Cell characteristic detection device and cell characteristic detection kit

Abstract

A cell characteristic detection device (10) is provided with a substrate (20) and a pair of resin supports (30) provided perpendicularly from the substrate (20) so as to be elastically deformable. The cell characteristic detection device (10) is capable of detecting the amount of displacement ([Delta] W) of the supports (30) from the outside in a state in which a cell aggregate (15) is held between the pair of supports (30) by the pair of supports (30).

Description

Technical Field

[0001] This invention relates to devices and kits for detecting cell characteristics. Background Technology

[0002] Cell characteristic detection devices are known for detecting the properties of cells. For example, Patent Document 1 discloses a cell characteristic detection device that can detect the contractile properties of muscle cells held on a collagen-based support having a long strip by using a strain gauge connected to a connecting portion at one end of the strip.

[0003] Existing technical documents

[0004] Patent documents

[0005] Patent document 1: Japanese Patent Application Publication No. 2011-030574. Summary of the Invention

[0006] The problem that the invention aims to solve

[0007] In the cell characteristic detection device of Patent Document 1, the cell support is mainly composed of collagen. In addition, since it is used with the entire support immersed in a liquid containing a compound, there is a problem that non-specific adsorption of the compound is likely to occur.

[0008] Therefore, it is desirable to realize a device for detecting cell characteristics that are difficult to adsorb nonspecifically into compounds.

[0009] Methods for solving problems

[0010] The cell characteristic detection device of the present invention is characterized in that the cell characteristic detection device comprises: Substrate; and A pair of resin supports, which are elastically deformable and vertically disposed from the substrate. With the cell aggregate held between the pair of supports, the cell characteristic detection device can detect the displacement of the supports from the outside.

[0011] According to this configuration, only the front end of the vertically positioned support in the cell characteristic detection device can be immersed in the liquid. Moreover, since the support is made of resin, the compound is unlikely to undergo non-specific adsorption in terms of both contact area and material.

[0012] Furthermore, the cell characteristic detection kit of the present invention includes: the aforementioned cell characteristic detection device; and

[0013] container, The inner surface of the container was treated to inhibit non-specific cell adsorption.

[0014] According to this configuration, since a container with a treatment applied to its inner surface to inhibit non-specific adsorption of cells is used, non-specific adsorption of cells to the container is difficult to occur while ensuring that cell aggregates are adsorbed onto the device for detecting cell characteristics.

[0015] The 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.

[0016] As one approach for the aforementioned cell characteristic detection devices... The pair of supports is preferably a pair of membranes arranged opposite each other.

[0017] Based on this configuration, by changing the thickness of a pair of membranes, the resolution of displacement measurement and the maximum displacement measurement can be easily changed.

[0018] As one approach for the aforementioned cell characteristic detection devices... Preferably, the pair of membranes are made of a resin material with a Young's modulus of 100 MPa or more and 4500 MPa or less, and the pair of membranes have a thickness of 5 μm or more and 400 μm or less.

[0019] Based on this configuration, the resolution of displacement measurement and the maximum displacement to be measured can be set to more appropriate values.

[0020] In one preferred embodiment of the aforementioned cell characteristic detection device, the pair of supports comprises: a support body extending downward from the substrate; and a curved end formed by bending the lower end of the support body.

[0021] Based on this configuration, the cell aggregates can be stably maintained using the curved ends.

[0022] As one approach for the aforementioned cell characteristic detection devices... Preferably, the pair of supports are made of polystyrene-based resin, polypropylene-based resin, or polyethylene-based resin.

[0023] Based on this composition, it is even more difficult for compounds to undergo non-specific adsorption onto devices used for detecting cell characteristics.

[0024] As one approach for the aforementioned cell characteristic detection devices... The cell aggregates are preferably skeletal muscle cell aggregates, cardiomyocyte aggregates, or smooth muscle cell aggregates.

