Cellular characteristic detection device and cellular characteristic detection set
The cell characteristic detection device with resin supports and treated container surfaces addresses nonspecific adsorption issues, enhancing the accuracy of cell characteristic detection by minimizing compound interaction, thus improving measurement reliability.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2024-04-10
- Publication Date
- 2026-03-24
AI Technical Summary
Existing cell characteristic detection devices using collagen supports are prone to nonspecific adsorption of compounds due to immersion in liquid, which affects the accuracy of cell characteristic detection.
A cell characteristic detection device utilizing a pair of elastically deformable resin supports suspended from a substrate, with a container having a treated inner surface to inhibit nonspecific adsorption, allowing only the tip portion to be immersed in liquid, and a configuration that enables displacement measurement of the supports.
Minimizes nonspecific adsorption, enabling more accurate detection of cell characteristics by reducing compound interaction with the device and container, thereby improving the reliability of cell aggregate measurements.
Smart Images

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Abstract
Description
[Technical Field]
[0001] This invention relates to a device for detecting cell characteristics and a cell characteristic detection set. [Background technology]
[0002] Cell characteristic detection devices are known for detecting the characteristics of cells. For example, Patent Document 1 discloses a cell characteristic detection device capable of detecting the contractile characteristics of muscle cells held on a collagen-based support having a long section, using a strain gauge connected to a connecting section at one end of the long section. [Prior art documents] [Patent Documents]
[0003] [Patent Document 1] Japanese Patent Publication No. 2011-030574 [Overview of the project] [Problems that the invention aims to solve]
[0004] In the cell characteristic detection device described in Patent Document 1, the support that holds the cells is mainly made of collagen, and because the entire support is used immersed in a liquid containing the compound, there was a problem in that nonspecific adsorption of the compound was likely to occur.
[0005] Therefore, there is a need for a device for detecting cell characteristics that is less prone to non-specific adsorption of compounds. [Means for solving the problem]
[0006] The cell characteristic detection device according to the present invention is circuit board and The system comprises a pair of resin supports that are elastically deformable and suspended from the substrate, The invention is characterized in that, while a cell aggregate is held between the pair of supports by the pair of supports, the amount of displacement of the supports can be detected from the outside.
[0007] With this configuration, only the tip portion of the vertically mounted support of the cell characteristic detection device can be immersed in the liquid, and since the support is made of resin, non-specific adsorption of compounds is unlikely to occur in terms of both contact area and material.
[0008] Furthermore, the cell characteristic detection set according to the present invention includes the above-mentioned cell characteristic detection device, Equipped with a container, The inner surface of the aforementioned container is treated to inhibit the non-specific adsorption of cells.
[0009] This configuration uses a container with an inner surface treated to suppress nonspecific cell adsorption, thus ensuring the adsorption of cell aggregates to the cell characteristic detection device while minimizing the occurrence of nonspecific cell adsorption to the container.
[0010] 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.
[0011] The above-described cell characteristic detection device, in one embodiment, The pair of supports is preferably a pair of film bodies arranged opposite each other.
[0012] With this configuration, the resolution of the displacement measurement and the maximum displacement that can be measured can be easily changed by changing the thickness of the pair of film bodies.
[0013] The above-described cell characteristic detection device, in one embodiment, Preferably, the pair of film bodies are made of a resin material with a Young's modulus of 100 MPa or more and 4500 MPa or less, and have a thickness of 5 μm or more and 400 μm or less.
[0014] This configuration allows for more appropriate values for both the resolution of displacement measurement and the maximum measurable displacement.
[0015] In one aspect, it is preferable that the pair of the supports of the above-described device for detecting cell characteristics has a support main body portion extending downward from the substrate and a bent end portion formed by bending the lower end portion of the support main body portion.
[0016] According to this configuration, the cell aggregate can be stably held by the bent end portion.
[0017] In one aspect, the above-described device for detecting cell characteristics It is preferable that the pair of the supports is made of a polystyrene-based resin, a polypropylene-based resin, or a polyethylene-based resin.
[0018] According to this configuration, non-specific adsorption of a compound to the device for detecting cell characteristics is less likely to occur.
[0019] In one aspect, the above-described device for detecting cell characteristics It is preferable that the cell aggregate is a skeletal muscle cell aggregate, a cardiomyocyte aggregate, or a smooth muscle cell aggregate.
[0020] According to this configuration, by using the device for detecting cell characteristics in which non-specific adsorption of a compound is less likely to occur, more accurate detection of the muscle contraction characteristics of a skeletal muscle cell aggregate, a cardiomyocyte aggregate, or a smooth muscle cell aggregate becomes possible.
[0021] In one aspect, the above-described device for detecting cell characteristics It is preferable that a contact body capable of contacting the pair of the supports from the inside when the cell aggregate contracts is provided in the region on the substrate side between the pair of the supports.
[0022] [[ID=3It is preferable that a plurality of contact bodies, each having a different length from the substrate, are detachably provided on the substrate.
[0024] With this configuration, the resistance of the contact point to the contracting cell aggregate varies depending on the length of the contact point, so that the resistance is adjusted to the culture conditions of the cell aggregate.
[0025] Further features and advantages of the present invention will become clearer through the following description of exemplary and non-limiting embodiments, with reference to the drawings. [Brief explanation of the drawing]
[0026] [Figure 1] Perspective view of the cell characteristic detection device of the cell characteristic detection set of the first embodiment. [Figure 2] Perspective view of the container for the cell characteristic detection set of the first embodiment. [Figure 3] Schematic diagram of the cell characteristic detection set and cell aggregate of the first embodiment [Figure 4] Perspective view of the support in the second embodiment [Figure 5] This is a cross-sectional view of the cell characteristic detection set of the third embodiment, showing the contact body attached to the substrate. [Figure 6] This is a cross-sectional view of the cell characteristic detection set of the third embodiment, in which a contact body longer from the substrate than the contact body shown in Figure 5 is attached to the substrate. [Figure 7] Perspective view of a support in another embodiment [Modes for carrying out the invention]
[0027] 1. First Embodiment The cell characteristic detection set 100 according to the first embodiment will be described below with reference to the drawings. The cell characteristic detection set 100 comprises a cell characteristic detection device 10 and a container 50. Figure 1 is a perspective view of the cell characteristic detection device 10, Figure 2 is a perspective view of the container 50, and Figure 3 is a schematic diagram of the cell characteristic detection set 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, comprises a substrate 20 and a pair of resin supports 30 that are elastically deformable and suspended from the substrate 20. Furthermore, the cell characteristic detection device 10 can detect the displacement of the supports 30, for example, the displacement ΔW shown in Figure 3, from the outside while the cell aggregate 15 is held between the pair of supports 30 by the pair of supports 30. Note that a cell aggregate refers to a mass of cells formed by the aggregation of multiple cells.
[0028] In this embodiment, the substrate 20 is a rectangular resin plate, and four rectangular through-holes 22 are arranged in a row along its longitudinal direction, penetrating the substrate 20 in the thickness direction. On both longitudinal sides of the through-holes 22 of the substrate 20, there are bottom plate portions 24 that extend toward the center of the through-holes 22 and are supported in a cantilevered manner. The bottom plate portions 24 have support members 30 that are suspended downwards. As shown in Figure 1, in this embodiment, the support members 30 suspended from the bottom plate portions 24 provided on both sides of one through-hole 22 are paired together. In addition, in this embodiment, four sets of pairs of support members 30 are provided. Here, "suspended" means that they are provided in a way that they hang down. In the example of Figure 1, a pair of support members 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.
[0029] The support 30 may be integrated with the substrate 20, or it may be detachably attached to the bottom plate portion 24 of the substrate 20. Here, as shown in Figure 3, the direction in which the pair of support 30 are aligned is defined as direction X1. In this embodiment, the longitudinal direction of the substrate 20 is the same as direction X1. The pair of support 30 are preferably made of polystyrene resin, polypropylene resin, or polyethylene resin.
[0030] As shown in Figure 2, the container 50 is provided with recesses 52 for holding liquid 55. The container 50 in this embodiment is a mold container formed from plastic, metal, or glass. A mold container is a container for holding cell aggregates 15 in a device, and is a container for agglomerating cells to form the shape of aggregates. The container 50 is provided with a plurality of recesses 52. The number of recesses 52 is preferably a multiple of the number of pairs of supports 30 per cell characteristic detection device 10 (in this example, "4"), and in this embodiment, eight recesses 52 are provided. In this case, two cell characteristic detection devices 10 are attached to one container 50.
[0031] Figure 3 shows the detection of the displacement ΔW of the support 30, i.e., the measurement of the displacement of the cell aggregates 15. In Figure 3, the cell aggregates 15 and the support 30 in a state where the tip is bent due to the contraction of the cell aggregates 15 are shown by dashed lines. The cell aggregates 15 are, for example, skeletal muscle cell aggregates, cardiomyocyte aggregates, or smooth muscle cell aggregates produced by differentiation induction from induced pluripotent stem cells. Preferably, the cell characteristic detection device 10 is also used for culturing the cell aggregates 15. Even more preferably, the cell characteristic detection device 10 is also used for differentiation induction and maturation of the cell aggregates 15. For example, cell aggregates 15 before differentiation induction are attached to the respective tips of the pair of support 30 of the cell characteristic detection device 10. Next, the tips of the pair of supports 30 and the cell aggregates 15 before differentiation induction may be immersed in the liquid culture medium of a culture vessel (not shown), and the cell aggregates 15 may be cross-linked between the pair of supports 30 while differentiation induction is performed, thereby holding the target cell aggregates 15, such as cardiomyocyte aggregates, between the pair of supports 30.
[0032] In this embodiment, the pair of support bodies 30 are a pair of film bodies arranged opposite each other. As shown in Figure 3, the pair of support bodies 30 are thin films, each having a width B1, a thickness H1, and a length L1 from the bottom plate portion 24 to the tip. The pair of support bodies 30 are suspended from the substrate 20 so that the thickness direction is the same as direction X1, and the tip side (lower end side) is flexible in the thickness direction, allowing for elastic deformation in the direction X1 connecting the pair of support bodies 30. As a result, when the cell aggregate 15 held by the pair of support bodies 30 contracts, both tips of the pair of support bodies 30 elastically deform in the direction toward each other, i.e., in direction X1. If the displacement of one support body 30 in this direction X1 is ΔW, then the displacement of the cell aggregate 15 in direction X1 is twice ΔW.
[0033] If the maximum displacement that the support 30 can elastically deform is defined as the maximum measurable displacement ΔWmax, then the maximum measurable displacement ΔWmax and the resolution can be changed by changing the thickness H1, without changing the measuring instrument that detects the displacement ΔW, the resin material of the support 30, or the length L1 and width B1 of the support 30. The pair of support bodies 30, which are film bodies, are preferably made of a resin material with a Young's modulus E of 100 MPa to 4500 MPa. They are also preferably made of a resin material with a Young's modulus E of 300 MPa to 4300 MPa. Even more preferably, they are made of a resin material with a Young's modulus E of 400 MPa to 4000 MPa. Furthermore, the pair of support bodies 30 preferably have a thickness H1 of 5 μm to 400 μm. They are also preferably made of a thickness H1 of 7 μm to 200 μm. Even more preferably, they have a thickness H1 of 8 μm to 100 μm. Note that the Young's modulus E in this specification is a measured value at 25°C (room temperature).
[0034] When the pair of film supports 30 are made of polystyrene 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 film supports 30 are made of polypropylene 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. As specific examples of the pair of film supports 30, Table 1 shows the Young's modulus E, the maximum measured displacement ΔWmax, length L1, width B1, and thickness H1 for Example 1, which is a support 30 made of polystyrene, and for Example 2, which is a support 30 made of polypropylene. [Table 1]
[0035] The resolution can also be changed by changing the measuring instrument that detects the displacement ΔW. The cell characteristic detection set 100 of this embodiment has a transparent or translucent container 50, and an optical microscope 60 capable of measuring the displacement ΔW of the support 30 is provided below the container 50. The optical microscope 60 corresponds to the measuring instrument that detects the displacement ΔW. The container 50 contains a transparent or translucent liquid 55. Preferably, illumination is provided above the container 50. The liquid 55 is, for example, a liquid containing a low molecular weight compound, and by measuring the displacement ΔW of the support 30 and obtaining it as tension information, it is possible to evaluate the effect (toxicity) of the compound on cardiomyocyte aggregates, evaluate the efficacy of the compound on disease models of cardiomyocyte aggregates, and search for the optimal compound for inducing differentiation into cardiomyocyte aggregates.
[0036] Returning to Figure 2, the inner surface 52a of the recess 52 in the container 50 is subjected to a non-specific cell adsorption suppression treatment. This non-specific cell adsorption suppression treatment is a treatment that suppresses the non-specific adsorption of cells. This non-specific cell adsorption suppression treatment can be performed, for example, by hydrophilization treatment. More specifically, the non-specific cell adsorption suppression treatment can be performed by a treatment that includes at least one group selected from the group consisting of groups represented by the following formulas (1), (2), (3), and (4) on the inner surface 52a of the recess 52.
[0037] [ka]
[0038] Here, in equation (1), R 12 is an NH or oxygen atom. m is an integer from 0 to 4. 13 R is a hydrogen atom, a hydroxyl group, or a methoxy group. In formula (3), 32 is a hydrogen atom or a methyl group. n is an integer between 2 and 100.
[0039] Furthermore, non-specific adsorption suppression of cells can be performed by forming a coating layer mainly composed of a polymer containing specific hydrophilic structural units in the recess 52. Here, the hydrophilic structural units in the polymer that forms the main body of the coating layer may include at least one structural unit selected from the group consisting of structural units represented by the following formulas (5), (6), (7), and (8).
[0040] [ka]
[0041] Here, * represents conjugation. In equation (5), R 11 R is a hydrogen atom or a methyl group. 12 is an NH or oxygen atom. m is an integer from 0 to 4. 13 R is a hydrogen atom, a hydroxyl group, or a methoxy group. In formula (6), R 21is a hydrogen atom or a methyl group. In formula (7), R 31 is a hydrogen atom or a methyl group. R 32 is a hydrogen atom or a methyl group. n is an integer from 2 to 100.
[0042] As an example, regarding the structural unit represented by formula (5), when R 11 is a hydrogen atom, examples of the monomer serving as a raw material for the hydrophilic structural unit include N-(2-hydroxyethyl)acrylamide (HEAA). Also, when R 11 is a methyl group, examples of the monomer serving as a raw material for the hydrophilic structural unit include 2-hydroxyethyl methacrylate (HEMA).
[0043] Further, the hydrophilic structural unit in the polymer that is the main component of the coating layer may contain a structural unit represented by the following formula (9).
[0044] [Chemical formula]
[0045] Here, * represents a bond. In formula (9), R 41 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.
[0046] The polymer that is the main component of the coating layer may further contain a hydrophobic structural unit. In this case, the hydrophobic structural unit can include at least one structural unit selected from the group consisting of the structural units represented by the following formula (10) and formula (11). <00002R is a hydrogen atom or a methyl group. 52 R is a linear 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 This is either a hydrogen atom or a methyl group.
[0049] Examples of linear or branched alkyl groups having 1 to 10 carbon atoms include methyl, ethyl, propyl, methylethyl, butyl, 1,2-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, and hexyl groups. Examples of alicyclic alkyl groups having 3 to 8 carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.
[0050] The total content of hydrophilic constituent units in the polymer that forms the main body of the coating layer is preferably 10 mol% or more. The total content of hydrophilic constituent units is preferably 20 mol% to 80 mol%, and more preferably 30 mol% to 70 mol%. 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% to 80 mol%, and more preferably 50 mol% to 70 mol%.
