Cell culture sets, cell characteristic detection sets, and cell culture devices

Abstract

This system enables the creation of cell culture sets that can be combined with the necessary number of cell culture devices or culture vessels to suit the user's experimental system. [Solution] The cell culture set 1 comprises a substrate 20A to 20D, a pair of elastically deformable resin supports 30 suspended from the substrate 20A to 20D, a cell culture section 10A to 10D capable of culturing cell aggregates between the pair of supports 30, a container section 50A to 50D capable of containing at least a portion of the pair of supports 30 together with culture medium, connecting parts 21 and 51 provided on at least one of the cell culture section 10A to 10D and the container section 50A to 50D, and bonded parts 22 and 52 having a structure capable of being bonded to the connecting parts 21 and 51.

Description

Technical Field

[0001] The present invention relates to a cell culture set, a cell characteristic detection set, and a cell culture device.

Background Art

[0002] Output devices (output devices) are known for evaluating cell characteristics. For example, Patent Document 1 discloses an output device capable of detecting the contraction characteristics of muscle cells held on a collagen-based support having a long portion by a strain gauge connected to a connecting portion provided at one end of the long portion. The output device is used by immersing a cell culture device in which muscle cells are cultured on a support in a culture medium filled in a culture vessel. Evaluation of cell characteristics using an output device such as that of Patent Document 1 is carried out with cell culture and evaluation as a series of experiments.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] Cell characteristic evaluation experiments may involve conducting multiple experiments in parallel during cell culture and evaluation. For example, this applies when evaluating the function, responsiveness, and degree of differentiation of cells cultured under multiple experimental conditions, or when screening drugs mixed into culture media. However, the output device described in Patent Document 1 is designed for applying muscle cell samples cultured under a single condition to a single evaluation system and is not suitable for conducting multiple experiments in parallel. On the other hand, there are well-plate type culture vessels for cell culture that have numerous recesses, but the number of recesses often does not match the number of experimental systems being conducted, and in such cases, the remaining recesses are not used and are wasted. Furthermore, many cell culture devices that hold cells have special structures, and many culture vessels have special surface treatments, so these are often expensive.

[0005] Therefore, there is a need for a cell culture set that can combine the required number of cell culture units or culture vessels according to the user's experimental system, as well as a cell culture device that can combine the required number of cell culture units. [Means for solving the problem]

[0006] The cell culture set according to the present invention comprises a substrate and a pair of elastically deformable resin supports suspended from the substrate, and is characterized by having a cell culture section in which cell aggregates can be cultured between the pair of supports, a container section in which at least a portion of the pair of supports together with a culture medium, a connecting section provided on at least one of the cell culture section and the container section, and a bound section having a structure that can be bound to the connecting section.

[0007] Furthermore, the cell characteristic detection set according to the present invention is a cell characteristic detection set including the cell culture set described above, wherein at least a portion of the pair of supports holding the cell aggregates is housed in the container portion into which the culture medium is introduced, and the characteristics of the cell aggregates can be detected by detecting the amount of displacement of the supports from outside the cell culture set.

[0008] With these configurations, the user can assemble at least one of the required number of cell culture sections and container sections according to their experimental system. Furthermore, at least one of the assembled cell culture sections and container sections can be removed as needed. Therefore, at least one of the cell culture sections and container sections is less likely to be wasted, and they can be easily combined flexibly according to experimental conditions, etc.

[0009] Furthermore, since the above-mentioned cell characteristic detection set has multiple cell culture sections or multiple container sections connected together, it is possible to prepare multiple cell aggregates cultured under different conditions within a single cell culture set, and to simultaneously or sequentially detect the characteristics of multiple cell aggregates from outside the cell culture set.

[0010] Furthermore, the cell culture device according to the present invention comprises a substrate and a pair of elastically deformable resin supports suspended from the substrate, and is a cell culture device capable of culturing cell aggregates between the pair of supports, characterized in that it comprises a bonding portion provided on the substrate and a bonded portion provided on the substrate and having a structure capable of bonding with the bonding portion.

[0011] This configuration allows for the creation of a cell culture device by combining the necessary number of cell culture sections according to the user's experimental system. Furthermore, the combined cell culture sections can be removed as needed. Therefore, the device is less likely to be wasted, and it can be easily combined flexibly according to experimental conditions, etc.

[0012] Preferred embodiments of the present invention will be described below. However, the scope of the present invention is not limited by the examples of preferred embodiments described below.

[0013] In the cell culture set according to the present invention, it is preferable that the binding portion is a protruding portion that extends in the direction of binding, and the bound portion is a recessed portion that is recessed in the direction of binding.

[0014] This configuration makes it easy to connect multiple adjacent cell culture sections and container sections.

[0015] In the cell culture set according to the present invention, it is preferable that the coupling part is a protrusion protruding from the outer surface of the substrate or the container part, and the coupled part is a locking hole formed in the outer surface of the substrate or the container part.

[0016] According to this configuration, it is easy to couple a plurality of adjacent cell culture parts and container parts.

[0017] In the cell culture set according to the present invention, it is preferable that at least one of the coupling part and the coupled part is provided at an opposing position in the substrate or the container part.

[0018] According to this configuration, it is easy to couple at least the substrate or the container parts in series.

[0019] In the cell culture device according to the present invention, it is preferable that the coupling part is a ridge protruding in the coupling direction from the substrate, and the coupled part is a concave groove recessed in the coupling direction of the substrate.

[0020] According to this configuration, it is easy to firmly and smoothly combine a required number of cell culture parts.

[0021] In the cell culture device according to the present invention, it is preferable that the coupling part is constituted by a magnet provided in the coupling direction of the substrate, and the coupled part is constituted by a magnet or a magnetic body provided in the coupling direction of the substrate.

[0022] According to this configuration, it is easy to simply and promptly combine a required number of cell culture parts.

[0023] Further features and advantages of the present invention will become more apparent from the following description of exemplary and non-limiting embodiments described with reference to the drawings.

