, and at the same time control the instrument.

It should be noted that the above-mentioned definitions of each element are not limited to the various specific structures or shapes mentioned in the embodiments, and those skilled in the art can simply replace them with well-known ones, for example: (1) electrophysiological The filter circuit of the module can also be high-pass filtered first, and then low-pass filtered; (2) The AD8606 chip used in the electrochemical module can be replaced by a TLC2262 chip.

The specific embodiments described above have further described the purpose, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above descriptions are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims (8)

1. A neural information detection system, comprising: Upper computer module; The electrophysiological module includes N electrophysiological signal channels, N=64; An electrochemical module, including M electrochemical signal channels, where M≤N; The electrical stimulation module includes J electrical stimulation signal channels, where J≤N; The data acquisition module is connected with the electrophysiological signal module and the electrochemical module, and is used for electrophysiological data collected by N electrophysiological signal channels in the electrophysiological module and electrochemical data collected by M electrochemical signal channels in the electrochemical module Perform sampling and analog-to-digital conversion; The analog switch array includes N analog switch channels. The N analog switch channels are divided into four groups, and each group contains 16 analog switch channels. Each analog switch channel in the N analog switch channels includes: electrophysiological A signal switch whose front end is connected to a microelectrode, and whose rear end is connected to one of the N electrophysiological signal channels, wherein each of the M analog switch channels in the N analog switch channels An analog switch channel also includes: an electrochemical signal switch, whose front end is connected to a microelectrode, and whose rear end is connected to one electrochemical signal channel in the M electrochemical signal channels; Each analog switch channel in the J-way analog switch channel also includes: an electrical stimulation signal switch, the front end of which is connected to a microelectrode, and its rear end is connected to one of the J-way electrical stimulation signal channels; Each of the analog switch channels of the K analog switch channels except the J analog switch channel in the N analog switch channels also includes: a grounding switch, whose front end is connected to a microelectrode, and its rear end is connected to a reference voltage or land; The central processing module is connected with the analog switch array and the data acquisition module, and is used to control the electrophysiological signal switch in each analog switch channel in the N analog switch channels, and each analog switch channel in the M analog switch channels Closing and opening of the electrical stimulation signal switch in the electrochemical signal and each analog switch channel in the J analog switch channel; it is also used to receive the electrophysiological data and electrochemical data after analog-to-digital conversion by the data acquisition module; Wherein, only one of the electrophysiological signal switch, the electrochemical signal switch, and the electrical stimulation signal switch in the same analog switch channel can be in a closed state, and when the J analog switch channel is controlled When the electrical stimulation signal switch in at least one of the analog switch channels is in a closed state, the grounding switch controlling each analog switch channel of the K analog switch channels is in a closed state; The buffer module is connected with the central processing module, and is used for buffering the electrophysiological signals received by the central processing module; The USB transmission circuit is connected with the central processing module and connected with the upper computer module through the USB port, and is used for transferring the data in the cache module to the upper computer module. 2. The nerve information detection system according to claim 1, wherein, 16 analog switch channels of each group, together with 1 reference interface and 1 ground interface, a total of 18 interfaces are connected to the microelectrode array. 3. The neural information detection system according to claim 1, wherein said M=4. 4. The neural information detection system according to claim 1, wherein said J=4. 5. neural information detection system according to claim 1, wherein, The central processing module is also connected to the electrical stimulation module, and is used to control the amplitude, frequency, and/or waveform of the electrical stimulation signal in the electrical stimulation signal channel of the J circuit. 6. The neural information detection system according to claim 1, wherein said N=64, M=4, and said J=4. 7. The nerve information detection system according to any one of claims 1 to 6, wherein the host computer module is used to receive data acquisition parameters input by a user; The USB transmission circuit is connected to the central processing module, and is connected to the upper computer module through the USB port, and is used to transmit the data acquisition parameters received by the upper computer module to the central processing module; The data collection module is also used for sampling and analog-to-digital conversion of the electrophysiological data collected by N electrophysiological signal channels in the electrophysiological module according to the data collection parameters. 8. The neural information detection system according to any one of claims 1 to 6, wherein each analog switch channel in the N analog switch channels further comprises: The front end of the preamplifier circuit is connected to a microelectrode, and the rear end is connected to the front end of the corresponding electrophysiological signal switch, so as to realize impedance matching with the microelectrode.