Signal processing device, signal processing method, and signal processing program

Abstract

To provide a technique of separating a desired signal component from a signal obtained from a biological sample.SOLUTION: A signal processor has: a first signal acquisition part 51 and a second signal acquisition part 52 which acquire a first signal D11 and a second signal D12 being time series data; a first signal processing part 53 and a second signal processing part 54 which acquire a first processed signal D21 and a second processed signal D22 from the first signal D11 and the second signal D12; and a difference processing part 55 which acquires a separation signal D3 being a difference between the first processed signal D21 and the second processed signal D22. The first signal processing part 53 and the second signal processing part 54 perform at least a standardization processing to the first signal D11 and the second signal D12, by which scales between the first signal D11 and the second signal D12 can be appropriately matched. Thus, in the case where the second signal D12 is a signal in which a signal proportional to the first signal D11 is superposed with a signal finer than the signal, a component of the finer signal can be appropriately extracted.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to a signal processing device, a signal processing method, and a signal processing program for processing signals obtained from a biological sample. [Background technology]

[0002] In the field of biomeasurement, in which signals are acquired and analyzed from biological samples, the acquired signals may contain multiple superimposed components. A method for separating each component from such a signal is described in, for example, Patent Document 1.

[0003] In the method of Patent Document 1, the signals are separated using a frequency limiting filter or an averaging filter, taking advantage of the difference in properties such as the frequency of the two signals. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2011 / 074702 [Patent Document 2] Japanese Patent Publication No. 2020-150852 Summary of the Invention [Problem to be solved by the invention]

[0005] In the method of Patent Document 1, when a frequency limiting filter is used, the frequency band of the target signal must be known in advance. This makes it difficult to deal with signals with unknown frequency bands. Furthermore, when an averaging filter is used in the method of Patent Document 1, problems arise such as a decrease in real-time performance due to averaging and difficulty in detecting minute signal fluctuations.

[0006] Meanwhile, in the field of electrophysiology, ion channel detection devices are known that elucidate the behavior of single or collective cellular ion channels. Widely used ion channel detection devices include intracellular action potential detection devices using the patch clamp method and extracellular action potential detection devices using the micro-multielectrode array (MEA) method. Conventional measurement methods such as the patch clamp method and the MEA method only measure action potentials inside and outside the cells.

[0007] Patent Document 2 describes a technique for simultaneously measuring a voltage component derived from the extracellular action potential of a neuron and a current component derived from a neurotransmitter, as an application of the micro-multielectrode array (MEA) method. In this case, a current component corresponding to the voltage component derived from the extracellular action potential may be superimposed on the measured current value. When attempting to separate such measured current values ​​into the component derived from the extracellular action potential and the component derived from the neurotransmitter using the method of Patent Document 1, it is difficult to extract the current component derived from the neurotransmitter, which is a very small current component.

[0008] The present invention has been made in view of the above circumstances, and has as its object to provide a technique for separating a desired signal component from a signal obtained from a biological sample. [Means for solving the problem]

[0009] In order to solve the above problems, a first invention of the present application is a signal processing device for processing two biological signals, comprising: a first signal acquisition unit that acquires a first signal that is time-series data; a second signal acquisition unit that acquires a second signal that is time-series data; a first signal processing unit that performs at least a standardization process on the first signal and acquires a first processed signal; a second signal processing unit that performs at least a standardization process on the second signal and acquires a second processed signal; and a difference processing unit that acquires a separated signal that is a difference between the first processed signal and the second processed signal. The first signal is a measurement value of an extracellular potential of a neuron, and the second signal is a measurement value of an extracellular current of the neuron obtained simultaneously with the first signal. .

[0010] A second invention of the present application is a signal processing device of the first invention, wherein the first signal processing unit performs logarithmic processing on the first signal and then standardization processing to obtain the first processed signal, and the second signal processing unit performs logarithmic processing on the second signal and then standardization processing to obtain the second processed signal.

[0012] The first part of this application 3 The invention is a signal processing method for processing two biological signals, comprising: a) a first signal acquisition step of acquiring a first signal that is time-series data; b) a second signal acquisition step of acquiring a second signal that is time-series data; c) a first signal processing step of performing at least a standardization process on the first signal to acquire a first processed signal; d) a second signal processing step of performing at least a standardization process on the second signal to acquire a second processed signal; and e) a difference processing step of acquiring a separated signal that is the difference between the first processed signal and the second processed signal. The first signal is a measurement of an extracellular potential of a neuron, and the second signal is a measurement of an extracellular current of the neuron obtained simultaneously with the first signal. .

[0013] The first part of this application 4 The invention is 3 A signal processing method of the invention, wherein in step c), the first signal is logarithmically processed and then standardized to obtain the first processed signal, and in step d), the second signal is logarithmically processed and then standardized to obtain the second processed signal.

[0015] The first part of this application 5 The invention is a program for causing a computer to process two biological signals, the program causing the computer to execute A) a first signal acquisition step of acquiring a first signal which is time-series data, B) a second signal acquisition step of acquiring a second signal which is time-series data, C) a first signal processing step of performing at least a standardization process on the first signal to acquire a first processed signal, D) a second signal processing step of performing at least a standardization process on the second signal to acquire a second processed signal, and E) a difference processing step of acquiring a separated signal which is the difference between the first processed signal and the second processed signal. The first signal is a measurement of an extracellular potential of a neuron, and the second signal is a measurement of an extracellular current of the neuron obtained simultaneously with the first signal. .

[0016] The first part of this application 6 The invention is5 A program of the invention, wherein in step C), the first signal is logarithmically processed and then standardized to obtain the first processed signal, and in step D), the second signal is logarithmically processed and then standardized to obtain the second processed signal. [Effects of the Invention]

[0018] The first to third inventions of this application 6 According to the invention, standardization allows the scales of the first signal and the second signal to be properly matched. When the second signal is a signal in which a signal proportional to the first signal and a signal weaker than the first signal are superimposed, the first signal and the second signal have similar shapes, and the weak signal component appears as a slight difference in shape between the two signals. Therefore, by standardizing the first signal and the second signal to properly match the scales and take the difference, the weak signal component can be properly extracted. Special The first signal corresponds to the extracellular action potential of the neuron, and the second signal includes a current component derived from the extracellular action potential of the neuron, which is roughly proportional to the first signal, and a current component derived from a neurotransmitter, which is a smaller component than the first signal. Therefore, the method of the present invention is particularly useful.

[0019] In particular, the second invention of the present application, 4 Invention and 6 According to the invention, the first and second signals are not simply normalized, but the measurement data is logarithmized before use. Logarithmization increases the weighting of weak signals, making it easier to extract weak signals. [Brief explanation of the drawings]

[0021] [Figure 1] FIG. 2 is a schematic diagram showing electrical connections of the measurement system according to the first embodiment. [Figure 2] FIG. 1 is a perspective view of a cell retention container according to a first embodiment. [Figure 3] FIG. 2 is a functional block diagram of a signal processing unit according to the first embodiment. [Figure 4] 4 is a flowchart showing the flow of signal processing performed in the signal processing unit according to the first embodiment. [Figure 5] FIG. 2 is a diagram conceptually illustrating a first signal, a second signal, and a separated signal in the first embodiment. [Figure 6] 10 is a flowchart showing the flow of signal processing according to a modified example. [Figure 7] 10 is a flowchart showing the flow of signal processing according to another modified example. DETAILED DESCRIPTION OF THE INVENTION

[0022] Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the following description, the direction parallel to the bottom surface of the cell-retention container will be referred to as the "horizontal direction," and the direction perpendicular to the horizontal direction will be referred to as the "vertical direction." However, the orientation of the cell-retention container during use does not necessarily require the bottom surface of the cell-retention container to be in the horizontal direction.

[0023] 1. First Embodiment <1-1. Measurement system> First, a measurement system 100 including a signal processing device 1 according to a first embodiment of the present invention will be described with reference to Fig. 1. Fig. 1 is a schematic diagram showing the electrical connections of the measurement system 100 according to the first embodiment of the present invention. This measurement system 100 is a system for measuring the electrical properties of cells or tissues contained in a cell retention container 20 and processing the measurement data.