Brief Description of the Drawings

[0024] [Figure 1] Exploded perspective view for explaining the cell characteristic detection set according to the first embodiment [Figure 2] Cross-sectional view explaining the coupling part and the coupled part in the device piece (cell culture part) according to the first embodiment [Figure 3] Planar view explaining the coupling part and the coupled part in the device piece (cell culture part) according to the first embodiment [Figure 4] Cross-sectional view explaining the coupling part and the coupled part in the container piece (container part) according to the first embodiment [Figure 5] Planar view of the cell culture device and the device piece (cell culture part) according to the second embodiment [Figure 6] Planar view of the container and the container piece (container part) according to the second embodiment [Figure 7] Perspective view showing other coupling parts and other coupled parts in the device piece (cell culture part) [Figure 8] Perspective view showing other coupling parts and other coupled parts in the container piece (container part) [Figure 9] Perspective view explaining the cell culture set according to the third embodiment [Figure 10] Exploded perspective view explaining the device piece (cell culture part) according to the third embodiment [Figure 11] Front cross-sectional view of the device piece (cell culture part) according to the third embodiment [Figure 12] Planar view of the substrate body of the device piece (cell culture part) according to the third embodiment [Figure 13] Perspective view of the mounting member of the device piece (cell culture part) according to the third embodiment [Figure 14] Diagram showing the procedure for fixing the mounting member and the support to the substrate body in the device piece (cell culture part) according to the third embodiment [Figure 15] Diagram showing the procedure for fixing the mounting member and the support to the substrate body in the device piece (cell culture part) according to the third embodiment [Figure 16] Diagram explaining the usage method of the device piece (cell culture part) according to the third embodiment [Figure 17]Decomposed perspective view illustrating a modified example of the device piece (cell culture section) of the third embodiment. [Figure 18] Decomposed perspective view illustrating a cell culture device according to the fourth embodiment. [Figure 19] Front cross-sectional view of the cell culture device according to the fourth embodiment. [Figure 20] Decomposed perspective view illustrating a cell culture device according to the fifth embodiment. [Figure 21] Plan view of the substrate body of the cell culture device according to the fifth embodiment. [Figure 22] Plan view of the substrate body of another example of the fifth embodiment [Figure 23] Plan view of the substrate body of another example of the fifth embodiment [Modes for carrying out the invention]

[0025] [First Embodiment] A cell characteristic detection set 100 according to the first embodiment of the present invention will be described with reference to Figures 1 to 4. The cell characteristic detection set 100 of the present invention is used by placing the bottom surface of the container 50 of the cell culture set 1 on a workbench or the like. In the following description of this specification, when terms indicating direction are used, unless otherwise specified, the vertical direction, up-down direction and height direction refer to the up-down direction of the paper in each figure.

[0026] Figure 1 is an exploded perspective view of the cell characteristic detection set 100. The cell characteristic detection set 100 includes the cell culture set 1 and enables the detection of cell characteristics from outside the cell culture set 1. The cell culture set 1 comprises a cell culture device 10, which is made up of multiple cell culture device pieces 10A, 10B, 10C, and 10D (hereinafter referred to as device pieces 10A, etc., each being an example of a cell culture section), and a container 50, which is made up of multiple container pieces 50A, 50B, 50C, and 50D (each being an example of a container section). The device pieces 10A, 10B, 10C, and 10D can be combined with each other, and the container pieces 50A, 50B, 50C, and 50D can be combined with each other for use. In the following, when each piece and each component piece is shown collectively, it will also be referred to as device piece 10A to 10D.

[0027] Each device piece 10A to 10D comprises rectangular plate-shaped substrates 20A to 20D and a pair of elastically deformable resin supports 30 suspended vertically from each of the substrates 20A to 20D. Here, "suspended vertically" means that it is provided in a way that it hangs down. In the example in Figure 1, the pair of supports 30 are provided hanging vertically, but this is not limited to this, and they may be provided at an inclination of ±10 degrees to ±20 degrees relative to the vertical, for example. The device pieces 10A to 10D have the same structure and size, except for the protrusions 21 (an example of a connecting part) and recesses 22 (an example of a connected part). Device pieces 10B and 10C have the same structure and size, including the protrusions 21 and recesses 22. In this embodiment, the device pieces 10A to 10D are connected in a line in the order of 10A, 10B, 10C, and 10D to form a cell culture device 10 having four pairs of supports. Cell culture set 1 allows for the culture of cell aggregates between a pair of supports 30.

[0028] Each container piece 50A to 50D is a rectangular parallelepiped culture vessel having one recess 54 capable of accommodating at least a portion of a pair of supports 30 along with a culture medium 55 (an example of a liquid). Each container piece 50A to 50D has the same structure and size, except for the protrusions 51 (an example of a connecting part) and the locking holes 52 (an example of a connected part). Container pieces 50B and 50C have the same structure and structure, including the protrusions 51 and the locking holes 52. In this embodiment, the container pieces 50A to 50D are connected in a row in the order 50A, 50B, 50C, and 50D to form a 4-well container 50.

[0029] The number of recesses 54 in this container 50 is preferably a multiple of the number of pairs of supports 30 in one cell culture device 10 (in this example, "4"), and in this embodiment, four recesses 54 are provided. In this case, one cell culture device 10 is attached to one container 50.

[0030] The cell characteristic detection set 100 is used by immersing at least the portion of a pair of support bodies 30 of the cell culture device 10 that holds cell aggregates in culture medium 55 introduced into a container 50. For example, the movement of the support bodies 30 can be measured from an external measuring instrument 80 of the cell culture set 1. That is, the container 50 and culture medium 55 are transparent or translucent, and the movement of cell aggregates can be detected via the movement of the support bodies 30. The substrates 20A to 20D and each support body 30 that constitute the cell culture device 10 may also be transparent or translucent, and the movement of the support bodies 30 or cell aggregates may be detected from the cell culture device 10 side.

[0031] The substrate 20 of the cell culture device 10 according to this embodiment is provided with a projection 21 that protrudes in the bonding direction X, and a recess 22 that is bondable to the projection 21 and recessed in the bonding direction X. With this configuration, multiple adjacent device pieces 10A to 10D can be easily joined by joining each substrate 20A to 20D like a puzzle.

