JP3242816B2 - Information processing device using living tissue - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an information processing apparatus using a living body, which mimics the information processing mechanism of the living body.

[0002]

2. Description of the Related Art A conventional computer is mainly composed of an inorganic material such as a silicon semiconductor, and executes a serial logic operation by a Von Neumann method. However, such a method has a drawback that although it is possible to perform a logical operation accurately, it is difficult to perform a large number of information processes in parallel, and is not good at pattern recognition and the like. . On the other hand, higher organisms easily perform pattern recognition and learning, as is well known. Therefore, by elucidating the principles on which pattern recognition, learning, and memory functions such as those found in the brain are performed and imitating them, various functions that could not be satisfied with the von Neumann type computer It is said that it is possible to realize a computer having a computer, for example, a biocomputer.

[0003]

However, at present, the above-mentioned biocomputer has not been realized. In order to realize this, it is considered that an information processing apparatus capable of inputting a signal from a computer to a living tissue and outputting a signal from the living tissue to a computer is required. This is because such a device is considered to be one of the basic components for realizing the above-described biocomputer. Therefore, it is desired to realize an information processing apparatus capable of inputting a signal from a computer to a living tissue and outputting a signal from the living tissue to a computer.

[0004]

Therefore, according to the information processing apparatus using a living body of the present invention, a living tissue which has been treated (stained) with a fluorescent dye whose fluorescence intensity changes in response to a change in the state of a cell. Stimulating signal input means having a predetermined arrangement of a number of contacts used in contact with the living tissue to input a signal for stimulating the living tissue to the living tissue; A fluorescence measurement unit for measuring fluorescence emitted from the tissue at a plurality of units of the living tissue, and arbitrarily applying a stimulation signal to one or a plurality of contacts among a plurality of contacts of the stimulation signal input unit. And control means for recording a fluorescence intensity pattern measured by the fluorescence measurement means corresponding to the applied stimulus signal.

Here, as the fluorescent dye whose fluorescence intensity changes in response to a change in the state of a cell, various types of fluorescent dyes according to the purpose can be used. For example, a so-called membrane potential-sensitive fluorescent dye whose fluorescence intensity changes in response to a change in membrane potential, or a fluorescent dye whose fluorescence intensity changes in response to a change in intracellular ion concentration (for example, sodium, potassium, calcium or Examples of the fluorescent dye used include various fluorescent dyes that respond to changes in the concentration of various ions such as chlorine.

[0006] Any suitable living tissue can be used. For example, the nervous system is a typical example of a living tissue that can be used. The stimulus signal is not particularly limited,
Typically, it can be an electrical signal. This is because the electric signal is easy to control. Of course, a heat signal, an optical signal, or the like may be used depending on the design. Also, it is preferable that each of the plurality of contacts be configured to be capable of independently applying a stimulus signal. This is because a stimulus signal can be applied to a plurality of portions of the living tissue in parallel, so that a patterned stimulus signal can be input to the living tissue. Further, the fluorescence measuring means can be constituted by, for example, a device including a fluorescence microscope and a sensor, such as a photodiode array or a CCD array, which is directly or indirectly connected to the fluorescence microscope and includes a plurality of pixels. The control means is typically an electronic circuit, and can be constituted by, for example, a general computer.

[0007]

According to the structure of the present invention, an arbitrary stimulus signal can be input to the living tissue from the outside via the stimulus signal input means.
In addition, the response result of the living tissue to the input stimulus signal can be taken out by the fluorescence measuring means. Also,
Since a plurality of contacts are provided, it is possible to apply a stimulus signal to individual portions of the living tissue, for example, cell units. Further, it becomes possible to apply a stimulus signal to one of a large number of contacts, or to apply a stimulus signal in a pattern with a certain intention using a plurality of contacts. Then, the response of the living tissue corresponding to the application of the stimulus signal in these various modes can be recorded.

[0008]

Embodiments of the present invention will be described below with reference to the drawings. However, the drawings used in the description are schematically shown to the extent that the present invention can be understood. In each of the drawings used for description, the same components are denoted by the same reference numerals, and overlapping description may be omitted.

1. Description of Configuration FIG. 1 is a diagram illustrating a configuration of an information processing apparatus 10 (hereinafter, may be abbreviated as information processing apparatus 10) using a living tissue according to an embodiment. The information processing apparatus 10 shown in FIG.
, 11 is a biological tissue, 13 is a stimulus signal input means,
Reference numeral 15 denotes a fluorescence measurement unit, and 17 denotes a control unit.

