JP2019213491A - Cell-capturing device and cell-capturing apparatus - Google Patents

Abstract

To preferably perform connection and removal of an outer flow channel, and suppress entry of bubbles to the inside even in the case where the connection and removal are repeated.SOLUTION: A cell-capturing device 1 comprises: flow channels 3A, 4A, 7A, 7B as introduction flow channels for introducing test solution or treatment solution into the device; a flow channel 9A as a discharge flow channel for discharging introduced liquid to the outside; and a housing 50 in which the flow channels are provided inside the housing. The device has: flow channel connection parts 81 to 86 to which acicular device connection parts are attachable; elastic materials 811, 821, 831, 841, 851, 861 which are housed in the flow channel connection parts, and control opening/closing of liquid circulation by inserting and removing the device connection parts; and supporting members 812, 822, 832, 842, 852 supporting the elastic materials. The elastic materials have a recessed part at a position corresponding to a moving route of the tip of the device connection parts of principal surface on a supporting member side in the state where the materials are housed in the flow channel connection parts.SELECTED DRAWING: Figure 8

Description

  The present invention relates to a cell capturing device and a cell capturing device.

  As a method of separating rare cells such as circulating tumor cells (CTCs) from a test solution such as blood, a method of capturing rare cells by a filter using a difference in cell size and deformability is used as a method for separating rare cells such as circulating tumor cells (CTC). It has been known. For example, Patent Document 1 discloses a cell trapping device having a housing in which a filter is housed. Patent Document 1 discloses a configuration in which an opening / closing valve is provided at a flow path connecting portion to which an external flow path is connected.

JP-A-2005-198595

  However, in the cell capturing device described in Patent Literature 1, connection and disconnection of the external flow path are performed many times. If the connection and disconnection of the external flow path are repeated, the open / close capability of the flow path by the open / close valve of the cell capturing device is reduced, and air bubbles may be mixed inside. On the other hand, it is conceivable to control the elasticity of the elastic material for the purpose of maintaining the opening / closing ability of the flow path, but in this case, the connection of the external flow path may not be properly performed due to the deformation of the elastic material. Is also conceivable.

  The present invention has been made in view of the above, and a cell capturing device capable of suitably connecting and disconnecting an external flow path and suppressing mixing of air bubbles into the inside even when these steps are repeated. And a cell capture device.

  In order to achieve the above object, a cell capturing device according to one embodiment of the present invention includes an introduction channel for introducing a test solution or a processing solution for treating cells in the test solution into the inside, A discharge channel for discharging the test liquid or the processing solution to the outside, and a housing provided with the introduction flow channel and the discharge flow channel, a cell capturing device including: A flow path connecting part that communicates with the introduction flow path or the discharge flow path at the bottom and is attachable to a needle-like device connection part for flowing the test liquid or the processing liquid between the outside and the outside. And piercing the device connection part in accordance with the attachment of the device connection part to the flow path connection part, which is housed in the flow path connection part, and removing the device connection part to the flow path connection part Disconnect the device connection part Thereby, an elastic material that controls opening and closing of the flow of the test liquid or the processing liquid, and a support member that is attached to the opening of the flow path connection part and supports the elastic material housed in the flow path connection part The elastic member has a concave portion at a position corresponding to a movement path of a tip of the device connection portion on a main surface of the support member side in a state housed in the flow path connection portion. Having.

  Further, the cell capturing device according to an aspect of the present invention includes the above-described cell capturing device, a test liquid storage container that stores the test liquid, and the introduction flow of the test liquid storage container and the cell capturing device. An external flow path connecting the flow path, the test liquid flow path having the device connection portion attached to the flow path connection portion of the introduction flow path, and cells captured by the cell capture device. A processing liquid storage container for storing the processing liquid for processing, and an external flow path connecting the processing liquid storage container and the introduction flow path of the cell capturing device, wherein the flow path of the introduction flow path A treatment liquid flow path having a device connection part connectable to the connection part, and an external flow path connected to the discharge flow path of the cell capturing device, wherein the flow path connection part of the discharge flow path Device connection part that can be connected to An external discharge channel, a selecting means for selecting a liquid to be supplied to the cell capturing device from the test liquid and the treatment liquid, and the test liquid storage based on a selection result of the selecting means. Liquid supply means for supplying a test liquid from a container or a processing liquid from the processing liquid storage container to the cell capturing device.

  According to the above-described cell capturing device and the cell capturing device, since the concave portion is provided at a position corresponding to the attachment position of the device connecting portion for the elastic material accommodated in the flow channel connecting portion, the device connecting portion is provided on the cell capturing device. At the time of attachment, the length of contact between the tip of the device connection portion and the elastic material can be shortened. Therefore, even if the attachment / detachment of the device connection portion to / from the flow passage connection portion is repeated, the elastic material can be prevented from being deteriorated or damaged by the tip of the device connection portion, so that the airtightness of the elastic material can be suitably maintained. Dripping. As described above, according to the cell trapping device and the cell trapping device, the connection and disconnection of the external flow path are suitably performed, and even when these steps are repeated, the intrusion of bubbles into the inside is suppressed. .

  Here, the elastic material has a concave portion at a position corresponding to a movement path of a tip of the device connection portion, of the main surface on the bottom side in a state of being housed with respect to the flow path connection portion. can do.

  As described above, in the case where the device has a concave portion at a position corresponding to the movement path of the distal end of the device connection portion on the main surface on the bottom side in a state housed with respect to the flow path connection portion, When the connecting portion is attached to the cell capturing device, the length of the contact between the distal end of the device connecting portion and the elastic material can be shortened, so that the elastic material can be further prevented from being deteriorated or damaged.

  The elastic material may have a form in which, in a cross section along a connection line indicating a movement path of a tip of the device connection portion, an outer peripheral surface has a shape corresponding to the flow path connection portion.

  As described above, when the outer peripheral surface of the elastic material has a shape corresponding to the flow path connecting portion, the contact area between the flow path connecting portion and the outer peripheral surface of the elastic material is increased. It is possible to suitably prevent liquid leakage or the like at the connection surface.

  In the above-described cell capturing device, an embodiment may further include a control unit that controls attachment and detachment of the device connection unit to and from the channel connection unit.

  As described above, the configuration having the control unit that controls the attachment and detachment of the device connection unit to and from the road connection unit allows the operator of the cell capture device to attach and detach the device connection unit to and from the cell capture device. Can be prevented, and work efficiency can be improved.

  ADVANTAGE OF THE INVENTION According to this invention, while connecting and disconnecting an external flow path is performed suitably, even if these are repeated, the cell trapping device and the cell trapping device which can suppress mixing of air bubbles into an inside are provided. You.

It is a schematic structure figure of a cell capture device. It is a perspective view of a cell capture device. It is an exploded perspective view of a cell capture device. It is an exploded perspective view of a cell capture device. It is a perspective view of a support member of a cell capture device. FIG. 6 is a sectional view taken along line VI-VI of FIG. FIG. 7 is a diagram schematically illustrating a cell capturing device, and is a diagram illustrating a cross section taken along line VII-VII of FIG. 2. FIG. 8 is a diagram schematically illustrating a cell capturing device, and is a diagram illustrating a cross section along line VIII-VIII in FIG. 7. FIG. 9 is a diagram schematically illustrating a cell capturing device, and is a diagram illustrating a cross section along line IX-IX in FIG. 7. It is a figure showing other examples of an elastic material.

  DESCRIPTION OF EMBODIMENTS Hereinafter, embodiments for carrying out the present invention will be described in detail with reference to the accompanying drawings. In the description of the drawings, the same elements are denoted by the same reference numerals, and redundant description is omitted.

  FIG. 1 is a diagram illustrating the configuration of the cell capturing device according to the present embodiment. The cell capturing device is a device that captures cells contained in a test liquid by filtering a cell dispersion liquid serving as a test liquid with a filter. Further, by using a treatment solution such as a staining solution for the cells captured by the filter, the cells are specified and the number of individual cells is counted. Examples of the cell dispersion liquid serving as a test liquid include blood, but the liquid is not limited to blood as long as rare liquids to be captured are dispersed. The cell trapping device is, for example, from blood containing circulating cancer cells (CTC), which is a kind of rare cells, to red blood cells, platelets, and white blood cells contained in blood (hereinafter, these are collectively referred to as “blood cell components”). , While being used for capturing CTC. Examples of rare cells include circulating endothelial cells (CEC) in addition to the above-mentioned CTC. The cell capturing device can separate rare cells to be captured from other components contained in a test solution such as other cells using a filter (for example, rare cells are larger than other components). , Rare cells have a lower deformability than other components and cannot pass through a filter, etc.).

  As shown in FIG. 1, a cell capturing device 100 according to the present embodiment includes a cell capturing device 1 in which a filter for capturing cells is provided, and supplies a processing liquid (reagent) to the cell capturing device 1. Flow path 3 (treatment liquid flow path: external flow path) composed of a tube for supplying the test liquid to the cell capturing device 1 (test liquid flow path: external flow path) Road) is provided. The type of the tube is not particularly limited, and for example, a flexible tube such as a soft tube can be used. Further, a plurality of types of tubes may be used in combination. In FIG. 1, the cell capturing device 1 and the flow path 3 are separated from each other, and the cell capturing device 1 and the flow path 4 are separated from each other. However, when a process for capturing and observing cells using the cell capturing device 100 is performed. These are connected. In this regard, the same applies to the flow path 9 described later.

  On the upstream side of the flow path 3, a plurality of processing liquid storage containers 5 containing different processing liquids (reagents) are provided. Examples of the processing liquid to be charged into the processing liquid storage container 5 include a staining liquid for staining cells, a washing liquid for washing cells and the like captured by a filter, a fixing liquid for protecting cells from decay, and staining. Examples include, but are not limited to, a permeate to allow the solution to penetrate into the cells. Although the plurality of processing liquid storage containers 5 shown in FIG. 1 are sealed by the cover member 5A, the configuration is not particularly limited.

  Tubes 6 are respectively inserted into the plurality of processing liquid storage containers 5 to form individual flow paths (processing liquid flow paths). These flow paths are connected to the selection valve 8, and the processing liquid connected to the flow path 3 is selected by rotating the selection valve 8, and the processing liquid containing the selected processing liquid is stored. The tube 6 inserted into the liquid container 5 and the flow path 3 are connected. Note that the mechanism used for selecting the processing liquid storage container is not limited to the selection valve 8, and other configurations can be used.

  A test liquid storage container 10 in which blood containing cells is stored as a test liquid is connected to the flow path 4 connected to the cell capturing device 1 during use. The processing liquid and the test liquid are not supplied to the cell capturing device 1 at the same time, but one of them is supplied. Control of which of the processing liquid and the test liquid is supplied is switched by valves 12 and 13 attached to the flow paths 3 and 4, respectively. For example, when supplying a test solution to the cell capturing device 1, the valve 12 is closed and the valve 13 is opened. As the valves 12 and 13, a pinch valve that presses and deforms a tube to shut off the flow can be used. The type of valve is not particularly limited, but when a pinch valve is used as the valve, a soft tube is used as the tube. Depending on the type of the tube, the type of the valve and the type of the pump described below are appropriately changed. The material of the tube may be changed only in the region where the valve or the pump is provided.

  In the drawings after FIG. 1, XYZ axes are shown for explanation. The XY plane indicated by the XY axes corresponds to a so-called horizontal plane, and the Z axis indicates a vertical line. Further, it is not for the purpose of indicating the direction of arrangement as the whole of the cell capturing device 100 according to the present embodiment, but for explaining the configuration of the cell capturing device 1. That is, the processing liquid storage container 5 and the test liquid storage container 10 that constitute the cell capturing device 100 are containers for storing liquids, respectively. On the other hand, an opening of the container is provided above along the Z axis. However, this arrangement and the like can be appropriately changed.

  When supplying any of the treatment liquid and the test liquid to the cell capturing device 1, the flow paths 3, 4 on the upstream side of the cell capturing device 1 are connected to the cell capturing device 1, and A flow path 9 (flow path for discharging outside the system) formed of a tube on the downstream side of the cell capturing device 1 is connected to the cell capturing device 1. Then, the liquid is supplied by sucking the target liquid by driving a pump 14 (supply means) provided on the flow path 9.

  The pump 14 has a structure that can change the flow rate of the liquid in the flow path by changing the rotation speed. As the pump 14, for example, a peristaltic pump (peristaltic pump) that sequentially moves a peristaltic point by pressurizing the tube can be used, but the type of the pump can be appropriately changed. By driving the pump 14, a liquid such as a processing liquid or a test liquid flows inside the flow channel 3 or the flow channel 4 in a direction toward the cell capturing device 1 and is supplied to the cell capturing device 1. The liquid that has passed through the cell capturing device 1 flows into the waste liquid container 16 via the flow path 9. With these structures, the cells in the test liquid are captured by the filter provided on the flow path in the cell capturing device 1, and the desired processing is performed by the processing liquid or the like.

  The end portions of the flow paths 3, 4, 9 on the cell capturing device 1 side are provided with device connection portions 31, 41, 91 each having a hollow shape like an injection needle and having a tip portion processed into a needle shape. By inserting the device connection portions 31, 41, 91 into the cell capturing device 1, the flow paths 3, 4, 9 and the cell capturing device 1 are connected. The device connection parts 31, 41, 91 may be fixed by a support tool or the like so that the arrangement thereof cannot be changed. By moving the cell capturing device 1 while supporting the device connecting portions 31, 41, and 91, and attaching and detaching the cell capturing device 1, the device connecting portions 31, 41, and 91 are individually moved. In comparison, the work efficiency is improved. However, the device connection units 31, 41, and 91 may be individually moved. The control unit 15 (see FIG. 1) for automatically connecting / disconnecting the device connection units 31, 41, 91 to / from the cell capturing device 1 may be provided. By adopting such a configuration, it is possible to prevent the operator of the cell capturing device 100 from connecting / disconnecting the device connecting portions 31, 41, 91 to / from the cell capturing device 1, thereby improving the efficiency of the operation. Can be

  Although details will be described later, in the cell capturing device 1, the flow path 3 (processing liquid flow path) is not directly connected to a filter in the cell capturing device, but is connected to a pre-processing unit in the cell capturing device 1. After passing through, the cell is once again introduced into the cell capturing device 1 through the connection channel 7 formed of a tube connected to the outside of the cell capturing device 1. Device connection portions 71 and 72 are provided at both ends of the connection flow path 7. By inserting the device connecting portions 71 and 72 into the cell capturing device 1, the connection channel 7 and the cell capturing device 1 are connected. With such a structure, the processing liquid introduced from the flow channel 3 is supplied to the filter via the pre-processing unit in the cell capturing device 1. The device connecting portions 71 and 72 may be fixed by supports or the like similarly to the device connecting portions 31, 41 and 91, or may be configured to be attached to the cell capturing device 1 first.

  The cell capturing device 1 is movably supported by the moving device 17, for example. The moving device 17 includes a fixed base 18, a mounting base 19 movable on the fixed base along the XY plane, and a drive motor 20. The rotation of the drive motor 20 causes the mounting base 19 to move. It moves in the X-axis direction and / or the Y-axis direction. By fixing the cell capturing device 1 to the mounting table 19, the cell capturing device 1 can move together with the mounting table 19. Although the moving direction is not limited to the above, the connection / disconnection between the flow paths 3, 4, 9 and the connection flow path 7 and the cell capturing device 1 is switched by the movement of the cell capturing device 1 by the moving device 17. Can be

  The control of each unit described above is performed by control by a control unit (selection unit, liquid supply unit / not shown). Specifically, the drive of the selection valve 8, the valves 12 and 13, and the movement of the cell capturing device 1 by the movement device 17 are performed according to an instruction from the control unit. The control unit is provided with a program input function for inputting a program that enables control of driving, stopping, and the like for each of the above-described units, and each device is sequentially operated as described above by the input program. A drive mechanism to operate is added. The control unit 30 selects a line through which the liquid flows, and based on the selection result, the control unit instructs each unit to open and close the valve and drive the pump.

  Next, the cell capturing device 1 will be described with reference to FIGS. 2 is a perspective view of the cell capturing device 1, FIGS. 3 and 4 are exploded perspective views of the cell capturing device 1, FIG. 5 is a perspective view of a resin support member, and FIG. 6 is a line VI-VI of FIG. FIG. 7 to 9 schematically show the configuration of the cell capturing device 1. FIG. FIG. 7 schematically shows a cross section taken along line VII-VII of FIG. FIG. 8 schematically shows a cross section taken along line VIII-VIII of FIG. Further, FIG. 9 schematically shows a cross section along the line IX-IX of FIG.

  The cell capturing device 1 has a configuration in which a filter 60 (see FIGS. 3, 4, and 7) having a plurality of through holes 61 is sandwiched between an upper member 51 and a lower member 52 of a housing 50. The filter 60 is disposed in a space formed therein when the upper member 51 and the lower member 52 are combined. The filter 60 is made of, for example, metal and has a plurality of through holes 61 formed in the thickness direction. The housing 50 of the cell capturing device 1 is composed of an upper member 51 and a lower member 52. Further, in the cell capturing device 1, the above-described flow paths 3 (device connection sections 31), 4 (device connection sections 41) and 9 (device connection sections 91) and connection flow paths 7 (device connection sections 71 and 72) are connected. Elastic members 811, 821, 831, 841, 851, 861 (see FIGS. 3 and 4) attached to each of the flow path connecting portions 81, 82, 83, 84, 85, and 86, and a support for supporting the elastic materials. And members 812, 822, 832, 842, 852 (see FIGS. 3 and 4). The size of the cell capturing device 1 is, for example, about 30 mm × 40 mm in plan view (XY directions), and the thickness (Z direction) is about 5 mm to 15 mm.

  The upper member 51 of the cell capturing device 1 is connected to a flow path 3A (introduction flow path: see FIGS. 3, 4, 6, 7, and 8) connected to the flow path 3 formed of a tube, and to the flow path 4. Flow path 4A (introduction flow path: see FIGS. 7 and 8), and flow path 7A (introduction flow path: see FIGS. 3, 4, 7, and 8) connected to the connection flow path 7 formed of a tube; Having. In addition, the upper member 51 is provided with a concave portion 531 that forms a pre-processing portion 53 that is a space region formed in the housing 50 by being combined with a concave portion provided in the lower member 52. The channel 3A communicates with the recess 531 (see FIGS. 7 and 8). In addition, the upper member 51 is provided with an introduction region 54 formed above the filter 60 and serving as a space for guiding the liquid to the through hole 61 of the filter 60. The flow path 7A and the flow path 4A communicate with the introduction region 54 (see FIGS. 7 and 8).

  The lower member 52 of the cell capturing device 1 includes a flow path 9A (discharge flow path: see FIGS. 3, 4, 7, and 9) connected to the flow path 9 formed of a tube, and a connection flow path formed of a tube. 7 (introduction channel: see FIGS. 3, 4, 6, 7, and 9). In addition, the lower member 52 is provided with a concave portion 532 that forms the pre-processing portion 53 that is a space region formed in the housing 50 by being combined with the concave portion 531 provided in the upper member 51. The channel 7B communicates with the recess 532 (see FIGS. 7 and 9). Further, the lower member 52 is formed below the filter 60 so that the depth of the central part is formed deeper than the peripheral part, and serves as a space for discharging the liquid that has passed through the through hole 61 of the filter 60 to the outside. A discharge area 55 is provided. The flow path 9A communicates with the discharge area 55 (see FIGS. 7 and 9). Further, a flow path 3B different from the flow path 9A is connected to the discharge area 55. The channel 3B is a process (pre-treatment) of filling the inside of the cell capture device 1 with a treatment liquid (for example, a washing solution) before introducing a test liquid into the cell capture device 1 and performing a process relating to cell capture. It is used when performing. By introducing the treatment liquid from the flow path 3B and filling the inside of the cell capturing device 1 with the liquid from the discharge area 55 side of the cell capturing device 1, air remaining in the device can be eliminated. When using the flow path 3B, the device connecting part 31 connected to the flow path 3 is connected to the flow path 3B to introduce the processing liquid into the device. The configuration of the connection part with the device connection part 31 is the same as the other flow paths 3A, 4A, 7A, 7B, 9A and the like.

  In the present embodiment, the “introduction channel” in the cell capturing device 1 refers to the channels 3A, 4A, 7A, and 7B in the stage preceding the filter 60 among the channels provided inside the cell capturing device 1. The “discharge flow path” refers to a flow path 9 </ b> A downstream of the filter among flow paths provided inside the cell capturing device 1. The “treatment liquid flow path” is connected to the flow path 3 connected to the upstream of the flow path 3A of the cell capturing device 1 and to the upstream of the flow path 7A connected to the introduction region 54. Connection flow path 7. In addition, the “test liquid flow path” refers to the flow paths 4 connected to the upstream side of the flow path 4A of the cell capturing device 1, respectively.

  The through-hole 61 provided in the filter 60 sandwiched between the upper member 51 and the lower member 52 has such a size that a cell to be captured cannot pass through. The size, shape, arrangement, and the like of the through holes 61 in the filter 60 can be appropriately changed based on the number of cells to be captured.

  Further, the upper member 51 has an end of the flow channel 3A of the cell trapping device 1 opposite to the end of the concave portion 531 and an end of the flow channel 7A opposite to the end of the introduction region 54. A flow path connecting portion 81 integrally formed with the end of the flow path is provided. In the upper member 51, a flow path connecting portion 83 is provided at an end of the flow path 4A opposite to the end on the introduction region 54 side. Further, the lower member 52 has an end on the side opposite to the end on the discharge region 55 side of the flow path 3B, an end on the side opposite to the end on the concave portion 532 side of the flow path 7B, and A flow path connecting portion 82 formed integrally with the end of the passage 9A opposite to the end on the discharge region 55 side is provided.

  Each of the flow path connecting portions 81, 82, 83, 84, 85, and 86 is a concave portion formed on the surface of the housing 50 (the upper member 51 or the lower member 52), and has an inner diameter (a width in the concave portion). The diameter is larger than the diameter of the flow path communicating with the flow path connection part. Therefore, the end of the flow path 3 </ b> A communicates with the bottom surface of the flow path connecting portion 81 provided on the upper member 51 (the surface opposite to the surface of the upper member 51). Similarly, the end of the flow path 7A communicates with the bottom surface of the flow path connecting portion 82 provided on the upper member 51, and the end of the flow path 7A communicates with the bottom surface of the flow path connecting portion 83 provided on the upper member 51. Department is communicating. The end of the flow path 7B communicates with the bottom surface of the flow path connecting portion 84 provided on the lower member 52 (the surface opposite to the surface of the lower member 52). Similarly, the end of the flow path 3 </ b> B communicates with the bottom surface of the flow path connection portion 85 provided on the lower member 52, and the flow path 3B communicates with the bottom surface of the flow path connection portion 86 provided on the lower member 52. The end of the road 9A communicates.

  In the present embodiment, a description will be given of a case where the flow path connecting portions 85 and 86 are integrally formed. However, originally, the flow path connecting portions 85 and 86 are formed at the end portions of the flow path in the cell capturing device. It is provided individually for each. This is to prevent contamination of the liquid flowing through the flow path. However, even when formed as an integral recess like the flow path connecting portions 85 and 86, the contamination of the liquid can be improved by changing the material, shape, size, etc. of the internal elastic material to improve the airtightness. The possibility of occurrence of nation can be reduced.

  The elastic members 811, 821, 831, 841, 851, and 861 will be described. Here, description will be first made with reference to the elastic member 811, but the shape and arrangement of the elastic members 821, 831, 841, 851, 861 are basically the same as those of the elastic member 811. As shown in FIG. 8 and the like, the elastic member 811 is accommodated in the flow path connecting portion 81. The elastic material 811 is made of, for example, silicone rubber or a thermoplastic elastomer. The hardness of the elastic member 811 can be, for example, about 30 Shore A to 50 Shore A. By setting the hardness of the elastic member 811 in the above range, the function of the elastic member 811 as an on-off valve described later can be suitably exerted.

  The elastic member 811 has a substantially ring shape (see FIGS. 3 and 4), but is not open at the center and is in a closed state. As a result, the elastic member 811 has a shape in which a concave portion 801 having a concave central portion is provided at the center of both main surfaces of the substantially disk-shaped main body. In particular, the concave portion 801 provided on the main surface on the side where the support member 812 is provided is arranged to face the device connecting portion 31 before being attached to the cell capturing device. The connection line C1 (see FIG. 8) passing through the concave portions 801 formed on both main surfaces overlaps with the central axis of the flow path 3A and extends in the same direction. This connection line C1 is a line corresponding to the movement position of the tip of the device connection part. Further, in the cross section of the elastic member 811 including the connection line C1, two circular body portions are continuous via the connection line C1 (see FIG. 8). The elastic member 811 is accommodated in the flow path connecting portion 81 and is pressed to the bottom side of the flow path connecting portion 81 by a support member 812 attached to the outside of the elastic material 811 (on the surface side of the housing 50). Supported.

  As shown in FIG. 5A, the support member 812 has a shape that closes the opening of the flow path connection part 81, and has a protrusion 813 inserted into the flow path connection part 81. Further, the support member 812 may have a claw or the like for fixing the support member 812 to the upper member 51 in a state where the flow path connection portion 81 is closed. Further, the support member 812 has a through hole 814 for inserting the tip of the device connection portion 31 (see FIG. 8) connected to the flow path 3 into the flow path 3A.

  When the support member 812 is attached and the device connecting portion is not attached, the elastic member 811 is almost filled with the flow path connecting portion 81. Note that the “state in which the flow path connecting portion 81 is substantially filled” is a state in which a part of the outer surface of the elastic member 811 is in contact with an inner surface different from the bottom surface of the flow path connecting portion 81. Means a state in which the movement of the elastic member 811 is almost impossible. As described above, since the elastic member 811 is supported by the support member 812 while substantially filling the flow path connecting portion 81, it is possible to prevent liquid leakage from the internal flow path 3 </ b> A via the flow path connecting part 81. In addition, when the device connection portion is attached, the volume (excluding the device connection portion) in the flow path connection portion 81 becomes smaller due to the volume of the device connection portion, so that the elastic member 811 is in a compressed state. Therefore, even when the device connection portion is attached, it is possible to prevent liquid leakage from the inside through the periphery of the device connection portion and the like.

  When the device connection part 31 is inserted into the through hole 814 of the support member 812 and the tip of the device connection part 31 penetrates the elastic member 811, the state is such that the tip of the device connection part 31 is introduced into the flow path 3 </ b> A. When the device connecting portion 31 penetrates the elastic member 811, the connecting line C1 extends along the extending direction of the flow path 3A through the concave portion 801 formed at the center of both main surfaces of the elastic member 811 (see FIG. 8)), the distal end of the device connection portion 31 is inserted. As a result, the flow path 3 and the flow path 3A are connected via the device connection unit 31.

  The elastic member 821 accommodated in the passage connecting portion 82, the elastic member 831 accommodated in the passage connecting portion 83, the elastic member 841 accommodated in the passage connecting portion 84, and the passage connecting portion 85 As shown in FIGS. 8 and 9, the elastic member 851 accommodated with respect to the elastic member 811 and the elastic member 851 accommodated with respect to the channel connecting portion 86 are provided for each channel connecting portion similarly to the elastic member 811. Will be accommodated. Also, as for the support members 822, 832, 842, and 852 attached to the flow path connection portions 82, 83, 84, 85, and 86, similarly to the support member 812, the protrusions inserted into the flow path connection portions and It has a through-hole into which a device connection part can be inserted (see FIG. 5: support members 822, 842, 852 are shown in FIGS. 5 (a) and 5 (b)). In addition, since the support member 852 is attached to the flow path connecting portions 85 and 86 formed integrally, two through holes 854 and 855 are provided for one convex portion 853.

  Each of the elastic members 821, 831, 841, 851, and 861 has a shape in which a concave portion 801 whose central portion is recessed is provided at the center of both main surfaces of the substantially disk-shaped main body, and the center line is the flow path 7A. , 4A, 7B, 3B, and 9A are disposed at positions corresponding to the axial directions of the respective central axes. The elastic members 851 and 861 are housed adjacent to each other in the integrally formed flow passage connecting portions 85 and 86, but the other elastic materials are individually housed in the respective flow passage connecting portions. . The respective elastic members are supported by the support members 822, 832, 842, 852 in a state of being accommodated in the flow path connection portion.

  In this state, when the device connection portion is provided in the support member and inserted into the through hole, and the tip of the device connection portion penetrates the elastic material along the center line of the elastic material, the tip of the device connection portion becomes the inner flow path. And the device connection part and the flow path are connected.

  Although FIG. 9 shows a state in which the device connection unit 31 is inserted into the through hole 854, the device connection unit 31 is inserted only in the preprocessing as described above, and is actually used. At this time (when introducing the test liquid), the device connection portion 31 is removed from the through hole 854. However, as described above, the device connection portion 31 is inserted only in the pretreatment, and the device connection portion 31 may be removed from the through hole 854 when used (when the test liquid is introduced). . Further, the configuration may be such that the test liquid is introduced in a state where the device connection portion 31 or another member or the like is inserted into the through hole 854. When the test liquid is introduced with the device connection part 31 or the like introduced into the through-hole 854, the inside is pressurized using a pump or the like, or a resistor (baffle plate) is provided in the flow path. Thus, it is possible to prevent the liquid from flowing out to the outside via the device connection unit 31.

  When the device connection unit is attached, the elastic material is compressed according to the volume of the attached device connection unit. When the device connecting portion is attached while being supported by the support member, the elastic material is compressed in a state of being in close contact with the device connecting portion. Therefore, the elastic material can stably prevent liquid leakage in a state where the device connection portion is attached. Also, when the device connection is removed, the elastic material is not compressed by the device connection, but the state of being supported by the support member is maintained, so that the liquid leakage is stabilized even when the device connection is removed. Can be prevented.

  As described above, the elastic members 811, 821, 831, 841, 851, and 861 are accommodated in the flow path connecting portions 81, 82, 83, 84, 85, and 86 of the cell capturing device 1, respectively. These elastic members 811, 821, 831, 841, 851, 861 are pressed by the support members 812, 822, 832, 842, 852 and fixed in the flow path connecting portions 81, 82, 83, 84, 85, 86. Is done. Further, when the device connecting portions inserted into the through holes of the support members 812, 822, 832 from the outside penetrate the elastic members 811, 821, 831, 841, 851, 861, the device connecting portions and the device connecting portions are inserted. Thus, the external flow path and the flow path in the cell capturing device 1 are connected. As described above, in the flow channel connecting portions 81, 82, 83, 84, 85, 86, the elastic members 811, 821, 831, 841, 851, 861 are connected to the cell capturing device 1 communicating with the flow channel connecting portions. It has a function as an on-off valve for controlling the opening and closing of the internal flow path.

  The sizes of the elastic members 811, 821, 831, 841, 851, 861 accommodated in the flow path connecting portions 81, 82, 83, 84, 85, 86, respectively, and the supporting members 812, 822, 832, 842, The shape (disposition and size of the through-holes) of 852 and the like depend on the shapes of the flow passage connecting portions 81, 82, 83, 84, 85, 86 and the disposition and shape of the flow passages communicating with the flow passage connecting portions. Is appropriately changed.

  Here, in the cell trapping device 100 according to the present embodiment, attachment and detachment of the cell trapping device 1 and the device connection portions 31, 41, 71, 72, 91, etc. are repeatedly performed. For this reason, the elastic members 811, 821, 831, 841, 851, 861 housed in the flow path connecting portions 81, 82, 83, 84, 85, 86 receive loads accompanying attachment and detachment of the device connecting portions, respectively. Will be.

  When the attachment / detachment of the device connection part to / from the flow path connection part (stabbing / pulling of the device connection part into / out of the elastic material) is repeated, the elastic material deteriorates and the airtightness in the device is reduced. Repeating attachment / detachment of the device connection portion means that the needle-like tip portion of the device connection portion is repeatedly stabbed at the same position of the elastic material (the area exposed in the through hole of the support member). , And cracks occur in the elastic material many times. Therefore, the region where the device connection portion is repeatedly pierced and the periphery thereof are repeatedly deformed, and the region after the device connection portion is gradually removed becomes difficult to be closed. Therefore, the airtightness of the elastic material is not maintained, and liquid leakage or the like may occur.

  Also, by inserting the device connection portion into the elastic material, especially when the elastic material moves to the flow path side together with the tip of the device connection portion and is deformed when the device connection portion moves inside the elastic material. There is. In this case, the device connection portion may be returned to the original shape by penetrating the elastic material, but it is difficult to return to the original shape, and the elastic material may be damaged. As described above, by repeatedly attaching / detaching the device connecting portion to / from the flow channel connecting portion, the elastic material may be deteriorated or damaged mainly by the influence of the tip of the device connecting portion.

  On the other hand, in the cell capturing device according to the present embodiment, the central portion of the main surface of the elastic material (for example, the elastic material 811) on the side facing the device connection portion, more specifically, the tip of the device connection portion Has a concave portion 801 at a position corresponding to the movement path of the moving object. Then, the device connecting portion is connected to the cell capturing device by being inserted into the concave portion 801 of the elastic material. As described above, by providing the concave portion 801 at a position corresponding to the attachment position of the device connection portion for the elastic material accommodated in the flow path connection portion, when attaching the device connection portion to the cell capturing device, The length of the contact between the tip and the elastic material can be reduced. Therefore, even if the attachment / detachment of the device connection part to / from the flow path connection part (stabbing / pulling of the device connection part into / out of the elastic material) is repeated, the elastic material is prevented from being deteriorated or damaged by the tip of the device connection part. be able to. On the other hand, in the above-mentioned elastic material, the thickness of the elastic material can be sufficiently ensured in a region other than the concave portion 801 provided in the central portion, so that a sufficient thickness for maintaining airtightness can be ensured. . Therefore, in the above-described cell capturing device, the airtightness of the elastic material is suitably maintained.

  Further, since the concave portion 801 is provided at the center portion like the elastic material (for example, the elastic material 811) described above, when the device connecting portion comes into contact with the elastic material, the concave portion 801 is connected to the device. This guides the tip of the device connection portion, so that the tip of the device connection portion can be appropriately inserted into the elastic material along the connection line C1. Therefore, the connection between the device connection unit and the cell capturing device 1 is appropriately performed.

  Further, the above-described elastic material (for example, elastic material 811) has a concave portion 801 in a central portion of a main surface on a side opposite to a main surface on a side facing the device connection portion. That is, the concave portion 801 is provided at the center of both main surfaces through which the tip of the device connection portion passes. With such a structure, the length of contact between the distal end of the device connection portion and the elastic material can be further reduced, so that the deterioration and damage of the elastic material due to the distal end of the device connection portion can be further suppressed. .

  In addition, the concave portion 801 provided for the elastic material is provided corresponding to the position where the tip of the device connecting portion inserted into the flow path passes. Therefore, in the elastic material, the concave portion 801 is provided near the center of each main surface. The connection line C1 corresponds to the movement line at the tip of the device connection unit. Therefore, even when the concave portion 801 is provided only on one main surface (the concave portion 801 is provided only on the surface facing the device connection portion), the connection line extending along the extending direction of the flow path 3A. It is sufficient that the concave portion 801 is provided at a position corresponding to C1. Regardless of whether the concave portion 801 is provided on one side or both surfaces, the above-described effect can be obtained as long as the tip of the device connecting portion moves along the connection line C1 passing through the concave portion 801. Therefore, the “central portion” where the concave portion 801 is provided may be an area where the connection line C1 passes, and does not need to include the center of the elastic material.

  A modified example of the elastic member will be described with reference to FIG. FIGS. 10A and 10B show modified examples of the elastic material. The elastic member 802 shown in FIG. 10A has, for example, a D-shaped cross-sectional shape on one side with respect to the connection line C1 passing through the concave portion 801 among the cross-sectional shapes as compared with the elastic member 811. . In the elastic member 811, the cross-sectional shape on one side of the connecting line C <b> 1 passing through the concave portion 801 was a circular shape (a shape in which a part thereof was missing). Therefore, the contact area between the elastic member 811 and the wall surface (side wall surface) of the flow path connecting portion 81 was small (see FIG. 8). On the other hand, the elastic member 802 has a D-shaped cross section on one side, and in a cross section along the connection line C1, the outer peripheral surface of the elastic member 802 is not a curve but a straight line. That is, the outer peripheral surface of the elastic member 802 has a shape corresponding to the flow path connecting portion 81. Accordingly, since the contact area between the side wall surface of the flow path connecting portion 81 and the elastic member 802 is increased, liquid leakage or the like at the connecting surface between the flow path connecting portion 81 and the elastic member 802 can be suitably prevented.

  The elastic member 804 shown in FIG. 10B has a sectional shape on one side across the connection line C1 passing through the concave portion 801 in the sectional shape as compared with the elastic member 802 shown in FIG. It has a shape. That is, the elastic member 804 has a flat surface without the concave portion 801 provided on the main surface on the side of the flow path 3A. In the elastic member 804, similarly to the elastic member 802, the outer peripheral surface of the elastic member 800 is not a curve but a straight line in a cross section along the connection line C1. Therefore, since the contact area between the side wall surface of the flow path connecting portion 81 and the elastic member 804 is increased, liquid leakage or the like at the connecting surface between the flow path connecting portion 81 and the elastic member 804 can be suitably prevented. Since the concave portion 801 is not provided on the one main surface, the length of the contact between the distal end of the device connecting portion and the elastic material is longer than that of the elastic material 802.

  When an outer peripheral surface that comes into contact with the flow path connection portion is provided like the elastic materials 802 and 804, the outer diameter of the elastic materials 802 and 804 needs to be appropriately selected according to the flow path connection portion. is there. That is, if the outer diameter of the elastic material is smaller than that of the flow path connecting portion, the above-described effect of improving the airtightness may not be sufficiently obtained.

  As described above, the embodiments of the present invention have been described, but the present invention is not limited to the above embodiments, and various changes can be made. For example, the configuration of each unit of the cell capturing device 100 is not limited to the above, and for example, the shape of the cell capturing device 1 can be appropriately changed.

  Although the case where the pre-processing unit 53 is included as the cell capturing device 1 has been described, the pre-processing unit 53 may not be included. In that case, the configuration and the like of the flow channel in the cell capturing device 1 are also appropriately changed. For example, in the above embodiment, the connection channel 7 is provided outside the cell capturing device 1, but in the case of a cell-free capturing device having no pretreatment unit 53, the channel 3A to which the channel 3 is connected is used. Is connected to the introduction region 54 above the filter 60. Therefore, when the cell capturing device does not have a pretreatment unit, the channels 7A and 7B are not required.

  Further, the shapes of the introduction area and the discharge area where the filter is provided can be changed as appropriate. In the above-described cell capturing device 1, the introduction region 54 is provided above (+ Z direction) the filter 60 disposed along the XY plane, and the discharge region 55 is provided below the filter 60. Can also be changed as appropriate.

  Further, in the cell capturing device 1, a process of filling the inside of the cell capturing device 1 with a processing liquid (for example, a washing liquid) before introducing a test liquid into the cell capturing device 1 and performing a process related to capturing cells. Although the flow path 3B used in the case of performing is performed, the flow path 3B need not be provided. As described above, the flow path provided in the cell capturing device 1 can be appropriately changed according to a method of handling the test liquid and the processing liquid (for example, a method of introducing into the cell capturing device 1 and a method of discharging the same).

  Further, in the cell capturing device 100 according to the present embodiment, the arrangement, the flowing direction, and the like of the treatment liquid connected to the cell capturing device 1 can be appropriately changed. For example, after capturing desired cells on the filter 60 of the cell capturing device 1 using the cell capturing device 100, washing the cells with a washing solution or the like, introducing a treatment solution for lysis into the inside, and dissolving the captured cells. It is conceivable to recover the liquid after dissolution. The cell capturing device 100 can also be used for the above-mentioned applications. In this case, the flow path connected to the device connection unit connected to each flow path of the cell capturing device 1 can be appropriately changed. In addition, the type of liquid used as the processing liquid is appropriately changed. Further, the moving direction of the liquid in the cell capturing device 1 may be changed.

  The flow path connecting portions 81 to 85 can also be appropriately changed according to the design of the flow path in the cell capturing device 1 or the structure of the housing 50. For example, in the above-described embodiment, a case has been described in which a plurality of flow paths are connected to the flow path connection part 85, but the number of flow paths connected (communicated) to one flow path connection part is as follows. It can be changed as appropriate. One elastic material is accommodated in the flow path connection portion corresponding to one flow path, and the number of flow paths connected to the flow path connection portion is changed in that the elastic material is supported by the support member. The same is true. However, in consideration of maintaining airtightness and preventing mixing of liquid types, it is preferable that one elastic member is accommodated in one flow path connecting portion.

  In addition, the configuration of the cell capturing device 100 can be appropriately changed. For example, if necessary, a device such as a deaerator may be added to the components of the cell capturing device 100 described in the above embodiment.

  DESCRIPTION OF SYMBOLS 1 ... Cell capture device, 3, 3A, 3B, 4, 4A, 7A, 7B, 9, 9A ... Flow path, 5 ... Treatment liquid storage container, 7 ... Connection flow path, 10 ... Test liquid storage container, 15 ... Control means, 31, 41, 71, 72, 91 device connection section, 50 housing, 51 upper member, 52 lower member, 53 pretreatment section, 54 introduction area, 55 discharge area, 60 ... Filter, 17: moving device, 81, 82, 83, 84, 85, 86: flow path connecting portion, 100: cell trapping device, 802, 804, 811, 821, 831, 831, 841, 851, 861 ... elastic material , 812, 822, 832, 842, 852... Support members.

Claims (5)

An introduction flow path for introducing a test liquid or a processing liquid for processing cells in the test liquid therein, and a discharge flow for discharging the introduced test liquid or the processing liquid to the outside A cell, a housing provided with the introduction flow path and the discharge flow path provided therein, a cell trapping device,
A flow path connecting part that communicates with the introduction flow path or the discharge flow path at the bottom and is attachable to a needle-like device connection part at the tip for flowing the test liquid or the processing liquid with the outside. When,
It is accommodated in the flow path connection part, stabs the device connection part according to the attachment of the device connection part to the flow path connection part, and according to the removal of the device connection part from the flow path connection part. An elastic material for controlling opening and closing of the flow of the test liquid or the processing liquid by pulling out the device connection portion,
A support member attached to the opening of the flow path connection part, for supporting the elastic material housed in the flow path connection part,
Have
The cell capturing device, wherein the elastic material has a concave portion at a position corresponding to a movement path of a tip of the device connecting portion on a main surface of the support member side in a state where the elastic material is accommodated in the flow channel connecting portion. .   2. The elastic member according to claim 1, wherein the elastic member has a concave portion at a position corresponding to a movement path of a tip of the device connecting portion on the main surface on the bottom side in a state housed with respect to the flow path connecting portion. 3. The cell capture device according to any one of the preceding claims.   The cell capturing device according to claim 1, wherein the elastic member has a shape corresponding to an outer peripheral surface of the elastic member. A cell capture device according to any one of claims 1 to 3,
A test solution storage container for storing the test solution,
A test having an external flow path connecting the test liquid storage container and the introduction flow path of the cell capturing device, the device connection part being attached to the flow path connection part of the introduction flow path. A liquid flow path;
A processing liquid storage container that stores the processing liquid for processing the cells captured in the cell capturing device,
An external flow path connecting the processing liquid storage container and the introduction flow path of the cell capturing device, the processing liquid flow having a device connection portion connectable to the flow path connection portion of the introduction flow path. Road and
An external flow path connected to the discharge flow path of the cell capturing device, the external discharge flow path having a device connection portion connectable to the flow path connection portion of the discharge flow path,
Selection means for selecting a liquid to be supplied to the cell capturing device from the test liquid and the treatment liquid,
Based on the selection result of the selection means, a liquid sending means for supplying a test liquid from the test liquid storage container or a processing liquid from the processing liquid storage container to the cell capturing device,
A cell capturing device, comprising:   The cell capturing device according to claim 4, further comprising a control unit configured to control attachment and detachment of the device connection unit to and from the channel connection unit.

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