[0025] Based on this configuration, by using a cell characteristic detection device that makes it difficult for compounds to undergo non-specific adsorption, it is possible to detect the muscle contraction characteristics of skeletal muscle cell aggregates, cardiomyocyte aggregates, or smooth muscle cell aggregates with higher precision.

[0026] As one approach for the aforementioned cell characteristic detection devices... Preferably, an abutment is provided in the region on the substrate side between the pair of supports, the abutment being able to abut against the pair of supports from the inside when the cell aggregate contracts.

[0027] According to this configuration, a pair of supports that deform due to the contraction of the cell aggregates abut against each other, with the abutments acting as a resistance to the contraction of the cell aggregates. As a result, the device for detecting cell characteristics enables the vigorous growth of cell aggregates.

[0028] As one approach for the aforementioned cell characteristic detection devices... Preferably, a plurality of abutments of different lengths from each other are detachably disposed on the substrate.

[0029] According to this configuration, the resistance of the contact body to the shrinking cell aggregate varies depending on the length of the contact body. Therefore, a resistance matching the culture conditions of the cell aggregate is applied to the shrinking cell aggregate.

[0030] Other features and advantages of the invention will become clearer from the following description of exemplary and non-limiting embodiments with reference to the accompanying drawings. Attached Figure Description

[0031] Figure 1 This is a perspective view of the cell characteristic detection device of the cell characteristic detection kit according to the first embodiment.

[0032] Figure 2 This is a perspective view of the container of the cell characteristic detection kit according to the first embodiment.

[0033] Figure 3 This is a schematic diagram of the cell characteristic detection kit and cell aggregates according to the first embodiment.

[0034] Figure 4 This is a perspective view of the support body according to the second embodiment.

[0035] Figure 5 This is a cross-sectional view of the cell characteristic detection kit according to the third embodiment, showing the abutment mounted on the substrate.

[0036] Figure 6 This is a cross-sectional view of the cell characteristic detection kit according to the third embodiment, showing the length ratio from the substrate. Figure 5The diagram shows the abutment body of a certain length mounted on a substrate.

[0037] Figure 7 This is a perspective view of the support structure in other implementation methods. Detailed Implementation

[0038] 1. First Implementation Method

[0039] Hereinafter, the cell characteristic detection kit 100 of the first embodiment will be described with reference to the accompanying drawings. The cell characteristic detection kit 100 includes a cell characteristic detection device 10 and a container 50. Figure 1 This is a three-dimensional view of the cell characteristic detection device 10. Figure 2 This is a 3D diagram of container 50. Figure 3 This is a schematic diagram of the cell characteristic detection kit 100 and the cell aggregate 15. The cell characteristic detection device 10, which detects the characteristics of cells, specifically the characteristics of the cell aggregate 15, includes a substrate 20 and a pair of resin supports 30 that are elastically deformable and vertically disposed from the substrate 20. Furthermore, the cell characteristic detection device 10 can detect the displacement of the supports 30 from the outside while the cell aggregate 15 is held between the supports 30. Figure 3 The displacement ΔW is shown. It should be noted that a cell aggregate refers to a block of cells formed by the aggregation of multiple cells.

[0040] In this embodiment, the substrate 20 is a rectangular resin plate with four rectangular through holes 22 arranged along its length and extending through its thickness. On both sides of the through holes 22 along their length, a base plate portion 24 is provided, facing the center of the through hole 22 and supported in a cantilevered manner. The base plate portion 24 has a support body 30 vertically disposed downwards. Figure 1 As shown, in this embodiment, the support bodies 30, vertically mounted on the base plate portion 24 on both sides of a through hole 22, are arranged in pairs. Furthermore, in this embodiment, four groups consisting of pairs of support bodies 30 are provided. Here, "vertically mounted" means mounted in a downward drooping manner. Figure 1 In the example, the pair of supports 30 are arranged in a vertically downward manner, but are not limited to this. For example, they can be arranged at an angle of ±10 degrees to ±20 degrees relative to the vertical.

[0041] The support 30 can be integral with the substrate 20, or it can be detachably disposed on the bottom plate portion 24 of the substrate 20. Here, for example... Figure 3 As shown, the orientation of the pair of supports 30 is designated as direction X1. In this embodiment, the length direction of the substrate 20 is the same as direction X1. Preferably, the pair of supports 30 are made of polystyrene-based resin, polypropylene-based resin, or polyethylene-based resin.

[0042] like Figure 2 As shown, a recess 52 containing liquid 55 is provided in the container 50. The container 50 in this embodiment is a cast container made of plastic, metal, or glass. The cast container is used to hold the cell aggregates 15 within the device; it is a container used to aggregate cells into an aggregate form. Multiple recesses 52 are provided in the container 50. The number of recesses 52 is preferably a multiple of the number of pairs of supports 30 corresponding to each cell characteristic detection device 10 (in this example, "4"). In this embodiment, eight recesses 52 are provided. In this case, two cell characteristic detection devices 10 are mounted in one container 50.

[0043] Figure 3 This is a diagram showing the detection of the displacement ΔW of the support 30, i.e., the measurement of the displacement of the cell aggregate 15. Figure 3 In the diagram, double-dotted lines represent cell aggregates 15 and supports 30 whose front ends are bent due to the contraction of cell aggregates 15. Cell aggregates 15 are, for example, skeletal muscle cell aggregates, cardiomyocyte aggregates, or smooth muscle cell aggregates induced from the differentiation of artificial pluripotent stem cells. Preferably, the cell characteristic detection device 10 is also used to culture cell aggregates 15. More preferably, the cell characteristic detection device 10 is also used for the differentiation induction and maturation of cell aggregates 15. For example, the cell aggregates 15 before differentiation induction are attached to the respective front ends of a pair of supports 30 of the cell characteristic detection device 10. Then, the front ends of the pair of supports 30 and the cell aggregates 15 before differentiation induction are immersed in a liquid culture medium in a culture container (not shown), allowing the cell aggregates 15 to cross-link between the pair of supports 30 while differentiation induction is performed, thereby holding the target cell aggregate 15, such as a cardiomyocyte aggregate, between the pair of supports 30.

[0044] In this embodiment, the pair of supports 30 are a pair of membranes arranged opposite each other. For example... Figure 3 As shown, the pair of supports 30 serving as the membrane body are each in the shape of a thin film, having a width B1, a thickness H1, and a length L1 from the base plate portion 24 to the front end. The pair of supports 30 are perpendicularly disposed from the substrate 20 with their thickness direction aligned with direction X1, and their front end sides (lower ends) are bent along the thickness direction, allowing them to elastically deform in direction X1, which connects the pair of supports 30 to each other. Therefore, if the cell aggregate 15 held by the pair of supports 30 contracts, it elastically deforms in the direction X1, where the two front ends of the pair of supports 30 are close together. If the displacement of one side of the support 30 in direction X1 is defined as ΔW, then the displacement of the cell aggregate 15 in direction X1 is twice ΔW.

[0045] If the maximum displacement that the support 30 can elastically deform is set as the maximum displacement ΔWmax to be measured, then the change in the maximum displacement ΔWmax and the resolution can be achieved by changing the thickness H1, without changing the measuring instrument for detecting the displacement ΔW, the resin material of the support 30, the length L1 of the support 30, or the width B1 of the support 30. Preferably, the pair of supports 30 serving as the membrane body are made of a resin material with a Young's modulus E of 100 MPa or more and 4500 MPa or less. More preferably, they are made of a resin material with a Young's modulus E of 300 MPa or more and 4300 MPa or less. Even more preferably, they are made of a resin material with a Young's modulus E of 400 MPa or more and 4000 MPa or less. In addition, it is preferable that the pair of supports 30 have a thickness H1 of 5 μm or more and 400 μm or less. More preferably, they have a thickness H1 of 7 μm or more and 200 μm or less. Even more preferably, they have a thickness H1 of 8 μm or more and 100 μm or less. It should be noted that the Young's modulus E in this instruction manual is the value measured at 25℃ (room temperature).

