JP2000041658A - Bioelectric signal recorder, bioelectric signal recording, and electric stimulation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bioelectric signal recording unit that can perform both electric stimulation and bioelectric signal recording with a single micro-electrode and can record the bioelectric signals in an extremely short time after an electric stimulation. SOLUTION: This bioelectric signal recorder is provided with an micro- electrodes, an. input amplifier 21 that is connected between an electric stimulation signal generator 12 and the main amplifier and amplifies the bioelectric signals from the micro-electrodes, a direct current potential retention circuit 22 that retain the direct current potential of the bioelectric signals to be input to the main amplifier 21, an adding machine 26 that adds the electric stimulation signals from the electric stimulation signal generator 12 to the direct current potential from the direct current potential retention circuit, the interface circuit that has the first switching circuit between the input amplifier and the main amplifier, the second switching circuit between the adding machine 26 and the direct current potential retention circuit, and the third switching circuit between the micro-electrodes 14 and the adding machine 26 and a controlling means that controls the first through the third switching circuits.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bioelectric signal recording device, a bioelectric signal recording method, and an electric stimulation method, and more particularly, to an electric stimulation for living tissues and cells other than the human body. The present invention relates to a technique that is effective in recording responses of living tissues and cells to the tissue.

[0002]

2. Description of the Related Art Hitherto, electrical stimulation of living tissues and cells has been performed by applying a constant voltage or constant current pulse signal directly to microelectrodes or through an insulating circuit. Normally, the signal generator used for electrical stimulation needs to have a low output impedance,
This bioelectric signal recording requires a high input impedance amplifier. Therefore, as a method of applying electrical stimulation to living tissue and cells using a single microelectrode and recording a bioelectric signal, conventionally, a manual switching is performed and a single microelectrode is used as a signal generator. Or other than connecting to an amplifier.

[0003]

However, in the case where manual switching is performed for electrical stimulation and recording of a bioelectric signal and a single microelectrode is connected to a signal generator or an amplifier, the time required for the switching operation is required. (Several seconds or more), there has been a problem that either electrical stimulation or bioelectric signal recording is impossible. Further, in a measurement system having a high input impedance, since it is generally very sensitive to noise, it is impossible to extend the cable from the input portion and perform switching at a distance, and the switch section should be located very close to the input section. Need to be installed. Therefore, the manual switching operation often involves vibration, and it is extremely difficult to use the method in combination with a method in which the influence of vibration is remarkable, such as a method using a glass tube microelectrode widely used for recording a bioelectric signal. There was a problem.

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problems of the prior art, and an object of the present invention is to provide a bioelectric signal recording apparatus which uses a single microelectrode to generate electric stimulation and bioelectric signal. It is an object of the present invention to provide a technique capable of performing both recordings and recording a bioelectric signal in a very short time after electrical stimulation.

Another object of the present invention is to provide a method for recording a bioelectric signal, in which one or more microelectrodes out of a plurality of microelectrodes are automatically and sequentially applied to living tissues or cells other than the human body. It is an object of the present invention to provide a technique capable of giving an electric stimulus and recording a bioelectric signal corresponding to the plurality of electric stimuli without being affected by vibration or the like.

Another object of the present invention is to provide a technique that enables accurate control of the intensity of electrical stimulation in an electrical stimulation method.

[0007] The above and other objects and novel features of the present invention will become apparent from the description of the present specification and the accompanying drawings.

[0008]

SUMMARY OF THE INVENTION Among the inventions disclosed in the present application, the outline of a representative one will be briefly described.
It is as follows.

That is, the present invention provides a bioelectric signal recording apparatus, in which a microelectrode, an electrostimulation signal generator for applying an electrostimulation signal to the microelectrode, and a main amplifier for amplifying the bioelectric signal from the microelectrode. Recording means for recording a bioelectric signal amplified by the main amplifier; and the microelectrode, an interface circuit connected between the electrical stimulation signal generator and the main amplifier, wherein the microelectrode An input amplifier for amplifying bioelectric signals from
A DC potential holding circuit that holds a DC potential of a bioelectric signal input to the main amplifier, and an adder that adds an electrical stimulation signal from the electrical stimulation signal generator and a DC potential from the DC potential holding circuit. A first switch circuit connected between the input amplifier and the main amplifier, a second switch circuit connected between the adder and the DC potential holding circuit, An interface circuit having a third switch circuit connected between the adder and the first to third interface circuits;
And control means for controlling the switch circuit.

