CN102247137B - Microelectrode array-based multichannel neural information detection system - Google Patents
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Abstract
本发明公开了一种基于微电极阵列的多通道神经信息检测系统，涉及神经生物学检测技术，包括模拟开关阵列，电生理信号检测电路，电化学信号检测电路，电刺激信号发生电路，多路AD转换电路，温度检测电路，高速USB传输电路，无线蓝牙通讯模块和计算机上运行的数据处理软件等。本发明多通道神经信息检测系统可用于在体动物或离体组织的电生理和电化学神经信息获取，其结合不同种类的微电极阵列可在二维或三维尺度上对多个神经元的电生理信号和电化学信号进行检测，获得更为全面和准确的实验数据，实现神经元双向双模的应用实施。
The invention discloses a multi-channel neural information detection system based on a microelectrode array, which relates to neurobiological detection technology, including an analog switch array, an electrophysiological signal detection circuit, an electrochemical signal detection circuit, an electrical stimulation signal generation circuit, and a multi-channel AD conversion circuit, temperature detection circuit, high-speed USB transmission circuit, wireless bluetooth communication module and data processing software running on the computer, etc. The multi-channel neural information detection system of the present invention can be used for the acquisition of electrophysiological and electrochemical neural information of in vivo animals or isolated tissues, and it can be used for the electrical monitoring of multiple neurons on a two-dimensional or three-dimensional scale in combination with different types of microelectrode arrays. Physiological signals and electrochemical signals are detected to obtain more comprehensive and accurate experimental data, and realize the application and implementation of bidirectional and dual-mode neurons.
Description
Technical field
The present invention relates to neurobiology detection technique field, is a kind of detection system that changes in order to detect simultaneously a plurality of neuron bioelectrical activities and neurotransmitter.
Background technology
The information transmission of neurocyte is completed jointly by pulsed discharge and neurotransmitter (chemical substance), detect simultaneously electricity physiological signal and neurotransmitter changes of contents, nationality has important scientific meaning and clinical value with the pathogeny of studying some disease, nerve signal transmission, drug reaction etc.Organism for each process of response and the information processing of extraneous event, all needs to relate to the combined effect of many neurocytes simultaneously, disclose this complex mechanism wherein, must obtain the electrical activity information of the neurocyte of enough numbers.Traditional electrode or single Technology of Microelectrodes can not satisfy clinical and scientific research detects demand.Therefore the electrical activity of a plurality of brain neurons and neurotransmitter information are carried out synchronous recording and can provide a kind of facility, acquisition of information instrument reliably for Neuroscience Research, have very important significance for fields such as neuroscience basic research, sacred disease treatment (as epilepsy, Parkinson's disease), brain-computer interface, high-flux medicaments sifting and safety pharmacologies.
Summary of the invention
The objective of the invention is to disclose a kind of multi-channel nerve information detecting system based on microelectrode array, the function of the software control microelectrode array by computer is arranged, to satisfy the requirement of different experiments, and detect simultaneously Electrophysiology and electrochemical signals, with solve neurocyte continuously, the test problems of multi-channel detection and faint electric physiology and electrochemical signals.
For achieving the above object, technical solution of the present invention is:
A kind of multi-channel nerve information detecting system based on microelectrode array, it realizes that in conjunction with analog switch array the two-way function of electrode switches, and realizes that by electrophysiologicalsignal signal detection module and electrochemical signals detection module neuronic bimodulus multi-channel synchronous detects;
The multi-channel nerve information detecting system, comprise: central processor unit, coprocessor unit, analog switch array, temperature observation circuit, the stimulus signal generation module, electrophysiologicalsignal signal detection module, electrochemical signals detection module, the multi-channel parallel acquisition module, cache circuit, high speed USB communication interface, wireless blue tooth communication interface and computer software; Wherein, central processor unit connecting multi-channel parallel acquisition module, cache circuit, coprocessor unit, and communicate by high speed USB chip and computer; Coprocessor unit connects wireless blue tooth communication interface, electrophysiologicalsignal signal detection module, analog switch array, stimulus signal generation module, Electrochemical Detection module, temperature observation circuit; Analog switch array connects stimulus signal generation module, Electrochemical Detection module, microelectrode array, also is electrically connected to the parallel acquisition module by the electrophysiologicalsignal signal detection module;
Microelectrode array is electrically connected to temperature observation circuit.
