Biological simulation system device

Abstract

A biological simulation system device (1) is provided with: a container (2) in which a plurality of functional units (6a-6d) are exchangeably accommodated; and a flow path member (3) that is disposed on the front side of the container (2) and that partitions at least a portion of flow paths (33a, 33b) that communicate the plurality of functional units (6a-6d) housed in the container (2).

Description

Technical Field

[0001] The present invention relates to a biological simulation system device for innovative drug research and the like. Background Art

[0002] In recent years, as an alternative technology to animal experiments, a biological simulation system (MPS: Microphysiological System) device has attracted attention. For example, a fluid device having a microplate with a plurality of interconnected wells is disclosed in Patent Document 1. In the case of the fluid device disclosed in this document, a manifold for distributing fluid to a plurality of wells, a pump for pumping fluid into the wells, etc. are arranged outside the fluid device. In addition, these external instruments are connected to the wells via tubes.

[0003] Prior Art Documents

[0004] Patent Documents

[0005] Patent Document 1: Pamphlet of International Publication No. 2020 / 013851 Summary of the Invention

[0006] Problems to be Solved by the Invention

[0007] In the case of the fluid device disclosed in this document, when reorganizing the functions of the fluid device, an operator needs to correctly connect each of the plurality of wells to an external instrument having a desired function via a tube one by one. In addition, when observing a sample after an experiment, it is necessary to remove the fluid device from the tube and transport the fluid device to an observation instrument (such as an inverted microscope). Moreover, the fluid device is mainly used in an incubator, and the above operations are very difficult and cumbersome. Thus, the usability of conventional biological simulation systems is low. Accordingly, an object of the present invention is to provide a biological simulation system with excellent usability.

[0008] Means for Solving the Problems

[0009] (1) To solve the above problems, the biological simulation system device of the present invention is characterized in that the biological simulation system device includes: a container for removably accommodating a plurality of functional units; and a flow path member disposed on the front side of the container, which divides at least a part of a flow path that connects the plurality of functional units accommodated in the container.

[0010] Here, the "plurality of functional units" includes a plurality of functional units of the same type and a plurality of functional units of different types. In addition, the "flow path member that divides at least a part of the flow path" includes a flow path member that divides the entire flow path and a flow path member that divides only a part of the flow path.

[0011] According to this configuration, multiple functional units can be replaced relative to the container. Therefore, by replacing any of the functional units, the functions of the biological simulation system device can be easily reorganized. Therefore, compared with conventional simple in vitro devices, it is possible to simulate a variety of biological environments corresponding to desired organs, diseases, etc. with higher reproducibility.

[0012] In addition, in the biological simulation system device according to the present invention, multiple functional units can be connected through a flow path preset in the flow path member. Therefore, compared with the case where multiple functional units are connected by tubes through manual operations, misconnections can be suppressed. In addition, since the flow path is divided by the flow path member, the flow path is less likely to deform compared with tubes. Therefore, it is easy to achieve a desired flow rate and flow path resistance.

[0013] In addition, in the biological simulation system device according to the present invention, an instrument that has been conventionally treated as an external instrument can be accommodated as a constituent member of the functional unit in the container. Therefore, the biological simulation system device can be miniaturized. In addition, multiple functional units can be integrated. Therefore, the processability is excellent. Thus, the biological simulation system device of the present invention has excellent usability.

[0014] (1-1) Preferably, the following configuration is adopted: among the multiple functional units accommodated in the container, at least one of the functional units is a liquid delivery unit having an airbag pump that can expand and contract elastically, and the airbag pump sends the fluid stored inside itself to the flow path by the elastic restoring force during contraction. According to this configuration, it is possible to pump the fluid without power using the elastic restoring force. Therefore, the processability is excellent.

[0015] (2) In the configuration of (1) above, preferably, the following configuration is adopted: when viewed from the front and back directions, the size of the container is the size of a multi well plate conforming to industrial standards. Here, "industrial standards" include international standards (ISO, IEC, etc.) and domestic standards of various countries (JIS, DIN, ANSI, BS, etc.). According to this configuration, the size of the container is set to the size of a multi well plate conforming to industrial standards. Therefore, the versatility with respect to instruments assumed to be of the same size is high.

[0016] (3)In any of the above configurations, it is preferably configured as follows: The container has a rectangular bottom wall portion having a pair of long side portions arranged opposite to each other, and a pair of short side portions connecting the pair of long side portions to each other and arranged opposite to each other; a pair of side wall portions erected from the pair of long side portions on the front side; and a partition wall portion connecting the pair of side wall portions to each other, extending parallel to the short side portions, and dividing the space between the pair of side wall portions into a plurality of accommodation portions, and the accommodation portions are interchangeable with respect to the plurality of functional units. According to this configuration, the accommodation portions are interchangeable with respect to the plurality of functional units. Therefore, the functional units can be replaced in units of accommodation portions.

[0017] (4)In any of the above configurations, it is preferably configured as follows: The flow path member has a plurality of abutting portions arranged opposite to the plurality of functional units accommodated in the container, the abutting portions abut against the functional units from the front side, and the flow path opens at the back of the abutting portions. According to this configuration, the functional units can be positioned with respect to the flow path member through the abutting portions. In addition, the fluid can flow between the flow path and the functional units via the abutting portions.

[0018] (5)In any of the above configurations, it is preferably configured as follows: The flow path member divides a plurality of the flow paths inside. According to this configuration, a plurality of flow paths can be divided only by the flow path member without using other members. In addition, the relative positional relationship of the plurality of flow paths can be fixed.

[0019] (5-1)In any of the above configurations, it is preferably configured as follows: The biological simulation system device has a flow rate control portion that controls the flow rate of the fluid flowing in any of the flow paths. According to this configuration, the flow rate of the fluid in a desired flow path can be controlled.

[0020] (5-2)In the configuration of the above (5-1), it is preferably configured as follows: The flow rate control portion adjusts at least one of the shape of the flow path in the path length direction and the shape in a direction intersecting (for example, orthogonal) to the path length direction. According to this configuration, by adjusting the flow path shape, the flow rate can be simply controlled without using other members.

[0021] (6)In any of the above configurations, it is preferably configured as follows: The biological simulation system device includes a cover member disposed on the front side of the flow path member and having a higher rigidity than the flow path member. According to this configuration, the flow path member can be protected by the cover member.

[0022] (6-1)In the configuration of the above (6), it is preferably configured as follows: The biological simulation system device includes a fastening member that fastens the cover member to the container. According to this configuration, the cover member and the container can be integrated by the fastening member.

[0023] (6-2) In the configuration of the above (6-1), the following configuration is preferred: after fixing the functional unit through the flow path member, the container and the flow path member are integrated by the cover member and the fastening member. According to this configuration, the container and the flow path member can be integrated by the cover member and the fastening member. In addition, the deviation of the fastening force due to the skill difference of the operator can be suppressed.

[0024] (6-3) In the configuration of the above (6-1) or (6-2), the following configuration is preferred: the flow path member has a plurality of abutting portions arranged opposite to the plurality of functional units accommodated in the container, the functional unit has an opening portion opposite to the abutting portion, and the abutting portion has a press-fitting portion press-fitted into the opening portion. According to this configuration, the cover member and the container can be fastened by the fastening member, thereby specifying the press-fitting amount of the press-fitting portion relative to the opening portion. In addition, the functional unit can be positioned relative to the flow path member.

[0025] (7) In the configuration of any one of the above (6-1) to (6-3), the following configuration is preferred: the cover member has a front-side engaging portion, the container has a back-side engaging portion, and the fastening member engages with the front-side engaging portion and the back-side engaging portion. According to this configuration, by engaging and disengaging the fastening member with respect to the front-side engaging portion and the back-side engaging portion, the fastening member can be attached and detached with respect to the cover member and the container. That is, the cover member, the flow path member, and the container can be assembled and separated.

[0026] (8) In the configuration of the above (7), the following configuration is preferred: the container has a rectangular bottom wall portion having a pair of long side portions arranged opposite to each other, a pair of short side portions connecting the pair of long side portions to each other and arranged opposite to each other; a pair of side wall portions erected from the pair of long side portions on the front side; and a partition wall portion connecting the pair of side wall portions to each other, extending in parallel with the short side portions, and partitioning the space between the pair of side wall portions into a plurality of accommodating portions. When viewed from the front and back directions, the size of the container conforms to the size of an industrial standard perforated plate, and the accommodating portions are interchangeable with the plurality of functional units. The flow path member has a flow rate control portion that divides the plurality of flow paths inside and controls the flow rate of the fluid flowing in any of the flow paths; and a plurality of abutting portions arranged opposite to the plurality of functional units accommodated in the container, and the abutting portions abut against the functional units from the front side, and the flow paths open at the back of the abutting portions. The container, the flow path member, and the cover member are transparent. This configuration has the effects of the above (1) to (7) configurations. In addition, the container, the flow path member, and the cover member are transparent. Therefore, it is easy to observe.

[0027] (9)In any of the above configurations, it is preferably configured as follows: the container has: a bottom wall portion; and a side wall portion that stands upright from the bottom wall portion on the front side, and the side wall portion has an opening that penetrates itself. According to this configuration, the outside and the inside of the container can be simply connected via the opening.

[0028] (10)In any of the above configurations, it is preferably configured as follows: the container has a bottom wall portion, and the bottom wall portion has an opening that penetrates itself. According to this configuration, the functional unit can be simply positioned using the opening.

[0029] (11)In any of the above configurations, it is preferably configured as follows: the flow path member has a contact portion, the functional unit has an opening, the contact portion has a press-fitting portion that is press-fitted into the opening, and the press-fitting portion is made of a material containing at least one of PDMS and resin.

[0030] According to this configuration, the press-fitting portion of the contact portion of the flow path member is press-fitted into the opening of the functional unit. Therefore, the functional unit can be simply positioned relative to the flow path member. In addition, the sealing performance between the flow path member and the opening can be improved.

[0031] (11-1)In the configuration of the above (11), it is preferably configured as follows: the flow path member has, from the front side toward the back side: a soft layer made of PDMS; and a hard layer made of resin and having a higher rigidity than the soft layer. The soft layer has a soft layer protrusion that protrudes toward the back side, the hard layer has a cylindrical hard layer protrusion that protrudes toward the back side, the soft layer protrusion is disposed radially inside the hard layer protrusion, and a sealing member made of an elastic body is annularly provided on the outer peripheral surface of the hard layer protrusion. The contact portion has the soft layer protrusion, the hard layer protrusion, and the sealing member, the press-fitting portion has a portion of the contact portion that is more toward the back side than the sealing member and the sealing member, and the sealing member elastically contacts the opening of the functional unit from the radial inside.

[0032] According to this configuration, the sealing member is sandwiched between the hard layer protrusion of the flow path member and the opening of the functional unit. By the elastic deformation of the sealing member, the fluid sealing performance (liquid tightness, air tightness, etc.) of the opening can be ensured.

[0033] (11-2)In the configuration of the above (11-1), it is preferably configured as follows: the press-fitting portion has a shape in which the cross-sectional area becomes smaller toward the lower side, the functional unit is a culture portion, the culture portion has a culture vessel having the opening and storing a culture solution inside, and a bubble storage space for storing bubbles in the culture solution is defined in a portion directly below the sealing member inside the culture vessel.

[0034] According to this configuration, directly below the sealing member, in other words, near the upper end of the inner peripheral surface of the side wall portion of the incubator, a bubble storage space is defined. Therefore, the bubbles in the culture solution can move upward by the buoyancy of the bubbles themselves and move into the bubble storage space. Therefore, the observation confirmability during observation can be ensured.

[0035] (12) In any of the above configurations, it is preferably configured as follows: the flow path is used to degas the functional unit. There are cases where bubbles are accidentally mixed into the functional unit for liquid (for example, the culture unit using the culture solution). Assume a case where a biological simulation system device having a functional unit for liquid is used in an environment where rapid decompression may occur (such as outer space, etc.). In this case, due to decompression, the bubbles in the liquid may expand, and there is a risk of malfunction in the functional unit. In this regard, according to this configuration, the functional unit can be degassed via the flow path. Therefore, it is possible to suppress malfunctions in the functional unit caused by bubbles.