The present invention is characterized in that a plurality of pairs of the microelectrode and the interface circuit are provided.

According to the present invention, there is provided a bioelectric signal recording method, wherein one or more microelectrodes among a plurality of microelectrodes are automatically selected in sequence to sequentially apply to living tissues or cells other than the human body. An electrical stimulus is applied, and a plurality of bioelectric signals corresponding to the plurality of the electrical stimuli are detected and recorded by a detection electrode.

Further, the present invention relates to an electric stimulation method for applying electric stimulation to living tissues or cells other than the human body using microelectrodes, wherein an electric stimulation signal applied from the electric stimulation signal generator to the microelectrodes is provided. In addition, the DC potential of the microelectrode immediately before the application of the electrical stimulation signal is added, and offset compensation of the DC potential of the microelectrode is performed.

[0013]

Embodiments of the present invention will be described below in detail with reference to the drawings.

In all the drawings for describing the embodiments, those having the same functions are denoted by the same reference numerals, and their repeated description will be omitted.

[First Embodiment] FIG. 1 is a block diagram showing a schematic configuration of a bioelectric signal recording apparatus according to a first embodiment of the present invention. In the figure, 10 is a personal computer, 11 is a main amplifier for recording a bioelectric signal, 12 is an electric stimulus signal generator, 13 is an interface circuit, 1
Reference numeral 4 denotes a microelectrode. In the bioelectric signal recording device of the present embodiment, an interface circuit 13 is provided between the microelectrode 14 and the main amplifier 11 for recording bioelectric signals and the electric stimulus signal generator 12, and the main amplifier 11, the electric stimulus signal The generator 12 and the interface circuit 13 are controlled by the personal computer 10. The bioelectric signal amplified by the main amplifier 11 is
The data is converted from analog to digital, and is recorded on recording means (for example, a hard disk) of the personal computer 10.

FIG. 2 is a block diagram showing a specific configuration of the interface circuit 13 shown in FIG. In the figure, 21 is an input amplifier, 22 is a DC potential holding circuit, 2
3 is a switch circuit (1), 24 is a switch circuit (2),
25 is a switch circuit (3), and 26 is an adder. FIG.
The switch circuits (1) to (3) are controlled by the control signal from the personal computer 10 at the timing shown in FIG. That is, normally, the switch circuit (2) 24 and the switch circuit (3) 25 are off, the switch circuit (1) 23 is on, the main amplifier 11 is connected to the microelectrode 14, and the electrical stimulation signal generator 12 is in a disconnected state. When electrical stimulation is performed on living tissue or cells, the main amplifier 11 is disconnected from the microelectrode 14 by first turning on the switch circuit (2) 24 and turning off the switch circuit (1) 23. At this time, the input DC potential of the main amplifier 11 is held by the DC potential holding circuit 22 at the DC potential immediately before disconnection. Next, the switch circuit (3) 25 is turned on. At this time, the DC potential from the DC potential holding circuit 22 is added to the electric stimulus signal from the electric stimulus signal generator 12 by the adder 26. The DC potential of the microelectrode 14 is unchanged.

In this state, the electric stimulus signal from the adder 26 is applied to the microelectrode 14, and the electric stimulus is performed on the living tissue or cells. By keeping the switch circuit (3) 25 on, the switch circuit (2) 24 on and the switch circuit (1) 23 off for a certain period of time after the end of the electrical stimulation, the electric charge injected into the microelectrode 14 by the electrical stimulation is reduced. It discharges through the low impedance circuit on the side of the electrical stimulation signal generator 12. With the above operation, the electrical stimulation and the recording of the bioelectric signal by the single microelectrode 14 can be performed, and the period during which the bioelectric signal cannot be stored due to the input of the electrical stimulation signal can be suppressed to a short time.