Here, the living tissue 11 is treated with a membrane potential-sensitive fluorescent dye as a fluorescent dye whose fluorescence intensity changes in response to a change in the state of cells. In this embodiment, a guinea pig small intestine autonomic nerve as a living tissue is treated with a membrane potential-sensitive fluorescent dye. Specifically, a small intestinal autonomic nervous system submuscous plexus was extracted from a 2-week-old guinea pig weighing approximately 150 g, and was extracted with a Ringer's solution containing 100 μg / ml of Ringer's solution whose oxygen concentration was increased by reflux of 95% oxygen / 5% carbon dioxide. PH containing membrane potential sensitive fluorescent dye Di-8-ANNEPS
After being immersed in a 7.0 Ringer's solution for 10 minutes, a cleaning treatment with a Ringer's solution is performed. However,
If the living tissue alone is used, the living tissue will die.
It is used in a state where it is placed in a container 11b (for example, a petri dish) which is filled and circulated with a Ringer's solution (a predetermined Ringer's solution) whose oxygen concentration is increased by a reflux of% oxygen / 5% carbon dioxide. The membrane potential-sensitive fluorescent dye Di-8-ANNEPS used herein is disclosed, for example, in Document I (Biophys. J. (1994) 67 (1) 208-16). It was obtained by the inventor of the present application.

Further, in this case, the stimulus signal input means 13 is an enlarged plan view of the entire part shown in FIG. 2A and an enlarged part (P part in FIG. 2A) shown in FIG. 2B. As shown in the figure, the insulating substrate 13a, the contact 13b, and the insulating film 1
3c. And this stimulus signal input means 1
3 is immersed in a predetermined Ringer's solution 11a in a container 11b, and the biological sample is placed on the surface of the input means 13 on which the contact 13b is formed. However, a large number of contacts 13b are provided on the insulating substrate 13a,
00, of course, are provided in a 10 × 10 matrix. These contacts 13b are individually connected to the control means 17 via a wiring section (not shown), and a stimulus signal between the arbitrary contact and the predetermined Ringer's solution 11a is 100 m in this case.
The configuration is such that a voltage of V can be applied. Further, in this case, the contact 13b and the wiring portion
It is constituted by forming a pattern of an Au (gold) thin film on a. Further, the insulating film 13c is formed by each contact 13b.
Is provided with an opening 13ca for exposing the portion. The size of the contact 13b, the line width of the wiring portion, and the size of the opening 13ca provided in the insulating film 13c can be arbitrarily determined according to the design. Here, the width of the contact 13b and the line width of the wiring portion are used. Is 1 mm and the length of the contact 13 b is 1
mm, and the opening 13ca is 3 × 3 mm.

In this embodiment, the fluorescence measuring means 15 comprises a fluorescence microscope 15a and a photodiode array 15b connected to an eyepiece 15aa of the fluorescence microscope. In this case, the photodiode array 15b uses an area sensor having 24 × 24 pixels. In the fluorescence microscope 15a shown in FIG.
15ab is a fluorescence side interference filter, 15ac is a dichroic mirror, 15ad is an objective lens, 15ae is an excitation light side interference filter, and 15af is a light source. Light source 15af
A material that can emit light for exciting the fluorescent dye of the living tissue 11 is used. After light having a wavelength suitable for exciting the fluorescent dye among the light from the light source 15af passes through the excitation light side interference filter 15ae, a part of the light is guided to the living tissue 11 by the dichroic mirror 15ac. On the other hand, the fluorescence emitted from the living tissue is
d, guided to the photodiode array 15b via the dichroic mirror 15ac, the fluorescent interference filter 15ab, and the eyepiece 15aa.

The control means 17 arbitrarily applies a stimulus signal to one or a plurality of the contacts 13 b of the stimulus signal input means 13, and controls the fluorescent light corresponding to the applied stimulus signal. This is to record the fluorescence intensity pattern measured by the measuring means 15. This control means 17
Is constituted by a computer in this embodiment. Specifically, an electric signal can be arbitrarily applied to one or more of the many contacts 13b of the stimulus signal input means 13, and
The computer is configured to have at least a function of storing an output from each pixel of the photodiode array 15b.

2. Next, in order to deepen the understanding of the information processing apparatus of the present invention,
An example of a processing operation in the information processing apparatus 10 according to the embodiment will be described.