Described multi-channel nerve information detecting system, the two-way function of its described electrode is for detecting and stimulatory function; Neuronic bimodulus detects, and is electric physiology and Electrochemistry Information detection; The electrophysiologicalsignal signal detection module comprises artefact elimination circuit and preamplifier circuit, coprocessor unit is connected with analog switch array and is eliminated circuit with artefact and be connected, artefact is eliminated circuit and is connected with central processor unit through preamplifier circuit, by the conducting state of control simulation switch arrays, select with the use function to each electrode.
Described multi-channel nerve information detecting system, its described analog switch array, by computer software control, the analog switch array that microelectrode array is connected arranges, thereby make each electrode select different purposes, be connected respectively to electrophysiologicalsignal signal detection module, electrochemical signals detection module, stimulus signal generation module, reference or ground, according to concrete requirement of experiment, change easily the function of microelectrode array and arrange thus.
Described multi-channel nerve information detecting system, its described Electrochemical Detection module coordinates with electric physiological detection module, control by analog switch array, do Electrochemical Detection or do electric physiological detection with each electrode on the selection microelectrode array, thereby realize that electrochemical signals and electricity physiological signal multi-channel synchronous that detection site arranges detect.
Described multi-channel nerve information detecting system, its described wireless blue tooth communication interface is connected with coprocessor unit, computer directly arranges the parameter of each module by coprocessor unit, avoid taking the bandwidth of USB, thereby strengthened the response speed of system, make system when processing huge data volume, in time the instruction of responsive computer.
Described multi-channel nerve information detecting system, its described coprocessor unit adopts 32 ARM chips at a high speed, detect the content of neurotransmitter by the electrochemistry module, and the work between each module in coherent system, alleviate the workload of central processing unit, improve the real time response speed of system.
Described multi-channel nerve information detecting system, its described stimulus signal generation module, adopt the high accuracy analog-digital chip of dual power supply, realize the self-defining bipolar voltage of frequency, amplitude and waveform or current waveform, making the net charge that stimulates on rear electrode is zero, the damage of reduction to neurocyte avoids residual charge to the electrolysis of electrode simultaneously, extends the service life of electrode.
Described multi-channel nerve information detecting system, its described bipolar voltage or current waveform are to adopt the variable connector of alternative to realize, variable connector is controlled by computer software.
Described multi-channel nerve information detecting system, its described temperature sensing circuit, employing sensitivity is the micro temperature sensor of 0.1 ℃, to realize the accurate Real-Time Monitoring to the in vitro tissue culture environment, avoids or the too high tissue activity reduction that bring too low due to temperature.
Nerve information detection system of the present invention, the electric physiology and the electrochemistry nerve information that are used in body animal or in vitro tissue obtain.It is in conjunction with different types of microelectrode array, as be suitable for Utah electrode, the Michigan electrode that detects in somatic nerves information and be suitable for the plane MEA electrode that exsomatizednerve information detects, can detect a plurality of neuronic electricity physiological signals and electrochemical signals on two dimension or three dimension scale, obtain more comprehensive and accurate experimental data, realize the application implementation of two-way (detect and the apply electricity irritation) bimodulus of neuron (neuron electricity physiological signal and electrochemical signals).
Description of drawings
Fig. 1 is the schematic diagram of generation current, boosted voltage signal in the present invention;
Fig. 2 is the theory diagram of analog switch array in the present invention;
Fig. 3 is the schematic diagram of the preposition amplification of electric physiology in the present invention;
Fig. 4 is a kind of microelectrode array schematic diagram that can be combined with the multi-channel nerve information detecting system in the present invention;
Fig. 5 is that the present invention is used for the block diagram of system that multi-channel nerve information detects;
Fig. 6 is by utilizing the present invention to be surveyed neuron spike potential overlaid waveforms figure;
Fig. 7 is the software control interface of switch arrays of the present invention;
Fig. 8 is the software control flow chart of switch arrays of the present invention.