FIG. 4 shows a transient phenomenon of a potential change occurring in the microelectrode 14 when the electrical stimulation is performed by the bioelectric signal recording device of the present embodiment and a case where the electrical stimulation is performed by the conventional bioelectric signal recording device. 7 is a graph showing a result of comparison with a transient phenomenon of a potential change occurring in the microelectrode 14. When the electrical stimulation is performed by the bioelectric signal recording device, the transient phenomenon of the potential change generated in the microelectrode 14 causes the main amplifier 11 to saturate. Is specified. As is apparent from FIG. 4, in the conventional bioelectric signal recording device, the main amplifier 11 is saturated by the electric stimulation signal, and the electric charge injected into the microelectrode 14 is discharged with a long time constant. A long-running transient has occurred. In addition, the conventional bioelectric signal recording device shown in FIG.
The switch circuit 35 is turned on when electrical stimulation is performed. On the other hand, in the bioelectric signal recording apparatus of the present embodiment, the electric charge injected into the microelectrode 14 by the electric stimulation is discharged through the low impedance circuit of the electric stimulation signal generator 12, so that the transient phenomenon occurs. You can see that it is kept very small.

In the bioelectric signal recording apparatus according to the present embodiment, the output (DC potential) from the DC potential holding circuit 22 is used.
Is added to the electrical stimulus signal from the electrical stimulus signal generator 12 to control the electrical stimulus intensity accurately.

FIG. 6 is a diagram showing an example of a waveform of a bioelectric signal actually measured using the bioelectric signal recording apparatus according to the present embodiment. The waveform shown in FIG. 6 shows that the switch circuit (3) 25 is turned on 7 μs earlier than the electrical stimulus signal, and the switch circuit (2) 24 is turned on and the switch circuit (1) 23 is turned off 10 μs earlier. Set, and
This is a waveform recorded when this state is maintained for 1 ms after the application of the electric stimulus signal. As is clear from the waveform diagram of FIG. 6, in the bioelectric signal recording apparatus of the present embodiment, the bioelectric signal was recorded at about 2 ms after the input of the electric stimulus signal. That is, in the bioelectric signal recording device of the present embodiment, electrical stimulation is performed with a single microelectrode 14, and a response to the stimulus can be recorded with the same microelectrode 14 at least at about 2 ms after the end of the electrical stimulation. .

FIG. 7 is a diagram showing an example in which electrical stimulation is performed using the biological recording apparatus of the present embodiment and a biological electrical signal from one cell is recorded. Note that in FIG.
0 is the recorded bioelectric signal from the cell. FIG. 7 shows stimulus intensities of 2.1 V, 2.2 V, 2.3 V, and 2.4.
Recording was performed 32 times for each of the four conditions of V. FIG. 7 shows that a remarkable difference in response was obtained for a slight difference in electrical stimulus intensity of 0.1 V, and that reproducible results were obtained under each condition. Is shown. This is because the output (DC potential) from the DC potential holding circuit 22 is added to the electrical stimulus signal from the electrical stimulus signal generator 12 to perform offset compensation of the DC potential of the microelectrode 14 and to perform electrical stimulus. This shows the effect of discharging the electric charge accumulated at the interface between the microelectrode 14 and the solution through the low impedance circuit on the side of the electrical stimulation signal generator 12.

In the bioelectric signal recording apparatus according to the present embodiment, a plurality of sets of the interface circuit 13 and the microelectrode 14 shown in FIG. 1 or FIG. By controlling with the personal computer 10, it is possible to record a plurality of whole biological reactions individually (or in parallel) without generating vibration. Further, in the bioelectric signal recording device of the present embodiment, a constant voltage electric stimulation signal is output from the electric stimulation signal generating device 12, but a constant current electric stimulation signal is output from the electric stimulation signal generating device 12. It is also possible. In this case, the switch circuit (2) 24 and the adder 26 shown in FIG.

[Second Embodiment] FIG. 8 is a block diagram showing a schematic configuration of a bioelectric signal recording apparatus according to a second embodiment of the present invention. In the figure, 13a to 13n are interface circuits, 14a to 14n are microelectrodes, 21a to 2a.
1n is an input amplifier, 22a to 22n are DC potential holding circuits, 23a to 23n are switch circuits (1), 24a to 2
4n is a switch circuit (2), 25a to 25n are switch circuits (3), and 26a to 26n are adders. The bioelectric signal recording apparatus according to the present embodiment has n interface circuits (13a to 13n) and n microelectrodes (14a to 14a).
14n), that is, n sets of the interface circuit 13 and the microelectrode 14 shown in FIG. 1 or FIG. 2 are provided, and the switch circuit group in the interface circuits (13a to 13n) is controlled by the personal computer 10. It was done.

In the bioelectric signal recording apparatus of the present embodiment, the interface circuits (13a to 13n)
It is modularized using a plurality of integrated circuits.

That is, an amplifier element and a switch circuit (1) (23a-23) are used as input amplifiers (21a-21n).
n), switch circuits (2) (24a to 24n), and switch circuits (3) (25a to 25n) using analog switch circuit elements, and a DC potential holding circuit (22a
To 22n) to form one module by combining the sample and hold circuits. This module is configured as a system in which n (for example, 64) modules are connected in parallel and the whole is controlled by one personal computer 10. It should be noted that the module realized by the bioelectric signal recording device of the present embodiment can itself be a single integrated circuit device.

According to the bioelectric signal recording device of the present embodiment, the interface circuits (13a to 13n) are modularized, and each switch circuit (23a to 23n, 24a to 24n) is controlled by a control signal from the personal computer 10.
n, 25a to 25n), so that the interface circuits (13a to 13n) are installed very close to the microelectrodes (14a to 14n), and are completely affected by vibration. It is possible to perform stable bioelectric signal recording without the need.

Third Embodiment FIG. 9 is a diagram for explaining a bioelectric signal recording apparatus according to a third embodiment of the present invention. FIG. 10 is an enlarged view of a portion A shown in FIG. FIG. The bioelectric signal recording device according to the present embodiment is different from the bioelectric signal recording device according to the second embodiment in a measurement method using the glass tube microelectrode 15 which is a method widely used as a method for measuring a bioelectric signal. Is used in combination. That is, as shown in FIG. 9, the glass tube microelectrode 15 was inserted into one cell of the cell group mounted on the substrate 17 having 64 microelectrodes 14, and a control signal from the personal computer 10 was used. By remote control, 64 microelectrodes 14 are sequentially connected one by one to the electrostimulation signal generator 12 to perform electrostimulation, and the cell membrane current obtained from the glass tube microelectrode 15 is amplified by the amplifier 16 and recorded. It was made. FIG. 10 also shows the cell membrane current output from the glass tube microelectrode 15 at this time.

As described above, a measurement system having a high input impedance is generally very sensitive to noise.
It is impossible to extend the cable from the input part and switch it away, and it is necessary to install the switch part very close to the input part. For this reason, the measurement method using the glass tube microelectrode 15 has a drawback that it is extremely weak to vibration. However, the measurement method using the glass tube By using together with the bioelectric signal recording device described in Embodiment 2, stable bioelectric signal recording can be performed without being affected by vibration or the like at all. In addition,
When the measurement method using the glass tube microelectrode 15 and the bioelectric signal recording apparatus described in the second embodiment are used together, the main amplifier 11 shown in FIG. It can be omitted. As described above, the invention made by the inventor has been specifically described based on the embodiment. However, the present invention is not limited to the embodiment, and can be variously modified without departing from the gist of the invention. Of course, it is.

[0029]

The effects obtained by typical ones of the inventions disclosed in the present application will be briefly described as follows.

(1) According to the present invention, a single microelectrode can perform both electrical stimulation and bioelectric signal recording, and can record a bioelectric signal in a very short time after the electrical stimulation.

(2) According to the present invention, a plurality of microelectrodes can be switched to measure a bioelectric signal corresponding to each of the plurality of microelectrodes. At this time, problems such as vibration do not occur.
It can be used in combination with a measurement method using a glass tube microelectrode.

(3) According to the present invention, precise control of the electric stimulus intensity is possible, and a response with excellent reproducibility can be obtained.

[Brief description of the drawings]

FIG. 1 is a block diagram illustrating a schematic configuration of a bioelectric signal recording device according to a first embodiment of the present invention.

FIG. 2 is a block diagram showing a specific configuration of the interface circuit shown in FIG.

FIG. 3 is a timing chart showing on / off timings of the switch circuits (1) to (3) shown in FIG. 2;

FIG. 4 shows a transient phenomenon of a potential change occurring at a microelectrode when performing electrical stimulation with the bioelectric signal recording device of the first embodiment and a microscopic phenomenon when performing electrical stimulation with a conventional bioelectric signal recording device. 6 is a graph showing a result of comparison with a transient phenomenon of a potential change occurring in an electrode.

FIG. 5 is a block diagram showing a schematic configuration of an example of a conventional bioelectric signal recording device.

FIG. 6 is a diagram illustrating an example of a waveform of a bioelectric signal actually measured using the bioelectric signal recording device according to the first embodiment.

FIG. 7 is a diagram showing an example in which electrical stimulation is performed using the biological recording device of the first embodiment and a biological electrical signal from one cell is recorded.

FIG. 8 is a block diagram illustrating a schematic configuration of a bioelectric signal recording device according to a second embodiment of the present invention.

FIG. 9 is a diagram for explaining a bioelectric signal recording device according to a third embodiment of the present invention.

FIG. 10 is an enlarged view showing a portion A shown in FIG. 9;

[Explanation of symbols]

10 personal computer, 11 main amplifier, 12
... Electrical stimulus signal generator, 13, 13a-13n ... Interface circuit, 14, 14a-14n ... Microelectrode
15: glass tube microelectrode, 16: amplifier, 17: substrate,
21, 21a to 21n: input amplifier, 22, 22a to 2
2n: DC potential holding circuit, 23, 23a to 23n: switch circuit (1), 24, 24a to 24n: switch circuit (2), 25, 25a to 25n: switch circuit (3),
26, 26a to 26n: adder, 35: switch circuit.

Claims (5)

[Claims] A microelectrode; an electrostimulation signal generator for applying an electrostimulation signal to the microelectrode; a main amplifier for amplifying a bioelectric signal from the microelectrode; and a bioelectric amplifier amplified by the main amplifier. Recording means for recording a signal; and the microelectrode; an interface circuit connected between the electrical stimulation signal generator and the main amplifier; and an input amplifier for amplifying a bioelectric signal from the microelectrode. A DC potential holding circuit that holds a DC potential of a bioelectric signal input to the main amplifier, and an adder that adds an electrical stimulation signal from the electrical stimulation signal generator and a DC potential from the DC potential holding circuit. A first switch circuit connected between the input amplifier and the main amplifier, and a second switch connected between the adder and the DC potential holding circuit An interface circuit having a path, a third switch circuit connected between the microelectrode and the adder, and control means for controlling the first to third switch circuits of the interface circuit. A bioelectric signal recording device, characterized in that: 2. The apparatus according to claim 1, wherein a plurality of sets of said microelectrodes and said interface circuit are provided.
A bioelectric signal recording device according to claim 1. 3. The bioelectric signal recording device according to claim 1, wherein the interface circuit is modularized. 4. A method for automatically selecting one or more microelectrodes from among a plurality of microelectrodes in order to sequentially apply electrical stimulation to living tissue or cells other than the human body, A bioelectric signal recording method, wherein a plurality of bioelectric signals are detected and recorded by a detection electrode. 5. An electric stimulation method for applying electric stimulation to living tissues or cells other than the human body using microelectrodes, comprising the steps of: An electrical stimulation method comprising adding a DC potential of the microelectrode immediately before applying the electrical stimulation signal and performing offset compensation of the DC potential of the microelectrode.