CN101349691B - Neuron and device for detecting nerve signal transfer characteristic between neuron clusters - Google Patents
Neuron and device for detecting nerve signal transfer characteristic between neuron clusters Download PDFInfo
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- CN101349691B CN101349691B CN2008101963699A CN200810196369A CN101349691B CN 101349691 B CN101349691 B CN 101349691B CN 2008101963699 A CN2008101963699 A CN 2008101963699A CN 200810196369 A CN200810196369 A CN 200810196369A CN 101349691 B CN101349691 B CN 101349691B
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Abstract
The invention discloses a device for exploring neural signal transfer behavior between each portion of a single neuron and neuronal population, which comprises an electrode unit which is distributed according to an array, wherein the electrode unit comprises an exciting electrode and a detecting electrode, and an exciting control switch and a detecting control switch are respectively connected on the exciting electrode and the detecting control electrode, and further comprises an electrode unit selective circuit for controlling the exciting control switch and the detecting control switch. The device adopts the electrode unit selective circuit to connect the control switch of an electrode unit, namely the exciting control switch and the detecting control switch, thereby selectively controlling the electrode unit, reducing the total amount of lead-out wires of the exciting control switch and the detecting control switch of the electrode unit, greatly reducing the number of electrode lead-out wires which are externally led out by electrodes when the working condition on an electrode which can be controlled is achieved, and overcoming the problem that the number of electrode arrays are limited by the number of lead-out wires.
Description
Technical field
The present invention relates to a kind of be used to the to comprise human vertebrate neuron and the research device of neuron colony electrical activity signal transmission characteristic, relate in particular to MN and device for detecting nerve signal transfer characteristic between neuron clusters that a kind of microelectronics system is assisted.
Background technology
From introducing microelectrode array (Microelectrode Array such as Thomas in 1972; MEA) surveyed since the biologically active of cells cultured; Scientist has developed the MEA of various ways, is used for the cell of cultivating that comprises neuron is carried out electric signal record and excitation.Yet these MEA are discrete with the microelectronics system of acquisition of signal and excitation mostly.Calendar year 2001; Germany Max Planck Biochemical Research Peter Fromherz and Gunther Zeck the neuron of snail is placed on the silicon chip that 16 excitation/record two-way function electrode positions are arranged; Each electrode position surrounds with 6 micro plastic posts that prevent that neuron from moving, and is being close between the neuron and is forming interface between neuron and the silicon chip like this.They have designed a voltage stimulator under each neuron; Produce a kind of whole neuronic electric pulse that runs through; And be transferred to another neuron by a neuron; Turn back to silicon chip at last again, thereby can transmit through silicon-neuron-neuron-silicon loop at the clear signal of neuron aspect Shanghai Stock Exchange.But because each contact site of all these MEA needs an extension line, electrode number receives the restriction of array extension line.For example; Extreme electrode number of sites/extension line number of the MEA that Germany MCS company produces is 60; Max Planck Biochemical Research MEA contain 16 excitation/record two-way function electrode site, this is not enough to generate with transmission characteristic and carry out the more research of microcosmic discerning between the neuron colony signal.
2007, the inventor submitted the application for a patent for invention (application number 200710191698.x) of an electrod-array to.This invention with the structure applications of similar MOS single tube read-write memory in the design of extensive electrod-array; When making the duty of each electrode points controlled; Reduce the number of the outer extension line of electrode pair significantly: counting for array is the electrod-array of N * N, and electrode outlet line can be from N
2Bar reduces to the 4N bar.N=32 for example, then extension line will reduce to 128 from 1024.Overcome the restricted problem of increase extension line number along with the electrod-array number.Yet because this patent adopts directly outer add mode to row and column control voltage, the number of chip extension line (except the power lead) is only from N
2Bar reduces to the 4N bar.On the basis of this patent, the present invention proposes the employing of row and column control voltage and applies scheme chronologically, can the chip extension line further be dropped to the 2N+3 bar from the 4N bar.
Summary of the invention
Technical matters to be solved by this invention provides a kind of electrode outlet line that can reduce, and utilizes the microelectronics method to explore the device of nerve signal transmission characteristic between each position of single neuron and the neuron colony.
For solving the problems of the technologies described above; The present invention adopts following technical scheme: a kind of device that is used to explore nerve signal transmission characteristic between each position of single neuron and the neuron colony; Comprise that electrode unit, this electrode unit according to array distribution comprise exciting electrode and exploring electrode; On exciting electrode and exploring electrode, be connected with the excitation CS respectively and survey CS; Also comprise electrode unit selection circuit, this electrode unit selects first group of output terminal of circuit to be connected with each row energization CS, selects second group of output terminal of circuit to be connected with each row detection CS.
Described electrode unit is selected the shift register structure with string and translation function of circuit for being made up of first order d type flip flop chain and second level d type flip flop chain; The shared clock signal control end of all d type flip flops in the described first order d type flip flop chain; The shared clock signal control end of all d type flip flops in the d type flip flop chain of the described second level; The signal output part of described first order d type flip flop chain is connected with the signal input part of second level d type flip flop chain; The output terminal of first group of d type flip flop of described second level d type flip flop chain is connected with the excitation CS, and the output terminal of second group of d type flip flop of described second level d type flip flop chain is connected with the detection CS.
Described excitation CS adopts first metal-oxide-semiconductor; The source electrode of this first metal-oxide-semiconductor is connected with exciting electrode; The drain electrode of first metal-oxide-semiconductor is as the pumping signal input end, and the grid of first metal-oxide-semiconductor is connected as the output terminal of energizing switch control end with first group of d type flip flop of second level d type flip flop chain.
Described detection CS adopts second metal-oxide-semiconductor; The drain electrode of this second metal-oxide-semiconductor is connected with exploring electrode; The source electrode of second metal-oxide-semiconductor is as the detectable signal output terminal, and the grid of second metal-oxide-semiconductor is connected as the output terminal of search switch control end with second group of d type flip flop of second level d type flip flop chain.
The present invention is used to explore the device of nerve signal transmission characteristic between each position of single neuron and the neuron colony, comprises microelectrode array unit, electrode unit selection circuit, microelectronics nerve signal exciter array and microelectronics nerve signal detection device array with bioelectrical signals detection and incentive functions.The microelectrode array unit is positioned at the center of whole device, adopts the form of similar calculator storage work, and the duty of each electrode points in the microelectrode array (excitation or detection) is controlled through " OK " switch and " row " switch.Each electrode points of microelectrode array can be regarded as with computer memory similar one can " read " (detection) can " write " (excitation) position.The shift register that electrode unit selects the circuit employing to have string and translation function passes through control signal 1 input end serial input of shift register; Convert into behind the multiple signals from output terminal and line output, send into the energizing switch control end and the search switch control end of electrod-array unit then.Microelectronics nerve signal exciter array and microelectronics nerve signal detection device array are positioned at the periphery of microelectrode array unit, and microelectronics nerve signal detection device adopts the shared mode of row, and microelectronics nerve signal driver adopts the shared mode of row.Cultivate neuron in the microelectrode array district; When choosing certain electrode points that contacts with micromechanisms such as neuronic cell space, dendron or aixs cylinders to be " writing " state through the switch of electrod-array unit; Signal in the microelectronics nerve signal driver is sent into microstructures such as neuronic cell space, dendron or aixs cylinder through selected electrode points; Signal through neuronic these microstructures after, the electrode points that is in " reading " duty through another that contacts with it again gets into microelectronics nerve signal detection device and carries out processing and amplifying.
The sniffer that is used to explore nerve signal transmission characteristic between each position of single neuron and the neuron colony of the present invention adopts the CMOS technology of standard to realize.Between the micromechanisms such as single neuronic cell space, dendron and aixs cylinder of utilizing this sniffer and can cultivating microelectrode array zone on the silicon chip by means of nerve signal generator, dark storage oscilloscope and microscope and the importing into of the nerve signal between a plurality of neuron colony, integration, spontaneous and bring out to generate and spread out of characteristic and conduct a research.
Compared with prior art, the present invention has the following advantages:
1) the present invention adopts electrode unit to select the CS of circuit connection electrode unit; Promptly encourage CS and survey CS; Thereby electrode unit is selected control; Reduce the excitation CS and detection CS extension line total number of electrode unit, when realizing that the electrode points duty is controlled, reduced the number of the outer extension line of electrode pair significantly.For example: counting for array is the electrod-array of N * N, and electrode outlet line can be from N
2Bar reduces to the 2N+3 bar.N=32 for example, then electrode outlet line will reduce to 67 from 1024.Overcome the restricted drawback of increase extension line number along with the electrod-array number.
2) with the structure applications of similar MOS single tube read-write memory in the design of extensive electrod-array; And with the string of shift register-and translation function be used for electrode unit and select circuit; With 1 the input end serial input of control signal through shift register; Convert the signal of multidiameter delay output into, again multiple signals are sent into the action line control end and detection row control end of electrode unit respectively.Total is simple, is easy to realize the control to single electrode unit, and can be integrated on the small silicon chip, can draw the number of pad outward the area of entire chip is reduced greatly through reducing electrode pair.
3) the microelectronic chip device that the present invention designed integrates micron order electrod-array, electrode unit with bioelectrical signals detection and incentive characteristic and selects circuit, nerve signal detection device array and nerve signal exciter array.Can realize between each structure such as single pericaryon, dendron and aixs cylinder and the microexamination of signal transfer characteristic between the neuron colony.
Description of drawings
Fig. 1 is an acquisition of signal and excitation microelectronic chip system functional block diagram between neuron of the present invention and multi-neuron cluster.1. electrod-array unit among the figure, 2. binding line, the 3.PCB plate, 4. pad, 5. neurocyte, 6. silicon chip, 7. extension line, 8. nerve signal exciter array, 9. nerve signal detection device array, 10. electrode unit is selected circuit.
Fig. 2 is an electrode unit embodiment circuit diagram of the present invention.
Fig. 3 is that electrode unit of the present invention is selected circuit block diagram.
Fig. 4 is that electrode unit of the present invention is selected the circuit embodiments circuit diagram.
Fig. 5 is the circuit diagram of microelectrode matrix of the present invention.
Embodiment
As shown in Figure 1; The device that is used to explore nerve signal transmission characteristic between each position of single neuron and the neuron colony of the present invention; Comprise that electrode unit 1, electrode unit selection circuit 10, electrode unit 1 according to N * N array distribution comprise exciting electrode 12 and exploring electrode 14; Exciting electrode 12 is connected with nerve signal exciter array 8, and exploring electrode 14 is connected with nerve signal detection device array 9, on exciting electrode 12 and exploring electrode 14, is connected with excitation CS 11 respectively and surveys CS 13; Electrode unit is selected the shift register structure with string and translation function of circuit 10 for being made up of first order d type flip flop chain 17 and second level d type flip flop chain 18; Wherein first order d type flip flop chain 17 is connected and composed by 2n d type flip flop, and second level d type flip flop chain 18 is is also connected and composed by 2n d type flip flop, the shared clock signal control end 19 of all d type flip flops in the first order d type flip flop chain 17; The shared clock signal control end 20 of all d type flip flops in the second level d type flip flop chain 18; The signal output part of first order d type flip flop chain 17 connects the signal input part of second level d type flip flop chain 18, and the d type flip flop that constitutes second level d type flip flop chain 18 is divided into two groups, and first group is 1～n; Second group is n+1～2n; The output terminal 15 of first group of d type flip flop connects excitation CS 11, and the output terminal 16 of second group of d type flip flop of second level d type flip flop chain 18 connects surveys CS 13, with reference to figure 2, Fig. 3, Fig. 4 and Fig. 5.
Excitation CS 11 adopts first metal-oxide-semiconductor, and the source electrode of this first metal-oxide-semiconductor is connected with exciting electrode 12, and the drain electrode of first metal-oxide-semiconductor is as pumping signal input end V
i, the grid of first metal-oxide-semiconductor is as energizing switch control end V
IcBe connected with the output terminal 15 of first group of d type flip flop of second level d type flip flop chain 18.
Survey CS 13 and adopt second metal-oxide-semiconductor, the drain electrode of this second metal-oxide-semiconductor is connected with exploring electrode 14, and the source electrode of second metal-oxide-semiconductor is as detectable signal output terminal V
o, the grid of second metal-oxide-semiconductor is as search switch control end V
OcBe connected with the output terminal 16 of second group of d type flip flop of second level d type flip flop chain 18.