[0032] Figure 2 is a cross-sectional view illustrating the coupling structure of device piece 10B and device piece 10C, and Figure 3 is a plan view illustrating the structures of device pieces 10B and 10C. The recessed portion 22 of device pieces 10B and 10C is provided by partially cutting out the central corner of one side of the upper surface of the substrate 20 from above. On the other hand, the protruding portion 21 of device pieces 10B and 10C is a rectangular plate shape with a thickness less than the thickness of the substrate 20B, and is formed flush with the upper surface of the substrate 20. With this configuration, the bottom surface 22A of the recessed portion 22 becomes a receiving portion for the back surface 21A of the protruding portion 21, preventing device piece 10B from sliding downward and forming a stable coupling state. The thickness T2 of the protrusions 21 in the device pieces 10B and 10C is preferably 1 / 2 to 5 / 6 of the thickness T1 of the substrates 20B and 20C, and the depth D1 of the recesses 22 in the device pieces 10B and 10C is preferably 1 / 2 to 5 / 6 of the thickness T1 of the substrate 20. It is desirable that the thickness T2 and depth D1 be approximately the same so that the substrates 20B and 20C become flush when joined together. It is desirable that the width dimensions W1 and W2 of the protrusions 21 and recesses 22 be set so that the protrusions 21 can be press-fitted into the recesses 22, so that the protrusions 21 do not easily come off the recesses 22, but can be removed with a little force.

[0033] In this embodiment, device pieces 10B and 10C are provided with a protrusion 21 and a recess 22 at opposing positions on the substrate 20B, respectively. This configuration makes it easy to connect the device pieces in series to form a connected cell culture device 10. In this embodiment, in the connected cell culture device 10, only the protrusion 21 is provided on device piece 10A located at one end, and only the recess 22 is provided on device piece 10D located at the other end (Figure 1). Thus, device pieces 10A and 10D located at the ends only need to have at least one of the protrusion 21 and the recess 22 in the connection direction X.

[0034] Next, container pieces 50B and 50C will be described in detail. As mentioned above, container piece 50B and container piece 50C have the same structure and size, so container piece 50B will be described as a representative example. As shown in Figure 4, container piece 50B has a projection 51 protruding from container piece 50B and a locking hole 52 formed on the bottom surface of container piece 50B, and container pieces 50B and 50C can be connected to each other by inserting the projection 51 of container piece 50B into the locking hole 52 of container piece 50C. In this embodiment, the projection 51 is composed of a support portion 51a extending in the connection direction X and a columnar portion 51b protruding upward from the end of the support portion 51a. In this embodiment, the locking hole 52 is a hole drilled from the bottom surface side of container piece 50B and extending upward. With this configuration, it is easy to smoothly and stably connect multiple adjacent container pieces 50B and 50C. It is desirable that the outer diameter of the projection 51 and the inner diameter of the locking hole 52 be designed such that the projection 51 does not easily come out of the locking hole 52, but can be released with a little force, so that the projection 51 can be press-fitted into the locking hole 52.

[0035] In this embodiment, the container piece 50B is provided with a projection 51 and a locking hole 52 at opposing positions on the container piece 50B. With this configuration, it is easy to connect the container pieces in series to form a connected container 50. In the connected container 50, the container piece 50A located at one end is provided only with the projection 51, and the container piece 50D located at the other end is provided only with the locking hole 52. Thus, the container pieces 50A and 50D located at the ends only need to be provided with at least one of the projection 51 and the locking hole 52 in the connection direction X.

[0036] The cell culture device 10 and container 50 of the first embodiment can be modified to expand the number of sets in the cell culture device 10 or the number of wells in the container 50 by using one or more pieces of the same shape as each intermediate piece. For example, by inserting four device pieces 10B next to each other and joining them, it is possible to expand to a cell culture device with 8 sets. Conversely, it is possible to reduce the number of sets in the cell culture device 10 or the number of wells in the container 50 by reducing the number of intermediate pieces. For example, by removing device pieces 10B and 10C from the cell culture device 10 and joining device piece 10A and device piece 10D, it is possible to reduce to a cell culture device with 2 sets.

[0037] Next, we will describe the other configurations of each device piece 10A to 10D and each container piece 50A to 50D.

[0038] In this embodiment, each device piece 10A to 10D of the cell culture device 10 has a support 30 fixed to the substrate 20 so as to be suspended from each substrate 20A to 20D as described above, but the method of fixing the support 30 to the substrate 20 is not limited. Each substrate 20A to 20D may have a fixing portion for a pair of support 30. The pair of support 30 may be detachable from the substrates 20A to 20D. In this embodiment, the substrates 20A to 20D are made of resin plate material. The thickness T1 of the substrates 20A to 20D is not particularly limited, but for example, the thickness T1 of the substrate 20 in the portion having the protrusion 21 and recess 22 is 2 to 5 mm.

[0039] As described above, the pair of supports 30 in this embodiment are made of resin and consist of a pair of opposing film bodies. The film bodies can be formed using, for example, polystyrene resin, polypropylene resin, or polyethylene resin. The Young's modulus of the material constituting the film body is not particularly limited, but is preferably 100 MPa or more and 4500 MPa or less. The Young's modulus of the material constituting the film body is more preferably 300 MPa or more and 4300 MPa or less, and even more preferably 400 MPa or more and 4000 MPa or less.

[0040] Furthermore, the thickness of the support 30 according to this embodiment is not particularly limited, but is preferably 5 μm or more and 400 μm or less. The thickness of the support 30 is more preferably 7 μm or more and 200 μm or less, and even more preferably 8 μm or more and 100 μm or less.

[0041] The container pieces 50A to 50D in this embodiment are containers formed from plastic, metal, or glass. In this embodiment, an example is shown in which the projection 51 (support portion 51a and columnar portion 51b) is integrally molded with the container piece, but the support portion 51a and the columnar portion 51b may be made of separate materials. In that case, for example, one end of the support portion 51a, which is made from a plate-like piece, can be fixed to the bottom surface of the container piece 50B (the surface on which the container 50 is placed on the workbench), and a columnar member that will become the columnar portion 51b can be fixed to the other end of the support portion 51a so as to protrude upward. Also, in this embodiment, the locking hole 52 is provided in a position that does not overlap with the recess 54, but this is not limited to this, and the locking hole may be provided at the bottom of the recess 54. The materials of the support portion 51a and the columnar portion 51b may be the same as those of the container pieces 50A to 50D, or they may be different.

[0042] It is desirable that the inner surface 54a of the recess 54 in container pieces 50A to 50D be treated to suppress nonspecific cell adsorption. Nonspecific cell adsorption suppression treatment is a treatment that suppresses the nonspecific adsorption of cells. Nonspecific cell adsorption suppression treatment can be carried out, for example, by hydrophilization treatment, and more specifically, by oxygen plasma treatment or coating treatment mainly consisting of polymers containing specific hydrophilic constituent units.