The magnification of the fluorescence microscope 15a is set to 100 here.
Double it. This magnification is set so that the observation target site of the living tissue 11 can be accommodated in the measurable region of the photodiode array 15b, and is, of course, an example, and is not limited to this magnification. However, the photodiode array 15b
Among the 24 × 24 pixels, the pixels protruding from the field of view of the eyepiece 15aa of the fluorescence microscope 15a are not used for fluorescence measurement here. This situation is schematically shown in FIGS. 3 and 4B. That is, what is shown in a substantially hexagonal shape in FIGS. 3 and 4 is the field of view of the fluorescence microscope 15a, and in each of the figures, each horizontal line portion corresponds to each pixel 15ba of the photodiode array 15b.

Next, a part of the living tissue 11 corresponding to P1 in the pixel coordinate system shown in FIG. 3 is provided as a stimulus signal through the contact 13b of the stimulus signal input means 13. Of 100 mV is applied. When such a stimulus signal is applied to a living tissue, an ion channel opens and closes in cells affected by the stimulus signal among a large number of cells provided in the living tissue, and thus the membrane potential changes in these cells. Here, since the living tissue is treated with the membrane potential-sensitive dye, this change in membrane potential appears as a change in fluorescence intensity. For this reason, a pixel (pixel of the photodiode array) receiving light from a cell affected by the stimulus signal among a large number of cells included in the living tissue receives the change in the fluorescence intensity. Electric signals can be detected. For example, the fluorescence intensity pattern obtained from the living tissue when the point P1 in the living tissue is stimulated is as shown in FIG. Further, the fluorescence intensity pattern obtained from the living tissue when the P1 point and the P2 point (see FIG. 4) in the living tissue were stimulated was as shown in FIG. Here, in FIG. 3 and FIG. 4, a zigzag signal is obtained from the pixel affected by the stimulus signal, but each zigzag portion is shown in an enlarged view in FIG. . In FIG. 5, the horizontal axis represents time, and the vertical axis represents fluorescence intensity (arbitrary unit; in fact, an electrical signal obtained by photoelectrically converting the fluorescence intensity).

As apparent from FIGS. 3 and 4, it is possible to input a signal to the living tissue from the computer (control means 17) and output the response of the living tissue to this signal from the living tissue to the computer. I understand. 3 and 4 that if the position of the living tissue 11 to which the stimulus signal is applied is changed, the output from the living tissue, that is, the distribution of the fluorescence intensity is different. From these facts, it can be considered that the device of the embodiment is an information processing device using a living tissue (in other words, a bio element).

Although the embodiment of the present invention has been described above, the present invention is not limited to the above embodiment. For example, fluorescent dyes and living tissues to be used are not limited to the above materials. The configurations of the stimulus signal input unit and the fluorescence measurement unit are not limited to the above configurations.

[0019]

As is apparent from the above description, according to the information processing apparatus using the living tissue of the present invention, the living tissue treated with a fluorescent dye whose fluorescence intensity changes in response to a change in the state of a cell. A predetermined means for inputting a stimulation signal to the living tissue; a predetermined means for measuring fluorescence emitted from the living tissue in response to the stimulation signal; and controlling the stimulation signal input means and the fluorescence intensity measuring means. Since the control device includes the predetermined control means, it is possible to input a signal from the computer to the living tissue and output a signal from the living tissue to the computer.

[Brief description of the drawings]

FIG. 1 is an explanatory diagram of an information processing apparatus using a living tissue according to an embodiment.

FIG. 2 is an explanatory diagram of a stimulus signal input unit.

FIG. 3 is an explanatory diagram of a processing operation.

FIG. 4 is an explanatory view of the processing operation following FIG. 3;

FIG. 5 is an explanatory diagram of the processing operation following FIG. 4;

[Explanation of symbols]

 10: Information processing apparatus of Example 11: Living tissue treated with membrane potential sensitive dye 11a: Predetermined Ringer's solution 11b: Container 13: Stimulation signal input means 13a: Insulating substrate 13b: Contact 13c: Insulating film 13ca: Opening provided in insulating film 15: Fluorescence measuring means 15a: Fluorescence microscope 15b: Photodiode array 15ba: One pixel of photodiode array 17: Control means

Claims (1)

(57) [Claims] 1. A living tissue which has been treated with a fluorescent dye whose fluorescence intensity changes in response to a change in the state of a cell, and which is used by being brought into contact with the living tissue to input a signal for stimulating the living tissue. Stimulus signal input means having a large number of contacts in a predetermined arrangement; fluorescence measurement means for measuring fluorescence emitted from the living tissue in response to the stimulus signal at a plurality of units of the living tissue; To arbitrarily apply a stimulus signal to one or a plurality of contacts of a number of contacts of the signal input means, and record a fluorescence intensity pattern measured by the fluorescence measurement means corresponding to the applied stimulus signal. An information processing apparatus using a living tissue, comprising: