CN102247137A - Microelectrode array-based multichannel neural information detection system - Google Patents
Microelectrode array-based multichannel neural information detection system Download PDFInfo
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Abstract
The invention discloses a microelectrode array-based multichannel neural information detection system and relates to neurobiological detection technology. The microelectrode array-based multichannel neural information detection system comprises an analogue switch array, an electrophysiological signal detection circuit, an electrochemical signal detection circuit, an electrical stimulation signal generation circuit, multiple analogue to digital (A-to-D) converter circuits, a temperature detection circuit, a high-speed universal serial bus (USB) transmission circuit, a wireless Bluetooth communication module, data processing software to be run on a computer and the like. The multichannel neural information detection system disclosed by the invention can be used for acquiring electrophysiological and electrochemical neural information of in vivo animals or in vitro tissue; and by combining with different kinds of microelectrode arrays, the multichannel neural information detection system can detect the electrophysiological and electrochemical signals of a plurality of neurons in a two-dimensional or three-dimensional scale, acquire more complete and accurate experimental data, and realize bidirectional and double-mode application and implementation of neurons.
Description
Technical field
The present invention relates to neurobiology detection technique field, is a kind of in order to detect the detection system that a plurality of neuron bioelectrical activities and neurotransmitter change simultaneously.
Background technology
The information transmission of neurocyte is finished jointly by pulsed discharge and neurotransmitter (chemical substance), detect electricity physiological signal and neurotransmitter changes of contents simultaneously, nationality has important scientific meaning and clinical value with the pathogeny of studying some disease, nerve signal transmission, drug reaction etc.Organism all needs to relate to the combined effect of many neurocytes for each process of the response and the information processing of extraneous incident simultaneously, disclose this complex mechanism wherein, must obtain the electrical activity information of the neurocyte of enough numbers.Traditional electrode or single microelectrode technology can not satisfy clinical and scientific research detects demand.Therefore the electrical activity of a plurality of brain neurons and neurotransmitter information being carried out synchronous recording can be for Neuroscience Research provides a kind of facility, information be obtained instrument reliably, 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 neuroelectricity physiology and electrochemical signals simultaneously, with solve neurocyte continuously, the detection problem 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 connects multi-channel parallel acquisition module, cache circuit, coprocessor unit, and communicates 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 with the parallel acquisition module by the electrophysiologicalsignal signal detection module;
Microelectrode array is electrically connected with 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 the detection of electrochemistry information; The electrophysiologicalsignal signal detection module comprises artefact elimination circuit and preamplifier circuit, coprocessor unit is eliminated circuit with artefact respectively with analog switch array and is connected, artefact is eliminated circuit and is connected with central processor unit through preamplifier circuit, by the conducting state of control analog switch array, select with function of use 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 connected is provided with, 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 the function of microelectrode array easily and arrange thus.
Described multi-channel nerve information detecting system, its described Electrochemical Detection module cooperates 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 is provided with detect.
Described multi-channel nerve information detecting system, its described wireless blue tooth communication interface links to each other with coprocessor unit, computer directly is provided with the parameter of each module by coprocessor unit, avoid taking the bandwidth of USB, thereby strengthened the response speed of system, make system when handling 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 the 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 frequency, amplitude and self-defining bipolar voltage of waveform or current waveform, making the net charge that stimulates on the rear electrode is zero, reduction is avoided the electrolysis of residual charge counter electrode simultaneously to nerve cell damage, prolongs 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 that variable connector is controlled by computer software.
Described multi-channel nerve information detecting system, its described temperature sensing circuit, employing sensitivity is 0.1 ℃ micro temperature sensor, with the accurately in real time monitoring of realization to the in vitro tissue culture environment, avoids owing to temperature is crossed the low or too high tissue activity's reduction that brings.
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 the plane MEA electrode of the nerve information detection that is suitable for exsomatizing, can on two dimension or three dimension scale, detect a plurality of neuronic electricity physiological signals and electrochemical signals, obtain more comprehensive and accurate experimental data, realize the application implementation of neuron two-way (detecting and apply electricity irritation) bimodulus (neuron electricity physiological signal and electrochemical signals).
Description of drawings
Fig. 1 is for producing the schematic diagram of electric current, boosted voltage signal among the present invention;
Fig. 2 is the theory diagram of analog switch array among the present invention;
Fig. 3 is the schematic diagram of the preposition amplification of electric physiology among the present invention;
A kind of microelectrode array sketch map of Fig. 4 for being used in combination with the multi-channel nerve information detecting system among the present invention;
Fig. 5 is used for the block diagram of system that multi-channel nerve information detects for the present invention;
Fig. 6 is surveyed neuron spike potential overlaid waveforms figure by utilizing the present invention;
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 that in conjunction with analog switch array two-way (detect with stimulate) function of electrode switches, 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 connects the multichannel collecting 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 is formed.