[0043] According to the cell characteristic detection set 100 and cell culture set 1 of this embodiment, the user can combine any number of device pieces 10A to 10D and container pieces 50A to 50D in series, like puzzle pieces, according to the user's experimental system. Furthermore, after assembly, some of the device pieces 10A to 10D or some of the container pieces 50A to 50D can be removed as needed. In this way, the user can combine the necessary number of device pieces 10A to 10D and container pieces 50A to 50D according to the experimental conditions, making it easier to utilize the device pieces and container pieces effectively without waste. In addition, according to the cell characteristic detection set 100 of this embodiment, since multiple device pieces 10A to 10D and multiple container pieces 50A to 50D are connected, multiple cell aggregates (four cell aggregates in this embodiment) cultured under different conditions can be prepared in the cell culture set 1, and the characteristics of multiple cell aggregates can be detected simultaneously or sequentially from the measuring instrument 80 outside the cell culture set. In this way, it is not necessary to replace the entire cell culture device 10 and container 50 for each evaluation experiment, and the effort required to set up the measuring instrument 80 can also be reduced.

[0044] [Second Embodiment] Next, the cell characteristic detection set according to the second embodiment will be described with reference to Figures 5 and 6. The cell characteristic detection set according to the second embodiment includes a cell culture device 60 and a container 70, which differ from those of the first embodiment. The following description will focus on the differences between the cell culture device 60 and the container 70 from the first embodiment. Points not specifically described will be the same as those of the first embodiment.

[0045] In the cell culture device 60 according to the second embodiment, device pieces are not only bonded in the bonding direction X, but also further bonded in the bonding direction Y, which is orthogonal to the bonding direction X in the plane direction of the substrate 20. Specifically, the bonded cell culture device 60 consists of a total of 12 device pieces 60A to 60L, 4 in the bonding direction X and 3 in the bonding direction Y. Similarly, the container 70 also consists of a total of 12 container pieces 70A to 70L, 4 in the bonding direction X and 3 in the bonding direction Y.

[0046] In this embodiment, device pieces 60A and 60L, device pieces 60B and 60K, device pieces 60C and 60J, device pieces 60D and 60I, and device pieces 60F and 60G are all pieces of the same shape, and the pieces are standardized to reduce the number of different types of pieces.

[0047] In this embodiment, the cell culture device 60 has device pieces 60E to 60H, each having at least one of the protrusions 21 and recesses 22 at opposing positions in the bonding direction Y on the substrate 20, so that the device pieces can be bonded in both the bonding directions X and Y.

[0048] Furthermore, in this embodiment, the container 50 is also provided with container pieces 70E to 70H having at least one of the projection 51 and the locking hole 52 at opposing positions in the coupling direction Y on the container 50, so that the container pieces can be coupled in both the coupling directions X and Y.

[0049] The cell culture device 60 and container 70 of the second embodiment can be modified to expand the number of sets in the cell culture device 60 or the number of wells in the container 70 by repeatedly using multiple identical pieces in the middle. For example, in the cell culture device 60, the number of sets can be expanded to 16 by inserting identical device pieces 60E to 60H next to each other and connecting them. Conversely, the number of sets in the cell culture device 60 or the number of wells in the container 70 can be reduced by decreasing the number of pieces in the middle. For example, in the cell culture device 60, the number of sets can be reduced to 9 by removing device pieces 60B, 60F, and 60J and connecting device pieces 60A, 60E, and 60I with device pieces 60C, 60G, and 60K.

[0050] (Variations of the first and second embodiments) Modifications of the first and second embodiments will now be described. Note that the configurations disclosed in each of the following embodiments can be applied in combination with configurations disclosed in other embodiments, as long as this does not create a conflict.

[0051] In the first and second embodiments described above, a configuration in which both the cell culture device and the container have a connecting portion and a bound portion was described as an example. However, in the present invention, the connecting portion and the bound portion only need to be provided on at least one of the cell culture device and the container.

[0052] In the present invention, the cell culture section (device piece) has a substrate 20, and the container section (container piece) has a three-dimensional shape, so the two have fundamentally different structures. For this reason, as in the first and second embodiments, it is preferable that the cell culture device 10 and the container 50 each have a connecting part and a connected part with different structures. However, the container 50 may be provided with a protrusion 21 and a recess 22, or the substrate 20 of the cell culture device 10 may be provided with a projection 51 and a locking hole 52.

[0053] In the first and second embodiments described above, the protrusion 21 of the cell culture section is plate-shaped with a thickness less than the thickness of the substrate 20, and the depth of the recess 22 of the cell culture section is less than the thickness of the substrate 20. However, in the cell culture device of the present invention, as shown in Figure 7, the thickness of the protrusion 21 may be approximately the same as or identical to the thickness of the substrate 20, and the depth of the recess 22 may also be approximately the same as or identical to the thickness of the substrate 20.

[0054] In the first and second embodiments described above, a configuration in which the locking holes 52 and projections 51 are provided on the bottom surface of the container portion was explained as an example. However, the surface on which the locking holes 52 and projections 51 are provided on the container portion is not limited, and it is sufficient for the locking holes 52 and projections 51 to be provided on any surface of the container portion. For example, as shown in Figure 8, a configuration in which two sets of connecting parts and connected parts are provided on the surface of the container portion facing the connecting direction X may be used.

[0055] In the first and second embodiments described above, the cell culture portion's protrusion 21 is rectangular in shape in plan view, and a corresponding recess 22 is described as an example (Figure 3, etc.). However, the shape of the protrusion 21 in plan view is not limited to a rectangle and may be other shapes, for example, approximately circular or triangular, with the width dimension W2 at the tip of the protrusion 21 being larger, and a constricted portion being formed on the substrate side of the protrusion 21 so that the width dimension W2 is smaller. With this configuration, it is easier to create a structure that is difficult to detach in the joining direction, like a jigsaw puzzle.

[0056] In the first and second embodiments described above, a configuration was explained in which, after binding, the binding portion or the bound portion is not located on the outermost edge of the cell culture device or container. However, in the cell culture set after binding, the binding portion (protrusion 21 or projection 51) or the bound portion (recess 22 or locking hole 52) may be located on the outermost edge of the cell culture device or container. By configuring in this way, the number of patterns of binding portions and bound portions for the cell culture portion and container portion that need to be prepared can be greatly reduced. For example, multiple device pieces 10B from the first embodiment may be bound together to form a cell culture portion with multiple sets, and multiple container pieces 50B may be bound together to form a container portion with multiple wells. Similarly, in the second embodiment, device pieces 60F, container pieces 70F, etc., may be used to form a cell culture portion with multiple sets and a container portion with multiple wells, respectively.

[0057] In the first and second embodiments described above, a cell characteristic detection set 100 was described as an example in which a measuring instrument 80 is used to measure the movement of the support 30. However, the cell characteristic detection set of the present invention only needs to be able to detect the characteristics of the cell aggregate by detecting the amount of displacement of the support from outside the cell culture set. For example, the amount of displacement ΔW of the support 30 may be detectable from the outside by connecting a strain gauge to the support 30. Furthermore, the cell culture device 10 or container 50 does not need to be light-transmitting, and the cell characteristic detection set 100 only needs to be able to detect the amount of displacement ΔW from the outside.

[0058] [Third Embodiment] Next, the cell culture set 2 and the cell characteristic detection set containing it according to the third embodiment will be described with reference to Figures 9 to 16. The cell culture set 2 according to the third embodiment comprises a cell culture device 12 and a container 90 that differ from those of the first embodiment. The following description will focus on the differences between the cell culture device 12 and the container 90 from the first embodiment. Points that are not specifically described will be the same as those of the first embodiment.

[0059] As shown in Figures 9 to 11, the cell culture device 12 is constructed by connecting device pieces 12A of the same shape in a row. Each device piece 12A comprises a substrate 23 and a pair of resin supports 31 suspended from the substrate 23, forming a single cell culture section. The supports 31 are elastically deformable and supported by the substrate 23. In this embodiment, the cell culture device 12 is provided with a connecting portion (projection 26) and a connectable portion (locking hole 27) on the substrate 23 of each device piece 12A. In this embodiment, since four device pieces 12A are connected, the cell culture device 12 comprises four sets of pairs of supports 31 on a connected body of four substrates 23. Note that the connected body of the substrates 23 of the device pieces 12A in the third embodiment corresponds to the substrate of the cell culture device 12.

[0060] As shown in Figures 10 and 11, in the device piece 12A, the substrate 23 includes a substrate body 24 and a mounting member 40, which are configured to be detachable.

[0061] As shown in Figures 10 and 12, the substrate body 24 has an outer frame 25 and a mounting portion 28. These are integrally formed. The outer frame 25 is formed in the shape of a rectangular frame. In detail, the outer frame 25 is formed in a flat, approximately square shape with the four corners chamfered in a C-shape when viewed from above. Two protrusions 26 and two corresponding locking holes 27 are provided on the outer sides of the outer frame 25 at opposing positions when viewed from above. That is, the device piece 12A has two protrusions 26 which are the connecting portion and two locking holes 27 which are the connected portion, at opposing positions on the substrate 23. Because the four corners of the outer frame 25 are chamfered, it is easy to widen the gap between the connected device pieces 12A with a finger or the like, and easy to detach the connected protrusions 26 and locking holes 27.

[0062] In this embodiment, a rectangular void G is formed within the space enclosed by the outer frame 25, extending vertically (in the thickness direction of the substrate 23). In addition, a pair of opposing portions within the outer frame 25 are provided with mounting portions 28 that extend in the central part along the connection direction of the outer frame 25. These mounting portions 28 are the parts to which the mounting member 40 is attached. The mounting portions 28 protrude toward the center of the void G.

[0063] On the side surface of the mounting portion 28, an engagement recess 28A is formed, which is recessed from one side to the other along the connecting direction of the outer frame 25. In other words, the engagement recess 28A is open toward the side of the mounting portion 28. An engagement projection 42, which is formed to protrude from the mounting member 40, engages with this engagement recess 28A.

[0064] As shown in Figure 10, the mounting member 40 is attached to the substrate body 24 in the gap G. The mounting member 40 in this embodiment has a rectangular parallelepiped mounting body 41 and a pair of engaging protrusions 42 that protrude from both sides in the longitudinal direction from the mounting body 41. These are integrally formed.

[0065] In this embodiment, the mounting body 41 is formed as a hollow member. The longitudinal length of the mounting body 41 is approximately equal to the distance between two adjacent mounting portions 28. The size of the engaging projection 42 is approximately equal to the size of the engaging recess 28A formed in the mounting portion 28. The mounting member 40 is attached to the substrate body 24 in such a manner that a pair of engaging projections 42 are inserted from the side into and engage with the corresponding engaging recesses 28A. It is preferable that the engaging projections 42 are press-fitted into the engaging recesses 28A because it makes it less likely for the mounting body 41 to fall off the mounting portion 28. It is also advantageous that complementary structures (such as protrusions and notches) are provided on the surfaces of the engaging recesses 28A and the engaging projections 42 that come into contact with each other, as this makes it less likely for the mounting portion 28 to fall off.

[0066] As shown in Figure 13, the corners of the rectangular parallelepiped engaging projection 42 are chamfered portions 42A with rounded edges. Having such chamfered portions 42A on the engaging projection 42 allows for smooth and snag-free insertion of the engaging projection 42 into the engaging recess 28A from the side.

[0067] In this embodiment, the support 31 is made of the same material as the support 30 in the first embodiment. That is, the support 31 is made of the same resin material and Young's modulus film as the support 30 in the first embodiment, and has the same thickness. However, the shape of the support 31 is different from that of the support 30 in the first embodiment. As shown in Figure 10, the support 31 in this embodiment has a mounting portion 32 and an extended portion 33. The mounting portion 32 is formed in a rectangular shape corresponding to the side surface on the mounting body 41 of the mounting member 40 where a pair of engaging protrusions 42 are formed. A rectangular opening 32a is formed through the mounting portion 32. The opening 32a is formed in a rectangular shape corresponding to the outer shape of the engaging protrusions 42 of the mounting member 40. The extended portion 33 extends downward from the mounting portion 32. The area near the tip (near the lower end) of the extended portion 33 is formed in a narrower strip shape than the mounting portion 32. In this embodiment, an example is illustrated and explained in which the tip (lower end) of the extended portion 33 of the support 31 is bent in a direction that brings the pair of support 31 closer to each other. However, the tip of the extended portion 33 may not be bent and may extend downward.