[0046] When the pair of supports 30 serving as the membrane body are made of polystyrene-based resin, the Young's modulus E is preferably 3000 MPa or more and 4000 MPa or less, and the thickness H1 is preferably 40 μm or more and 55 μm or less. When the pair of supports 30 serving as the membrane body are made of polypropylene-based resin, the Young's modulus E is preferably 1500 MPa or more and 2500 MPa or less, and the thickness H1 is preferably 50 μm or more and 65 μm or less. Specific examples of the pair of supports 30 serving as the membrane body are given in Table 1, which shows the Young's modulus E, the measured maximum displacement ΔWmax, the length L1, the width B1, and the thickness H1 of Example 1 (a support 30 made of polystyrene) and Example 2 (a support 30 made of polypropylene).

[0047] Table 1

[0048] The resolution can also be changed by altering the measuring device for detecting displacement ΔW. In this embodiment, the cell characteristic detection kit 100 has a transparent or semi-transparent container 50, and an optical microscope 60 capable of measuring the displacement ΔW of the support 30 is located below the container 50. The optical microscope 60 corresponds to the measuring device for detecting displacement ΔW. A transparent or semi-transparent liquid 55 is contained in the container 50. Illumination is preferably provided above the container 50. The liquid 55 is, for example, a liquid containing low-molecular-weight compounds. By measuring the displacement ΔW of the support 30 and acquiring it as tension information, it is possible to evaluate the effects (toxicity) of the compound on cardiomyocyte aggregates, evaluate the efficacy of the compound in disease models of cardiomyocyte aggregates, and explore the most suitable compound for inducing differentiation into cardiomyocyte aggregates.

[0049] Return to Figure 2 The inner surface 52a of the recess 52 in the container 50 is subjected to a treatment that inhibits non-specific adsorption of cells. This treatment inhibits non-specific adsorption of cells refers to the treatment that inhibits non-specific adsorption of cells. The treatment that inhibits non-specific adsorption of cells can be carried out, for example, by a hydrophilization treatment. More specifically, the treatment that inhibits non-specific adsorption of cells can be carried out by a treatment that includes at least one group selected from the group group represented by the following formulas (1), (2), (3) and (4).

[0050]

[0051] Here, in equation (1), R 12 It represents an NH or oxygen atom. m is an integer from 0 to 4. R 13 It can be a hydrogen atom, a hydroxyl group, or a methoxy group. In formula (3), R 32 It can be a hydrogen atom or a methyl group. n is an integer from 2 to 100.

[0052] Furthermore, the treatment to inhibit non-specific adsorption of cells can be carried out by forming a coating in the recess 52, which is mainly composed of a polymer containing specific hydrophilic constituent units. Here, the hydrophilic constituent units in the polymer that is the main body of the coating can include at least one constituent unit selected from the group consisting of constituent units represented by the following formulas (5), (6), (7) and (8).

[0053]

[0054] Here, Represents the key. In equation (5), R 11 It can be a hydrogen atom or a methyl group. R 12 It represents an NH or oxygen atom. m is an integer from 0 to 4. R 13 It can be a hydrogen atom, a hydroxyl group, or a methoxy group. In formula (6), R 21 It can be a hydrogen atom or a methyl group. In formula (7), R 31 It can be a hydrogen atom or a methyl group. R 32 It can be a hydrogen atom or a methyl group. n is an integer from 2 to 100.

[0055] As an example, regarding the constituent unit represented by equation (5), as R 11 Monomers that are hydrophilic building blocks when the hydrogen atom is present are examples of raw materials, such as N-(2-hydroxyethyl)acrylamide (HEAA). Additionally, as R... 11 Monomers that are hydrophilic constituents when methyl is used, for example, 2-hydroxyethyl methacrylate (HEMA).

[0056] In addition, the hydrophilic constituent units in the polymer that forms the main body of the coating may include constituent units represented by the following formula (9).