[0024] Here, the term "cells" refers not only to cells cultured in the cell holding container 20 described below, but also to cells of biological tissues such as brain slice samples contained in the cell holding container 20. In the measurement system 100, the cells to be measured are, for example, nerve cells such as dopaminergic nerve cells and serotonergic nerve cells.

[0025] The measurement system 100 includes a cell holding container 20, a measurement device 30, and a signal processing device 1.

[0026] FIG. 2 is a perspective view of a cell retention container 20 according to a first embodiment of the present invention. The cell retention container 20 is one embodiment of a cell retention container that accommodates and retains cells and culture medium therein and measures the electrical properties of the retained cells. The cell retention container 20 of this embodiment is a container for culturing cells therein and measuring the electrical properties of the cultured cells. Specifically, the cell retention container 20 of the present invention is used together with a measuring device 30, and the extracellular voltage of cells cultured in the cell retention container 20 and the current when a voltage is applied are measured.

[0027] 2, the cell retention container 20 has a main body 9 having a cup-shaped inner surface 90, a plurality of array electrodes 81, a plurality of peripheral electrodes 82, and an insertion electrode 83. Cells and culture medium are retained in the internal space 900 of the cell retention container 20. The sample retained in the cell retention container 20 may be cells and a preservation solution, biological tissue and a culture medium, biological tissue and a preservation solution, etc.

[0028] The inner surface 90 of the main body 9 has a flat bottom surface 91 and side surfaces 92 extending upward from the edge of the bottom surface 91. The main body 9 in this embodiment is cylindrical with a bottom. However, the bottom of the main body 9 may have other shapes such as an elliptical or rectangular shape, or may have a hemispherical shape, as long as it is cup-shaped. When culturing cells, the cells are seeded with the center of the bottom surface 91 as the center. This positions the cells with the center of the bottom surface 91 as the center.

[0029] The plurality of array electrodes 81 and the plurality of peripheral electrodes 82 are each fixed to the bottom surface 91. The plurality of array electrodes 81 are arranged two-dimensionally in the center of the bottom surface 91. In this embodiment, the electrode unit 8 has 16 array electrodes 81 arranged in four vertical rows and four horizontal rows. Note that all electrodes not labeled with reference numerals in FIG. 2 are array electrodes 81. Furthermore, the array electrodes 81 may be, for example, carbon nanotube electrodes whose surfaces are covered with a thin film of carbon nanotubes.

[0030] The peripheral electrodes 82 are arranged on the peripheral portion of the bottom surface 91. That is, the peripheral electrodes 82 are arranged outside the array electrodes 81. In this embodiment, the electrode unit 8 has four peripheral electrodes 82 arranged at equal intervals in the circumferential direction. The peripheral electrodes 82 are made of, for example, carbon nanotube electrodes.

[0031] The inserted electrode 83 is an electrode inserted into the space 900 of the main body 9. In this embodiment, the inserted electrode 83 is a cylindrical electrode extending in the vertical direction. In this embodiment, the inserted electrode 83 is arranged outside the plurality of arrayed electrodes 81. The inserted electrode 83 may be a plate-shaped electrode placed on the bottom surface 91, or may have any shape as long as it can be arranged within the space 900. The inserted electrode 83 is formed of, for example, platinum (Pt).

[0032] 1 , some of these electrodes 81, 82, and 83 are used as a first working electrode 21, a counter electrode 22, a reference electrode 23, and a second working electrode 24, which are connected to the measurement device 30. Specifically, one of the plurality of arrayed electrodes 81 is used as the first working electrode 21. The inserted electrode 83 is used as the counter electrode 22. One of the plurality of peripheral electrodes 82 is used as the reference electrode 23. Furthermore, another of the plurality of arrayed electrodes 81 is used as the second working electrode 24.

[0033] Here, when cells are placed in cell retention container 20, the cells are placed so that first working electrode 21 and second working electrode 24 are placed within an area that will come into contact with the cells. Specifically, when cells are cultured in cell retention container 20, the cells are seeded so that they overlap first working electrode 11 and second working electrode 14. After cell culture, first working electrode 21 and second working electrode 24 may be set from among array electrodes 81 whose upper surfaces are sufficiently covered with cells. On the other hand, when the measurement target is tissue, the tissue is placed so that it covers both first working electrode 21 and second working electrode 24.

[0034] On the other hand, when placing the cells in the cell holding container 20, the cells are placed so that at least the reference electrode 23 is placed outside the cell placement area. In other words, the cells are placed so that the cells are not placed on at least one of the peripheral electrodes 82.

[0035] The measuring device 30 includes a voltage monitoring circuit 31, a current detection circuit 32, a voltage detection circuit 33, and a current value calculation unit 34. The voltage monitoring circuit 31, the current detection circuit 32, and the voltage detection circuit 33 are arranged on, for example, one substrate.

[0036] The voltage monitoring circuit 31 is a circuit with a voltage source that applies a voltage between the first working electrode 21 and the counter electrode 22 and monitors the applied voltage between the first working electrode 21 and the reference electrode 23. The voltage monitoring circuit 31 outputs a monitoring voltage Vm that is proportional to the voltage between the first working electrode 21 and the counter electrode 22.

[0037] Current detection circuit 32 is connected to first working electrode 21 and detects the current flowing through first working electrode 21. Current detection circuit 32 outputs current detection voltage Vi having a voltage value proportional to the current between first working electrode 21 and counter electrode 22.

[0038] Voltage detection circuit 33 detects the voltage between reference electrode 23 and second working electrode 24. Voltage detection circuit 33 outputs a detected voltage Vv that is proportional to the voltage between second working electrode 24 and reference electrode 23.

[0039] The current value calculation unit 34 receives the monitored voltage Vm detected by the voltage monitoring circuit 31 and the current detection voltage Vi, which is the output voltage of the current detection circuit 32. The current value calculation unit 34 calculates the detection current It, which corresponds to the current value of the current flowing through the first working electrode 21, based on the monitored voltage Vm and the current detection voltage Vi.

[0040] The signal processing unit 10 separates the current component In derived from the neurotransmitter contained in the detected current It from the detected voltage Vv and the detected current It detected by the measuring device 30. The specific configuration of the signal processing unit 10 will be described later.

[0041] The current value calculation unit 34 and the signal processing unit 10 are realized by, for example, a personal computer 40. Furthermore, the signal processing device 1 of this embodiment is configured by the personal computer 40 having the signal processing unit 10. Note that in this embodiment, the current value calculation unit 34 and the signal processing unit 10 are realized by the same personal computer 40, but the present invention is not limited to this. The current value calculation unit 34 and the signal processing unit 10 may be realized by different personal computers. Furthermore, the current value calculation unit 34 may be a microcontroller provided on the same board as the voltage monitoring circuit 31, the current detection circuit 32, and the voltage detection circuit 33.

[0042] The personal computer 40 is composed of an arithmetic processing unit 401 such as a CPU, a memory 402 such as a RAM, and a storage unit 403 such as a hard disk drive. A signal processing program P is stored in the storage unit 403 of the personal computer 40. The arithmetic processing unit 401 of the personal computer 40 executes the signal processing program P. This realizes the signal processing of the signal processing unit 10, which will be described later. That is, this realizes the current value calculation unit 34 and the signal processing unit 10.

[0043] The signal processing program P is read from, for example, a storage medium M on which the signal processing program P is stored, and stored in the storage unit 403 of the computer 40. The storage medium M is, for example, a CD-ROM, a DVD-ROM, a flash memory, etc. However, the signal processing program P may also be input to the computer 40 via a network.

[0044] The personal computer 40 is connected to a display unit 41 including a display device and an input unit 42 including a keyboard, a mouse, and the like.

[0045] <1-2. Signal processing device> Next, the signal processing unit 10 constituting the signal processing device 1 will be described with reference to Fig. 3. Fig. 3 is a functional block diagram of the signal processing unit 10.

[0046] The signal processing unit 10 processes two biological signals, a first signal D11 and a second signal D12. Specifically, the signal processing unit 10 uses the first signal D11 to remove a component proportional to the first signal D11 from the second signal D12 and separate and extract other components. The signal processing unit 10 processes time-series data of the detected voltage Vv detected by the measuring device 30 as the first signal D11 and time-series data of the detected current It calculated by the measuring device 30 as the second signal D12.

[0047] As shown in Figure 3, the signal processing unit 10 has a first signal acquisition unit 51, a second signal acquisition unit 52, a first signal processing unit 53, a second signal processing unit 54, and a difference processing unit 55 as processing units realized through operational control.

[0048] While measurement is being performed by the measurement device 30, the detected voltage Vv is input to the first signal acquisition unit 51 from the measurement device 30. The first signal acquisition unit 51 acquires time-series data Vv(t) of the detected voltage Vv as a first signal D11.

[0049] While measurement is being performed by the measurement device 30, the detected current It is input to the second signal acquirer 52 from the measurement device 30. The second signal acquirer 52 acquires time-series data It(t) of the detected current It as the second signal D12. The detected current It(t) is time-series data corresponding to the current detection voltage Vi acquired at the same timing as the detected voltage Vv(t). Note that if the acquired second signal D12 is in opposite phase to the first signal D11, the first signal acquirer 51 and the second signal acquirer 52 invert either the first signal D11 or the second signal D12 to align the phases.

[0050] The first signal processing unit 53 performs at least a standardization process on the first signal D11 to obtain a first processed signal D21. In this embodiment, the first signal processing unit 53 performs a logarithmic process on the first signal D11 and then a standardization process to obtain the first processed signal D21.

[0051] The second signal processing unit 54 performs at least a standardization process on the second signal D12 to obtain a second processed signal D22. In the present embodiment, the second signal processing unit 54 performs a logarithmic process on the second signal D12 and then a standardization process to obtain the second processed signal D22.

[0052] The difference processing unit 55 obtains a separated signal D3 which is the difference between the first processed signal D21 and the second processed signal D22.

[0053] The flow of signal processing in the signal processing unit 10 will be described below with reference to Figures 4 and 5. Figure 4 is a flowchart showing the flow of signal processing performed in the signal processing unit 10. Figure 5 is a diagram conceptually showing the detected voltage Vv(t), the detected current It(t), and the separated signal Z(t).

[0054] First, while measurement is being performed by the measurement device 30, the detected voltage Vv and the detected current It are simultaneously input from the measurement device 30 to the signal processing unit 10 (step S1). At this time, the first signal acquisition unit 51 acquires time-series data Vv(t) of the detected voltage Vv as a first signal D11. The second signal acquisition unit 52 acquires time-series data It(t) of the detected current It as a second signal D12. Note that if the acquired second signal D12 is in opposite phase to the first signal D11, the first signal acquisition unit 51 and the second signal acquisition unit 52 invert either the first signal D11 or the second signal D12 to align the phases.

[0055] That is, step S1 includes a first signal acquisition step of acquiring a first signal D11, which is time-series data, and a second signal acquisition step of acquiring a second signal D12, which is time-series data.

[0056] When the measurement in the measuring device 30 is completed, the first signal acquiring unit 51 passes the first signal D11 to the first signal processing unit 53. In addition, the second signal acquiring unit 52 passes the second signal D12 to the second signal processing unit .

[0057] The detected voltage Vv(t) and the detected current It(t) are time series data corresponding to the extracellular potential and extracellular current over the same period (period on the time axis). The detected voltage Vv(t) corresponds to the extracellular action potential of a neuron. The detected current It(t) includes a current component Iv(t) derived from the extracellular action potential of the neuron and a current component In(t) derived from a neurotransmitter. Here, the current component Iv(t) derived from the extracellular action potential is roughly proportional to the detected voltage Vv(t) derived from the extracellular action potential.

[0058] In the following steps, this fact is utilized to subtract the current component Iv(t) derived from the extracellular action potential from the detected current It(t) to extract the current component In(t) derived from the neurotransmitter.

[0059] Next, the first signal processing unit 53 performs logarithmic processing on the input first signal D11 to calculate a first logarithmic signal (step S2). If the first signal D11 is represented as Vv(t) and the first logarithmic signal obtained by logarithmizing the first signal D11 is represented as X1(t), then the following can be expressed:

[0060]

number

[0061] When the first signal D11 has a zero or negative value, the first signal processing unit 53 may correct the first signal D11 before calculating the first logarithmic signal. Specifically, when there is a data period (period on the time axis) in which Vv(t)≦0, the first signal processing unit 53 adds a constant K1 to the first signal D11 for all periods so that Vv(t)+K1>0 is always satisfied.

[0062] Next, the first signal processing unit 53 performs a standardization process on the calculated first logarithmic signal to obtain a first processed signal D21 (step S3). Then, the first signal processing unit 53 passes the obtained first processed signal D21 to the difference processing unit 55.

[0063] Specifically, in step S3, the average value x1 and variance σ1 of the first logarithmic signal X1(t) in the data period (period on the time axis) are calculated. Then, the first processed signal D21 is calculated using the following equation. In the following equation, the first processed signal D21 is represented by Y1(t).

[0064]

number

[0065] Steps S2 and S3 constitute a first signal processing step in which at least a standardization process is performed on the first signal D11 to obtain a first processed signal D21. In this embodiment, in the first signal processing step of steps S2 and S3, the first signal D11 is logarithmized and then standardized to obtain the first processed signal D21.

[0066] Following steps S2 and S3, or in parallel with steps S2 and S3, steps S4 and S5 are performed. In step S4, the second signal processing unit 54 performs logarithmic processing on the input second signal D12 to calculate a second logarithmic signal. If the second signal D12 is denoted by It(t) and the second logarithmic signal obtained by logarithmizing the second signal D12 is denoted by X2(t), then the following can be expressed:

[0067]

number

[0068] If the second signal D12 has a zero or negative value, the second signal processing unit 54 may correct the second signal D12 before calculating the first logarithmic signal. Specifically, if there is a data period (a period on the time axis) in which It(t)≦0, the second signal processing unit 54 adds a constant K2 to the second signal D12 for all periods so that It(t)+K2>0 is always satisfied.

[0069] Next, the second signal processing unit 54 performs a standardization process on the calculated second logarithmic signal to obtain a second processed signal D22 (step S5). Then, the second signal processing unit 54 passes the obtained second processed signal D22 to the difference processing unit 55.

[0070] Specifically, in step S5, the average value x2 and variance σ2 of the second logarithmic signal X2(t) in the data period are first calculated. Then, the second processed signal D22 is calculated using the following equation. In the following equation, the second processed signal D22 is represented by Y2(t).

[0071]

number

[0072] Steps S4 and S5 constitute a second signal processing step in which at least a standardization process is performed on the second signal D12 to obtain a second processed signal D22. In this embodiment, in the first signal processing step of steps S4 and S5, the second signal D12 is logarithmized and then standardized to obtain the second processed signal D22.

[0073] After steps S2 to S3 and steps S4 to S5 are completed, the difference processing unit 55 calculates the difference between the first processed signal D21 and the second processed signal D22 to obtain a separated signal D3 (step S6). Step S6 is a difference processing step for obtaining a separated signal D3, which is the difference between the first processed signal D21 and the second processed signal D22. When the separated signal D3 is represented by Z(t), it can be expressed as follows:

[0074]

number

[0075] As described above, the detected voltage Vv(t), which is the first signal D11, is a measured voltage derived from the extracellular action potential of a neuron. The detected current It(t), which is the second signal D12, is a superposition of a current component Iv(t) derived from the extracellular action potential of a neuron and a current component In(t) derived from a neurotransmitter. The current component Iv(t) derived from the extracellular action potential is approximately proportional to the detected voltage Vv(t) derived from the extracellular action potential. Therefore, by appropriately separating the component proportional to the first signal D11 from the second signal D12, a signal corresponding to the current component In(t) derived from a neurotransmitter can be obtained.

[0076] 5 shows a schematic example of the detected voltage Vv(t) derived from the extracellular action potential, which is the first signal D11, the detected current It(t) which is the second signal D12, and Z(t) which is the separated signal D3. By performing the signal processing shown in steps S1 to S6 described above, the component derived from the first signal D11 contained in the second signal D12 is removed, as shown in FIG. 5, and a separated signal Z(t) corresponding to the signal component (current component derived from the neurotransmitter) In(t) contained only in the second signal D12 can be obtained.

[0077] In this embodiment, in steps S3 and S5, the signal derived from the first signal D11 (first logarithmic signal) and the signal derived from the second signal D12 (second logarithmic signal) are standardized, respectively. By standardizing, the scales of the signal derived from the first signal D11 (first logarithmic signal) and the signal derived from the second signal D12 (second logarithmic signal) can be appropriately matched.

[0078] In particular, when the second signal D12 (detected current It(t)) is a signal in which a signal (current component Iv(t)) proportional to the first signal D11 (detected voltage Vv(t)) is superimposed on a signal (current component In(t)) that is smaller than the first signal D11, as in this embodiment, the first signal D11 and the second signal D12 have similar shapes, and the small signal component appears as a slight difference in shape between the two signals. Therefore, by standardizing the first signal and the second signal to appropriately match the scales and take the difference, the small signal component (current component In(t)) can be appropriately extracted.

[0079] In this embodiment, logarithmic processing is performed in steps S2 and S4 before the standardization processing in steps S3 and S5. By logarithmizing the first signal D11 and the second signal D12, the weighting of signals in the smaller value range is increased to provide stationarity. This allows for more appropriate extraction of the weak signal component (current component In(t)).

[0080] In this embodiment, the first signal processing unit 53 and the second signal processing unit 54 perform processing including standardization throughout the entire data period of the first signal D11 and the second signal D12, but the present invention is not limited to this. The period (time period) for data processing may be set to a predetermined period (e.g., 10 seconds), and the first signal D11 and the second signal D12 may be divided into these periods for processing including standardization.

[0081] <2. Modifications> Although one embodiment of the present invention has been described above, the present invention is not limited to the above embodiment.

[0082] Fig. 6 is a flowchart showing the flow of signal processing according to one modification. In the above embodiment, the first signal processing unit 53 and the second signal processing unit 54 logarithmically convert the first signal D11 and the second signal D12 and then standardize them. In contrast, in the example of Fig. 6, the first signal processing unit 53 and the second signal processing unit 54 do not perform logarithmic conversion on the first signal D11 and the second signal D12, but only perform standardization.

[0083] In the example of FIG. 6, first, similarly to the above embodiment, the first signal acquirer 51 and the second signal acquirer 52 acquire the first signal D11 and the second signal D12, respectively (step S1A).

[0084] Next, the first signal processing unit 53 performs standardization processing on the first signal D11 to obtain a first processed signal D21 (step S2A), and the second signal processing unit 54 performs standardization processing on the second signal D12 to obtain a second processed signal D22 (step S3A).

[0085] Thereafter, the difference processing unit 55 calculates the difference between the first processed signal D21 and the second processed signal D22 to obtain the separated signal D3 (step S4A).

[0086] 6, it is sufficient that the first signal processing unit 53 and the second signal processing unit 54 at least perform standardization processing on the first signal D11 and the second signal D12 before performing differential processing (step S4A). Even in this case, by matching the scales of the first signal D11 and the second signal D12, it is possible to obtain a separated signal D3 from which components common to the first signal D11 and the second signal D12 have been appropriately removed.

[0087] Fig. 7 is a flowchart showing the flow of signal processing according to another modification. In the above embodiment, the first signal processing unit 53 and the second signal processing unit 54 logarithmically convert the first signal D11 and the second signal D12 and then standardize them. In contrast, in the example of Fig. 7, the first signal processing unit 53 and the second signal processing unit 54 perform logarithmic conversion on the first signal D11 and the second signal D12 after standardizing them.

[0088] In the example of FIG. 7, first, similarly to the above embodiment, the first signal acquirer 51 and the second signal acquirer 52 acquire the first signal D11 and the second signal D12, respectively (step S1B).

[0089] Next, the first signal processing unit 53 performs standardization processing on the first signal D11 to obtain a first standardized signal (step S2B), and then performs logarithmic processing on the first standardized signal to obtain a first processed signal D21 (step S3B).

[0090] The second signal processing unit 54 also performs standardization processing on the second signal D12 to obtain a second standardized signal (step S4B), and then performs logarithmic processing on the first standardized signal to obtain a second processed signal D22 (step S5B).

[0091] Thereafter, the difference processing unit 55 calculates the difference between the first processed signal D21 and the second processed signal D22 to obtain the separated signal D3 (step S6B).

[0092] When the scales of the first signal D11 and the second signal D12 are significantly different, by first performing the standardization process and then the logarithmic process in this manner, it is possible to prevent the weighting of components similar to the first signal D11 contained in the second signal D12 from being significantly different in logarithmic conversion due to the difference in scale.

[0093] In the above embodiment and modified examples, the first signal processing unit 53 and the second signal processing unit 54 perform only standardization processing or standardization processing and logarithmic conversion processing on the first signal D11 and the second signal D12, but the present invention is not limited to this. The first signal processing unit 53 and the second signal processing unit 54 may perform standardization processing and other necessary processing on the first signal D11 and the second signal D12.

[0094] For example, the first signal processing unit 53 and the second signal processing unit 54 may perform a process of removing known noise on the first signal D11 and the second signal D12 in addition to the standardization process. Furthermore, when the signals to be processed are signals other than the detected voltages and detected currents in the above-mentioned neurons, a signal processing step such as a filtering process suited to the properties of the signals may be performed in addition to the standardization process.

[0095] Furthermore, the configuration of the measurement system and the detailed configuration of the cell retention container may differ from those shown in the drawings of the present application. Furthermore, the elements appearing in the above-described embodiments and modifications may be combined as appropriate within the scope of not causing any contradiction. [Explanation of symbols]

[0096] 1. Signal Processing Device 10 Signal Processing Section 51 First signal acquisition unit 52 Second signal acquisition unit 53 First signal processing section 54 Second signal processing section 55 Differential Processing Unit D11 1st signal D12 2nd signal D21 1st processed signal D22 Second processed signal D3 Separation Signal

Claims

1. A signal processing device for processing two biological signals, comprising: a first signal acquisition unit that acquires a first signal that is time-series data; a second signal acquisition unit that acquires a second signal that is time-series data; a first signal processing unit that performs at least a standardization process on the first signal to obtain a first processed signal; a second signal processing unit that performs at least a standardization process on the second signal to obtain a second processed signal; a difference processing unit that obtains a separation signal that is a difference between the first processed signal and the second processed signal; and the first signal is a measurement of an extracellular potential of a neuron; A signal processing device, wherein the second signal is a measurement value of an extracellular current of the neuron obtained simultaneously with the first signal.

2. 2. The signal processing device according to claim 1, the first signal processing unit performs a logarithmic process on the first signal and then a standardization process on the first signal to obtain the first processed signal; The second signal processing unit performs a logarithmic process on the second signal and then a standardization process on the second signal to obtain the second processed signal.

3. A signal processing method for processing two biological signals, comprising: a) a first signal acquisition step of acquiring a first signal which is time-series data; b) a second signal acquisition step of acquiring a second signal which is time-series data; c) a first signal processing step of performing at least a standardization process on the first signal to obtain a first processed signal; d) a second signal processing step of performing at least a standardization process on the second signal to obtain a second processed signal; e) a differential processing step of obtaining a separation signal that is the difference between the first processed signal and the second processed signal; Including, the first signal is a measurement of an extracellular potential of a neuron; A signal processing method, wherein the second signal is a measurement value of an extracellular current of the neuron obtained simultaneously with the first signal.

4. 4. A signal processing method according to claim 3, In the step c), the first signal is logarithmized and then standardized to obtain the first processed signal; In the step d), the second signal is logarithmically converted and then standardized to obtain the second processed signal. Signal processing methods.

5. A program for causing a computer to process two biological signals, the program comprising: A) a first signal acquisition step of acquiring a first signal which is time-series data; B) a second signal acquisition step of acquiring a second signal which is time-series data; C) a first signal processing step of performing at least a standardization process on the first signal to obtain a first processed signal; D) a second signal processing step of performing at least a standardization process on the second signal to obtain a second processed signal; E) a differential processing step of obtaining a separation signal that is the difference between the first processed signal and the second processed signal; Execute the first signal is a measurement of an extracellular potential of a neuron; The second signal is a measurement of an extracellular current of the neuron obtained simultaneously with the first signal.

6. 6. The program according to claim 5, In the step C), the first signal is logarithmically converted and then standardized to obtain the first processed signal; In the step D), the second signal is logarithmically converted and then standardized to obtain the second processed signal. program.

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