[0068] As described above, the device piece 12A according to this embodiment includes a substrate 23 which comprises a substrate body 24 having a gap G at the installation position of a pair of support bodies 31, and a mounting member 40 which is attached to the substrate body 24 in the gap G. The substrate body 24 has an engagement recess 28A that opens toward the side and engages with the mounting member 40, and the mounting member 40 is fixed to the substrate body 24 by engaging with the engagement recess 28A while holding the pair of support bodies 31. In detail, as shown in Figure 10, the support bodies 31 are attached to the mounting member 40 at the portion of the mounting part 32 by fitting the opening 32a of the mounting member 40 onto the engagement projection 42 of the mounting member 40. Then, the mounting member 40, while holding the pair of support bodies 31, is inserted into the gap G of the substrate body 24, and the pair of engagement projections 42 engage with the corresponding engagement recess 28A from the side, thereby integrally fixing the mounting member 40 and the pair of support bodies 31 to the substrate body 24 (Figures 14 and 15).

[0069] The manufacturing method for the device piece 12A of this embodiment includes a component preparation step, a support holding step, and a mounting member fixing step. These steps are performed in the order of component preparation step → support holding step → mounting member fixing step.

[0070] The component preparation process is the process of preparing each component of the device piece 12A. In the component preparation process, the components of the device piece 12A are prepared, which include a substrate body 24 having a gap G at the installation position of a pair of support bodies 31, and mounting members 40 that are attached to the substrate body 24 in the gap G. The substrate body 24 and the mounting members 40 can be formed using a general thermoplastic resin, for example by injection molding or transfer molding. In the device piece 12A of this embodiment, one mounting member 40 is prepared for each substrate body 24.

[0071] In addition, the support 31, which is a film, is also prepared during the parts preparation process. The support 31 can be formed by trimming a film made of, for example, polystyrene resin, polypropylene resin, or polyethylene resin into a predetermined shape. In this embodiment, two support 31 are prepared for each mounting member 40.

[0072] The support holder holding step is the step of having the mounting member 40 hold a pair of support holders 31. In the support holder holding step, the pair of support holders 31 are attached to the mounting member 40 by fitting the opening 32a formed in the support holder 31 onto the engaging projection 42 of the mounting member 40 (Figure 10).

[0073] The mounting member fixing step is the step of fixing the mounting member 40, which holds the pair of support bodies 31, to the substrate body 24. In the mounting member fixing step, the pair of engaging protrusions 42 of the mounting member 40, which holds the pair of support bodies 31, are engaged with the corresponding engaging recesses 28A from the side (Figures 14 and 15). This procedure integrally fixes the mounting member 40 and the pair of support bodies 31 to the substrate body 24. Because the engaging protrusions 42 are engaged with the engaging recesses 28A from the side, the support bodies 31 are less likely to interfere with the substrate 23.

[0074] According to the manufacturing method of this embodiment, a device piece 12A comprising a substrate 23 and a pair of resin supports 31 elastically deformable and suspended from the substrate 23 can be easily assembled and manufactured. Furthermore, when this device piece 12A is used, for example, as a cell characteristic detection device for detecting the characteristics of cells, by immersing only the tip portion of the suspended resin supports 31 in the test solution, nonspecific adsorption of compounds can be made less likely in terms of both contact area and material. Thus, a device piece 12A that is less prone to nonspecific adsorption of compounds and has excellent manufacturability can be provided.

[0075] As shown in Figures 9 and 16, the container 90 according to this embodiment is a single-piece 4-well container with four recesses 91 on its upper surface 92. The container 90 according to this embodiment is a mold container for culturing and holding cell aggregates between a pair of supports 31 by immersing the tip portions of the supports 31 in a cell suspension (not shown). The recesses 91 are rectangular in shape in plan view from a midway point in the depth direction of the container 90 downwards, and the recesses 91 have mold recesses 91A that correspond in shape and size to the width dimension of the supports 31. The mold recesses 91A make it possible to hold cell aggregates at the tips of the pair of supports 31. The cell aggregates held between the pair of supports 31 are cultured in culture medium filled in recesses of another container section (not shown) similar to that of the first embodiment, and their movement and other characteristics are observed or detected by a measuring instrument 80 or the like. That is, in this embodiment, a cell characteristic detection set is formed with the cell culture device 12 and another container section into which culture medium has been introduced (not shown).

[0076] According to the cell culture device 12 and cell culture set 2 of the third embodiment, as shown in Figure 16, the user can combine any number of device pieces 12A in series like puzzle pieces to suit their experimental system. Furthermore, some of the device pieces 12A can be removed after assembly as needed. In this way, the user can combine only the necessary number of device pieces 12A according to the experimental conditions, making it easier to avoid wasting device pieces and to utilize them effectively. According to the device piece 12A of the third embodiment, the combined device pieces 12A do not easily come apart, maintaining a stable bond, while still being easy to remove as needed.

[0077] Furthermore, with the cell characteristic detection set of this embodiment, a cell culture device 12 can be formed by combining multiple device pieces 12A, allowing multiple cell aggregates cultured under different conditions to be prepared in a culture vessel. The characteristics of multiple cell aggregates can then be detected simultaneously or sequentially from an external measuring instrument 80 of the cell culture set. Thus, it is not necessary to replace the entire cell culture device 12 and container each time an evaluation experiment is conducted, and the effort required to set up the measuring instrument 80 can also be reduced.

[0078] [Fourth and fifth embodiments] Next, the cell culture devices 13 and 14 of the fourth and fifth embodiments will be described with reference to Figures 18 to 23. The cell culture devices 13 and 14 of the fourth and fifth embodiments shown below have the same shape as the support 31, etc., as in the third embodiment, but the structure of the bonding and bonded parts provided on the substrate 23 differs from that of the cell culture device 12 of the third embodiment. In the fourth and fifth embodiments described below, a cell culture device in which two device pieces are bonded will be described as an example, but the number of device pieces bonded in the cell culture device is not limited. Also, the shapes of the substrate 23, support 31, etc., are not limited to those of the third embodiment.