[0057]

[0058] Here, Represents the key. In equation (9), R 41 It is an alkyl group having a carbonyl group and an amino group. p is an integer from 1 to 1000. q is an integer from 40 to 4995. r is an integer from 0 to 4000. s is an integer from 1 to 3.

[0059] The polymer that forms the body of the coating may also contain hydrophobic constituent units. In this case, the hydrophobic constituent units may include at least one constituent unit selected from the group consisting of constituent units represented by the following formulas (10) and (11).

[0060]

[0061] Here, Represents the key. In equation (10), R 51 It can be a hydrogen atom or a methyl group. R 52 It is a straight-chain or branched alkyl group having 1 to 10 carbon atoms, an alicyclic alkyl group having 3 to 8 carbon atoms, or a combination thereof. In formula (11), R 61 It can be a hydrogen atom or a methyl group.

[0062] As examples, alkyl groups with 1 to 10 carbon atoms, whether straight-chain or branched, include methyl, ethyl, propyl, methylethyl, butyl, 1,2-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, and hexyl. Alicyclic alkyl groups with 3 to 8 carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0063] The total content of hydrophilic constituent units in the polymer that forms the coating is preferably 10 mol% or more. The total content of hydrophilic constituent units is preferably 20 mol% or more and 80 mol% or less, more preferably 30 mol% or more and 70 mol% or less. Furthermore, the total content of hydrophobic constituent units in the polymer is preferably 90 mol% or less. The total content of hydrophobic constituent units is preferably 40 mol% or more and 80 mol% or less, more preferably 50 mol% or more and 70 mol% or less.

[0064] In addition to the hydrophilic and hydrophobic constituent units mentioned above, the polymer that forms the main body of the coating may also include crosslinking constituent units. The content of crosslinking constituent units may be, for example, 0.05 mol% or more and 20 mol% or less, preferably 0.5 mol% or more and 10 mol% or less.

[0065] With this coating, the contact angle between the inner surface 52a of the recess 52 and pure water is 3° or more and 90° or less at 25°C (room temperature). By hydrophilizing the inner surface 52a of the recess 52, non-specific adsorption of compounds onto the inner surface 52a of the recess 52 can be suppressed. It should be noted that in order to make the contact angle less than 3°, the processing required becomes complicated, which is sometimes not preferable from a cost perspective. On the other hand, if the contact angle is greater than 90° and too large, the degree of hydrophilicity decreases, and the ability to suppress non-specific adsorption of compounds may decrease. By setting the contact angle to 3° or more and 90° or less, non-specific adsorption of compounds onto the inner surface 52a of the recess 52 can be suppressed at a lower cost.

[0066] The contact angle between the inner surface 52a of the recess 52 and pure water is preferably 5° or more, and more preferably 8° or more. Furthermore, the contact angle between the inner surface 52a of the recess 52 and pure water is preferably 80° or less, and more preferably 70° or less.

[0067] 2. Second Implementation Method

[0068] The following is for reference Figure 4 The support 30 of the second embodiment will be described. In this embodiment, the shape of the support 30 differs from that of the first embodiment described above. Hereinafter, the description will focus on the differences from the first embodiment. It should be noted that aspects not specifically described are the same as in the first embodiment. The pair of supports 30 have a support body portion 32 extending downward from the substrate 20, and a bent end portion 34 formed by bending the lower end of the support body portion 32. In addition, in this embodiment, a recess 36 is provided on the support body portion 32. By providing this recess 36, the cell aggregate 15 held by the pair of supports 30 can be aggregated as a whole. Therefore, the thickness of the cell aggregate 15 near the recess 36 increases, and when the cell aggregate 15 pulsates, stress is less likely to concentrate locally on the cell aggregate 15, resulting in the cell aggregate 15 being less likely to be damaged. Specifically, as Figure 4As shown, the pair of supports 30 are a pair of membranes arranged opposite each other, and the curved ends 34 are formed by bending the lower ends of the support body 32 of the membrane. The support body 32 has recesses 36 on both sides in the width direction. By placing the cell aggregates 15 on the curved ends 34, the cell aggregates 15 can be stably held by the pair of curved ends 34 of the pair of supports 30. The pair of curved ends 34 can be formed by bending the lower ends of the support body 32 in a direction separating them from each other, or by bending them in a direction approaching each other. Preferably, by placing the cell aggregates 15 on the pair of curved ends 34 and culturing them, the cultured cell aggregates 15 surround the pair of curved ends 34. In this way, the cell aggregates 15 can be held more stably.

[0069] 3. Third Implementation Method

[0070] The following is for reference Figure 5 and Figure 6 The cell characteristic detection kit 100 of the third embodiment is described. Figure 5 This is a cross-sectional view of the cell characteristic detection kit 100 according to the third embodiment, which shows the abutment 70 mounted on the substrate 20. Figure 6 This is a cross-sectional view of the cell characteristic detection kit 100 according to the third embodiment, showing the length ratio from the substrate 20. Figure 5 The diagram shows a longer abutment 70 mounted on a substrate 20.

[0071] The cell characteristic detection kit 100 of the third embodiment differs from the cell characteristic detection kit 100 of the first and second embodiments in that the cell characteristic detection device 10 also has an abutment 70. Hereinafter, the description will focus on the differences from the first and second embodiments. It should be noted that aspects not specifically described are the same as in the first and second embodiments.

[0072] like Figure 5 As shown, the abutment 70 is disposed in the region on the side of the substrate 20 between the pair of supports 30, so that it can abut against the pair of supports 30 from the inside when the cell aggregate 15 contracts. The region on the side of the substrate 20 refers to the region between the substrate 20 and the cell aggregate 15. The spacing between each support 30 and the abutment 70 is set such that each support 30 deforms due to the contraction of the cell aggregate 15 and abuts against the abutment 70. Figure 5In the example, the abutment 70 is mounted on the substrate 20 to droop from the substrate 20 toward the cell aggregate 15 in the region between the pair of supports 30. It should be noted that if the abutment 70 is located in the region on the substrate 20 side between the pair of supports 30, the abutment 70 can be mounted in a location other than the substrate 20. Furthermore, a single abutment 70 may not necessarily abut against both of the pair of supports 30. For example, a pair of abutments 70 can be provided, and each abutment 70 can abut against different supports 30.

[0073] Due to the contraction of the cell aggregate 15, the pair of supports 30 elastically deform, starting from the portion of each support 30 on the substrate 20 side, so that the lower ends of each support 30 approach each other. Due to the deformation of the supports 30 caused by the contraction of the cell aggregate 15, the abutment 70 abuts against each of the pair of supports 30. The abutment 70, deformed by the contraction of the cell aggregate 15, abuts against the pair of supports 30, thereby inhibiting the deformation of the pair of supports 30. Therefore, the abutment 70 becomes a resistance to the contraction of the cell aggregate 15. As a result, for example, when using a normal cell line, the cell aggregate 15 grows vigorously by applying resistance to the contracted cell aggregate 15. On the other hand, when using a diseased cell line, the cell aggregate 15 grows weakly by applying resistance to the contracted cell aggregate 15.

[0074] Preferably, the abutment 70 is detachably mounted on the substrate 20. This allows the abutment 70 to be removed when no resistance is needed for the shrinking cell aggregates 15, thus preventing resistance from being applied to the shrinking cell aggregates 15. Therefore, the presence or absence of resistance to the shrinking cell aggregates 15 can be switched depending on the degree of culture of the cell aggregates 15.

[0075] Preferably, there are multiple abutment bodies 70 that can be freely attached and detached from the substrate 20. Furthermore, it is preferable that the multiple abutment bodies 70 have different lengths from the substrate 20. The length of the abutment body 70 from the substrate 20 is the length from the lower surface of the bottom plate portion 24 of the substrate 20 to the lower end of the abutment body 70. The longer the distance from the substrate 20, the further away the support body 30 abuts against the abutment body 70 (i.e., closer to the cell aggregate 15) when the cell aggregate 15 shrinks. Therefore, the resistance exerted by the abutment body 70 on the shrinking cell aggregate 15 varies with the length of the abutment body 70, increasing as the length of the abutment body 70 increases. As a result, by mounting abutment bodies 70 of a length that matches the culture conditions of the cell aggregate 15 onto the substrate 20, it is possible to apply an appropriate amount of resistance to the shrinking cell aggregate 15, corresponding to the culture conditions of the cell aggregate 15.

[0076] Specifically, Figure 6 The length L3 of the contact body 70 from the substrate 20 is shown to be... Figure 5The abutment 70 shown is a distance L2 from the substrate 20. If... Figure 6 As shown, the length L3 of the contact body 70 from the substrate 20 is greater than that of the contact body 70. Figure 5 The distance L2 between the contact body 70 and the substrate 20 is long, so when the cell aggregate 15 contracts, Figure 6 The abutment 70 shown is in contact with Figure 5 The abutment 70 shown is located closer to the cell aggregate 15 than the support 30. Therefore, Figure 6 The abutment 70 shown applies force to the contracted cell aggregate 15. Figure 5 The abutment 70 shown has greater resistance.

[0077] During culture, the cell aggregates 15 grow stronger or weaker in a shorter time by gradually increasing the resistance applied during their contraction. Therefore, by sequentially replacing the contact points 70 with shorter distances from the substrate 20 to longer distances from the substrate 20 when culturing the cell aggregates 15, strong or weak cell aggregates 15 can be cultured efficiently.

[0078] 4. Other implementation methods

[0079] (1) In the first embodiment described above (refer to) Figure 3 The following description uses an optical microscope 60 to measure the displacement ΔW of the support 30 from below a transparent or semi-transparent container 50 as an example. However, the description is not limited to this example; for instance, the optical microscope 60 can also measure the displacement ΔW from the side of the transparent container 50. Furthermore, the measuring instrument for detecting the displacement ΔW can be any instrument other than an optical microscope. Additionally, for example, by connecting a strain gauge to the support 30, the displacement ΔW of the support 30 can be detected from the outside. Furthermore, the container 50 does not necessarily need to be transparent; any cell characteristic detection kit 100 capable of detecting the displacement ΔW from the outside is acceptable.

[0080] (2) In the first embodiment described above (refer to) Figure 1 The example described in the document is a pair of membranes with a pair of supports 30 arranged opposite each other. However, it is not limited to this example; for example, the shape of the supports 30 can also be cylindrical or prismatic.

[0081] (3) In the second embodiment described above (refer to) Figure 4 The diagram illustrates a support 30 with a recess 36 and a curved end 34. However, as... Figure 7As shown, for the support body 30, the support main body 32 can be formed as a flat surface, and a cutout 37 can be provided in the support main body 32. The cutout 37 is formed on the side of the support main body 32 in the width direction. According to this configuration, in the support main body 32, the portion further to the front end than the cutout 37 can be easily bent, and a bent portion corresponding to the bent end 34 described in the second embodiment can be easily formed afterwards. Furthermore, by bending the portion of the support main body 32 further to the front end than the cutout 37, the cell aggregate 15 is retained in the bent portion. Preferably, in the support main bodies 32 facing each other, the portion of each support main body 32 further to the front end than the cutout 37 is bent perpendicularly in the direction of approaching each other. Thus, similarly to the second embodiment, the cell aggregate 15 can be stably retained. Here, it is preferable that the cutout 37 is formed at a position 0.5 mm to 2.0 mm away from the front end of the support main body 32.

[0082] Figure 7 The example support 30 has a recess 36 and a cutout 37. Figure 7 The depression 36 shown is Figure 4 Similarly, the recesses 36 shown are formed on both sides of the support body 32 in the width direction. On the other hand, Figure 7 The length of the recess 36 shown is longer than the length of the recess in the longitudinal direction. Figure 4 The recess 36 shown is shorter in the longitudinal direction. The cut portion 37 is formed by cutting triangularly on both sides in the width direction, which are closer to the front end of the recess 36 in the supporting body portion 32. It should be noted that the position, size, and shape of the recess 36 and the cut portion 37 can be appropriately determined according to the type of cell aggregate 15.

[0083] (4) In the first embodiment described above (refer to) Figure 1 In this paper, cell aggregate 15 is described as an example of a skeletal muscle cell aggregate, cardiomyocyte aggregate, or smooth muscle cell aggregate prepared by differentiation-induced artificial pluripotent stem cells (iPS cells). However, it is not limited to this example. For example, cell aggregate 15 may also be a myocyte aggregate, adipocyte aggregate, osteocyte aggregate, nerve cell aggregate, epithelial cell aggregate, chondrocyte aggregate, or tendon tissue prepared by differentiation-induced differentiation of embryonic stem cells (ES cells), nuclear transfer embryonic stem cells (ntES cells), adult stem cells, umbilical cord blood stem cells, etc. Furthermore, cell aggregate 15 may also be prepared by methods other than differentiation-induced differentiation.

[0084] (5) It should be noted that, as long as no contradiction arises, the configurations disclosed in the above embodiments can also be combined with the configurations disclosed in other embodiments. Regarding other configurations, the embodiments disclosed in this specification are merely examples in all respects. Therefore, various changes can be made appropriately without departing from the spirit of this disclosure.

[0085] Industrial applicability

[0086] The technology disclosed herein can be used, for example, in a cellular property detection device for detecting the contractile properties of cardiomyocyte aggregates.

[0087] Explanation of reference numerals in the attached figures

[0088] 10: Devices for detecting cell characteristics.

[0089] 15: Cell aggregates.

[0090] 20: Substrate.

[0091] 30: Support structure.

[0092] 32: Supporting main body.

[0093] 34: Bending end.

[0094] 50: Container.

[0095] 52a: Inner surface.

[0096] 70: Contact body.

[0097] ΔW: Displacement.

Claims

1. A device for detecting cell characteristics, wherein, The device for detecting cell characteristics has the following features: substrate; as well as A pair of resin supports, which are elastically deformable and vertically disposed from the substrate. With the cell aggregate held between the pair of supports, the cell characteristic detection device can detect the displacement of the supports from the outside.

2. The device for detecting cell characteristics as described in claim 1, wherein, The pair of supports are a pair of membranes arranged opposite each other.

3. The device for detecting cell characteristics as described in claim 2, wherein, The pair of membranes are made of resin material with a Young's modulus of 100 MPa or more and 4500 MPa or less, and the pair of membranes have a thickness of 5 μm or more and 400 μm or less.

4. The device for detecting cell characteristics as described in claim 1, wherein, The pair of supports have: a support body portion extending downward from the substrate; and a curved end portion formed by bending the lower end portion of the support body portion.

5. The device for detecting cell characteristics as described in claim 1, wherein, The pair of supports are made of polystyrene-based resin, polypropylene-based resin, or polyethylene-based resin.

6. The device for detecting cell characteristics as described in claim 1, wherein, The cell aggregates are skeletal muscle cell aggregates, cardiomyocyte aggregates, or smooth muscle cell aggregates.

7. The device for detecting cell characteristics as described in claim 1, wherein, An abutment is provided in the region on the substrate side between the pair of supports, the abutment being able to abut against the pair of supports from the inside when the cell aggregate contracts.

8. The device for detecting cell characteristics as described in claim 7, wherein, A plurality of abutments, each with a different length from the substrate, are detachably disposed on the substrate.

9. A cell characteristic detection kit, wherein, The cell characteristic detection kit has the following features: The device for detecting cell characteristics according to any one of claims 1 to 8; and container, The inner surface of the container was treated to inhibit non-specific cell adsorption.

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