The device that is used to explore nerve signal transmission characteristic between each position of single neuron and the neuron colony of the present invention comprises microelectrode array, electrode unit selection circuit, microelectronics nerve signal exciter array and microelectronics nerve signal detection device array with bioelectrical signals detection and incentive functions.Wherein the structure of similar computing machine MOS single tube read-write memory is adopted in the microelectrode array design; The action line CS of electrode unit selects the also line output of circuit to link to each other with detection row switch control end and electrode unit; Electrode unit selects the circuit employing to have the serial input of data latching function and the shift register of line output; The control signal of serial input is sent into the switch control end of electrode unit circuit with the mode of multidiameter delay output after through shift register, as the control signal of electrode unit work.The nerve signal detection amplifier adopts the form of column electrode units shared, is used to amplify the nerve signal that is detected from the micromechanisms such as neuronic cell space, dendron and aixs cylinder that contact with it by exploring electrode.The nerve signal driver adopts the form of row electrod-array units shared, is used for the micromechanisms such as pericaryon, dendron and aixs cylinder that contact with exciting electrode are carried out the nerve signal excitation.
Claims (1)
1. MN and device for detecting nerve signal transfer characteristic between neuron clusters; Comprise that electrode unit (1), this electrode unit (1) according to array distribution comprise exciting electrode (12) and exploring electrode (14); On exciting electrode (12) and exploring electrode (14), be connected with excitation CS (11) respectively and survey CS (13); It is characterized in that: also comprise electrode unit selection circuit (10); This electrode unit selects first group of output terminal (15) of circuit (10) to be connected with each row energization CS (11), and this electrode unit selects second group of output terminal (16) of circuit (10) to be connected with each row detection CS (13);
Described electrode unit is selected the shift register structure with string and translation function of circuit (10) for being made up of first order d type flip flop chain (17) and second level d type flip flop chain (18); The shared clock signal control ends of all d type flip flops in the described first order d type flip flop chain (17) (19); The shared clock signal control ends of all d type flip flops in the described second level d type flip flop chain (18) (20); The signal output part of described first order d type flip flop chain (17) is connected with the signal input part of second level d type flip flop chain (18); The output terminal (15) of first group of d type flip flop of described second level d type flip flop chain (18) is connected with excitation CS (11), and the output terminal (16) of second group of d type flip flop of described second level d type flip flop chain (18) is connected with detection CS (13);
Excitation CS (11) adopts first metal-oxide-semiconductor, and the source electrode of this first metal-oxide-semiconductor is connected with exciting electrode (12), and the drain electrode of first metal-oxide-semiconductor is as pumping signal input end (V
i), the grid of first metal-oxide-semiconductor is as energizing switch control end (V
Ic) be connected with the output terminal (15) of first group of d type flip flop of second level d type flip flop chain (18);
Survey CS (13) and adopt second metal-oxide-semiconductor, the drain electrode of this second metal-oxide-semiconductor is connected with exploring electrode (14), and the source electrode of second metal-oxide-semiconductor is as detectable signal output terminal (V
o), the grid of second metal-oxide-semiconductor is as search switch control end (V
Oc) be connected with the output terminal (16) of second group of d type flip flop of second level d type flip flop chain (18).
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004049937A1 (en) * | 2002-12-05 | 2004-06-17 | University Of Ulster | Tissue mapping system and method |
| CN1810203A (en) * | 2005-12-30 | 2006-08-02 | 东南大学 | Microelectronic system aided nerve channel function recovering method and apparatus |
| WO2007080460A1 (en) * | 2005-09-15 | 2007-07-19 | Koninklijke Philips Electronics, N.V. | Apparatus and method for electrostimulation/sensing in vivo |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004049937A1 (en) * | 2002-12-05 | 2004-06-17 | University Of Ulster | Tissue mapping system and method |
| WO2007080460A1 (en) * | 2005-09-15 | 2007-07-19 | Koninklijke Philips Electronics, N.V. | Apparatus and method for electrostimulation/sensing in vivo |
| CN1810203A (en) * | 2005-12-30 | 2006-08-02 | 东南大学 | Microelectronic system aided nerve channel function recovering method and apparatus |
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