[0079] (Fourth embodiment) The cell culture device 13 according to the fourth embodiment has a configuration in which adjacent device pieces 13A are joined together by a sliding mechanism, as shown in Figure 18. As shown in Figure 19, each device piece 13A is provided with a protrusion 81 and a groove 82 on opposing outer positions in a plan view of the substrate 23 (outer frame 25). That is, the protrusion 81 that protrudes from the substrate 23 in the joining direction constitutes the joining portion, and the groove 82 that is recessed in the substrate 23 in the joining direction constitutes the part to be joined.

[0080] As in this embodiment, by providing a ridge 81 and a groove 82 on opposing outer surfaces of the substrate 23, the ridge 81 can be fitted into the groove of an adjacent device piece 13A in a sliding manner, making it easy to firmly and smoothly connect multiple device pieces 13A. In this embodiment, the cross section perpendicular to the longitudinal direction of the ridge 81 is wedge-shaped (i.e., the thickness of the side on the tip side that is separated from the substrate 23 is greater than the thickness of the base end side that connects to the outer frame 25), and the groove 82 is shaped to match, so that the connection between the device pieces 13A is not easily detached in the connection direction.

[0081] (Fifth embodiment) The cell culture device 14 according to the fifth embodiment has a configuration in which adjacent device pieces 14A are connected by magnetic force, as shown in Figure 20. By using a configuration that connects by magnetic force as in this embodiment, adjacent device pieces 14A can be easily and quickly connected and combined.

[0082] As shown in Figure 21, each device piece 14A is equipped with two columnar magnets 83A, 83B and two columnar magnets 84A, 84B, respectively, which serve as a coupling portion and a coupled portion, with one end face of each magnet exposed on the opposite outer surface of the substrate 23 (outer frame 25) in a plan view. By making magnets 83A and 84A opposite polarity to each other on the outer surface of the substrate 23, and magnets 83B and 84B opposite polarity to each other on the outer surface of the substrate 23, the magnets 83A and 83B provided on the substrate 23 constitute the coupling portion (or coupled portion), and the magnets 84A and 84B provided on the substrate 23 constitute the coupled portion (or coupling portion). In this embodiment, each magnet 83A, 83B, 84A, and 84B is inserted and fixed into a hole formed in the substrate 23 (outer frame 25), and one end face of each magnet is exposed in a state that is substantially flush with the outer surface of the outer frame 25.

[0083] In this embodiment, magnets 83A and 84A are attracted to and coupled to each other by magnetic force on the outer surface of the substrate 23 (outer frame 25), and magnets 83B and 84B are attracted to and coupled to each other by magnetic force. In this way, the substrate 23 is coupled at two points on one side, so that the coupling positions of the coupling part and the coupled part are less likely to shift. Furthermore, in this embodiment, magnets 83A and 83B have opposite magnetic poles on the outer surface of the substrate 23 (outer frame 25), so it is easier to balance the magnetic forces at the two coupling positions.

[0084] The types of magnets 83 (83A, 83B) and magnets 84 (84A, 84B) used in this embodiment are not particularly limited, but for example, neodymium magnets, ferrite magnets, samarium cobalt magnets, alnico magnets, etc. can be used. Among these, magnets with strong magnetic force are preferable so that the connection does not come undone even if the bonding part and bonded part are small, so it is desirable to use neodymium magnets.

[0085] In this embodiment, magnets 83A and 84A are composed of magnets having different magnetic properties, but they can be coupled by magnetic force, and one may be composed of a magnet and the other of a magnetic material that bonds with the magnet.

[0086] In addition to the configuration shown in Figure 21, as shown in Figure 22, elongated rod-shaped magnets 85A and 85B may be embedded in the outer frame 25 along two parallel sides of the outer frame 25. In this case, it is not necessary for both end faces of the rod-shaped magnets to be exposed on the outer surface of the outer frame 25, and as shown in Figure 23, the end faces of the rod-shaped magnets 86A and 86B do not need to be exposed from the outer frame 25. Furthermore, the end faces of the rod-shaped magnets 86A and 86B may be embedded in the outer frame 25. Moreover, the manner in which the magnets are embedded is not limited to those shown in Figures 20 to 23, and a configuration in which the side surface along the longitudinal direction of the elongated rod-shaped magnet is exposed from the opposing outer surface of the substrate 23 is also possible.

[0087] [Other embodiments] Other embodiments of the cell culture set, cell characteristic detection set, and cell culture device according to the present invention will be described. Note that the configurations disclosed in each of the following embodiments can be applied in combination with configurations disclosed in other embodiments, provided that this does not result in a contradiction.

[0088] In the first to fifth embodiments described above, specific bonding and bonding parts having particular structures were explained as examples. However, in the present invention, the structures of the bonding and bonding parts are not limited to the specific bonding structures described above, and various bonding types can be used, including conventionally known bonding methods. Furthermore, the combination and formation methods of the bonding and bonding parts are not limited, such as whether to provide a bonding or bonding part on each piece. Moreover, in the present invention, the bonding part provided on at least one of the cell culture part and the container part, and the bonding part that is bonded to the bonding part, may be provided with anti-slip structures such as ribs on the outer surface of the bonding part that is in contact with the bonding part and on the inner surface of the bonding part that is in contact with the bonding part.

[0089] In the first embodiment described above, a configuration in which four cell culture units and four container units are joined together was described as an example. In the second embodiment, a configuration in which twelve cell culture units and twelve container units are joined together was described as an example. In the third embodiment, a configuration in which four cell culture units are joined together was described as an example. However, the number of each cell culture unit or container unit joined together is not limited in the present invention. For example, there may be three or fewer, five to eleven, or thirteen or more. Furthermore, the shape of the joined cell culture device is not limited to a linear or rectangular shape in plan view, as in the first to third embodiments, but may be various shapes such as a stepped shape.

[0090] In the first to fifth embodiments described above, a configuration was described in which the connecting portion or the connected portion is provided at opposing positions on the substrate or container. However, the configuration is not limited thereto, and at least one of the connecting portion and the connected portion may be provided on two adjacent sides. Furthermore, the number of connecting portions and connected portions is not limited.