[0036] (12-1) In the configuration of the above (12), it is preferably configured as follows: the flow path communicates with a bubble storage portion disposed inside or outside the container. According to this configuration, the bubbles in the culture solution can be stored in the bubble storage portion.

[0037] If the bubble storage portion is disposed inside the container, the processing of bubbles can be completed within the biological simulation system device. Therefore, the processability is higher compared to the case where the bubble storage portion is disposed outside the container.

[0038] If the bubble storage portion is disposed outside the container, compared to the case where the bubble storage portion is disposed inside the container, the degree of freedom regarding the size, shape, etc. of the bubble storage portion is higher. In addition, compared to the case where the bubble storage portion is disposed inside the container, the influence of malfunctions caused by bubbles on the biological simulation system device can be reduced.

[0039] Advantages of the Invention

[0040] In the biological simulation system device according to the present invention, conventionally, an instrument that was treated as an external instrument could be accommodated as a constituent member of the functional unit in the container. Therefore, the biological simulation system device can be miniaturized. In addition, multiple functional units can be integrated. Therefore, the processability is excellent. In this way, the biological simulation system device of the present invention has excellent usability. In addition, since the recombination of the functional units is easy, the versatility is high. In addition, since the miniaturization of the biological simulation system device is easy, the workability is improved. In addition, since there is no need for a complicated operation such as connecting multiple functional units through a tube by manual work, contaminants can be reduced. Brief Description of the Drawings

[0041] Figure 1Is a perspective view of the biological simulation system device of the first embodiment.

[0042] Figure 2 Is a perspective view of the biological simulation system device.

[0043] Figure 3 Is a perspective top view of the biological simulation system device.

[0044] Figure 4 Is an exploded perspective view of the biological simulation system device.

[0045] Figure 5 Is an exploded perspective view of the biological simulation system device (excluding fastening members).

[0046] Figure 6 Is an exploded perspective view of the flow path member of the biological simulation system device.

[0047] Figure 7 Is Figure 6 An enlarged view within frame VII.

[0048] Figure 8 Is Figure 3 A cross-sectional view taken along the VIII-VIII direction.

[0049] Figure 9 Is an exploded perspective view of the flow path member, container, and functional unit of the biological simulation system device.

[0050] Figure 10 Is an exploded perspective view of the container and functional unit of the biological simulation system device.

[0051] Figure 11 Is an exploded perspective view of the liquid delivery section (excluding the tray) of the biological simulation system device.

[0052] Figure 12 Is Figure 3 A cross-sectional view taken along the XII-XII direction.

[0053] Figure 13 Is Figure 3 A cross-sectional view taken along the XIII-XIII direction.

[0054] Figure 14 Is a front-back direction exploded cross-sectional view of the part where the liquid delivery section of the biological simulation system device (excluding fastening members) is configured.

[0055] Figure 15 Is a front-back direction exploded cross-sectional view of the part where the liquid delivery section of the biological simulation system device is configured.

[0056] Figure 16It is a front - rear direction cross - sectional view of a part of the liquid delivery section of the biological simulation system device configured with the second embodiment.

[0057] Figure 17 It is a top view of the permeable part of the biological simulation system device of the third embodiment.

[0058] Figure 18 It is a perspective top view of the biological simulation system device of the fourth embodiment.

[0059] Figure 19 It is a perspective top view of the MPS device of the fifth embodiment.

[0060] Figure 20 It is a front view of the MPS device.

[0061] Figure 21 It is Figure 19 a cross - sectional view in the XXI - XXI direction.

[0062] Figure 22 It is Figure 21 an enlarged view within the frame XXII of

[0063] Figure 23 It is a front - rear direction partial cross - sectional view of the biological simulation system device of other embodiments.

[0064] Figure 24 It is a schematic top view of the biological simulation system device of the present invention. Detailed Embodiment

[0065] Hereinafter, the embodiments of the biological simulation system device of the present embodiment will be described. Hereinafter, the biological simulation system device will be appropriately abbreviated as the "MPS device".

[0066] <First Embodiment>

[0067] Figure 1 It shows a perspective view of the MPS device of the present embodiment. Figure 2 It shows a perspective three - dimensional view of the MPS device. Figure 3 It shows a perspective top view of the MPS device. Figure 4 It shows an exploded perspective view of the MPS device.

[0068] Figure 5 It shows an exploded perspective view of the MPS device (excluding fastening members). Figure 6 It shows an exploded perspective view of the flow path member of the MPS device. Figure 7 It shows Figure 6 an enlarged view within the frame VII of Figure 8 It shows Figure 3 a cross - sectional view in the VIII - VIII direction of Figure 9Exploded perspective view of the flow path components, container, and functional units of the MPS device. Figure 10 Exploded perspective view of the container and functional units of the MPS device. Figure 11 Exploded perspective view of the liquid supply section (excluding the tray) of the MPS device. Figure 12 Indicates Figure 3 Cross-sectional view taken along the XII-XII direction. Figure 13 Indicates Figure 3 Cross-sectional view taken along the XIII-XIII direction. Figure 14 Front-to-back exploded cross-sectional view of the part where the liquid supply section of the MPS device (excluding the fastening members) is disposed. Figure 15 Front-to-back exploded cross-sectional view of the part where the liquid supply section of the MPS device is disposed. In addition, in Figure 2 , Figure 3 , only the flow paths 33a and 33b are shown for the flow path member 3. Also, in Figure 3 , the fastening member 5 is indicated by a single-dot chain line. Also, Figure 14 , Figure 15 The part shown corresponds to the rear side part of the central axis A (front-to-back central axis of the MPS device 1) shown in Figure 12 .

[0069] [Configuration of MPS Device 1]

[0070] First, the configuration of the MPS device of the present embodiment will be described. As shown in Figures 1 - 5 , Figure 9 , Figure 10 , Figure 12 , Figure 13 , the MPS device 1 includes a container 2, a flow path member 3, a cover member 4, a fastening member 5, a supply section 6a, a liquid supply section 6b, a culture section 6c, and a waste liquid storage section 6d. The supply section 6a, the liquid supply section 6b, the culture section 6c, and the waste liquid storage section 6d are included in the concept of the "functional unit" of the present invention.

[0071] (Container 2)

[0072] As shown in Figure 3 , Figure 10 , the functional units (supply section 6a, liquid supply section 6b, culture section 6c, waste liquid storage section 6d) are disposed in the container 2 in a replaceable, addable, and position-changeable manner. The container 2 is transparent and made of polycarbonate. When observed from the up-down direction (front-back direction), the size of the container 2 is equivalent to the size of a 96-well plate conforming to the ANSI / SBS standard. The ANSI / SBS standard is included in the concept of the "industrial standard" of the present invention. The 96-well plate is included in the concept of the "multi-well plate" of the present invention.

[0073] The container 2 includes a bottom wall portion 20, a pair of side wall portions 21, three partition wall portions 22, and accommodating portions 23a to 23d. The bottom wall portion 20 is in the shape of a rectangular flat plate extending in the horizontal direction (the front-back, left-right direction, a direction orthogonal to the up-down direction). The bottom wall portion 20 has a pair of long side portions 200 and a pair of short side portions 201. The long side portions 200 extend in the left-right direction. The pair of long side portions 200 are arranged opposite to each other in the front-back direction. The short side portions 201 extend in the front-back direction. The pair of short side portions 201 connect the left ends and the right ends of the pair of long side portions 200 to each other. A rectangular opening portion 202 is formed in the bottom wall portion 20.

[0074] A pair of side wall portions 21 are erected upward from the pair of long side portions 200. The side wall portion 21 is in the shape of a rectangular plate. On the outer surface of the side wall portion 21 (the front surface of the front side wall portion 21 and the rear surface of the rear side wall portion 21), a dorsal guiding portion 210 is recessed. The dorsal guiding portion 210 is included in the concept of the "dorsal engaging portion" of the present invention. The dorsal guiding portion 210 extends in the left-right direction (the same direction as the front guiding portion 400 described later).

[0075] The three partition wall portions 22 connect the pair of side wall portions 21 to each other respectively. The partition wall portion 22 is in the shape of a rectangular plate. The height of the partition wall portion 22 in the up-down direction is lower than that of the side wall portion 21. The partition wall portion 22 extends in the front-back direction (the same direction as the short side portion 201). The three partition wall portions 22 divide the space between the pair of side wall portions 21 (the inner space of the container 2) and the opening portion 202 of the bottom wall portion 20 into four accommodating portions 23a to 23d.

[0076] When viewed from the up-down direction, the four accommodating portions 23a to 23d have the same size. The accommodating portions 23a to 23d are interchangeable with respect to a plurality of functional units. The accommodating portions 23a to 23d extend in the front-back direction. The four accommodating portions 23a to 23d are arranged in the left-right direction via the three partition wall portions 22. A frame portion 231 is disposed at the edge of the opening portion 230 of the accommodating portions 23a to 23d (the opening portion 202 of the bottom wall portion 20 is divided by the partition wall portion 22).

[0077] (Flow path member 3)

[0078] As Figure 5 、 Figure 9 、 Figure 12 、 Figure 13 shown, the flow path member 3 fixes the functional units (supply portion 6a, liquid feeding portion 6b, culturing portion 6c, waste liquid storage portion 6d). As Figure 9 shown, the flow path member 3 fixes the opening portions 601, 611c, 612 of the functional units (specifically, as Figure 9As shown, the opening 601 of the tray 60 in the waste liquid storage section 6d, the respective openings 611c of the four culture vessels 61c in the culture section 6c, the upper opening 612 of the introduction member 61 in the supply section 6a, and the upper opening 612 of the introduction member 61 in the liquid feeding section 6b (the same applies hereinafter) are hermetically sealed. The flow path member 3 is transparent and made of PDMS (polydimethylsiloxane, a type of silicone, an elastomer). The flow path member 3 has rubber elasticity. The flow path member 3 is in the shape of a rectangular flat plate extending in the horizontal direction. Chamfered portions 30 are arranged at the four corners of the flow path member 3. The flow path member 3 is arranged above (front side) the container 2.

[0079] As Figures 5 - 8 shown, the flow path member 3 includes a first layer (surface layer member) 31, a second layer (back layer member) 32, and two flow paths 33a and 33b. A first layer recess 310 is recessed in the lower surface of the first layer 31. A first recess 310a is recessed in the lower surface of the first layer recess 310. The second layer 32 is laminated on the lower side (back side) of the first layer 31. From the upper surface of the second layer 32, a second layer protrusion 320 is protrudingly provided. Three second recesses 320a are recessed in the upper surface of the second layer protrusion 320. When viewed in the vertical direction, the second layer protrusion 320 and the first layer recess 310 overlap each other. In addition, the second layer protrusion 320 is inserted into the first layer recess 310.

[0080] As Figure 9 shown, seven abutting portions 321 are protrudingly provided from the lower surface of the second layer 32. The abutting portions 321 are arranged to face the functional units accommodated in the container 2. The abutting portions 321 abut against the functional units from above. A press-in portion 321a is set at the lower end (front end) of the abutting portion 321. The press-in portion 321a is tapered with a thinner front end facing downward. At least a part of the press-in portion 321a is pressed into the openings 601, 611c, and 612 of the functional units.

[0081] As Figure 3 、 Figures 5 - 8As shown, two flow paths 33a and 33b are partitioned inside the flow path member 3. The flow paths 33a and 33b connect multiple functional units accommodated in the container 2. The flow paths 33a and 33b are composed of horizontal extension parts (extension parts in the horizontal direction (in the layer direction (the layer expansion direction of the first layer 31 and the second layer 32))) 330a to 330c and vertical extension parts (front-back direction extension parts) 331a to 331e. The horizontal extension parts 330a and 330c are formed in the gap between the lower surface of the second recess 320a and the first layer recess 310. The horizontal extension part 330b is formed in the gap between the upper surface of the first recess 310a and the second layer protrusion 320. That is, the horizontal extension parts 330a and 330c are formed at the boundary between the first layer 31 and the second layer 32. The horizontal extension parts 330a to 330c extend in the horizontal direction. The vertical extension parts 331a, 331d, and 331e are arranged in the second layer 32. The vertical extension parts 331b and 331c are respectively arranged across the first layer 31 and the second layer 32. The vertical extension parts 331a to 331e extend in the up-down direction. The upper ends of the vertical extension parts 331a to 331e are connected to the horizontal extension parts 330a to 330c. The lower ends of the vertical extension parts 331a to 331e open on the lower surface of the abutting part 321 (pressing-in part 321a).

[0082] As Figure 2 , Figure 3 shown, the flow path 33a extends across three adjacent accommodation parts 23a to 23c. The flow path 33a includes two horizontal extension parts 330a and 330b and three vertical extension parts 331a to 331c. Specifically, the vertical extension part 331a opens in the accommodation part 23a, the vertical extension part 331b opens in the accommodation part 23b, and the vertical extension part 331c opens in the accommodation part 23c. The horizontal extension part 330a connects the vertical extension part 331a and the vertical extension part 331b. The horizontal extension part 330b connects the vertical extension part 331b and the vertical extension part 331c.

[0083] As Figure 2 , Figure 3 shown, the flow path 33b extends across two adjacent accommodation parts 23c and 23d. The flow path 33b includes one horizontal extension part 330c and two vertical extension parts 331d and 331e. Specifically, the vertical extension part 331d opens in the accommodation part 23c, and the vertical extension part 331e opens in the accommodation part 23d. The horizontal extension part 330c connects the vertical extension part 331d and the vertical extension part 331e.

[0084] As Figure 3 , Figure 7As shown, the flow control unit 34 controls the flow rate of the culture solution flowing in the flow path 33a. The culture solution is included in the concept of "fluid" of the present invention. The flow control unit 34 is the horizontal extension part 330b. The cross-sectional area of the flow path of the horizontal extension part 330b is smaller than that of the vertical extension part 331b. In addition, the flow path wall resistance and the flow path shape of the horizontal extension part 330b and the vertical extension part 331b are different. Through these flow path cross-sectional areas, flow path wall resistances, flow path shapes, etc., the horizontal extension part 330b, in other words, the flow control unit 34 controls the flow rate of the culture solution.

[0085] (Cover member 4)

[0086] As Figure 5 , Figure 12 , Figure 13 shown, the cover member 4 strengthens the flow path member 3. The cover member 4 is disposed on the upper side of the flow path member 3. The cover member 4 is press-fitted into the flow path member 3 from above. The cover member 4 is transparent and made of polystyrene. The rigidity of the cover member 4 is higher than that of the flow path member 3. The cover member 4 has a rectangular box shape with an opening downward. The top wall portion 40 of the cover member 4 has a rectangular flat plate shape that extends horizontally. The upper surface of the top wall portion 40 is a smooth surface. A pair of front and side guide portions 400 project from the upper surface of the top wall portion 40. The front and side guide portions 400 are included in the concept of "front and side engaging portions" of the present invention. The front and side guide portions 400 extend in the horizontal direction (left and right direction). The pair of front and side guide portions 400 are disposed at the front and rear edges of the upper surface of the top wall portion 40. Four positioning portions 401 project from the lower surface of the top wall portion 40. When viewed from the up and down direction, the positioning portions 401 have an L shape. The four positioning portions 401 are disposed at the four corners of the lower surface of the top wall portion 40. The four positioning portions 401 are disposed outside the horizontal direction of the chamfered portions 30 at the four corners of the flow path member 3.

[0087] (Fastening member 5)

[0088] As Figures 1 - 4 , Figure 12 , Figure 13 , Figure 15 shown, a pair of fastening members 5 fix the cover member 4 to the container 2 equipped with the functional unit in a state of sandwiching the flow path member 3. As Figure 3 shown, when viewed from the up and down direction, the fastening members 5 are disposed at the front and rear edges of the MPS device 1. When viewed from the up and down direction, the fastening members 5 are disposed so as to avoid the culture portion 6c (observation object portion). The fastening members 5 are made of polycarbonate and extend in the horizontal direction (left and right direction).

[0089] Hereinafter, the rear fastening member 5 will be described as a representative of the pair of front and rear fastening members 5. As Figure 12 , Figure 15As shown, the fastening member 5 at the rear side is C-shaped with an opening facing forward (inward) when viewed in the left-right direction (the extending direction of the fastening member 5). The fastening member 5 includes a front-side guided portion 50, a back-side guided portion 51, and a connecting portion 52. The front-side guided portion 50 projects forward from the upper edge of the connecting portion 52. The front-side guided portion 50 is pressed against the front-side guiding portion 400 from above. The front-side guided portion 50 engages with the front-side guiding portion 400 from the front side (inside). The front-side guided portion 50 can slide relative to the front-side guiding portion 400 in the left-right direction. The back-side guided portion 51 projects forward from the lower edge of the connecting portion 52. The back-side guided portion 51 is pressed against the back-side guiding portion 210 from below. The back-side guided portion 51 can slide relative to the back-side guiding portion 210 in the left-right direction. Through the front-side guided portion 50 and the back-side guided portion 51, the cover member 4, the flow path member 3, and the container 2 are fixed in the up-down direction. In addition, the front-side fastening member 5 and the rear-side fastening member 5 are the same. The front-side fastening member 5 and the rear-side fastening member 5 are arranged symmetrically in the front-rear direction.

[0090] (Functional unit)

[0091] As Figure 10 shown, four accommodation portions 23a to 23d arranged in the left-right direction are defined in the container 2. A supply portion 6a is detachably accommodated in the accommodation portion 23a, a liquid feeding portion 6b is detachably accommodated in the accommodation portion 23b, a cultivation portion 6c is detachably accommodated in the accommodation portion 23c, and a waste liquid storage portion 6d is detachably accommodated in the accommodation portion 23d.

[0092] (Supply portion 6a)

[0093] A culture solution is supplied to the supply portion 6a from the outside of the MPS device 1. As Figure 10 shown, the supply portion 6a includes a tray 60, an introduction member 61, a connector 62 (see Figure 11 ), a tube 63a, and a check valve 64a. The tray 60 is transparent and made of polycarbonate. The tray 60 is in the shape of a rectangular box with an upward opening. The tray 60 is detachably disposed in the accommodation portion 23a. In the assembled state, the bottom wall portion 600 of the tray 60 is placed on the frame portion 231 of the opening portion 230 of the accommodation portion 23a. An opening portion 602 is formed in the side wall portion on the left side (outside) of the tray 60.

[0094] The introduction member 61 is in the shape of a rectangular parallelepiped. The introduction member 61 is detachably accommodated in the rear end portion of the inner space of the tray 60. Concave portions 610 are respectively disposed on the upper surface and the front surface of the introduction member 61. The two concave portions 610 are connected by a communication hole 611 extending in an L shape. As Figure 9As shown, at the opening 612 of the recess 610 on the upper surface, the press-fitting portion 321a of the abutting portion 321 of the flow path member 3 is press-fitted. The communication hole 611 of the introduction member 61 is connected to the flow path 33a (longitudinal extension portion 331a) via the press-fitting portion 321a.

[0095] The connector is disposed in the recess 610 on the front surface. The connector connects the communication hole 611 of the introduction member 61 to the tube 63a. The configuration of the connector will be described later (see Figure 11 ). The tube 63a can be attached to and detached from the introduction member 61 via the connector. The check valve 64a is connected to the tube 63a. As Figure 3 shown, the tube 90 connected to an infusion pump (such as an injection pump) can be connected to the check valve 64a from the outside of the MPS device 1. The check valve 64a allows the flow of the culture solution only in the direction from the infusion pump toward the introduction member 61. As Figure 3 shown, the tube 90 can be inserted into and removed from the inside of the tray 60 via the opening 602.

[0096] (Liquid feeding section 6b)

[0097] The culture solution is supplied from the supply section 6a to the liquid feeding section 6b. The liquid feeding section 6b can store the supplied culture solution. In addition, the liquid feeding section 6b can press the culture solution stored therein little by little to the culture section 6c. As Figures 10 - 12 shown, the liquid feeding section 6b includes a tray 60, an introduction member 61, a connector 62, and an airbag pump 63b. Specifically, the tray 60 is the same as the tray 60 of the supply section 6a (excluding the opening 602), the introduction member 61 is the same as the introduction member 61 of the supply section 6a, and the connector 62 is the same as the connector of the supply section 6a.

[0098] As Figure 9 shown, at the opening 612 of the recess 610 on the upper surface of the introduction member 61, the press-fitting portion 321a of the abutting portion 321 of the flow path member 3 is press-fitted. Via the press-fitting portion 321a, the communication hole 611 of the introduction member 61 is connected to the flow path 33a (longitudinal extension portion 331b).

[0099] The airbag pump 63b is connected to the communication hole 611 of the introduction member 61 via the connector 62. The airbag pump 63b is made of PDMS and has rubber elasticity. As Figure 3 indicated by the single-dot chain line in the figure, the airbag pump 63b can expand within the tray 60.

[0100] As Figure 11As shown, the connector 62 includes a tube portion 620, an inner flange 621, and an outer flange 622. The connector 62 has a Luer lock mechanism compliant with ISO80369-7. The inner flange 621 and the outer flange 622 are annularly mounted on the tube portion 620. The inner flange 621 is disposed on the rear side of the outer flange 622. The inner flange 621 is received in the front concave portion 610 of the introduction member 61. In the tube portion 620, the portion behind the inner flange 621 is pressed into the communication hole 611. A hollow flange 630b is disposed at the rear end of the airbag pump 63b. The hollow flange 630b has a bottomed cylindrical shape opening to the rear side. A through hole connected to the inside of the airbag pump 63b is formed in the front wall (bottom wall) of the hollow flange 630b. A thread groove (not shown in the figure) is recessed in the inner peripheral surface of the hollow flange 630b. The outer flange 622 is screwed into the thread groove. In the tube portion 620, the portion in front of the outer flange 622 is inserted into the inside of the airbag pump 63b.

[0101] (Culturing section 6c)

[0102] The culture solution is supplied from the liquid feeding section 6b to the culturing section 6c. The culturing section 6c cultures cells. As Figure 10 , Figure 13 shown, the culturing section 6c includes a base 60c, four culture vessels 61c, and three filters 62c. Four fixing holes 600c (the same number as the maximum number of culture vessels 61c) are formed in the base 60c. The culture vessels 61c are transparent and made of polystyrene. The culture vessels 61c have a bottomed cylindrical shape opening upward. The bottom wall portion 610c of the culture vessel 61c is fitted into the fixing hole 600c. The number of culture vessels 61c can be freely changed (increased or decreased) within the range of the number of fixing holes 600c. The position of the culture vessel 61c can be freely changed corresponding to the position of the fixing hole 600c. The lower surface of the bottom wall portion 610c is a smooth surface. Cells are accommodated inside the culture vessel 61c. The four culture vessels 61c are connected to each other in the front-rear direction. The filters 62c are made of polycarbonate and are disposed between a pair of adjacent culture vessels 61c via a seal (not shown in the figure). The filter 62c can only selectively transmit a predetermined substance (such as a signal transduction substance (exosomes, etc.)). As Figure 9 shown, at the opening 611c of the culture vessel 61c, the press-in portion 321a of the abutting portion 321 of the flow path member 3 is pressed in. Among the four culture vessels 61c, the rear culture vessel 61c is connected to the flow path 33a (longitudinal extension portion 331c) via the press-in portion 321a. In the rear culture vessel 61c, the culture solution is introduced from the airbag pump 63b via the flow path 33a. Among the four culture vessels 61c, the front culture vessel 61c is connected to the flow path 33b (longitudinal extension portion 331d) via the press-in portion 321a.

[0103] (Waste liquid storage section 6d)

[0104] The waste liquid after the experiment is stored in the waste liquid storage unit 6d. As Figure 10 shown, the waste liquid storage unit 6d includes a tray 60. The tray 60 is the same as the tray 60 of the liquid supply unit 6b. As Figure 9 shown, at the opening 601 of the tray 60, the press-fitting portion 321a of the abutting portion 321 of the flow path member 3 is press-fitted. The tray 60 is connected to the flow path 33b (longitudinal extension portion 331e) via the press-fitting portion 321a.

[0105] [Assembly method of the MPS device 1]

[0106] Next, the assembly method of the MPS device 1 of the present embodiment will be described. The assembly method includes a housing process, a press-fitting process, a fluid supply process, and a fastening process. In the housing process, the desired functional units are housed in the container 2. That is, as Figure 10 shown, first, the desired functional units (in this example, the supply unit 6a, the liquid supply unit 6b, the culture unit 6c, and the waste liquid storage unit 6d) are assembled outside the container 2. Next, the functional units are assembled to the container 2. Specifically, the supply unit 6a is installed in the housing portion 23a, the liquid supply unit 6b is assembled to the housing portion 23b, the culture unit 6c is installed in the housing portion 23c, and the waste liquid storage unit 6d is installed in the housing portion 23d. In addition, as Figure 3 indicated by the one-dot chain line in, the tube 90 connected to the infusion pump is connected to the check valve 64a of the supply unit 6a.

[0107] In the press-fitting process, the flow path member 3 is assembled to the functional unit. That is, as Figure 9 , Figure 14 shown, first, the flow path member 3 is brought close to the functional unit (supply unit 6a, liquid supply unit 6b, culture unit 6c, waste liquid storage unit 6d) from above. Next, the openings 601, 611c, and 612 of the functional unit are sealed by the abutting portion 321 of the flow path member 3. Specifically, the press-fitting portion 321a is press-fitted into the openings 601, 611c, and 612.

[0108] In the fluid supply process, the culture solution is supplied to the air bag pump 63b. That is, as Figure 3 shown, the culture solution is supplied from the infusion pump to the air bag pump 63b via the check valve 64a, the tube 63a, the communication hole 611 of the introduction member 61 of the supply unit 6a, the flow path 33a, and the communication hole 611 of the introduction member 61 of the liquid supply unit 6b. As Figure 3 indicated by the one-dot chain line in, by the supply of the culture solution, the air bag pump 63b expands while accumulating elastic energy.

[0109] Here, as Figure 3 , Figure 7As shown, the flow path cross-sectional area of the horizontal extension portion 330b is smaller than that of the vertical extension portion 331b. Therefore, the flow path resistance of the horizontal extension portion 330b is greater than that of the vertical extension portion 331b. Therefore, the culture solution flowing out of the horizontal extension portion 330a flows into the vertical extension portion 331b preferentially over the horizontal extension portion 330b. Therefore, as Figure 3 shown by the dash-dotted line in the figure, the culture solution preferentially flows into the airbag pump 63b. After the supply of the culture solution is completed, the tube 90 is removed from the check valve 64a via the opening 602. The check valve 64a prevents the backflow of the culture solution.

[0110] In the fastening process, the cover member 4 is assembled to the container 2 by a pair of fastening members 5. That is, as Figure 14 shown, first, the flow path member 3 is pressed into from above by the cover member 4. Next, as Figure 4 shown, a pair of fastening members 5 are assembled to the cover member 4 and the container 2. Specifically, the front-side guided portion 50 is slid relative to the front-side guide portion 400. And the back-side guided portion 51 is slid relative to the back-side guide portion 210. By the fastening member 5, the deformation of the cover member 4 is suppressed. In addition, by the cover member 4, the flow path member 3 is positioned relative to the openings 601, 611c, 612 of the functional unit. In addition, by the cover member 4, the press-in amount of the press-in portion 321a relative to the openings 601, 611c, 612 is fixed. Thus, the MPS device 1 is assembled.

[0111] [Operation of the MPS device 1]

[0112] Next, the operation of the MPS device 1 of the present embodiment will be described. The assembled MPS device 1 ( Figure 1 the state shown) is disposed in an incubator at a predetermined atmosphere (for example, temperature 37°C, humidity 95%, air composition 5 - 20% O2, 5 - 10% CO2, etc.). As Figure 2 , Figure 3 shown, the culture solution stored in the airbag pump 63b is discharged by the elastic energy accumulated in the airbag pump 63b. Here, the check valve 64a prevents the backflow of the culture solution. Therefore, the discharged culture solution preferentially flows into the horizontal extension portion 330b. Only, the flow path cross-sectional area of the horizontal extension portion 330b is smaller than that of the horizontal extension portion 330a. Therefore, in the horizontal extension portion 330b, the flow rate of the culture solution is restricted. Therefore, the culture solution flows in the horizontal extension portion 330b little by little for a long time. The culture solution flows into the rear-end incubator 61c via the horizontal extension portion 330b and the vertical extension portion 331c. The culture solution alternately passes through the four incubators 61c and the three filters 62c from the rear side to the front side. The passed culture solution, in other words, the waste liquid, flows from the front-end incubator 61c into the tray 60 of the waste liquid storage portion 6d via the flow path 33b.

[0113] When observing cells, an operator manually transports the MPS device 1 from the incubator to the stage of an inverted fluorescence microscope. The MPS device 1 is entirely transparent. In addition, a pair of fastening members 5 are arranged at the front and rear edges. Therefore, the culture section 6c, which is the observation target section, can be easily observed without opening the cover member 4. In addition, when the MPS device 1 is accommodated in the incubator, the culture section 6c, which is the observation target section, can also be easily observed.

[0114] [Function and effect]

[0115] Next, the function and effect of the MPS device of the present embodiment will be described. As Figure 10 shown, multiple functional units (in this example, the supply section 6a, the liquid feeding section 6b, the culture section 6c, and the waste liquid storage section 6d) can be replaced with respect to the container 2. Therefore, by replacing any of the functional units, the functions of the MPS device 1 can be easily reorganized. Therefore, compared with conventional simple in vitro devices, a variety of biological environments corresponding to desired organs, diseases, etc. can be simulated with higher reproducibility.

[0116] As Figure 6 shown, in the flow path member 3, pre-flow paths 33a and 33b are defined corresponding to the functional units accommodated in the container 2. Therefore, the multiple functional units can be easily connected. In addition, compared with the case where multiple functional units are connected by tubes through manual operation, misconnection can be suppressed. In addition, since the flow paths 33a and 33b are defined by the flow path member 3, the flow paths 33a and 33b are less likely to deform compared with tubes. Therefore, the desired flow rate and flow path resistance can be easily achieved. In addition, since it is not necessary to connect multiple functional units by tubes through manual operation, viruses, bacteria, dust, etc. are less likely to invade the inside of the functional units. Therefore, it is easy to ensure the cleanliness of the functional units. In addition, contaminants are less likely to be generated.

[0117] As Figures 6 - 8 shown, the flow path member 3 has a two-layer structure composed of a first layer 31 and a second layer 32. Therefore, the flow paths 33a and 33b can be defined using the boundary between the first layer 31 and the second layer 32. In the first layer recess 310 of the first layer 31, the second layer protrusion 320 of the second layer 32 is fitted. Therefore, the positioning of the first layer 31 and the second layer 32 is easy. The flow paths 33a and 33b are defined inside the flow path member 3. Therefore, the flow paths 33a and 33b can be defined without using other members. In addition, the relative positional relationship of the flow paths 33a and 33b can be fixed.

[0118] As Figure 9 、 Figure 12 、 Figure 13As shown, the abutting portion 321 abuts against the functional unit from above. The flow paths 33a and 33b open on the lower surface of the abutting portion 321 (the press-fitting portion 321a). Therefore, the functional unit can be positioned relative to the flow path member 3 by the abutting portion 321. In addition, the culture solution can flow between the flow paths 33a and 33b and the functional unit via the abutting portion 321.

[0119] As Figure 3 , Figure 7 shown, the flow path member 3 is provided with a flow rate control portion 34. The flow rate control portion 34 changes the cross-sectional shape of the horizontal extension portion 330b of the flow path 33a (the shape in the direction orthogonal to the path length direction of the flow path 33a) relative to the cross-sectional shape of the horizontal extension portion 330a. Therefore, the flow rate of the culture solution in the horizontal extension portion 330b can be adjusted without using an external control unit, power supply, wiring, etc.

[0120] As Figure 7 shown, the horizontal extension portion 330b (the flow rate control portion 34) is recessed in the first layer 31, and the horizontal extension portion 330a is recessed in the second layer 32. That is, a thin groove (the horizontal extension portion 330b) and a thick groove (the horizontal extension portion 330a) are formed in different layers. Therefore, groove processing is easier than in the case where a plurality of grooves (the horizontal extension portions 330a and 330b) having different groove widths and groove depths are formed in a single layer (in this case, of course, included in the concept of the horizontal extension portion of the present invention).

[0121] According to the MPS device 1 of the present embodiment, an instrument that has been conventionally treated as an external instrument (as an example, a pump ( Figure 5 shown air bag pump 63b)) can be accommodated in the container 2 as a constituent member of the functional unit. Therefore, the MPS device 1 can be miniaturized. In addition, a plurality of functional units can be integrated. Therefore, the processability is excellent. Thus, the MPS device 1 of the present embodiment has excellent usability.

[0122] Figure 3 shown, the size of the container 2 is set to the size of a 96-well plate conforming to the ANSI / SBS standard. Therefore, the versatility is high with respect to instruments (incubators, analysis devices (microscopes, etc.)) assuming the same size.

[0123] As Figure 10 shown, the sizes of the accommodating portions 23a to 23d are the same. The accommodating portions 23a to 23d are interchangeable with respect to a plurality of functional units. Therefore, the functional units can be replaced in units of the accommodating portions 23a to 23d.

[0124] As Figure 10As shown, the tray 60 is shared among multiple functional units. Therefore, compared with the case where the tray 60 is dedicated to any one functional unit, the manufacturing cost of the tray 60 and even the MPS device 1 can be reduced. In addition, the reorganization of the functional units is simple. The same applies to the introduction member 61 and the connector 62.

[0125] As Figure 10 shown, an opening 202 is formed in the bottom wall portion 20 of the container 2. Therefore, compared with the case where no opening 202 is formed (the case where the bottom wall portion 20 is solid), it is easier to align the focal length of the inverted fluorescence microscope.

[0126] Figure 12 , Figure 13 As shown, the rigidity of the cover member 4 shown is higher than that of the flow path member 3. Therefore, the flow path member 3 can be protected. In addition, the container 2 and the flow path member 3 can be integrated by the cover member 4 and the fastening member 5. In addition, the deviation of the fastening force due to the skill difference of the operator can be suppressed.

[0127] As Figure 15 shown, the distance between the lower surface of the front-side guided portion 50 and the upper surface of the back-side guided portion 51 is L1. In addition, the distance between the upper surface of the front-side guide portion 400 and the upper surface of the back-side guide portion 210 in a state where the lower surface of the press-in portion 321a is coplanar with the opening 612 (the state where the press-in portion 321a is not pressed into the opening 612) is L2. The distance L1 is shorter than the distance L2. Therefore, the cover member 4 and the container 2 can be fastened by the fastening member 5, thereby specifying the press-in amount of the press-in portion 321a with respect to the openings 601, 611c, 612 of the functional unit. In addition, the press-in portion 321a has a tapered shape that tapers downward at the front end. Therefore, a part of the downward press-in force applied from the flow path member 3 to the functional unit acts in the horizontal direction with respect to the functional unit. Therefore, the functional unit can be positioned horizontally with respect to the flow path member 3. In addition, since the press-in portion 321a is pressed into the openings 601, 611c, 612, the sealing performance between the flow paths 33a, 33b and the openings 601, 611c, 612 is high. In addition, contaminants are not easily generated.

[0128] As Figure 4 shown, the fastening member 5 can be attached to and detached from the cover member 4 and the container 2 by sliding in the left-right direction. Therefore, the cover member 4, the flow path member 3, and the container 2 can be easily assembled and separated.

[0129] As Figures 1 - 3 shown, the fastening member 5 is arranged over the entire length in the left-right direction (length direction) of the front and rear edges of the cover member 4. Therefore, the flexure of the cover member 4 can be suppressed over the entire length in the length direction.

[0130] AsFigure 2 , Figure 3 As shown in Figure 3 , when viewed from the up-down direction, the parts of the cover member 4, the flow path member 3, and the container 2 that overlap with the culture part 6c are all transparent. Therefore, the culture part 6c can be observed from the outside in the up-down direction of the MPS device 1. In addition, when viewed from the up-down direction, the fastening member 5 does not overlap with the culture part 6c. Therefore, the situation where the fastening member 5 obstructs the observation can be suppressed.

[0131] The upper surface of the top wall part 40 of the cover member 4 that overlaps with the culture part 6c and the lower surface of the bottom wall part 610c of the culture vessel 61c are both smooth. Therefore, during fluorescence observation, light is not easily refracted.

[0132] As Figure 5 shown in Figure 5 , the four positioning parts 401 are arranged outside the four chamfered parts 30 in the horizontal direction. Therefore, the flow path member 3 can be simply positioned relative to the cover member 4 in the horizontal direction.

[0133] As Figure 10 shown in Figure 10 , the liquid feeding part 6b includes an air bag pump 63b that can elastically deform. Therefore, the culture solution can be stored. In addition, the culture solution can be pressed by the elastic restoring force without a power source. That is, perfusion culture of the cells in the culture part 6c can be performed without a power source. In addition, the air bag pump 63b is accommodated in the tray 60. Therefore, the situation where the air bag pump 63b sags due to its own weight during expansion (when storing the culture solution) can be suppressed.

[0134] Assume that in the assembly method of the MPS device 1, after an operator integrally combines the cover member 4 and the flow path member 3 through manual work, the press-fitting part 321a of the flow path member 3 is press-fitted into the openings 601, 611c, 612 of the functional unit. In this case, the rigidity of the cover member 4 is higher than that of the flow path member 3. Therefore, it is not easily deformed. Therefore, it is necessary to Figure 9 press the seven press-fitting parts 321a of the flow path member 3 shown in Figure 9 into the seven openings 601, 611c, 612 of the functional unit at one time. This operation is cumbersome.

[0135] In this regard, according to the assembly method of the MPS device 1 of the present embodiment, first, an operator press-fits the press-fitting part 321a of the flow path member 3 into the openings 601, 611c, 612 of the functional unit through manual work (press-fitting process). Next, the cover member 4 is assembled to the container 2 (fastening process). Therefore, in the press-fitting process, the operator can press the seven press-fitting parts 321a into the seven openings 601, 611c, 612 of the functional unit step by step (for example, one by one) while appropriately flexing the flexible flow path member 3. Therefore, the operation is simple and reliable.

[0136] In addition, as Figure 2As shown, the flow path member 3 is transparent. Moreover, the flow path member 3 has rubber elasticity. Therefore, in a state where the cover member 4 is removed, it is possible to visually confirm the culture part 6c from the outside of the flow path member 3, and at the same time, a sample can be taken from the culture part 6c by inserting an injection needle into the flow path member 3. In addition, it is possible to add a medicament or the like to the culture part 6c. Furthermore, when the injection needle is pulled out, the needle mark is blocked by the rubber elasticity of the flow path member 3.

[0137] <Second Embodiment>

[0138] The difference between the MPS device of the present embodiment and the MPS device of the first embodiment is that there is no opening provided in the bottom wall portion of the container. In addition, there is no tray provided in the accommodation portion. Here, only the differences will be described. Figure 16 A front-rear direction cross-sectional view showing a part of the liquid feeding portion of the MPS device of the present embodiment is shown. In addition, for parts Figure 12 corresponding thereto, the same reference numerals are used.

[0139] As Figure 16 shown, no opening 202 is provided in the bottom wall portion 20 ( Figure 12 refer to). The lower surface of the bottom wall portion 20 is a smooth surface. In addition, the liquid feeding portion 6b does not have a tray 60 ( Figure 12 refer to). The introduction member 61 and the airbag pump 63b are directly accommodated in the accommodation portion 23b. The introduction member 61 is placed on the bottom wall portion 20. The airbag pump 63b is supported by the bottom wall portion 20 when it expands.

[0140] The MPS device 1 of the present embodiment has the same effects as those of the MPS device of the first embodiment for the common parts. As in the present embodiment, an opening may not be provided in the bottom wall portion 20. Even in this case, by making the bottom wall portion 20 transparent, the light transmittance can be ensured. In addition, as in the present embodiment, the functional unit may not have a tray.

[0141] <Third Embodiment>

[0142] The difference between the MPS device of the present embodiment and the MPS device of the first embodiment is the shape of the flow path. Here, only the differences will be described. Figure 17 A top view of the transparent part of the MPS device of the present embodiment is shown. In addition, for parts Figure 3 corresponding thereto, the same reference numerals are used. Figure 17 What is shown is the part corresponding to the frame XVII of Figure 3 .

[0143] As Figure 17As shown, the horizontal extension portion 330b of the flow path 33a includes a plurality of wide-width portions 330b1 and a plurality of narrow-width portions 330b2. The wide-width portions 330b1 and the narrow-width portions 330b2 are alternately arranged in the left-right direction (the path length direction of the horizontal extension portion 330b). The flow path cross-sectional area of the narrow-width portion 330b2 is smaller than that of the wide-width portion 330b1. Therefore, the flow path cross-sectional area of the horizontal extension portion 330b repeatedly expands and contracts along the left-right direction. The horizontal extension portion 330b corresponds to the flow rate control portion 34.

[0144] The MPS device of the present embodiment has the same effects as the MPS device of the first embodiment for the common components. As in the present embodiment, the flow rate control portion 34 can also adjust the shape in the path length direction of the flow path 33a. And, the flow rate control portion 34 can also adjust the flow path cross-sectional shape of the flow path 33a. That is, the flow rate control portion 34 only needs to adjust at least one of the shape in the path length direction of the flow path 33a and the flow path cross-sectional shape.

[0145] <Fourth Embodiment>

[0146] The difference between the MPS device of the present embodiment and the MPS device of the first embodiment is the shape of the flow path. Here, only the differences will be described. Figure 18 A perspective top view showing the MPS device of the present embodiment is presented. In addition, for the Figure 3 corresponding parts, the same reference numerals are used.

[0147] As Figure 18 shown, a plurality of flow paths 33a to 33d are pre-divided in the flow path member. In a state where the number and position of the incubators 61c in the culture section 6c are undetermined, the longitudinal extension portions of the flow paths 33a to 33d are sealed. If the number and layout of the incubators 61c are determined, the longitudinal extension portions of the desired flow paths 33a to 33d are opened corresponding to the number and layout of the incubators 61c, and the desired flow paths 33a to 33d are opened. In the Figure 18 example shown, corresponding to the number (three) and layout of the incubators 61c, only the flow paths 33a and 33c among the flow paths 33a to 33d are selectively opened. In the figure, as shown by the black dots, the remaining flow paths 33b and 33d are sealed.

[0148] The MPS device of the present embodiment has the same effects as those of the MPS device of the first embodiment in terms of the common components. As in the present embodiment, it is also possible to pre-form flow paths 33a to 33d that are not pre-opened in the flow path member, and after determining the number of culture vessels 61c arranged in the incubator 61c, only selectively open the necessary flow paths 33a and 33c. Of course, it is also possible that not only corresponding to the culture vessels 61c in the culture unit 6c, but also corresponding to the number of components (such as the tray 60 and the introduction member 61) arranged in other functional units and the layout, only selectively open the necessary flow paths among the multiple flow paths pre-divided in the flow path member.

[0149] <Fifth Embodiment>

[0150] The difference between the MPS device of the present embodiment and the MPS device of the first embodiment is that there is no configuration of a cover member, a tray, and a fastening member. In addition, it is the point that the accommodation part of the container extends in the left-right direction (the extending direction of the long side part of the bottom wall part of the container). Along with this, it is the point that the multiple culture vessels in the culture unit are connected in the left-right direction. In addition, it is the point that a plurality of openings are provided in each of the side wall part and the bottom wall part of the container. In addition, it is the point that a part (the third layer) of the flow path member is made of resin. In addition, it is the point that the press-in part is provided with an O-ring. Here, the differences will be mainly described.

[0151] Figure 19 A perspective top view showing the MPS device of the present embodiment. Figure 20 A front view showing the MPS device. Figure 21 Showing Figure 19 A sectional view taken along the XXI-XXI direction of Figure 22 Showing Figure 21 An enlarged view within the frame XXII of Figure 3 , Figure 5 , Figure 12 , Figure 13 The corresponding parts are denoted by the same reference numerals.

[0152] [Configuration of MPS Device 1]

[0153] First, the configuration of the MPS device of the present embodiment will be described. As Figures 19 - 22 shown, the MPS device 1 includes a container 2, a flow path member 3, a first connection part 6e, a culture part 6c, and a second connection part 6f. The first connection part 6e, the culture part 6c, and the second connection part 6f are included in the concept of the "functional unit" of the present invention.

[0154] (Container 2)

[0155] As Figures 19 - 21As shown, the container 2 includes a bottom wall portion 20, four side wall portions 21a, 21b, two partition wall portions 22, and accommodating portions 23e, 23c, 23f. The bottom wall portion 20 is in the shape of a rectangular flat plate extending in the horizontal direction. Fourteen openings 202 (the same number as the arrangement numbers of the introduction members 61 and the incubators 61c) are formed in the bottom wall portion 20.

[0156] Among the four side wall portions 21a, 21b, a pair of front and rear side wall portions 21a are erected upward from a pair of front and rear long side portions 200. The side wall portion 21a extends in the left - right direction (the extending direction of the long side portion 200). A pair of left and right side wall portions 21b are erected upward from a pair of left and right short side portions 201. The side wall portion 21b extends in the front - rear direction (the extending direction of the short side portion 201). As Figure 20 shown, six openings 212 are formed in the side wall portion 21a. The six openings 212 are arranged in the left - right direction. The opening 212 is in a U - shaped recessed downward.

[0157] As Figure 19 shown, the two partition wall portions 22 connect the pair of left and right side wall portions 21b to each other. The two partition wall portions 22 are arranged in the front - rear direction in parallel with the pair of side wall portions 21a. The partition wall portion 22 extends in the left - right direction. The two partition wall portions 22 divide the internal space of the container 2 into three accommodating portions 23e, 23c, 23f.

[0158] When viewed from the up - down direction, the three accommodating portions 23e, 23c, 23f have the same size. The accommodating portions 23e, 23c, 23f are interchangeable with respect to multiple functional units. As Figure 19 shown, the accommodating portions 23e, 23c, 23f extend in the left - right direction. The three accommodating portions 23e, 23c, 23f are arranged in the front - rear direction via the two partition wall portions 22. Among them, on the bottom surfaces (the upper surface of the bottom wall portion 20) of the accommodating portions 23c, 23f, six openings 202 are respectively arranged in the left - right direction. In the accommodating portion 23e, two openings 202 are arranged separated from each other in the left - right direction.

[0159] (Flow path member 3)

[0160] As Figure 21 、 Figure 22 shown, the flow path member 3 fixes the functional units (the first connection portion 6e, the culture portion 6c, the second connection portion 6f). The flow path member 3 liquid - tightly seals the openings 611c, 612 of the functional units (specifically, the openings 611c of each of the six incubators 61c of the culture portion 6c, the upper openings 612 of the two introduction members 61 of the first connection portion 6e, and the upper openings 612 of the six introduction members 61 of the second connection portion 6f).

[0161] As Figure 19 、Figures 21 - 22 As shown, the flow path member 3 includes a first layer 31 made of PDMS, a second layer (soft layer) 32 made of PDMS, a third layer (hard layer) 35 made of resin, eight flow paths 33e to 33l, and 14 abutting portions 37 (the same number as the arrangement numbers of the introduction member 61 and the incubator 61c). The first layer 31, the second layer 32, and the third layer 35 are stacked in order from the upper side to the lower side. The rigidity of the third layer 35 is higher than that of the first layer 31 and the second layer 32.

[0162] As Figure 22 shown, the second layer 32 includes 14 second layer protrusions (soft layer protrusions) 322 protruding downward. The second layer protrusions 322 are short-axis cylindrical. The third layer 35 includes 14 third layer protrusions (hard layer protrusions) 350 protruding downward. The third layer protrusions 350 are short-axis cylindrical. An annular groove 350b is arranged on the outer peripheral surface of the third layer protrusion 350. An O-ring (sealing member) 36 made of an elastic body is arranged in the annular groove 350b. The O-ring 36 has rubber elasticity. The second layer protrusions 322 are arranged radially inside the third layer protrusions 350. The second layer protrusions 322 penetrate the third layer protrusions 350 in the vertical direction. The rigidity of the third layer protrusions 350 is higher than that of the second layer protrusions 322 and the O-ring 36.

[0163] As Figure 21 , Figure 22 shown, the abutting portions 37 are arranged on the lower side of the third layer 35 (the plate-like portion other than the third layer protrusions 350). The abutting portions 37 are arranged opposite to the functional units. In the front accommodating portion 23e, the abutting portion 37 abuts against the first connecting portion 6e (the concave portion 610 of the introduction member 61) from the upper side. In the rear accommodating portion 23f, the abutting portion 37 abuts against the second connecting portion 6f (the concave portion 610 of the introduction member 61) from the upper side. In the accommodating portion 23c at the center in the front-rear direction, the abutting portion 37 is inserted into the culture portion 6c (the opening portion 611c of the incubator 61c) from the upper side.

[0164] As Figure 21 , Figure 22As shown, the abutting portion 37 includes the aforementioned second-layer protruding portion 322, the third-layer protruding portion 350, and the O-ring 36. In the abutting portion 37, the portion below the O-ring 36 and the O-ring 36 corresponds to the press-fitting portion 370. The press-fitting portion 370 is press-fitted into the opening portions 611c and 612 of the functional unit. The press-fitting portion 370 includes the second-layer protruding portion 322 made of PDMS, the third-layer protruding portion 350 made of resin, and the O-ring 36 made of an elastic body. That is, the press-fitting portion 370 is made of a material containing PDMS and resin. The O-ring 36 of the press-fitting portion 370 elastically contacts the inner peripheral surface of the opening portions 611c and 612 from the radially inner side of the opening portions 611c and 612. Through this elastic contact, the liquid tightness of the opening portions 611c and 612 is ensured.

[0165] If we focus on the vertical positional relationship of the O-ring 36, the lower surface (dorsal protruding end) 350a of the third-layer protruding portion 350, and the lower surface (dorsal protruding end) 322a of the second-layer protruding portion 322 in the press-fitting portion 370, then as Figure 22 shown, these components and parts are arranged in sequence from the upper side to the lower side on the O-ring 36, the lower surface 350a of the third-layer protruding portion 350, and the lower surface 322a of the second-layer protruding portion 322. In addition, if we focus on the radial (radial direction based on the central axis of the cylindrical shape of the second-layer protruding portion 322) positional relationship of the O-ring 36, the lower surface 350a of the third-layer protruding portion 350, and the lower surface 322a of the second-layer protruding portion 322 in the press-fitting portion 370, then these components and parts are arranged in sequence from the radially outer side to the radially inner side on the O-ring 36, the lower surface 350a of the third-layer protruding portion 350, and the lower surface 322a of the second-layer protruding portion 322. In this way, the press-fitting portion 370 (the lower end portion of the abutting portion 37) has a stepped shape (tapered with steps) that tapers downward at the front end.

[0166] As Figure 19 shown, the eight flow paths 33e to 33l extend across two adjacent accommodating portions 23e, 23c, and 23f. Specifically, the flow paths 33e and 33f extend across the accommodating portions 23e and 23c, and the flow paths 33g to 33l extend across the accommodating portions 23c and 23f. The eight flow paths 33e to 33l have the same configuration. In addition, the configuration of the eight flow paths 33e to 33l is the same as that of the flow path 33b shown in Figure 3 , Figure 6 . Hereinafter, on behalf of the eight flow paths 33e to 33l, the configuration of the right-front flow path 33e will be described.

[0167] As Figure 21 , Figure 22As shown, the flow path 33e is composed of a horizontally extending portion 330d and a pair of front and rear vertically extending portions 331f and 331g. The horizontally extending portion 330d is formed at the boundary between the first layer 31 and the second layer 32. The horizontally extending portion 330d extends in the front-rear direction (horizontal direction). The vertically extending portions 331f and 331g are disposed in the second layer 32. The vertically extending portions 331f and 331g extend in the up-down direction. The upper ends of the vertically extending portions 331f and 331g are connected to the horizontally extending portion 330d. The lower ends of the vertically extending portions 331f and 331g open at the lower surface of the abutting portion 37 (pressing-in portion 370). Specifically, the vertically extending portion 331f opens at the first connecting portion 6e of the accommodating portion 23e, and the vertically extending portion 331g opens at the culturing portion 6c of the accommodating portion 23c.

[0168] (Functional unit)

[0169] As Figure 19 shown, in the container 2, three accommodating portions 23e, 23c, and 23f arranged in the front-rear direction are partitioned. The first connecting portion 6e is detachably accommodated in the front-side accommodating portion 23e, the culturing portion 6c is detachably accommodated in the accommodating portion 23c at the center in the front-rear direction, and the second connecting portion 6f is detachably accommodated in the rear-side accommodating portion 23f.

[0170] (First connecting portion 6e)

[0171] The first connecting portion 6e is disposed in the accommodating portion 23e. The first connecting portion 6e connects the inside and outside of the MPS device 1. That is, the culture solution is supplied from the outside to the inside (e.g., the culturing portion 6c, etc.) via the first connecting portion 6e. In addition, the waste liquid is discharged from the inside to the outside (e.g., the waste liquid tank, etc.) via the first connecting portion 6e.

[0172] The first connecting portion 6e includes two introducing members 61. The introducing members 61 are disposed at both ends in the left-right direction of the first connecting portion 6e. The two introducing members 61 have the same configuration. Hereinafter, representing the two introducing members 61, the configuration of the introducing member 61 on the right side will be described.

[0173] The introducing member 61 is made of resin and has a rectangular parallelepiped shape. As Figure 21 shown, a concave portion 610 is disposed on the upper surface of the introducing member 61. The concave portion 610 on the upper surface communicates with the front surface through a communication hole 611 extending in an L shape.

[0174] At the opening portion 612 of the concave portion 610 on the upper surface, the pressing-in portion 370 of the abutting portion 37 of the flow path member 3 is pressed in. Via the pressing-in portion 370, the communication hole 611 of the introducing member 61 is connected to the flow path 33e (vertically extending portion 331f). A connector 62 is detachably disposed on the front surface of the introducing member 61. The connector 62 includes a pipe portion 620 and a flange 623. The flange 623 is annularly provided around the pipe portion 620. As Figures 19 - 21As shown, the flange 623 is received in the opening 212 of the side wall portion 21a (the opening 212 at the right end of the receiving portion 23e). As Figure 21 shown, in the tube portion 620, the portion behind (inside) the flange 623 is inserted into the communication hole 611. The convex portion 613 is protrudingly provided from the lower surface of the introduction member 61. The convex portion 613 is fitted into the opening 202 of the bottom wall portion 20 (the opening 202 at the right end of the receiving portion 23e). In the connector 62, a tube, an infusion pump (such as an injection pump), a waste liquid tank, a check valve, etc. can be connected.

[0175] (Cultivation portion 6c)

[0176] As Figure 21 、 Figure 22 shown, the cultivation portion 6c is disposed in the receiving portion 23c. The cultivation portion 6c is connected to the first connection portion 6e via the flow path 33e. The cultivation portion 6c is connected to the second connection portion 6f via the flow path 33g. The culture solution is supplied to the cultivation portion 6c from at least one of the first connection portion 6e and the second connection portion 6f. In addition, the waste liquid is discharged from the cultivation portion 6c to at least one of the first connection portion 6e and the second connection portion 6f.

[0177] In the present embodiment ( Figure 19 、 Figure 21 、 Figure 22 ), the structure of the cultivation portion 6c is substantially the same as that of the cultivation portion 6c shown in Figure 10 、 Figure 13 . The difference is that the cultivation portion 6c includes six cultivators 61c connected in the left - right direction (the extending direction of the long side portion 200 of the container 2 (the bottom wall portion 20)). In addition, the cultivation portion 6c does not have the Figure 10 、 Figure 13 shown base 60c. In addition, the bottom wall portion 610c of the cultivator 61c is fitted into the opening 202 of the bottom wall portion 20.

[0178] As Figure 22 shown, in the opening 611c of the cultivator 61c, the press - in portion 370 of the abutting portion 37 of the flow path member 3 is press - in. The cultivator 61c is connected to the flow paths 33e (the longitudinally extending portion 331g) and 33g via the press - in portion 370.

[0179] (Second connection portion 6f)

[0180] As Figure 21As shown, the second connection part 6f is arranged in the accommodation part 23f. The second connection part 6f connects the inside and outside of the MPS device 1. The structure of the second connection part 6f is substantially the same as that of the first connection part 6e. The difference is that the second connection part 6f has six introduction members 61 arranged in the left-right direction. The arrangement of the introduction members 61 of the second connection part 6f is symmetric front and back with respect to the arrangement of the introduction members 61 of the first connection part 6e. In addition, the structure of the introduction members 61 of the second connection part 6f is the same as that of the introduction members 61 of the first connection part 6e.

[0181] [Function and effect]

[0182] Next, the function and effect of the MPS device of this embodiment will be described. The MPS device of this embodiment has the same function and effect as the MPS device of the first embodiment in terms of the common parts of the structure.

[0183] As Figure 20 、 Figure 21 shown, an opening 212 is arranged in the side wall part 21a. The opening 212 penetrates the side wall part 21a in the front-rear direction (the inside and outside directions of the container 2). Therefore, the outside and the inside of the container 2 can be simply connected via the opening 212. Specifically, the connector 62 of the introduction member 61 penetrates the side wall part 21a via the opening 212. Through this connector 62, the outside and the inside of the container 2 can be simply connected.

[0184] As Figure 19 、 Figure 21 shown, a plurality of openings 202 are arranged in the bottom wall part 20. Through the openings 202, the positioning of the functional units can be simply performed. Specifically, the convex part 613 of the introduction member 61 of the first connection part 6e is engaged with the opening 202. Therefore, the positioning of the first connection part 6e can be simply performed. Similarly, the convex part 613 of the introduction member 61 of the second connection part 6f is engaged with the opening 202. Therefore, the positioning of the second connection part 6f can be simply performed. Similarly, the incubator 61c of the culture part 6c is engaged with the opening 202. Therefore, the positioning of the culture part 6c can be simply performed.

[0185] As Figure 21 、 Figure 22 shown, the press-in part 370 of the abutting part 37 of the flow path member 3 is pressed into the openings 612, 611c of the functional units (the first connection part 6e, the culture part 6c, the second connection part 6f). Therefore, the functional units and the container 2 can be simply positioned relative to the flow path member 3.

[0186] Specifically, for the horizontal positioning, by pressing the pressing portion 370 into the opening portions 612 and 611c, the central axis of the pressing portion 370 (the axis passing through the centroid (center of gravity of the figure) of the horizontal cross-section of the pressing portion 370 and extending in the vertical direction) and the central axes of the opening portions 612 and 611c (the axes passing through the centroids (centers of gravity of the figures) of the horizontal cross-sections of the opening portions 612 and 611c and extending in the vertical direction) can be made to coincide (alignment). Therefore, for the horizontal direction, the functional unit and the container 2 can be simply positioned relative to the flow path member 3.

[0187] In addition, for the vertical (up and down) positioning, by pressing the pressing portion 370 into the opening portions 612 and 611c, the lower surface of the third layer 35 (the portion around the bottom of the third layer protruding portion 350) can be made to abut against the edge of the opening portion 611c of the incubator 61c. Here, both the third layer 35 and the incubator 61c are made of resin. Therefore, the third layer 35 and the incubator 61c have higher rigidity compared to the case where these members are made of an elastic body. Therefore, the amount of pressing of the pressing portion 370 into the opening portions 612 and 611c can be specified. Therefore, for the vertical direction, the functional unit and the container 2 can be simply positioned relative to the flow path member 3.

[0188] In this way, according to the MPS device 1 of the present embodiment, by simply pressing the pressing portion 370 into the opening portions 612 and 611c, the functional unit and the container 2 can be simply positioned relative to the flow path member 3. In addition, the flow path member 3, the functional unit, and the container 2 can be simply assembled. Therefore, there is no need for Figure 13 the cover member 4 and the fastening member 5 shown.

[0189] In addition, by pressing the pressing portion 370 into the opening portions 612 and 611c, the sealing performance between the flow path member 3 and the opening portions 612 and 611c can be improved. Specifically, Figure 22 the pressing portion 370 shown includes a second layer protruding portion 322 made of PDMS, a third layer protruding portion 350 made of resin, and an O-ring 36 made of an elastic body. Here, the rigidity of the third layer protruding portion 350 is higher than that of the O-ring 36. In addition, the rigidity of the side wall portion of the incubator 61c is higher than that of the O-ring 36. Therefore, when the pressing portion 370 is pressed into the opening portion 611c, the O-ring 36 is preferentially elastically deformed. Through the elastic contact force (elastic restoring force) of the O-ring 36, the sealing performance between the outer peripheral surface of the third layer protruding portion 350 and the inner peripheral surface of the opening portion 611c (side wall portion) of the incubator 61c can be ensured. The pressing portions 370 of the first connection portion 6e and the second connection portion 6f have the same effect as the pressing portion 370 of the above-mentioned culture portion 6c.

[0190] Figure 22The elastic contact force of the O-ring 36 of the press-in part 370 shown acts in the diameter-reducing direction (compression direction) with respect to the third-layer protrusion 350. Here, the rigidity of the third-layer protrusion 350 is higher than that of the second-layer protrusion 322. Therefore, it is possible to suppress the case where the elastic contact force (compression force) of the O-ring 36 is transmitted to the second-layer protrusion 322 via the third-layer protrusion 350. Therefore, it is possible to suppress the case where the flow paths 33e (longitudinal extension part 331g) and 33g inside the second-layer protrusion 322 are deformed by the elastic contact force of the O-ring 36. The press-in parts 370 of the first connection part 6e and the second connection part 6f have the same effect as the press-in part 370 of the above-described culture part 6c.

[0191] Assume Figure 22 The case where the third-layer protrusion 350 shown is made of a soft elastic body, in other words, the case where the entire press-in part 370 is made of a soft elastic body (of course, this case is also included in the concept of the biological simulation system device of the present invention). In this case, when the press-in part 370 is pressed into the openings 612 and 611c, a part of the downward pressing force applied from the flow path member 3 to the functional unit is easily consumed by the deformation of the soft press-in part 370. In other words, the pressing force is likely to dissipate. Therefore, depending on the type and configuration of the functional unit, there is a case where the press-in operation of the press-in part 370 with respect to the openings 612 and 611c becomes difficult.

[0192] In this regard, Figure 22 The third-layer protrusion 350 shown is made of a resin with high rigidity. Therefore, when the press-in part 370 is pressed into the openings 612 and 611c, a part of the downward pressing force applied from the flow path member 3 to the functional unit is not easily consumed by the deformation of the press-in part 370. In other words, the pressing force is not likely to dissipate. Therefore, depending on the type and configuration of the functional unit, there is a case where the press-in operation of the press-in part 370 with respect to the openings 612 and 611c becomes simple.

[0193] At the time of microscopic observation, in a state where light is irradiated from above, observe from below with an inverted fluorescence microscope Figure 22 The inside of the incubator 61c shown. Therefore, from the viewpoint of ensuring observation confirmability, it is preferable that the inside of the incubator 61c is filled with the culture solution C. However, in practice, there is a case where air bubbles D are mixed in the inside of the incubator 61c, and the air bubbles D become an obstacle at the time of microscopic observation.

[0194] At this point, as described above, the pressing portion 370 (the lower end portion of the abutting portion 37) has a stepped shape (a stepped cone shape) that tapers toward the lower side (the direction of the gravitational force) with the front end becoming thinner. Therefore, the air bubbles D mixed into the interior of the incubator 61c can rise by the buoyancy of the air bubbles D themselves and move to the air bubble storage space (air bubble storage portion) E (specifically, directly below the O-ring 36, an annular space defined by the inner peripheral surface of the side wall portion of the radially outer incubator 61c and the outer peripheral surface of the third layer protruding portion 350 (or the outer peripheral surface of the third layer protruding portion 350 and the outer peripheral surface of the second layer protruding portion 322)). Therefore, it is possible to suppress the situation where the air bubbles D become an obstacle during microscopic observation. Therefore, the observation confirmability during microscopic observation can be improved.

[0195] As Figure 22 shown, the bottom wall portion 610c of the incubator 61c is exposed to the lower side of the container 2 through the opening 202 of the bottom wall portion 20 of the container 2. The lower surface of the bottom wall portion 610c is coplanar with the lower surface of the bottom wall portion 20. Therefore, compared with the case where the opening 202 is not provided (the bottom wall portion 20 is solid and the incubator 61c is placed on the upper surface of the bottom wall portion 20), it is easier to align the focal length of the inverted fluorescence microscope. In addition, the outer edge of the lower surface 322a (the lower end surface of the abutting portion 37) of the second layer protruding portion 322 has a corner. That is, a corner portion is arranged at the outer edge. A chamfered portion is not arranged at the outer edge. Therefore, the observation confirmability during microscopic observation can be improved.

[0196] <Others>

[0197] Above, the embodiments of the biological simulation system device of the present invention have been described. However, the embodiments are not limited to the above manner. It can also be implemented by various modified manners and improved manners that can be performed by those skilled in the art.

[0198] Figure 23 A front-rear direction partial cross-sectional view of the MPS device showing other embodiments. In addition, for the corresponding parts, the same reference numerals are used. As Figure 15 shown, the cover member 4 may not have the engaging claws 402. In addition, the container 2 may have an engaged concave portion 211. Moreover, the cover member 4 and the container 2 can be integrated by engaging the engaging claws 402 with the engaged concave portion 211. In addition, the flow path member 3 may be a single-layer structure. The flow path 33a may be formed at the boundary between the cover member 4 and the flow path member 3. The abutting portion 321 may abut (including elastic contact) against the edge of the opening 612 of the introducing member 61 over the entire circumference. That is, the abutting portion 321 may not have the pressing portion 321a (refer to Figure 23 ) Figure 12 ).

[0199] Figure 24Shows a schematic top view of the MPS device of the present invention. In addition, for the parts corresponding to Figure 3 , the same reference numerals are used. As Figure 24 shown, the accommodating parts 23a to 23d can be respectively divided into four blocks (shaded parts) B connected in the front-rear direction. When viewed from the front-back direction, the constituent members of the functional unit ( Figure 3 the shown introduction member 61, the airbag pump 63b, the tray 60, Figure 19 the shown introduction member 61, etc.) are preferably integer multiples of the size of the block B. For example, it is preferably that the introduction member 61 is one block B, the airbag pump 63b is three blocks B, and the tray 60 is four blocks B in size. In this way, if the size of the constituent members is determined based on the size of the block B, the space efficiency of the accommodating parts 23a to 23d becomes high. In addition, the reorganization of the constituent members of the functional unit is easy.

[0200] Figures 1 - 24 The constituent members of the MPS device 1 of the multiple embodiments shown can be appropriately reorganized. For example, the engaging claw 402 and the engaged concave portion 211 shown in Figure 23 can be loaded into Figure 12 , Figure 16 the shown MPS device 1. The single-layer structure flow path member 3 shown in Figure 23 can be loaded into Figure 12 , Figure 16 , Figure 21 the shown MPS device 1. The two-layer structure flow path member 3 shown in Figure 12 , Figure 16 can be loaded into Figure 21 , Figure 23 the shown MPS device 1. The three-layer structure flow path member 3 shown in Figure 21 can be loaded into Figure 12 , Figure 16 , Figure 23 the shown MPS device 1. The flow rate control part 34 shown in Figure 17 can be loaded into Figure 21 , Figure 23 the shown MPS device 1.

[0201] Regarding the number of functional units (supply unit 6a, liquid feeding unit 6b, culturing unit 6c, waste liquid storage unit 6d, first connection unit 6e, second connection unit 6f) arranged, there is no particular limitation on the number of functional units arranged relative to a single container 2. It can be one or multiple. There is no particular limitation on the layout of the functional units in a single container 2. There is no particular limitation on the number of functional units arranged relative to a single accommodation part 23a - 23f. It can be one or multiple. There is no particular limitation on the layout of the functional units in a single accommodation part 23a - 23f. There is no particular limitation on the number of constituent members of the functional units. It can be one or multiple.

[0202] Regarding Figure 10 For the supply unit 6a shown, a member (such as a tank for storing a culture solution, etc.) can also be arranged on the front side of the introduction member 61. Another valve (such as a three-way valve, etc.) can also be arranged instead of the check valve 64a. There is no particular limitation on the connection mechanism between the pipe 63a and the introduction member 61. Regarding the liquid feeding unit 6b, there is no particular limitation on the type of pump. It can also be a micropump or the like. There is no particular limitation on the connection mechanism between the pump and the introduction member 61.

[0203] Regarding the culturing unit 6c, there is no particular limitation on the number of culture vessels 61c arranged (number of connections). It can be one or multiple. There is no particular limitation on the material of the filter 62c. As long as the desired substance can selectively pass through. Regarding the waste liquid storage unit 6d, it can be a tray 60 or a bag. There is no particular limitation on the use of the culturing unit 6c. In addition to cells, it can also be used for culturing bacteria, yeast, algae, etc.

[0204] A pump unit for circulating the culture solution relative to the culturing unit 6c can also be arranged instead of the waste liquid storage unit 6d. In this way, the culture solution can be continuously supplied to the culturing unit 6c. Therefore, the biological simulation (in vivo environment reproducibility) of the MPS device 1 becomes higher.

[0205] There is no particular limitation on the type of functional units. For example, it can be a stirring part having a stirrer for stirring the culture solution, a sensor part for detecting a desired signal (electrical signal, optical signal, etc.) from the culturing unit 6c, a pressure applying part for applying a desired pressure (vibration, pressure, etc.) to the cells in the culturing unit 6c, etc. Multiple functional units of the same type can also be arranged in multiple accommodation parts 23a - 23d. For example, it can also be in Figure 3The accommodating portions 23b and 23d shown respectively dispose the liquid-feeding portions 6b. Moreover, the culture solution can be respectively supplied from the liquid-feeding portion 6b of the accommodating portion 23b to the culture portion 6c, and the medicament can be supplied from the liquid-feeding portion 6b of the accommodating portion 23d to the culture portion 6c. Various external instruments can also be connected to the MPS device 1. As external instruments, for example, an external pump (of course, a pump other than the airbag pump 63b), a large waste liquid tank, sensors, etc. can be cited.

[0206] There are no particular limitations on the shapes, sizes, positions, arrangement numbers, materials, transparency (hereinafter, appropriately collectively referred to as "shapes, etc.") of the cover member 4, the flow path member 3, the container 2, the fastening member 5, and the functional units. There is no limitation on the transparency of the cover member 4, the flow path member 3, and the container 2. It can be colorless and transparent or colored and transparent. When observed from the front and back directions, at least the portion corresponding to the culture portion 6c needs to be transparent. In addition, depending on the analysis object, the portion corresponding to the culture portion 6c can also be opaque. Regarding the materials of these members, materials that do not deform or deteriorate in the environment inside the incubator are preferred. There are no particular limitations on the materials of the container 2, the fastening member 5, and the tray 60. They can be polycarbonate, acrylic, polystyrene, etc. There are no particular limitations on the material of the introduction member 61. It can be polystyrene, PDMS, etc.

[0207] For the container 2, as Figure 10 , Figure 12 , Figure 21 shown, an opening 202 can also be provided in the bottom wall portion 20. In this way, the observation object portion (culture portion 6c) can be simply observed. In addition, as Figure 16 shown, an opening may not be provided in the bottom wall portion 20. In this way, the sealing property (airtightness, liquid tightness, etc.) of the inside of the container 2 (at least one of the accommodating portions 23a to 23d) can be simply ensured. Therefore, for example, cells can be cultured in a state where an internal pressure is applied. When no opening is provided in the bottom wall portion 20, the wall thickness of the bottom wall portion 20 is preferably 1 mm or less. In this way, it is not easy to obstruct the observability of the observation object portion. There are no particular limitations on the use of the MPS device 1. For example, it can be used for the observation of cells, etc., the observation of biological signals, the manufacture of new substances, etc.

[0208] Regarding Figure 20 shown, there are no particular limitations on the shape of the opening 212 in the side wall portion 21a. For example, it can also be a hole shape without an end (circular, elliptical, polygonal (triangle, quadrilateral, pentagon, hexagon, etc.)), a cut shape with an end (U-shaped, C-shaped, V-shaped, polygonal, etc.). It is only necessary for the opening 212 to penetrate the side wall portion 21a. The opening 212 can also be disposed in the side wall portion 21b.

[0209] There is no particular limitation on the material of the flow path member 3. It can be an elastomer or a resin. In the case of a resin, polystyrene, COP (cycloolefin polymer), COC (cycloolefin copolymer), etc. can be used. The entire flow path member 3 can also be made of an elastomer. In addition, the entire flow path member 3 can also be made of a resin. Additionally, it can be that a part of the flow path member 3 is made of an elastomer and the other part is made of a resin. For example, in the case where the flow path member 3 has a single-layer structure, it can be that a part of it is made of an elastomer and the other part is made of a resin. In addition, in the case where the flow path member 3 has a multi-layer structure, it can be that any layer (single layer or multi-layer) is made of an elastomer and the other layers are made of a resin. The flow path member 3 can have elasticity (including rubber elasticity) or can have no elasticity (including rubber elasticity). It can also be ensured through other members (gaskets, O-rings (e.g., Figure 22 the O-ring 36 shown) etc.) the elasticity of the flow path member 3. For example, it can also be that a gasket is sandwiched between the lower surface of the contact portion 321 shown in Figure 23 and the upper surface (around the concave portion 610) of the introduction member 61.

[0210] For Figure 22 the material of the O-ring (sealing member) 36 shown, there is no particular limitation. It can be made of an elastomer or a resin. It is only necessary to ensure the sealing between the outer peripheral surface of the third-layer protrusion 350 and the inner peripheral surface of the opening 611c of the incubator 61c through the elastic contact force of the O-ring 36.

[0211] There is no particular limitation on the number of layers of the flow path member 3. For example, it can also be that the third layer is laminated on the first layer 31 and the second layer 32, and the horizontal extension portions 330a to 330d are respectively defined at the boundary between the first layer 31 and the second layer 32 and the boundary between the second layer 32 and the third layer. In this way, when observed from the front and back directions, the horizontal extension portions 330a to 330d can be made to intersect three-dimensionally with each other.

[0212] There is no particular limitation on the extending direction of the flow paths 33a to 33l. It can be a direction relative to the front and back directions, along the layer direction, a direction intersecting the front and back directions and the layer direction. For the shape of the path length direction of the flow paths 33a to 33l, it can be linear, curved, a shape combining a straight line and a curve, etc. For the shape in the direction orthogonal to the path length direction of the flow paths 33a to 33l (flow path cross-sectional shape), it can also be polygonal (triangle, quadrilateral, hexagon, etc.), circular (circle, ellipse), semi-circular, etc. It can also form a so-called Tesla valve through the flow paths 33a to 33l (specifically, at least a part of at least one of the flow paths 33a to 33l). In this way, it is possible to suppress the backflow of the fluid without arranging movable parts such as check valves.

[0213] There is no particular limitation on the method of dividing the flow paths 33a to 33d. When the MPS device 1 has the cover member 4, the flow paths 33a to 33d may also be divided at the boundary between the cover member 4 and the flow path member 3. The flow paths 33a to 33l may also have branch portions. There is no particular limitation on the flow paths 33a to 33l that are the objects (flow control objects) of the flow rate control unit 34. The flow rate control unit 34 may be arranged in at least one of the flow paths 33a to 33l. It may not be arranged in at least one of the cover member 4 and the fastening member 5.

[0214] There is no particular limitation on the use of the flow paths 33a to 33l. For example, the flow paths 33a to 33l (specifically, at least one of the flow paths 33a to 33l) may be used for degassing of the functional unit. Specifically, the Figure 18 shown flow paths 33a to 33d may be used for degassing of the culture unit 6c. In this case, air bubbles may also be stored in the flow paths 33a to 33d themselves. That is, the flow paths 33a to 33d themselves may be used as the air bubble storage unit. In this way, the Figure 22 shown air bubble storage space E can be ensured in the flow paths 33a to 33d themselves. In addition, the flow paths 33a to 33d may be connected to the air bubble storage unit of a member different from the flow paths 33a to 33d. In this way, the Figure 22 shown air bubble storage space E can be ensured in a member other than the flow paths 33a to 33d. In this way, if the air bubble storage unit is arranged, the effects brought by the air bubble storage space E of the aforementioned fifth embodiment ( Figure 22 ) can be enjoyed.

[0215] Assume a case where the MPS device 1 having the culture unit 6c is used in an environment where rapid decompression may occur (such as outer space, etc.). In this case, there is a risk that the air bubbles in the culture solution (the gas may be air or a gas other than air) may expand due to decompression, resulting in an adverse condition in the culture unit 6c.

[0216] In this regard, if the flow paths 33a to 33d are connected to the air bubble storage unit, the incubator 61c of the culture unit 6c can be degassed via the flow paths 33a to 33d. Therefore, it is possible to suppress the occurrence of adverse conditions caused by air bubbles in the culture unit 6c. The same applies to the Figure 19 shown flow paths 33e to 33l.

[0217] The air bubble storage unit may also be arranged inside the container 2 (inside the MPS device 1). In this way, the processing of air bubbles can be completed inside the MPS device 1. Therefore, the processability is higher than the case where the air bubble storage unit is arranged outside the container 2.

[0218] The bubble storage unit may also be arranged outside the container 2 (outside the MPS device 1). In this way, compared with the case where the bubble storage unit is arranged inside the container 2, the degree of freedom regarding the size, shape, etc. of the bubble storage unit becomes higher. In addition, compared with the case where the bubble storage unit is arranged inside the container 2, the influence of the bubble-related defective conditions on the MPS device 1 can be reduced.

[0219] There are no particular limitations on the shape etc. of the abutting portions 321, 37. Regarding the number of arrangements of the abutting portions 321, 37, it may be the same as or different from the number of arrangements of the functional units required for fixing. There are no particular limitations on the shape etc. of the pressing portions 321a, 370. Regarding the number of arrangements of the pressing portions 321a, 370, it may be the same as or different from the number of arrangements of the functional units having the openings 601, 611c, 612. Regarding the shape of the pressing portions 321a, 370, the taper angle is not limited. The taper may be planar or curved. The pressing portions 321a, 370 may not be tapered. The pressing portions 321a, 370 may also be shaped such that the front end tapers in an inclined or stepped manner downward. It is sufficient that the cross-sectional area of the pressing portions 321a, 370 (specifically, the cross-sectional area in the direction (horizontal direction) orthogonal to the axial direction (vertical direction) of the pressing portions 321a, 370) becomes smaller downward. Of course, the cross-sectional area of the pressing portions 321a, 370 may also be constant over the entire length in the vertical direction. There are no particular limitations on the number of openings of the flow paths 33a to 33l with respect to a single abutting portion 321, 37. It may be single or multiple. There are no particular limitations on the arrangement direction of the MPS device 1. Figure 12 The shown central axis A may also be oriented in a direction intersecting the vertical direction, the horizontal direction, the vertical direction, and the horizontal direction.

[0220] Description of Reference Numerals

[0221] 1: MPS device (biological simulation system device); 2: container; 20: bottom wall portion; 200: long side portion; 201: short side portion; 202: opening portion; 21: side wall portion; 21a: side wall portion; 21b: side wall portion; 210: dorsal guide portion (dorsal engagement portion); 211: engaged concave portion; 212: opening portion; 22: partition wall portion; 23a - 23f: accommodation portion; 230: opening portion; 231: frame portion; 3: flow path member; 30: chamfered portion; 31: first layer; 310: first layer concave portion; 310a: first concave portion; 32: second layer; 320: second layer convex portion; 320a: second concave portion; 321: abutting portion; 321a: press - fitting portion; 322: second layer protruding portion; 322a: lower surface; 33a - 33l: flow path; 330a - 330d: horizontally extending portion; 330b1: wide portion; 330b2: narrow portion; 331a - 331g: vertically extending portion; 34: flow rate control portion; 35: third layer; 350: third layer protruding portion; 350a: lower surface; 350b: annular groove; 36: O - ring; 37: abutting portion; 370: press - fitting portion; 4: cover member; 40: top wall portion; 400: front - side guide portion (front - side engagement portion); 401: positioning portion; 402: engaging claw; 5: fastening member; 50: front - side guided portion; 51: dorsal - side guided portion; 52: connecting portion; 6a: supply portion (functional unit); 60: tray; 600: bottom wall portion; 601: opening portion; 602: opening portion; 61: introducing member; 610: concave portion; 611: communication hole; 612: opening portion; 613: convex portion; 62: connector; 620: pipe portion; 621: inner flange; 622: outer flange; 623: flange; 63a: pipe; 64a: check valve; 6b: liquid - feeding portion (functional unit); 63b: air - bag pump; 630b: hollow flange; 6c: culturing portion (functional unit); 60c: base; 600c: fixing hole; 61c: culture vessel; 610c: bottom wall portion; 611c: opening portion; 62c: filter; 6d: waste - liquid storage portion (functional unit); 6e: first connection portion (functional unit); 6f: second connection portion (functional unit); 90: pipe; A: central axis; B: block; C: culture solution; D: bubble; E: bubble storage space.

Claims

1. A biological simulation system device, wherein: The biological simulation system equipment comprises: a container for replaceably accommodating a plurality of functional units; and The flow path member is disposed on the front side of the container and divides at least a part of the flow path that communicates the plurality of functional units housed in the container.

2. The biological simulation system device according to claim 1, wherein: The dimensions of the container viewed from the front and back are those of a multi-well plate in accordance with industrial standards.

3. The biological simulation system device according to claim 1, wherein: The container has: A rectangular bottom wall portion having a pair of long sides arranged opposite to each other and a pair of short sides connecting the pair of long sides and arranged opposite to each other; a pair of side wall portions, which are erected from the pair of long sides and disposed on the front side; and a partition wall portion connecting the pair of side walls to each other, extending parallel to the short side portion, and partitioning the space between the pair of side walls into a plurality of accommodation portions, The receiving portion is interchangeable with respect to the plurality of functional units.

4. The biological simulation system device according to claim 1, wherein: The flow path member has a plurality of abutment portions, and the abutment portions are arranged to face the plurality of functional units accommodated in the container. The abutting portion abuts against the functional unit from the front side, The flow path opens at the rear surface of the abutment portion.

5. The biological simulation system device according to claim 1, wherein: The flow path member includes a flow control unit that divides the plurality of flow paths internally and controls a flow rate of a fluid flowing through any of the flow paths.

6. The biological simulation system device according to claim 1, wherein: The biological simulation system equipment comprises: a cover member disposed on the front side of the flow path member and having higher rigidity than the flow path member; and a fastening member that fastens the cover member to the container, After the functional unit is fixed by the flow path member, the container and the flow path member are integrated by the cover member and the fastening member.

7. The biological simulation system device according to claim 6, wherein: The cover member has a front side engaging portion, The container has a back-side engaging portion. The fastening member is engaged with the front-side engaging portion and the back-side engaging portion.

8. The biological simulation system device according to claim 7, wherein: The container has: A rectangular bottom wall portion having a pair of long sides arranged opposite to each other and a pair of short sides connecting the pair of long sides and arranged opposite to each other; a pair of side wall portions, which are erected from the pair of long sides and disposed on the front side; and a partition wall portion connecting the pair of side walls to each other, extending parallel to the short side portion, and partitioning the space between the pair of side walls into a plurality of accommodation portions, When viewed from the front and back, the size of the container is in accordance with the size of the multi-well plate of industrial specifications. The receiving portion is interchangeable with respect to the plurality of functional units. The flow path member includes: a flow control unit that divides the plurality of flow paths internally and controls the flow rate of the fluid flowing in any of the flow paths; and a plurality of abutment portions, which are arranged to face the plurality of functional units accommodated in the container, The abutting portion abuts against the functional unit from the front side, and the flow path opens at the back side of the abutting portion. The container, the flow path member, and the cover member are transparent.

9. The biological simulation system device according to claim 1, wherein: The container comprises a bottom wall portion and a side wall portion erected from the bottom wall portion on the front side. The side wall portion has an opening portion penetrating the side wall portion.

10. The biological simulation system device according to claim 1, wherein: The container has a bottom wall portion, The bottom wall portion has an opening portion penetrating the bottom wall portion.

11. The biological simulation system device according to claim 1, wherein: The flow path member has an abutment portion, The functional unit has an opening, The contact portion has a press-fit portion that is pressed into the opening portion, The press-fit portion is made of a material including at least one of PDMS and resin.

12. The biological simulation system device according to claim 1, wherein: The flow path is used to degas the functional unit.

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