WO2014034690A1

WO2014034690A1 - Object to be examined retention device in biological/chemical/physical phenomenon detection device, and examination device using same

Info

Publication number: WO2014034690A1
Application number: PCT/JP2013/072925
Authority: WO
Inventors: 孝司櫻井; 澤田　和明; 進寺川
Original assignee: 国立大学法人豊橋技術科学大学
Priority date: 2012-08-31
Filing date: 2013-08-27
Publication date: 2014-03-06
Also published as: JPWO2014034690A1

Abstract

Provided is an object to be examined retention device whereby it is possible to efficiently adjust a location relation between a sensor chip and an object to be examined, and to examine cells, etc., via a medium, etc., without removing the object to be detected from the medium, etc. Also provided is a detection device comprising the object to be examined retention device. An object to be examined retention device comprises: a cylindrical or ring-shaped region configuration part (2) having a hollow part which is capable of encircling a prescribed region of a sensor chip (4); and a sheet (3) which is disposed upon one aperture surface of this region configuration part, and which has an area appropriate to supporting an object to be examined. An examination device comprises, retained upon a base part (90): a stage (91) whereupon the object to be examined retention device is positioned; a horizontal direction rail part (92) which is anchored to the base part; a slider (93) which is capable of moving along the rail; a microscope (94) which is mounted upon the slider; and a sensor unit (95) which is mounted upon the slider. The sensor unit further comprises a probe (96) whereby the sensor chip is positioned facing the stage.

Description

Inspection object holding device in biological / chemical / physical phenomenon detection device and inspection device using the same

The present invention relates to an inspection object holding device in a biological / chemical / physical phenomenon detection device and an inspection device using the same, and particularly, an inspection object used in a physiological function inspection of a tissue or a cell forming a living body. The present invention relates to an object holding device and an inspection device.

In order to inspect the physiological functions of living tissues and cells, it has been attempted to detect biological, chemical, and physical phenomena of the tissues and cells. When detecting such phenomena, various sensors are used. Is used. The detection of biological / chemical / physical phenomena using various sensors is largely classified into a proximity type and a remote type depending on the relationship between the inspection object and the sensor. The proximity type is a method in which an inspection object and a sensor are brought close to each other (contact state or close enough not to touch), and mainly includes electrical sensing. On the other hand, in the remote type, the object to be inspected and the sensor are arranged with an appropriate distance, and mainly sensing by light or magnetism. Among these, the inventors of the present application are researching and developing proximity-type biological / chemical / physical phenomenon detection devices. The detection device includes a sensing unit whose potential changes according to a biological / chemical / physical phenomenon, a charge supply unit that supplies charges to the sensing unit, and a charge that exists between the charge supply unit and the sensing unit. A sensor comprising an injection control unit and a floating diffusion unit for accumulating the charge transferred from the sensing unit is used, and by arranging a plurality of the sensors to form a sensor chip, biological, chemical, It was possible to detect the distribution of physical phenomena (see Patent Document 1).

WO2007 / 108465 gazette 2004-113092

In general, when inspecting physiological functions such as a living body or a cell, the distance between the sensing unit of the sensor forming the sensor chip and the object to be inspected, and the object to be inspected in the area where the sensor is arranged (sensing area) The position of this would affect the accuracy and efficiency of the inspection. In other words, in the case of a device that detects biological / chemical / physical phenomena by contacting or approaching the sensing object to the sensing unit, the biological / chemical / physical part of the part where the testing object cannot contact or sufficiently approach the sensing unit. The phenomenon cannot be detected, and the inspection accuracy of the inspection object is affected. Moreover, in the detection apparatus which contacts a test object and a sensing part, the other sensing function for detecting the contact state of both needs to be added, and it had influence on inspection efficiency. This is the same in remote sensing, and accurately arranging the distance and position between the sensor and the inspection object can improve the inspection accuracy.

Also, when the inspection object is brought into contact with the sensor chip (especially the sensing area), when the inspection object is strongly pressed against the sensor, there is a risk of damaging the inspection object. In this case, the instrument may damage the sensor chip, and it has been difficult to bring the inspection object into contact with the sensor by applying a physical external force. In addition, even when approaching to the extent that they do not touch, if the sensor is extremely close to the object to be inspected, both may come into contact with each other in the approaching process, and there is a risk of damage etc. It was. The same was true for the remote type.

On the other hand, if the test object is to be subjected to a stage of culture or the like, the test object is collected from the medium or the like used for culture or the like and inspected by a biological / chemical / physical phenomenon detection device. However, no means has been developed for inspecting the test object together with the culture medium. In addition, although the cell culture chip | tip provided with detection means, such as a pH sensor, is developed (refer patent document 2), the pH sensor etc. which are used here are not for testing the cell during culture | cultivation but culture | cultivation. This was for detecting the state of the liquid, and the observation of cells during the culture period was by an optical microscope.

The present invention has been made in view of the above-mentioned points, and the object of the present invention is to efficiently adjust the positional relationship between the sensor and the test object, and for cells and the like that are to undergo culture etc. It is to provide an inspection object holding device that can be inspected without removing the inspection object from a culture medium or the like, and further to provide an inspection device having the inspection object holding device.

Therefore, as a result of intensive studies, the inventors of the present application have completed a suitable inspection object holding device and an inspection device using the same. That is, the present invention relating to the inspection object holding device is a biological / chemical / physical phenomenon detection device including a sensor chip in which a plurality of sensors having a sensing unit for detecting biological / chemical / physical phenomena are arranged to form a sensing area. A cylindrical or annular region constituting part having a hollow part capable of enclosing a predetermined range of the sensing area, and a device for holding the inspection object at an appropriate position with respect to each sensing part of the sensor chip, It is provided with the sheet | seat part which is provided in the one opening surface of a structure part, and has a suitable area which can carry | support a test object.

The inspection object holding device having the above-described configuration includes a sheet portion provided on one opening surface of a cylindrical body or an annular body forming the region configuration portion, and the sheet portion is configured to carry the inspection object on the sheet portion. Can be adjusted close to the sensor chip to adjust the three-dimensional positional relationship between the inspection object and the sensor. That is, the positional relationship on the surface of the sensing area formed on the sensor chip and the distance between them can be adjusted. Here, as the test object, various substances that form a living body are assumed, and in addition to blood and body fluid, an individual, a tissue, a cell, or the like that constitutes skin, bone, organ, or the like is included. Furthermore, cells during or after the culture are also included. In addition, the term “carrying” is not limited to the state of adhering to the surface of the sheet part, but the state infiltrated into the tissue constituting the sheet part, and the inspection liquid (such as physiological saline) in which the inspection object is diffused is the inspection object. It is a concept that includes a state in which the sheet portion is impregnated with the object.

Further, the present invention according to the inspection object holding device is a sheet portion in which the sheet portion is disposed so as to close the opening surface to an end surface forming one opening surface of the region constituting portion. There may be.

Since the inspection object holding device having the above configuration is in a state in which the sheet portion is provided on the entire end surface along one of the opening surfaces of the cylindrical body or the annular body forming the region configuration portion, the surface of the sheet portion In the state where the inspection object is carried on the sheet, the inspection object exists at the position of the sheet portion. Therefore, the positional relationship between the sensor and the inspection object can be adjusted by adjusting the position of the sheet portion, that is, the position of the end surface of the opening surface of the region constituting portion. Further, when the inspection object is to be carried on the outer surface of the sheet portion (the surface exposed to the outside of the region constituting portion, hereinafter referred to as the surface), the surface of the sheet portion is brought close to the sensing area. Thus, the inspection object can be brought close to a wide range of the sensing area. In addition, when the region constituent portion is a cylindrical body, the opening surface on the side where the sheet portion is provided and the opening surface on the opposite side are used separately. Both of them can be brought close to each other, and can be used in consideration of the distance to the sensing area (distinguishing between contact and approach).

Further, in the present invention according to the inspection object holding device, the sheet portion may be formed of a mesh-like or porous sheet material. In this case, the inside and the outside of the region constituent part communicate with each other through a mesh or a fine hole, and gas, liquid, ions, or the like can pass therethrough. With such a configuration, when the inspection object is carried on the surface of the sheet portion, the inner surface of the sheet portion (the surface located inside the region forming portion, hereinafter referred to as the back surface) is changed to the inspection object on the surface. On the other hand, gas or liquid can be supplied. Furthermore, even when the inspection object is carried on the back surface of the sheet part, the inspection object (only part of itself or ions, etc.) is moved to the front surface side of the sheet part through a mesh or a fine hole. Therefore, by bringing the seat portion close to the sensing area, it is possible to bring the inspection object (only itself or only a part of ions, etc.) close to the sensing area. Further, when cells or the like are cultured using the sheet part, water and nutrients can be supplied from the opposite side of the sheet part, and a sheet part suitable for the culture can be configured. The mesh or porous sheet material is selected from different types depending on the inspection object, and is appropriately selected according to the type of material to be passed through the sheet portion. The size of the mesh or micropore formed in these sheet materials can be changed according to the object to be passed (gas, liquid or ion, etc.), and the size of the mesh allows only gas or ion to pass through. Alternatively, by using the micropores, it is possible to allow only gas or ions to pass through while blocking the liquid. Furthermore, the size of the mesh or micropore may be selected according to the size of the inspection object. For example, when the inspection object is a living tissue, it is about 100 μm, and when it is a cell, it is about several μm. By doing so, it is possible to pass these biological tissues and cells to the extent that they are not detached from the sheet material.

In addition, since a general sensor chip forms a sensing area in which a plurality of small, square sensors each having a side of several tens of μm are regularly arranged vertically and horizontally, the mesh of the sheet material is used. Alternatively, fine holes (hereinafter simply referred to as “holes”) having the same size and the same size as the individual sensors may be used, and the sensors may be arranged so as to match the holes. Thereby, when the inspection object carried on the sheet material is divided and concentrated in each hole, the inspection object concentrated in the plurality of holes can be sensed by each sensor for each hole. This is the same whether the inspection object is carried on either the front surface or the back surface of the sheet portion. That is, when the inspection object is carried on the back surface of the sheet, the inspection object is divided and passed through each hole. When the inspection object is carried on the surface of the sheet portion, the inspection object is diffused to each hole. It moves so as to separate, and the inspection object concentrates in each hole.

As described above, the mesh or fine pores of the sheet portion are configured to allow gas, liquid, ions, etc. to pass through. However, when carrying an inspection object on the surface of the sheet, these passages are essential. It is not a condition. In other words, the inspection object carried on the surface of the sheet part may be brought close to the sensor chip by the sheet part, and when contacting, the inspection object can be appropriately pressed by the sheet part. The positional relationship between the object and the sensor can be adjusted.

Further, according to the present invention relating to the inspection object holding device, the sheet portion includes a mesh-like or porous flexible first sheet material, and a material having elasticity and a Young's modulus greater than that of the first sheet material. The structure formed by laminating | stacking the comprised 2nd sheet material of the network structure may be sufficient.

According to the inspection object holding device having the above configuration, the second sheet material maintains the planar state of the sheet portion by its elastic force, and the positional relationship between the sensing area and the sheet portion is stabilized. That is, when the inspection object is carried on the first sheet material, even if the first sheet material may be deformed due to the weight of the inspection object, the first sheet is caused by the strong elasticity of the second sheet material. The surface of the sensor and the surface of the sheet portion are maintained by maintaining the flat state of the material and deforming the inspection object to bend by contacting the sensing area when the first sheet material is brought close to the sensing area. Even when the distance between the sensor and the sensor is partially different, it is possible to correct the difference in distance from the sensor surface by restoring the first sheet material to a flat shape by the elastic force of the second sheet material. it can.

The first sheet material is disposed on the front surface side of the sheet portion, and the second sheet material is disposed on the back surface side of the sheet portion, whereby the first sheet material can be opposed to the sensor chip, An elastic force can be applied from the back side to the deformation of the sheet portion due to the presence of the inspection object carried on the surface. Here, the lamination of both sheet materials means that two types of sheet materials form a layer as a result, and does not indicate only a laminated state in which the surfaces of both sheet materials are in close contact. Further, the second sheet material having an elastic force means having a remarkable elastic force as compared with the first sheet material, and does not mean that the first sheet material has no elastic force at all. Absent.

Further, in the present invention according to the inspection object holding device, the region constituent part may be constituted by a wall surface constituent part formed in a cylindrical shape having a desired thickness and length.

In the case of the above configuration, the inside of the wall surface constituent portion has an appropriate volume, and when supplying the liquid via the sheet portion, the liquid can be stored in the wall surface constituent portion, and the inside It is also possible to insert the auxiliary electrode.

Further, the present invention according to the inspection object holding device is a configuration in which the wall surface constituent part has a fitting part in which an end face of the opening facing the sensor is fitted to the unevenness existing around the sensing area. May be.

According to the inspection object holding device having the above configuration, in addition to the adjustment of the distance between the sensor and the inspection object as described above, the inspection object can be positioned on the surface of the sensor chip on which a plurality of sensors are arranged. It is to make. That is, the surface of the sheet portion provided in the opening portion of the wall surface constituent part becomes the surface of the sensing area by the end face of the opening part of the wall surface part abutting and fitting at an appropriate position around the area where the sensing area is formed. It will be arranged (positioned) in a suitable state that can face the surface. For example, when an inspection object is carried at the center of the surface of the sheet material, the inspection object can be brought close to the center of the sensing area, and the inspection object has a sensor located near the center of the sensing area. As a center, the inspection state can be detected by a sensor arranged around the center. In addition, as described above, a sensor chip in which minute sensors with a square of several tens of μm are regularly aligned vertically and horizontally is used, and the holes of the sheet material are formed in the same size and arrangement as each sensor. In the case of using the sensor, the position of each sensor and the position of each hole can be matched, and the sensing accuracy can be improved by concentrating the object in the hole of the sheet material. .

Furthermore, the present invention according to the inspection object holding device is configured such that the wall surface constituent part holds an auxiliary electrode for applying a predetermined potential to the inspection object carried on the sheet part. Also good. In this case, the holding of the auxiliary electrode includes not only the state in which the auxiliary electrode is loosely fitted inside the wall surface component, but also the state in which the auxiliary electrode is fixed on the inner surface of the wall surface component or embedded in the wall surface component. It is a waste.

According to the inspection object holding device having the above-described configuration, when using a sensor including a sensing unit whose potential changes corresponding to a biological / chemical / physical phenomenon, the inspection object held on the sheet unit is predetermined. By applying this potential, it is possible to suppress changes in the sensor potential due to changes in the external environment. In addition, by inserting the auxiliary electrode into the wall surface constituting part, the weight of the entire inspection target holding device can be increased, and when the sheet part is faced downward and close to the sensing area, a pressing force with an appropriate weight is applied. Can be granted. In particular, in the case where the inspection object carried on the lower surface of the seat portion is pressed against the sensor, the pressing force due to the weight acts on the inspection object, and the inspection object is directed toward the periphery on the surface of the sensing area. It is also possible to diffuse.

The present invention according to an inspection apparatus is an inspection apparatus using the inspection object holding device having the above-described configuration, a stage held by a base, a multi-horizontal rail fixed to the base, and an upper portion of the rail Mounted on the side where the microscope is installed among the stage and the slider, and a microscope installed on one of the stage and the slider. A sensor unit having a biological / chemical / physical phenomenon detection device, and the inspection object holding device is installed on a side of the stage and the slider where the microscope and the sensor unit are not installed, and the sensor unit is The sensing area of the biological / chemical / physical phenomenon detection device is arranged so as to face the inspection object holding device. And it is characterized in that it has a probe composed.

According to the inspection apparatus having the above configuration, the inspection object held by the inspection object holding device is placed on the stage or the slider, and the microscope and the sensor unit are mounted on the side where the inspection object is not installed. Become. Therefore, since the position of the microscope and the sensor unit can be changed with respect to the inspection object held by the inspection object holding device by the movement of the slider, either one of them is selectively opposed. In addition, the object facing the inspection object can be changed only by moving the slider. The inspection object can be optically observed with a microscope, and the biological / chemical / physical phenomenon of the inspection object can be detected by bringing the probe of the sensor unit close to the inspection object. The microscope and the sensor unit are mounted on the same side (stage or slider), and the contents of inspection can be changed without changing the position of the inspection object by moving the slider along the rail. At this time, if the horizontal positioning of the inspection object is completed by the microscope, the horizontal positioning can be omitted when the sensor unit is used.

Further, the present invention according to the inspection apparatus may be configured such that the sensor unit includes a first moving unit that moves at least the probe in the vertical direction.

According to the inspection apparatus having the above-described configuration, the distance between the sensor chip provided on the probe and the inspection object can be adjusted after the horizontal positioning is possible using a microscope in advance. By adjusting the distance between the two, the biological / chemical / physical phenomenon of the inspection object can be detected at a suitable position. In particular, when it is necessary to bring the inspection object into contact with the sensor chip, the sensor chip can be moved to a state in which the sensor chip comes into contact with the inspection object. Since the inspection object at this time is carried on the sheet portion of the inspection object holding device, the probe tip (particularly, the sensor chip) does not collide with a hard material and suppresses breakage. It will be possible.

Further, according to the present invention, the sensor unit includes: a second moving unit that moves the probe in a direction parallel to the rail; and a third moving unit that moves the probe in a direction perpendicular to the rail. The structure provided may be sufficient.

検査 According to the inspection device having the above configuration, the sensor unit can also be adjusted in the horizontal direction. Therefore, the object to be inspected can be positioned directly using the probe of the sensor unit without being positioned by a microscope. Then, it becomes possible to optically observe the part where the biological / chemical / physical phenomenon is detected with a microscope.

According to the present invention relating to the inspection object holding device, since the inspection object can be carried on the sheet portion, the sensor chip abuts on the inspection object when the sensor chip and the inspection object are brought close to each other. Even so, since the sensor chip comes into contact with the flexible sheet portion, it can be easily brought close to the sensor chip while preventing damage to the sensor chip. Therefore, when adjusting the positional relationship between the sensor (sensing area) and the inspection object, it is not necessary to carefully adjust the distance between the two, and the positional relationship can be adjusted efficiently.

And when a sheet | seat part is comprised by laminating | stacking a flexible 1st sheet material and the 2nd sheet material with a large Young's modulus, the test object was carry | supported by the sheet | seat part (the surface side of a 1st sheet or In the state of being carried on the back side of the second sheet), even if the weight of the inspection object acts on the first sheet, the second sheet suppresses bending. By adjusting the distance between the sheet part and the sensor (sensing area) without causing the sheet part to bend, the inspection object and the sensor (sensing area) can be arranged at a desired distance. In addition, when the inspection object is brought into contact with the sensor (sensing area), by utilizing the restoring force due to the elastic deformation of the second sheet, it is possible to eliminate the bending of the sheet portion in the contact state, The sheet part can urge the inspection object to the surface of the sensing area (acts so as to apply a force in the direction according to the elastic force), and the inspection object carried on the sheet part is spread over a wide area of the sensing area. It becomes possible to diffuse.

In addition, when the sheet portion is composed of a mesh-like or porous sheet material, gas and liquid can pass through the holes of the sheet material, and when culturing the cells and the like carried on the sheet portion, Or a culture solution can be easily supplied, and after culturing, the cells and the like can be carried for examination. Therefore, it is not necessary to remove the cultured cells and the like from the medium, and the risk of damaging the cultured cells and the like can be suppressed. When the cultured cells or the like are carried on the back side of the sheet portion, the cells or the like do not contact the sensor, so that the cells or the like are prevented from adhering to the sensor or are left on the sensor. Since a cell or the like does not come into contact with some kind of substance, it is possible to detect a biological / chemical / physical phenomenon while reducing the influence of both. In this case, if only ions can permeate through the micropores in the sheet portion, the sensor (ion sensor) can detect the biological / chemical / physical phenomenon of the cell or the like.

Furthermore, in the configuration in which the opening edge of the wall surface configuration part can be fitted to the unevenness present around the sensing area, the positioning of the sensing area and the wall surface configuration part is completed by the fitting, If the inspection object is carried at a predetermined position (for example, near the center of the sheet part) of the sheet part provided in the wall surface constituent part, the inspection object can be inspected at a desired position. In addition, the sheet material with respect to the sensor chip is positioned so as to be in a predetermined state (for example, a state in which the position of each sensor forming the sensor chip and the hole of the sheet portion is matched), thereby concentrating on the hole of the sheet portion. The object can be detected by each sensor. Therefore, the sensor and the inspection object can be positioned more efficiently.

On the other hand, according to the present invention relating to the inspection apparatus, the inspection object and the microscope and sensor unit for inspection are installed separately on the stage and the slider, and the microscope and the sensor unit are on the same side (stage or slider). ), The inspection object held by the inspection object holding device on either the stage or the slider can be inspected by both observation with a microscope and sensing by the sensor unit. At this time, since both the microscope and the sensor unit are provided so as to face the inspection object, the inspection object can be positioned while observing the inspection object with the microscope, and the microscope and the sensor are positioned in the positioned state. The unit can be exchanged, and positioning in the inspection by the sensor unit is facilitated.

When the sensor unit is configured to be movable in the vertical direction, the distance between the probe (sensor chip) of the sensor unit and the object to be inspected is determined when the sensor unit is inspected after only positioning in the horizontal direction using a microscope. It is possible to adjust, and positioning at the time of inspection using the sensor chip can be executed efficiently.

Furthermore, when the sensor unit is configured to be movable in the horizontal direction, the positional relationship between the probe (sensor chip) and the inspection object can be adjusted by moving the sensor unit. In this case, since the inspection object is held on the stage by the inspection object holding device, when the probe (sensor chip) is brought close to the inspection object, the position thereof must be greatly deviated. As a result, it is possible to suppress damage to the probe and the inspection object, and it is also easy to bring them into contact with each other due to their approach. Therefore, efficient positioning is possible.

It is explanatory drawing which shows the outline of 1st embodiment concerning a test object holding | maintenance apparatus. It is explanatory drawing which shows the detail of 1st embodiment concerning a test object holding | maintenance apparatus. FIG. 3 is a cross-sectional view taken along the line III-III in FIG. It is explanatory drawing which shows the modification of 1st embodiment concerning a test subject holding | maintenance apparatus. It is explanatory drawing which shows the modification of 1st embodiment concerning a test subject holding | maintenance apparatus. It is explanatory drawing which shows the modification of 1st embodiment concerning a test subject holding | maintenance apparatus. It is explanatory drawing which shows the use condition of 1st embodiment concerning a test target object holding | maintenance apparatus. It is explanatory drawing which shows the use condition of 1st embodiment concerning a test target object holding | maintenance apparatus. It is explanatory drawing which shows the use condition of 1st embodiment concerning a test target object holding | maintenance apparatus. It is explanatory drawing which shows the use condition of 1st embodiment concerning a test target object holding | maintenance apparatus. It is explanatory drawing which shows the use condition of the modification of 1st embodiment concerning a test object holding | maintenance apparatus. It is explanatory drawing which shows the use condition of the modification of 1st embodiment concerning a test object holding | maintenance apparatus. It is explanatory drawing which shows 2nd embodiment concerning a test object holding | maintenance apparatus. It is explanatory drawing which shows the use condition of 2nd embodiment concerning a test target object holding | maintenance apparatus. It is explanatory drawing which shows the use condition of 2nd embodiment concerning a test target object holding | maintenance apparatus. It is explanatory drawing which shows 3rd embodiment concerning a test object holding | maintenance apparatus. It is explanatory drawing which shows the outline of embodiment concerning a test | inspection apparatus. It is explanatory drawing which shows the outline of embodiment concerning a test | inspection apparatus. It is explanatory drawing which shows the relationship between the test object holding | maintenance part on a stage, and a probe. It is a microscope picture in the state where the inspection subject was held in the inspection subject holding device. It is a detection image of the pH sensor which shows the measurement result by an experimental example.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. First, an embodiment of the invention related to the inspection object holding device will be described, and then an embodiment of the invention related to the inspection device will be described.

<First Embodiment of Inspection Object Holding Device>
FIG. 1 is a diagram showing an outline of a first embodiment of an inspection object holding device. As shown in this figure, the inspection object holding device 1 of the present embodiment has a configuration including a cylindrical wall surface constituent part (region constituent part) 2 and a sheet part 3. The seat portion 3 is provided in the entire area of the lower opening of the wall surface constituting portion 2, and is provided in a state where the lower opening end is closed by the seat portion 3. The sheet portion 3 is provided in a thin film shape by a material / structure capable of carrying an inspection object (attached / adsorbed or other state depending on the state of the inspection object). Further, the sheet portion 3 is made of a mesh-like material having fine holes 30 (or a porous material, hereinafter, both are collectively referred to as a porous material). Gas, liquid, ions, or the like can be passed through the inside and outside of the component 2. The holes 30 do not need to be formed when the gas or the like does not need to pass therethrough, and can be formed in a size that allows gas, liquid, ions, or the like to pass through selectively. The wall surface component 2 has a diameter that can surround a predetermined range of the sensor chip 4 (specifically, the sensing area 5) used in the biological / chemical / physical phenomenon detection device.

A sensing area 5 is formed in the sensor chip 4 used in the biological / chemical / physical phenomenon detection device, and the sensing area 5 is configured by arranging a plurality of sensors 50 vertically and horizontally. As disclosed in the above-mentioned Patent Document 1, each sensor 50 includes a sensing unit whose potential changes corresponding to a biological / chemical / physical phenomenon, a charge supply unit that supplies charges to the sensing unit, A device including a charge injection adjusting unit existing between the charge supply unit and the sensing unit, and a floating diffusion unit for storing the charge transferred from the sensing unit (both not shown) is used. . The sensing unit is formed on the surface of each sensor 50, and the biological / chemical / physical phenomenon of the inspection object close to each sensor 50 is detected by the sensing unit of each sensor. As described above, the biological / chemical / physical phenomenon is individually sensed by the plurality of sensors 50, so that the biological / chemical / physical phenomenon of the inspection object can be detected as a two-dimensional distribution by the detection device.

Therefore, by bringing the sheet portion 3 close to the sensor chip 4 (specifically, close to the sensing portion of the sensor 50 forming the sensing area 5), the inspection object carried on the sheet portion 3 Biological, chemical and physical phenomena can be detected. In addition, if the wall surface configuration part 2 is large enough to surround the sensing area 5, the wall surface configuration unit 2 is in contact with the sensor chip 4 even when the sheet unit 3 is in contact with the sensor chip 4. It can arrange | position so that it may not contact. Further, as shown in the figure, when the chamber component 6 can be provided around the sensing area 5, the wall component 2 can be arranged outside or inside the chamber component 6 as a reference. The positional relationship with each sensor 50 in area 5 can be adjusted.

By the way, although this embodiment is a structure by which the sheet | seat part 3 is provided in the one side opening part 21 of the cylindrical wall surface structure part 2, as shown to Fig.2 (a), this sheet | seat part 3 is a wall surface structure part. It adhere | attaches with the adhesive agent between the end surfaces 21a of the said opening part 21 of 2. As shown in FIG. The bonding surface is the entire end surface 21 a of the opening 21, and the sheet portion 3 is provided by adhering the vicinity of the edge of the entire periphery to the opening 21.

These wall surface constituent part 2 and sheet part 3 are both required to have low biological toxicity and be able to withstand high-pressure steam sterilization. Moreover, as the sheet | seat part 3 in this embodiment, it is provided with the porous material as above-mentioned, and the thing of the material which has a softness | flexibility is used. For example, a single layer of polyethylene or polypropylene or a laminate of a plurality of these layers is used, and a porous body is formed by a chemical treatment method, an irradiation etching method, a stretching method or a foaming method, and further stretched into a thin film. A sheet material (so-called polymer thick film: PTF) can be used. Further, high-functional plastics such as engineering plastics, polydimethylsiloxane (PDMS) resin which is a kind of silicone resin, and the like can be used. The thickness of the sheet portion 3 is 10 μm to 20 μm, and the hole diameter of the micropores 30 provided in the sheet portion 3 is appropriately selected according to the type of the test object, and is about 100 μm for a living tissue, Is a few μm. In addition, although the sheet | seat part 3 is made into the mesh shape (mesh shape) in the figure, this is what showed an example of porous easily, and is a porous sheet material which has the micropore 30 which penetrates the front and back. If so, the hole shape is not limited to a quadrangle, and may be a circle or other shapes.

The individual sensors 50 forming the sensing area 5 are formed in a substantially square shape with a side of several tens of μm. Therefore, the sheet portion 3 is formed in a mesh shape having the same shape and the same size of holes 30. Thus, each sensor 50 can be disposed while facing one hole 30 of the sheet portion 3. Further, when the hole 30 of the sheet portion 3 has a substantially square shape with a side of several μm, it matches the size of the sensor 50 according to the range (group) in which the plurality of holes 30 are gathered (a substantially square shape with a side of several tens μm Thus, a group of holes 30 can be arranged to face one sensor 50. As described above, when one sensor corresponds to one or a group of holes 30, the inspection object carried on the sheet portion 3 is concentrated in each hole 30, and the living thing corresponding to the concentrated inspection object is detected.・ Enables detection of chemical and physical phenomena. Note that the “concentration” of the inspection object in the hole 30 means that the inspection object is divided by a material portion (stripes forming a mesh shape) that forms a porous material and enters the inside of each hole 30 or each It means a state of penetrating into the hole 30.

In consideration of processability and strength, for example, a material arbitrarily selected from PDMS resin, agar, urethane, acrylic, polypropylene resin, styryl resin, high-performance plastic, glass, metal, etc. Can be used. PDMS resin is suitable for the wall surface constituting part 2 because it is easily molded and has an appropriate strength. In addition, when a soft material such as PDMS resin or agar or a material having heat flexibility is used, a stamp or the like can be printed on a partial surface of the wall surface constituting portion and is carried on the sheet portion 3. It is also possible to display the information on the inspection object and the position information carried by the stamp. Since such inscriptions can easily record information on inspection objects, when a plurality of inspection objects are simultaneously subjected to high-pressure steam sterilization processing or cryopreservation, it is possible to identify subsequent inspection objects. . As an adhesive for adhering the wall surface constituting part 2 and the sheet part 3, an adhesive mainly composed of ethyl 2-cyanoacrylate can be used. This is because this type of adhesive can easily bond the resin wall surface component 2 and the sheet portion 3 together. In addition, the said adhesive agent shows an example, it is not limited to this, The thing with slight toxicity to a biological body can be used.

FIG. 2B shows a state in which the sheet portion 3 is bonded to one opening portion 21 of the wall surface constituting portion 2 with the above-described constitution. As shown in this figure, the sheet part 3 can have its surface 31 entirely flat by adhering the peripheral part to the end face of the wall surface constituting part 2. Then, by carrying the inspection object on the surface 31 of the sheet part 3 and adjusting the position of the surface 31 of the sheet part 3, the position of the inspection object can be adjusted to a position suitable for the inspection. It can be done.

FIG. 3 shows a cross section of the present embodiment having the above-described configuration (shown in FIG. 2B). As shown in this figure, the sheet part 3 bonded to the end face of the one-side opening 21 of the wall surface constituting part 2 is in a state where its peripheral part is supported by the end face of the wall face constituting part 2, Not only the front surface 31 but also the back surface 32 is provided flat. Furthermore, the back surface 32 side of the sheet part 3 is in a hollow state except for the peripheral part bonded to the edge of the wall surface constituting part 2. Therefore, even when the surface 31 of the seat portion 3 is brought into contact with the sensing area 5 (FIG. 1), if the sensing area 5 is inside the wall surface constituent portion 2, the sensing area 5 is the seat portion. 3, and even when the sheet part 3 is brought into contact with the sensing area 5, the sheet part 3 is flexible, so that the individual sensors 50 forming the sensing area 5 are damaged. It is suppressed. In FIG. 3, the adhesive 7 is shown laminated in the middle between the wall surface constituting portion 2 and the sheet portion 3, but this is for the purpose of clarifying the presence of the adhesive 7, as shown in FIG. It is not provided with a wall thickness. Further, the length dimension of the wall surface component 2 and the thickness of the wall surface part and the thickness of the sheet part 3 are also shown in order to clarify the state of each member, but these dimensions are appropriately changed. To get.

Further, as shown in FIG. 3, the opening 21 of the wall surface constituting part 2 is arranged so that the sheet part 3 closes, but the micro hole 30 of the sheet part 3 (see FIG. 2A). And the gas or liquid can pass between the inside and outside of the wall surface constituting part 2. Therefore, by immersing the sheet portion 3 in a test solution (physiological saline) or the like, the test solution or the like permeates into the inside of the wall surface constituting portion 2 from the fine holes 30 of the sheet portion 3. Further, since the entire surface of the other opening 22 of the wall surface constituting part 2 is open, liquid can be supplied from the opening 22, and a test solution (physiological saline) or the like can be supplied to the sheet part 3. It becomes possible.

Here, in the case where the chamber component 6 is provided around the sensing area 5 as described above (see FIG. 1), the chamber component 6 and the wall surface component 2 store the test solution, the culture solution, and the like. Can be made. And the chamber structure part 6 is provided so that the sensing area 5 may be enclosed. Therefore, the wall surface component 2 may be fitted inside the chamber component 6 or may be disposed outside the chamber component 6, and the diameter of the wall surface component 2 will be different depending on any aspect. . That is, when the entire sensing area 5 is surrounded by the wall surface component 2, it is arranged outside the chamber component 6, so that the inner diameter is approximately the same as the outer diameter of the chamber component 6. In addition, when a part of the sensing area 5 is surrounded, it is fitted inside the chamber component 6, so that the inner diameter is smaller than the inner diameter of the chamber component 6. As a guide for the diameter of the wall surface constituting part 2, when it is assumed that the thickness of the chamber constituting part 6 is formed to be about 10% of the inner diameter, the inner diameter of the chamber constituting part 6 surrounding the entire sensing area 5 is assumed. 90% to 110%. In the case of a configuration in which the chamber component 6 is not provided, the wall surface component 2 is configured to have a size (100%) in which the chamber component 6 is to be provided. In this case, the wall surface constituting part 2 also functions as the chamber constituting part 6.

Further, by setting the length dimension of the wall surface constituting part 2 to be approximately the same as the diameter, it is possible to supply the liquid from the opening 22 of the wall surface constituting part 2 by the surface tension of the liquid. Therefore, since the culture solution (nutrient, water, etc.) can be supplied in a state where the living body tissue or cells are carried on the sheet part 3, these cells and the like can be supplied using the inspection object holding device of this embodiment. It is also possible to culture. In this case, the cultured cells and the like (inspection object) are maintained in the state of being supported on the sheet unit 3, and the sheet used for the culture can be inspected without moving to another apparatus.

In addition, when the adhesive 7 which adhere | attaches both forms the layer shape of moderate thickness, and the adhesive agent 7 is a material which has buffer property, when an impact is given with respect to the sheet | seat part 3. Can alleviate it. In addition, since an appropriate thickness is formed, even when the edge of the opening 21 is not a smooth surface (having fine irregularities), it is possible to bond the sheet portion 3 in close contact. It becomes.

Here, a modification of this embodiment will be described. FIG. 4 shows an example in which the length of the wall surface component 2 is short and formed in an annular shape (the region component 2 having no wall surface). Also in such a form, both sides of the annular shape are open (see FIG. 4A), and the sheet portion 3 is bonded to the end surface 21a of the one opening 21 to thereby open the opening 21. Can be closed (see FIG. 4B). In such a form, as shown in FIG. 5A, the entire thickness of the inspection object holding device can be reduced, and the sensor chip can be formed on both the front surface 31 and the back surface 32 of the sheet portion 3. 4 can be approached. Therefore, the inspection object can be brought close to the sensor while having an appropriate distance by bringing one of the surfaces close to the sensor chip 4 while the inspection object is held on the front surface 31 or the back surface 32. it can.

Further, as shown in FIG. 5 (b), the annular region component 2 may be configured to have a circular cross-sectional shape. In such a form, the sheet material 3 is bonded so as to cover the outer peripheral surface of the region constituting portion 2. By using the outer peripheral surface of the region constituting part 2 having a circular cross section, an area necessary for adhesion can be obtained. In any of the above forms, since the sheet portion 3 is provided in a smooth state with respect to one opening portion 21, one of the front surface 31 and the back surface 32 can be selected to carry the inspection object. It is.

Further, as shown in FIG. 6, there may be a form in which the wall surface constituting part 2 is formed in a rectangular tube shape. In the case of such a configuration, the sheet portion 3 can be arranged in a range that matches a sensing area 5 (see FIG. 1) in which a plurality of sensors 50 are aligned vertically and horizontally. It is possible to detect all the biological, chemical and physical phenomena of the diffused test object. Even in such a form, it may be formed as an annular shape having a short length.

Since the present embodiment is configured as described above, the inspection object can be brought close to the sensor chip by supporting the inspection object on the sheet portion 3. Then, the usage aspect of embodiment which concerns on the said test target object holding | maintenance apparatus is demonstrated. FIG. 7 shows a state in which the inspection object is carried on the sheet portion 3. FIG. 7A shows a state in which the inspection object A is carried on the surface 31 of the sheet portion 3, and FIG. 7B shows a state in which the sheet portion 3 is in contact with the sensing area 5. As shown in FIG. 7A, the inspection object A can be opposed to the sensing area 5 by supporting the inspection object A on the surface 31 of the sheet portion 3. And by making the sheet | seat part 3 fully approach the sensing area 5, the test object A can be made to contact the sensing area 5. FIG. At this time, as shown in FIG. 7 (b), the inspection object A in contact with the sensing area 5 is pressed by the surface 31 of the sheet portion 3, thereby diffusing the inspection object A over a wide range of the sensing area 5. In addition, the inspection object A can be brought into contact with the individual sensors constituting the sensing area 5 in the wide range. Note that the pressing by the sheet part 3 does not damage the inspection object A due to the flexibility of the sheet part 3, and the inspection object A can be brought into contact with the sensing area 5 with an appropriate pressing force. Further, in the above usage mode, when it is not necessary to pass gas, liquid, ions, or the like from the back surface to the surface of the sheet portion 3, the sheet portion 2 is a porous material if it has appropriate flexibility. It may not be constituted by.

By the way, in the case of the said use aspect, since the other opening part 22 is opening large inside the wall surface structure part 2, as shown to Fig.8 (a), the auxiliary electrode 8 is passed from the said opening part 22. As shown in FIG. Can be inserted. By inserting the auxiliary electrode 8, it is possible to supply a predetermined potential to the inspection object A, increase the overall weight, and increase the pressing force by the sheet portion 3. It is also possible to obtain. Then, by injecting a test solution (such as physiological saline) B into the hollow interior of the wall surface component 2, a potential can be supplied to the test object A through the test solution. In addition, since the auxiliary electrode 8 is for supplying a predetermined potential to the inspection object A, as shown in FIG. Good. Even when embedded in the wall surface component 2, the pressing force on the sheet portion 3 can be increased using the weight of the auxiliary electrode 8.

FIG. 9 shows a state in which the inspection object A is carried on the back surface 32 of the sheet portion 3. As shown in this figure, by bringing the surface of the sheet part 3 into contact with the sensing area 5, the inspection object A is brought close to the sensing area 5 without damaging the sensing area 5 due to the flexibility of the sheet part 3. be able to. At this time, by injecting a test solution (physiological saline or the like) into the inside of the wall surface constituting part 2, a part of a living body tissue or cell, which is the test object A (may be only ions), is formed into a sheet. It passes through the micropores of the part 3 and flows out to the surface 31 of the sheet part 3 and can be brought into contact with the sensor in the sensing area 5. Further, even if it does not flow out to the surface 31 of the sheet portion 3, it stays in the fine hole and is arranged in the state of being close to the sensing area 5. In addition, although the auxiliary electrode 8 may be inserted in the inside of the wall surface structure part 2, you may use it in the state embedded at the wall surface structure part 2 like illustration. Further, the surface 31 of the sheet portion 6 may be brought into contact with the sensing area 5, but may be used in a non-contact state with a slight gap.

Also, the inspection object holding device of the present embodiment can be used with the sheet portion 2 facing upward. FIG. 10 is a diagram showing this state. As shown in FIG. 10 (a), the inspection object A is carried on the surface 31 of the sheet part 3, and the inspection object A is brought into proximity with the sensing area 5 by bringing the sheet part 3 close to the sensing area 5. Can be brought into contact with the sensing area 5. As shown in FIG. 10 (b), even when the inspection object A is carried on the back surface 32 of the sheet portion 3, the test solution is obtained by immersing the wall surface component 2 in the test solution (such as physiological saline) B. Due to the surface tension of (such as physiological saline), the test solution (such as physiological saline) flows from the other opening 22 of the wall surface component 2 into the wall surface component 2, and the sheet portion 2 is moved to the sensing area. 5, the inspection object A can be brought into contact with the sensing area 5. In the usage pattern shown in FIG. 10, since the inspection object A and the inspection liquid B carried on the sheet part 3 do not drip onto the sensing area 5, the sheet part 3 and the inspection object A are not in the sensing area 5. By being in contact, the inspection object A or the like does not adhere to the sensing area 5, and a plurality of inspection objects A can be obtained by exchanging a plurality of wall surface components 2 carrying a plurality of different inspection objects A. The object A can be inspected. In the case where a predetermined charge is to be supplied to the inspection object A, the wall surface constituting portion 2 with the auxiliary electrode 8 embedded therein may be used. In addition, when supplying the test liquid B to the wall surface component 2, a container for storing the test liquid B is not shown, but the test liquid B is appropriately stored in a container having a capacity, and the test liquid B is stored on the wall surface. It is used to immerse the component 2.

Although the above-mentioned use mode illustrated and demonstrated what was comprised in the cylindrical body which has sufficient length dimension as the area | region structure part 2, it is fundamental use also when using what was comprised in the short cyclic | annular body. The embodiment is the same. That is, as shown in FIG. 11, the inspection object A is carried on the back surface 32 of the sheet portion 3 (see FIGS. 11A and 11B), or the surface 31 of the sheet portion 3 is to be inspected. Since the sheet A 3 is brought close to the sensing area 5 while the object A is carried (see FIG. 11C), the biological / chemical / physical phenomenon of the inspection object A can be detected. is there. In this case, the region configuration unit 2 may be disposed inside the chamber configuration unit 6 together with the sheet unit 3 (see FIGS. 11A to 11C). It can also be arranged outside (see FIG. 11D). In any state, the inspection object A carried on the sheet portion 3 can be brought close to the sensing area 5. In addition, in the case of the area | region structure part 2 by an annular body, since it is difficult to insert or embed | buy the auxiliary electrode 8, when it is necessary to supply a predetermined | prescribed electric charge with respect to the test object A, it is test The auxiliary electrode 8 is prepared separately from the object holding device. At that time, the test solution can be used by flowing into the chamber component 6. In addition, when the supply of the electric charge is unnecessary, a biological / chemical / physical phenomenon is detected in a non-contact state without using such an electrode.

Further, in the case where the micro holes 30 of the sheet portion 3 are configured in the same size and the same arrangement as the sensor 50, as shown in FIG. 12, they are used while adjusting the orientation of the sheet portion 3. As shown in the figure, a predetermined number of sensors 50 forming a general sensing area 5 are arranged vertically and horizontally, so that they are formed in a rectangular shape as a whole. Therefore, the sheet portion 3 having a shape corresponding to the rectangle is bonded to one opening portion 21 of the rectangular cylindrical wall surface constituting portion 2, and the sheet portion 3 is brought close to the sensing area 5. Further, by providing the chamber constituent part (omitted in FIG. 12) in a rectangular shape, the orientation of the sheet part 3 can be easily adjusted if the rectangular cylindrical wall surface constituent part 2 is made to coincide with the chamber constituent part. it can. In addition, although the figure has shown the cylindrical wall surface structure part 2, it is the same also when comprised by a cyclic | annular area | region structure part.

Thus, if the inspection object holding device of the above embodiment is used, the three-dimensional position between the sensor and the inspection object can be adjusted. Then, by bringing the inspection object A close to the sensing area 5 formed by arranging a plurality of sensors in a wide range, it is possible to detect a wide range of biological / chemical / physical phenomena caused by the sensing area 5. The distribution can be measured. Further, even when the inspection object A and the sensing area 5 are not in contact with each other, non-contact measurement can be performed by bringing the sheet portion 3 close as described above.

<Second Embodiment of Inspection Object Holding Device>
Next, a second embodiment will be described. FIG. 13 is a diagram showing an outline of the present embodiment. As shown in FIG. 13A, the sheet portion 3 is configured by laminating a porous first sheet material 3a and a mesh-like (network structure) second sheet material 3b. Both of these

sheet materials

3a and 3b are stacked in a layer form (although they are stacked in that sense), but are not integrated in an intimate state. That is, the second sheet material 3b is bonded to the end face of one of the openings 21 of the wall surface constituting portion 2, and the same portion of the first sheet material 3a is bonded to the second sheet material 3b.

The first sheet material 3a is made of the same material as the sheet portion used in the first embodiment, and a porous and flexible material is used. On the other hand, the second sheet material 3b is configured in a mesh shape with an elastic material (elastically deformable) having a larger Young's modulus than the first sheet material 3a. For example, a mesh material using nylon which is a polyamide fiber (so-called nylon mesh) can be used. The mesh shape of the second sheet material 3b means that the size of the mesh 30b is larger than the holes 30a of the first sheet material 3a, and the first sheet material 3a is formed in a mesh shape. In some cases, both are different in material and eye size. The reason why the second sheet material 3b has a mesh shape is to ensure air permeability and water permeability, and because the inspection object is supported exclusively by the first sheet material 3a, it is easy to pass the inspection object. It is to do. In addition, moderate elastic force can be obtained by comprising the 2nd sheet | seat material 3b with a polyamide-type fiber. In addition, as in the first embodiment, an adhesive mainly composed of ethyl 2-cyanoacrylate can be used as an adhesive for adhesion, and a material having irregularities by providing an appropriate thickness. Adhesion between them is possible.

As described above, since the first sheet material 3a is laminated on the surface side of the second sheet material 3b, as shown in FIG. 13B, the surface 31 of the sheet portion 3 is constituted by the first sheet 3a. The Therefore, even when it makes it contact | abut to the sensing area 5 (FIG. 1), when the surface of the 1st sheet material 3a contacts, the impact with the sensing area 5 can be relieve | moderated by the softness | flexibility. In addition, since the second sheet material 3b is laminated on the back surface side of the first sheet material 3a, the first sheet material 3a is supported by the first sheet material 3a in a state in which the first sheet material 3a is deformed by the contact. Even in a state in which bending is caused by the weight of the inspection object, the plane of the first sheet material 3a is maintained by the strong elasticity of the second sheet material 3b.

That is, as shown in FIG. 14A, when the inspection object A is carried on the surface 31 of the sheet part 3 and brought into contact with the sensing area 5, the inspection object A is present in the surface 31 of the sheet part 3. In the area where the inspection object A reaches the sensing area 5, a gap is formed between the inspection object A and the sensing area 5 in the area where the inspection object A does not exist. By pressing, the area where the inspection object A exists is deformed backward. In such a state, as shown in FIG. 14B, the second sheet material 3b exerts an elastic force from the back side of the first sheet material 3a so that the sheet portion 3 is restored to a flat shape. It can be made. Accordingly, the surface 31 of the sheet portion 3 becomes planar, and the inspection object A is gradually pushed out to the periphery in a state of being sandwiched between the sheet portion 3 and the sensing area 5, and is spread over a wide area of the sensing area 5. It will be diffused.

Further, as shown in FIG. 15 (a), in a state where the surface 31 of the sheet portion 3 faces upward and the inspection object A is carried on the surface 31, the weight of the inspection object A acts on the sheet portion 3, In this case, the first sheet material 3a can be maintained in a flat shape by the strong elasticity of the second sheet material 3b. Furthermore, as shown in FIG. 15B, the same applies to the case where the inspection object A is carried on the back surface 32 of the sheet portion 3. As shown in FIG. 15B, when the inspection object A is carried on the back surface 32 of the sheet portion 3, the inspection object A passes through the mesh of the second sheet material 3b. Even if the two

sheets

3a and 3b are stacked and configured to be thick, the position where the inspection object A is carried is the same as in the first embodiment. A similar state can be obtained.

<Third Embodiment of Inspection Object Holding Device>
Next, a third embodiment of the inspection object holding device will be described. FIG. 16 is a diagram showing an outline of the present embodiment. As shown in this figure, one opening 21 of the wall surface constituting part 2 includes a fitting part 23 that fits into the chamber constituting part 6. The fitting portion 23 is provided on the entire circumference of the opening portion 21, and the position of the wall surface constituting portion 2 is determined by fitting with the chamber constituting portion 6. The sheet portion 2 may be a single layer as in the first embodiment or may be a double layer as in the second embodiment, but a part of the end surface of the opening 21 is used as an adhesive surface. .

Thus, by providing the fitting part 23 in the wall surface constituting part 2, the test object A is carried substantially at the center of the sheet part 3, and the fitting part 23 is fitted to the chamber constituting part 6. The inspection object A is positioned substantially at the center of the sensing area 5 and facilitates the positioning of the inspection object A. In addition, when the fitting portion 23 is configured so that a predetermined gap is formed in advance between the surface 21 of the seat portion 2 and the sensing area 5 in the fitted state, the seat is obtained by fitting the two together. Positioning is performed with a predetermined distance between the part 2 and the sensing area 5.

As described above, the embodiment of the inspection object holding device can be configured such that, in any aspect, even when the sheet portion 3 is in contact with the sensing area 5, the wall surface constituting portion 2 is in contact with the sensing area 5. Therefore, damage to the individual sensors 50 can be suppressed. Moreover, when it adjoins in the state which has a predetermined | prescribed gap | interval between the sheet | seat part 3 and the sensing area 5, the damage with respect to the structure | tissue of the test target A, a cell, etc. can be avoided. When the inspection object A is brought close to the sensing area 5, the inspection object A can be diffused over a wide area of the sensing area 5. The phenomenon can be detected in a wide range. Even in this case, by pressing with the flexible sheet portion 3, it is possible to suppress damage to the tissue or cells of the inspection object A. Furthermore, since the sheet portion 3 is porous as described above, it becomes possible to culture the cells and the like in a state where the cells and the like are supported on the sheet portion 2, and while culturing or immediately after culturing, It can be inspected by a biological / chemical / physical phenomenon detection device as it is. Further, by using the sheet portion 3 having the holes 30 in the same size and in the same arrangement as the sensor 50 forming the sensing area 5, the biological, chemical, and physical phenomena of the inspection object A concentrated in each hole 30 can be measured. It can be detected by the sensor 50, and the accuracy of the two-dimensional distribution based on each piece of information detected by the sensing area 5 can be improved. Moreover, since liquid (test liquid B etc.) can be supplied to the test object A via the sheet | seat part 2, a chemical stimulus can be given with respect to the said test object, The change of the test object A in that case It is also possible to observe. Furthermore, it is possible to apply electrical stimulation by using the auxiliary electrode 8 or other electrodes.

<Embodiment concerning inspection apparatus>
Next, an embodiment of an inspection apparatus using the inspection object holding apparatus will be described. FIG. 17 is a schematic diagram of the front side of the present embodiment, and FIG. 18 is a schematic diagram of the back side. As shown in these drawings, in the inspection apparatus 9 according to the present embodiment, a stage 91 held by a base 90 is installed at substantially the center of the apparatus 9. Further, on the back side of the apparatus 9, a rail 92 extending horizontally in the horizontal direction and a slider 93 movable along the rail 92 are provided. In the present embodiment, an example in which an inspection object is installed on a stage 91 and a microscope 94 and a sensor unit 95 are mounted on a slider 93 is shown as a representative example. Therefore, a microscope 94 and a sensor unit 95 are mounted in parallel on the slider 93, and an inspection object holding device can be placed almost at the center of the stage 91. Accordingly, the movement of the slider 93 allows the inspection object held on the stage 91 to be observed by either the microscope 94 or the sensor unit 95. The microscope 94 is an optical microscope, and can be observed in a non-contact manner by bringing an objective lens close to an object to be inspected. The sensor unit 95 is equipped with the aforementioned biological / chemical / physical phenomenon detection device. ing. A probe 96 is formed at a lower end 96 of the sensor unit 95, and the sensor (sensing area 5) is provided at the end.

The sensor unit 95 is supported by a support portion 97 on the back side. The main body portion of the support portion 97 is formed with a moving portion (first moving portion) that enables vertical movement. Specifically, the main body portion of the support portion 97 is expanded and contracted by a rack and a pinion, and the length thereof is adjusted. In addition, a moving unit (second moving unit) 98 that enables movement in the left-right direction and a moving unit (third moving unit) 99 that allows movement in the front-rear direction are provided above the support unit 97. ing. The second moving part 98 is moved in a direction parallel to the rail 92, and the third moving part 99 is moved in the direction perpendicular to the rail 92. These movements are made possible by a slider that slides in a predetermined direction on the bed. Then, by supporting the sensor unit 95 on the uppermost slider that is moved by the third moving unit 99, the position of the sensor unit 95 can be changed according to each movement.

The stage 91 may be either a movable type or a fixed type, but in the case of the movable type, the position of the inspection object is confirmed while observing with the optical microscope 94, and the slider 93 is moved to thereby inspect the inspection object. The probe 96 can be arranged according to the position of the object. In this case, the distance between the probe 96 and the inspection object can be adjusted by adjusting only the vertical movement of the sensor unit 95. On the other hand, when the stage 91 is fixed, after moving the slider 93, the probe 96 is moved in the horizontal direction and the vertical direction in order to reach the position of the inspection object. In order to position the probe 96, there is a method in which a fluorescence reaction is detected with respect to the inspection object and the inspection object is specified by the fluorescence reaction. In this case, an optical sensor capable of detecting fluorescence is used as the sensor forming the sensor chip.

Here, as shown in FIG. 19, the inspection object A placed on the stage 91 is installed in a state of being held by the inspection object holding device 1. That is, the inspection object A is carried on the surface of the sheet portion 3 constituting the inspection object holding device 1. On the other hand, by bringing the probe 96 of the sensor unit 95 close to each other, the sensor chip (specifically, the sensing area 5) disposed on the probe 96 faces the inspection object A and is disposed at an appropriate interval. It is possible to make it contact or abut. When the inspection object A is brought into contact, the sensor chip (sensing area 5) is in a state in which the inspection object A is sandwiched between the sensor chip (sensing area 5) and the sheet part 3 of the inspection object holding device 1. It is possible to suppress damage to both the sensor chip (sensing area 5) and the inspection object A due to flexibility. The probe 96 in the figure has the same configuration as the sensor chip shown in the description of the inspection object holding device, but the probe 96 and the sensor chip may be configured separately. Further, the carrying of the inspection object A is not limited to the illustrated state, and there may be various aspects shown in the above-described embodiment of the inspection object holding device. Furthermore, in order to supply a test solution (such as physiological saline) or a culture solution to the test object A, the test object holding device 1 may be placed in a container 10 in which the test liquid or the like B is stored. This is because the inspection liquid etc. B is infiltrated into the sheet portion 3 and the inspection object A by the surface tension of the inspection liquid B by immersing the inspection object holding device 1 in the inspection liquid B stored in the container 10. . The container 10 that stores the test solution B or the like has a sufficiently larger diameter than the probe 96, so that the possibility of the probe 96 contacting the container 10 and being damaged can be eliminated.

Since the embodiment according to the inspection apparatus is as described above, it is possible to detect the biological / chemical / physical phenomenon with the sensor chip (sensing area 5) as well as observation with the optical microscope 94 for the inspection object A. . When detecting the biological / chemical / physical phenomenon by the sensor chip (sensing area 5), when the sensor chip (sensing area 5) is brought close to or in contact with the inspection object A, the inspection object A is a sheet portion. Therefore, the possibility of damage to both the inspection object A and the sensor chip (sensing area 5) can be suppressed. In addition, since the position of the inspection object A can be grasped by preceding the observation with the optical microscope 94, positioning at the time of inspection by the sensor chip (sensing area 5) can be facilitated. Furthermore, since the sensor chip (sensing area 5) and the probe 96 of the sensor unit 95 are provided, the inspection object A held therein can be replaced by exchanging the inspection object holding device 1, A similar inspection can be performed on a plurality of inspection objects.

Although embodiments of the present invention have been described as described above, the present invention is not limited to these embodiments. That is, in the embodiment according to the inspection object holding device, the description has been made centering on the wall surface configuration portion by the cylindrical body as a representative example of the region configuration portion, but the configuration may be an annular body in each embodiment, The shape is not limited to a circle (cylindrical / annular) or a quadrilateral (quadrangular / quadrangle), but may be other polygons. Moreover, although the material of each member was demonstrated, this is an illustration, Comprising: You may comprise with another material. Furthermore, although the example which uses an auxiliary electrode in some embodiment was shown, an auxiliary electrode can be used in all the forms, or you may abbreviate | omit an auxiliary electrode. On the other hand, in the embodiment according to the inspection apparatus, the illustrated microscope is an inverted microscope. However, the microscope is not limited to this, and the positional relationship between the microscope and the sensor unit with respect to the inspection object can be variously changed. it can. In particular, the microscope and the sensor unit may be mounted on the stage, the inspection object holding device may be installed on the slider, and the position of the inspection object may be changed while the microscope and the sensor unit are fixed.

<Experimental example 1>
Regarding the inspection object holding device, the inspection object was actually carried on the sheet portion. A micrograph of this state is shown in FIG. In this case, a nylon mesh and a porous sheet material are attached to one opening of a quadrangular cylindrical body (wall surface constituent portion) having a side of 5 mm. A nylon mesh having a network structure with an interval of 100 μm on one side was used, and a porous polyethylene sheet having pores with a side of several μm was used as the porous sheet. Moreover, PDMS resin was used for the wall surface constituting part. In the figure, the object to be inspected is carried on the surface of the sheet portion and taken from the back side of the nylon mesh. The inspection object can be confirmed along with the mesh of the nylon mesh. As is clear from this experimental example, the inspection object can be carried on the porous sheet, and by making the porous sheet close to the sensor chip, low invasiveness can be ensured.

<Experimental example 2>
Moreover, the comparison in the detection of biological / chemical / physical phenomena was performed with and without using the inspection object holding device prepared in Experimental Example 1. FIG. 21A shows the case where the inspection object holding device is used, and FIG. 21B shows the case where it is not used. In the case where the inspection object holding device is used, the inspection object is carried on the surface of the sheet portion of the inspection object holding device of Experimental Example 1, and the surface of the sheet portion is brought into contact with the sensing area of the sensor chip. The state where the inspection object holding device is not used is a state where the inspection object is directly attached to the sensing area of the sensor chip. For detection of biological / chemical / physical phenomena, for example, a pH sensor was used, and the change was measured over time. A circle with a broken line in the figure indicates the position of the inspection object. As shown in this figure, when the inspection object holding device is used, the state around the inspection object is measured from the beginning of the measurement, and the inspection object is detected even after 25 minutes. Yes. On the other hand, when the inspection object holding device is not used, the inspection object can be observed at the beginning of measurement, but its presence is unclear after 5 minutes. As is clear from this experimental example, even when the inspection object holding device is used, that is, even when the inspection object is carried on the porous sheet, the biological / chemical / physical phenomenon of the inspection object is detected. To get. Furthermore, when the inspection object holding device is used, the position of the sensor and the inspection object is maintained in a suitable state for a long time, so that an electrical stimulus or a chemical stimulus is applied, or It is possible to detect biological, chemical, and physical phenomena of the test object while culturing cells and the like.

DESCRIPTION OF SYMBOLS 1 Inspection object holding | maintenance apparatus 2 Wall surface structure part 3 Sheet part 3a First sheet material 3b Second sheet material 4 Sensor chip 5 Sensing area 6 Chamber structure part 7 Adhesive 8 Auxiliary electrode 9 Inspection apparatus 21 One side opening of wall surface structure part Part 21a Opening end face 22 Opening 23 on the other side of the wall constituting part Fitting part 30 Hole 30a in the sheet part Hole 30b in the first sheet material On the other hand, the mesh of the sheet material 31 The surface of the sheet part 32 The back surface 50 of the sheet part Sensor 90 Base 91 of inspection apparatus Stage 92 Rail section 93 Slider 94 Microscope 95 Sensor unit 96 Probe 97 Support section (first moving section)
98 Second moving part 99 Third moving part A Inspection object B Inspection liquid

Claims

In a biological / chemical / physical phenomenon detection apparatus including a sensor chip in which a plurality of sensors having a sensing unit for detecting a biological / chemical / physical phenomenon are arranged to form a sensing area, the sensor chip is appropriately positioned with respect to each sensing unit. A device for holding an inspection object,
A cylindrical or annular region constituent part having a hollow part that can surround a predetermined range of the sensing area, and a sheet part that is provided on one opening surface of the region constituent part and has an appropriate area capable of carrying an inspection object An inspection object holding device comprising:
2. The inspection object according to claim 1, wherein the sheet portion is a sheet portion disposed so as to close the opening surface at an end surface forming one opening surface of the region constituting portion. Holding device.
3. The inspection object holding apparatus according to claim 1, wherein the sheet portion is a mesh-like or porous sheet material.
The sheet portion is formed by laminating a mesh-like or porous flexible first sheet material and a net-structured second sheet material made of a material having elasticity and a higher Young's modulus than the first sheet material. The inspection object holding device according to claim 1, wherein the inspection object holding device is provided.
The inspection object holding apparatus according to any one of claims 1 to 4, wherein the region constituent part is a wall surface constituent part formed in a cylindrical shape having a desired thickness and length.
The said wall surface structure part is a wall surface structure part which has a fitting part with which the end surface of the opening part which opposes the said sensor fits into the unevenness | corrugation which exists in the circumference | surroundings of the said sensing area. Inspection object holding device.
The inspection according to claim 5 or 6, wherein the wall surface constituent part is a wall surface constituent part for holding an auxiliary electrode for applying a predetermined potential to an inspection object carried on the sheet part. Object holding device.
An inspection apparatus using the inspection object holding device according to any one of claims 1 to 7,
A stage held at the base,
Multiple horizontal rails fixed to the base;
A slider installed on the rail portion and movable along the rail portion;
A microscope installed on one of the stage and the slider;
The stage and the slider are mounted on the side where the microscope is installed, and include a sensor unit having a biological / chemical / physical phenomenon detection device,
The inspection object holding device is installed on the stage and the slider where the microscope and the sensor unit are not installed,
The inspection apparatus according to claim 1, wherein the sensor unit has a probe that is arranged in a state where a sensing area of the biological / chemical / physical phenomenon detection device can face the inspection object holding device.
9. The inspection apparatus according to claim 8, wherein the sensor unit includes a first moving unit that moves at least the probe in a vertical direction.
The sensor unit includes a second moving unit that moves the probe in a direction parallel to the rail, and a third moving unit that moves the probe in a direction perpendicular to the rail. The inspection device described.