[0091] In the first and second embodiments described above, a configuration in which the cell culture section and the container section have a substantially rectangular shape in plan view was described as an example, and in the third to fifth embodiments described above, a configuration in which the cell culture section has a substantially rectangular shape in plan view was described as an example. However, the shape of the cell culture section and the container section in plan view is not limited to a rectangular shape as long as at least one of the cell culture section and the container section can be joined, and may be triangular, a polygon with pentagons or more, or other shapes. Furthermore, in the first and second embodiments described above, a configuration in which the shape and dimensions of the cell culture section and the container section to be combined are substantially the same in plan view was described as an example. However, in the present invention, it is sufficient that the pair of supports 30 of each cell culture section and the recesses 54 of each container section are in corresponding positions, and the shapes of the cell culture section and the container section to be combined may be different in plan view.

[0092] In the first and second embodiments described above, a configuration in which the cell culture set is applied to the cell characteristic detection set was explained as an example. However, the cell culture set of the present invention is not limited to cell characteristic detection, as shown in the third embodiment, and can be used for any application including the cell culture process. The cell culture set of the present invention does not need to be used in all of the cell culture process, but may be used in at least some of the steps.

[0093] In the third to fifth embodiments described above, a configuration was explained in which the substrate 23 of each device piece 12A has both a connecting portion (such as a projection 26) and a connected portion (such as a locking hole 27). However, in the cell culture device according to the present invention, it is sufficient that the connected body of the substrate 23 as a whole has both a connecting portion and a connected portion, and individual device pieces 12A do not need to have both a connecting portion and a connected portion.

[0094] In the third to fifth embodiments described above, a configuration was described in which the connecting portion (protrusion, etc.) and the connected portion (connected portion, etc.) are provided on the substrate side of the cell culture device 12, and the connecting portion and connected portion are not provided on the container side. However, in the present invention, the connecting portion and connected portion may be provided on the container side (template container, culture container, observation container, etc.).

[0095] In the third to fifth embodiments described above, a configuration was described in which the engaging projection 42 of the mounting member 40 has a chamfered portion 42A that is chamfered in an R-shape. However, in the present invention, the presence or absence and form of the chamfer are arbitrary.

[0096] In the third to fifth embodiments described above, part or all of the inner surface of the recess 91 of the device piece 12A and the container 90 may be subjected to a non-specific adsorption inhibition treatment for cells.

[0097] In the third to fifth embodiments described above, an engagement recess opening to the side was provided in the substrate body, and a mounting member was described as an example in which the mounting member engages with this recess. However, the direction in which the engagement recess provided in the substrate body is open is not limited. For example, as shown in Figure 17, an engagement recess 29A opening upward may be provided in the mounting portion 29 of the substrate body 24. Alternatively, an engagement recess opening downward may be provided in the substrate body. Even when an engagement recess opening downward is provided in the substrate body, interference between the support and the substrate is less likely when fixing the support to the substrate.

[0098] With regard to other configurations, the embodiments disclosed herein are illustrative in all respects, and it should be understood that the scope of the present invention is not limited thereto. Those skilled in the art will readily understand that modifications can be made as appropriate without departing from the spirit of the invention. Therefore, other embodiments modified without departing from the spirit of the invention are naturally included within the scope of the present invention. [Industrial applicability]

[0099] The present invention can be used, for example, as a cell culture set or cell culture device for detecting the characteristics of cells. [Explanation of Symbols]

[0100] (First Embodiment) 1: Cell culture set 10: Cell culture devices 10A, 10B, 10C, 10D: Device piece (cell culture section) 20: Circuit board 21:Joining part (protrusion) 22: Joined part (recessed part) 30:Support 50: Container 50A, 50B, 50C, 50D: Container piece (container part) 51:Joining part (protrusion) 52: Joined part (locking hole) 54: Recess 54a: Inner surface 55:Liquid 100: Cell characteristic detection set (Second embodiment) 60: Cell culture devices 60A~60L: Device piece (cell culture section) 70: Container 70A~70L: Container piece (container part) (Third embodiment) 2: Cell culture set 12: Cell culture devices 12A: Device piece (cell culture section) 23: Circuit board 24: Main board 25: Outer frame 26:Protrusion (joint part) 27: Locking hole (joint part) 28: Mounting part 28A: Engagement recess 31:Support 32: Mounting part 32a: opening 33: Distraction part G:Gap 40: Mounting parts 41: Mounting unit 42: Engagement convex part 42A: Chamfered part 90: Container 91: Recess 91A Mold recess (Fourth embodiment) 81: Projection (joint part) 82: Groove (part to be joined) (Fifth embodiment) 83: Magnet (connecting part) 84: Magnet (coupled part)

Claims

1. A cell culture section comprising a substrate and a pair of elastically deformable resin supports suspended from the substrate, wherein cell aggregates can be cultured between the pair of supports, A container portion capable of accommodating at least a portion of the pair of supports together with the culture medium, A connecting portion provided in at least one of the cell culture section and the container section, A cell culture set having a binding portion and a binding portion having a structure that can bind to the aforementioned binding portion.

2. The cell culture set according to claim 1, wherein the connecting portion is a projection that protrudes in the direction of connection, and the connected portion is a recess that is recessed in the direction of connection.

3. The cell culture set according to claim 1, wherein the connecting portion is a projection protruding from the outer surface of the substrate or the container portion, and the connected portion is a locking hole formed on the outer surface of the substrate or the container portion.

4. The cell culture set according to claim 1, wherein at least one of the bonding portion and the bonded portion is provided at opposing positions on the substrate or the container portion.

5. A cell characteristics detection set comprising a cell culture set according to any one of claims 1 to 4, At least a portion of the pair of supports holding the cell aggregates is housed in the container portion into which the culture medium is introduced. A cell characteristic detection set that enables the detection of the characteristics of the cell aggregate by detecting the amount of displacement of the support from outside the cell culture set.

6. A cell culture device comprising a substrate and a pair of elastically deformable resin supports suspended from the substrate, wherein cell aggregates can be cultured between the pair of supports, A coupling portion provided on the substrate, A cell culture device comprising a substrate provided with a bonded portion having a structure capable of being bonded to the bonding portion.

7. The cell culture device according to claim 6, wherein the bonding portion is a ridge protruding from the substrate in the bonding direction, and the bonded portion is a groove recessed in the bonding direction of the substrate.

8. The cell culture device according to claim 6, wherein the bonding portion is composed of a magnet provided in the bonding direction of the substrate, and the bonded portion is composed of a magnet or magnetic material provided in the bonding direction of the substrate.

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