The specific embodiment
The present invention discloses a kind of multi-channel nerve information detecting system based on microelectrode array (as Fig. 4), it can realize two-way (detect and stimulate) function switching of electrode in conjunction with analog switch array, and realizes that by electrophysiologicalsignal signal detection module and electrochemical signals detection module neuronic bimodulus (electric physiology and Electrochemistry Information) multi-channel synchronous detects.As shown in Figure 5, system comprises CPU, coprocessor unit, analog switch array, temperature observation circuit, stimulus signal produces circuit, electric physiological detection module, Electrochemical Detection module, the multi-channel parallel acquisition module, cache circuit, high speed USB communication interface, wireless blue tooth communication interface and computer software.Wherein, CPU connecting multi-channel acquisition module, cache circuit, and communicate by high speed USB chip and computer; Coprocessor unit connects the Electrochemical Detection module, temperature observation circuit, and stimulus signal produces circuit, analog switch array, artefact is eliminated circuit, wireless blue tooth communication interface; The electrophysiologicalsignal signal detection module eliminates circuit by artefact and preamplifier circuit forms.
Analog switch array of the present invention is to realize by theory diagram as shown in Figure 2, the lead-in wire of microelectrode array is connected to analog switch array, can control the state of each switch by computer software, thereby control the functional mode of each electrode, same like this electrode can be multiplexed with respectively electrophysiologicalsignal signal detection electrode, electrochemical signals detecting electrode, electric stimulation electrode, reference electrode, ground electrode.Wherein software adopts Visual C++6.0 and Keil C to write, and controls interface and flow process as shown in Fig. 7,8.Can adjust flexibly arranging of microelectrode array according to concrete requirement during experiment, can select the interested tissue regions of any one electrode pair detect or stimulate, thereby improved greatly the spatial resolution that detects, can obtain more valuable signal.
pre-amplification circuit of the present invention is realized by circuit shown in Figure 3, this circuit adopts the difference input form, the instrument amplifier AD620 that selection has high cmrr amplifies as the first order, the common mode rejection ratio of bringing for fear of not mating of electric capacity descends, what adopt is that the direct-current coupling mode is amplified the microelectrode signal, but owing to all can there being tens dc polarization voltages to the hundreds of millivolt to exist in body or stripped experiment, for avoiding amplifier saturation, amplification is set to 10 times of left and right, connect high pass filter with the filtering direct current signal in the back of instrument amplifier, the size of cut-off frequency can be set according to specific requirement, generally be made as 0.1～10Hz, the high pass filter back connects the low pass filter that cut-off frequency is the 3KHz left and right, with filter away high frequency noise, assurance is recorded to nerve signal and has high s/n ratio, as shown in Figure 6.Different according to dissimilar neurocyte discharge magnitude, can also connect in the back multistage amplification to adjust total amplification, be generally 1000～5000 times.
For unipolar boost pulse, can charge to electrode, need the discharge of a period of time, can add the discharge artefact thus when recording, and also accelerate the electrolysis of electrode in tissue fluid or culture fluid, shorten the service life of electrode.For different experimental subjecies and dissimilar electrode, the size of stimulus signal and kind are also different, the present invention has designed a kind of circuit that can produce the bipolarity stimulus signal, the stimulus signal pulse that produces comprises positive pulse and negative pulse, thereby the net charge that can guarantee to be applied on electrode is 0, can avoid many harmful effects of being brought by traditional stimulus signal, and the stimulus signal that produces can be by the User Defined parameter.As shown in Figure 1, signal waveform by work in+/-10 DAC chip MAX504 of 5V produce, answer and can produce the bipolarity waveform of (comprising positive pulse and negative pulse), the parameter of stimulus signal: pulse width, impulse magnitude, pulse shape, pulse number, interval time etc., can arrange by No. 2 pin DIN of chip.The output signal of MAX504 is told two-way after following voltage through operational amplifier A D8674, wherein one the tunnel connects the V/I change-over circuit, is comprised of R1-R5 and two operational amplifiers, and wherein output current is determined by resistance R 4; Another road connects voltage amplifier circuit, formed by R6, R7 and an operational amplifier, the range (size is determined by the ratio of R6, R7) that stimulates to adjust output voltage, this two paths of signals can be received one 2 and select 1 switch, and final decision output is boosted voltage signal or galvanism signal.
The above is only the preferred embodiment of the present invention.Should be pointed out that for those skilled in the art's foundation creation principle of the present invention, can make many distortion and improvement, but these all fall into the protection domain of claim of the present invention.
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