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 electrophysiologicalsignal signal detection electrode, electrochemical signals detecting electrode, electric stimulation electrode, reference electrode, ground electrode respectively.Wherein software adopts Visual C++6.0 and Keil C to write, and control interface and flow process are shown in Fig. 7,8.Can adjust arranging of microelectrode array flexibly according to concrete requirement during experiment, can select the interested tissue regions of any one electrode pair to detect or stimulate, thereby improved the spatial resolution that detects greatly, 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 matching of electric capacity descends, what adopt is that the direct-current coupling mode is amplified the microelectrode signal, but owing in body or stripped experiment, all can there be tens dc polarization voltages to exist to the hundreds of millivolt, for avoiding amplifier saturated, amplification is set to about 10 times, 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, it is low pass filter about 3KHz that the high pass filter back connects cut-off frequency, with filter away high frequency noise, assurance records nerve signal and has high s/n ratio, as shown in Figure 6.According to dissimilar neurocyte discharge magnitude differences, can also connect multistage amplification in the back to adjust total amplification, be generally 1000～5000 times.
For unipolar boost pulse, can charge by counter electrode, need the discharge of a period of time, can when record, add the discharge artefact thus, and also quicken the electrolysis of electrode in tissue fluid or culture fluid, shorten the service life of electrode.At different experimental subjecies and dissimilar electrodes, the size of stimulus signal is also different with kind, the present invention has designed a kind of circuit that can produce the bipolarity stimulus signal, the stimulus signal pulse that is produced comprises positive pulse and negative pulse, thereby the net charge that can guarantee to be applied on the electrode is 0, can avoid many harmful effects of bringing by traditional stimulus signal, and the stimulus signal that is produced can be by the User Defined parameter.As shown in Figure 1, signal waveform by work in+/-10 DAC chip MAX504 of 5V produce, should 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, blanking time etc., can be provided with 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 made up of R1-R5 and two operational amplifiers, and wherein output current is by resistance R 4 decisions; Another road connects voltage amplifier circuit, form by R6, R7 and an operational amplifier, to adjust the range (size is determined by the ratio of R6, R7) that output voltage stimulates, 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 only is a preferred implementation 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.
Claims (9)
1. multi-channel nerve information detecting system based on microelectrode array, it is characterized in that, 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 connects multi-channel parallel acquisition module, cache circuit, coprocessor unit, and communicates 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 with the parallel acquisition module by the electrophysiologicalsignal signal detection module;
Microelectrode array is electrically connected with temperature observation circuit.
2. multi-channel nerve information detecting system as claimed in claim 1 is characterized in that, the two-way function of described electrode is for detecting and stimulatory function; Neuronic bimodulus detects, and is electric physiology and the detection of electrochemistry information; The electrophysiologicalsignal signal detection module comprises artefact elimination circuit and preamplifier circuit, coprocessor unit is eliminated circuit with artefact respectively with analog switch array and is connected, artefact is eliminated circuit and is connected with central processor unit through preamplifier circuit, by the conducting state of control analog switch array, select with function of use to each electrode.
3. multi-channel nerve information detecting system as claimed in claim 1, it is characterized in that, described analog switch array, by computer software control, the analog switch array that microelectrode array connected is provided with, thereby makes each electrode select different purposes, be connected respectively to electrophysiologicalsignal signal detection module, electrochemical signals detection module, stimulus signal generation module, reference or ground thus according to concrete requirement of experiment, are changed the function of microelectrode array easily and are arranged.
4. multi-channel nerve information detecting system as claimed in claim 1, it is characterized in that, described Electrochemical Detection module cooperates 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 is provided with detect.
5. multi-channel nerve information detecting system as claimed in claim 1, it is characterized in that, described wireless blue tooth communication interface links to each other with coprocessor unit, it is computer directly is provided with each module by coprocessor unit parameter, avoid taking the bandwidth of USB, thereby strengthened the response speed of system, made system when handling huge data volume, in time the instruction of responsive computer.
6. as claim 1,2 or 5 described multi-channel nerve information detecting systems, it is characterized in that, described coprocessor unit, adopt 32 ARM chips at a high speed, detect the content of neurotransmitter by the electrochemistry module, and the work between each module in the coherent system, alleviate the workload of central processing unit, improve the real time response speed of system.
7. multi-channel nerve information detecting system as claimed in claim 1, it is characterized in that, described stimulus signal generation module, adopt the high accuracy analog-digital chip of dual power supply, realize frequency, amplitude and self-defining bipolar voltage of waveform or current waveform, making the net charge that stimulates on the rear electrode is zero, reduces nerve cell damage, avoid the electrolysis of residual charge counter electrode simultaneously, prolong the service life of electrode.
8. multi-channel nerve information detecting system as claimed in claim 7 is characterized in that, described bipolar voltage or current waveform are to adopt the variable connector of alternative to realize that variable connector is controlled by computer software.
9. multi-channel nerve information detecting system as claimed in claim 1, it is characterized in that, described temperature sensing circuit, employing sensitivity is 0.1 ℃ micro temperature sensor, with the accurately in real time monitoring of realization, avoid because temperature is crossed the low or too high tissue activity's reduction that brings to the in vitro tissue culture environment.
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