[0051] The polymer that forms the main component of the coating layer may further contain crosslinkable structural units in addition to the hydrophilic and hydrophobic structural units described above. The content of crosslinkable structural units may be, for example, 0.05 mol% to 20 mol%, and preferably 0.5 mol% to 10 mol%.
[0052] By providing such a coating layer, the contact angle of the inner surface 52a of the recess 52 with respect to pure water at 25°C (room temperature) is set to be between 3° and 90°. By making the inner surface 52a of the recess 52 hydrophilic, the nonspecific adsorption of compounds onto the inner surface 52a of the recess 52 can be suppressed. However, setting the contact angle to less than 3° may be undesirable from a cost perspective due to the extensive processing required. On the other hand, if the contact angle exceeds 90°, the hydrophilicity decreases, which may reduce the ability to suppress the nonspecific adsorption of compounds. By setting the contact angle to be between 3° and 90°, the nonspecific adsorption of compounds onto the inner surface 52a of the recess 52 can be suppressed at a relatively low cost.
[0053] The contact angle of the inner surface 52a of the recess 52 with respect to pure water is preferably 5° or more, and more preferably 8° or more. Furthermore, the contact angle of the inner surface 52a of the recess 52 with respect to pure water is preferably 80° or less, and more preferably 70° or less.
[0054] 2. Second Embodiment In the following description, the support 30 according to the second embodiment will be explained with reference to Figure 4. In this embodiment, the shape of the support 30 differs from that of the first embodiment. In the following description, the differences from the first embodiment will be the main focus. Points that are not specifically explained will be the same as in the first embodiment. The pair of support 30 has 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 this embodiment, a recess 36 is provided in the support body portion 32. By providing this recess 36, the cell aggregate 15 held by the pair of support 30 can be aggregated as a whole. As a result, the thickness of the cell aggregate 15 near the recess 36 increases, making it less likely for stress to concentrate on a part of the cell aggregate 15 when the cell aggregate 15 pulsates, and as a result the cell aggregate 15 becomes less likely to be damaged. Specifically, as shown in Figure 4, the pair of support 30 are a pair of opposing film bodies, and the bent end portion 34 is formed by bending the lower end of the film body support body portion 32. The support body portion 32 is provided with recesses 36 on both sides in the width direction. By placing the cell aggregates 15 on the bent ends 34, the cell aggregates 15 can be stably held by the pair of bent ends 34 on the pair of support bodies 30. The pair of bent ends 34 may be formed by bending the lower ends of the support body portion 32 in directions that separate them from each other, or by bending them in directions that bring them closer together. Preferably, by placing the cell aggregates 15 on the pair of bent ends 34 and culturing them, the cell aggregates 15 after culturing will enclose the pair of bent ends 34. In this way, more stable retention of the cell aggregates 15 is possible.
[0055] 3. Third Embodiment In the following description, the cell characteristic detection set 100 according to the third embodiment will be explained with reference to Figures 5 and 6. Figure 5 is a cross-sectional view of the cell characteristic detection set 100 according to the third embodiment, showing the contact body 70 attached to the substrate 20. Figure 6 is a cross-sectional view of the cell characteristic detection set 100 according to the third embodiment, showing a contact body 70 attached to the substrate 20 that is longer in length from the substrate 20 than the contact body 70 shown in Figure 5.
[0056] The cell characteristic detection set 100 according to the third embodiment differs from the cell characteristic detection set 100 of the first and second embodiments in that the cell characteristic detection device 10 further comprises a contact body 70. The following description will focus on the differences from the first and second embodiments. Points not specifically described are the same as those in the first and second embodiments.
[0057] As shown in Figure 5, the contact body 70 is provided in the region on the substrate 20 side between the pair of support bodies 30 so that it can contact the pair of support bodies 30 from the inside when the cell aggregate 15 shrinks. The region on the substrate 20 side is the region between the substrate 20 and the cell aggregate 15. The distance between each support body 30 and the contact body 70 is set so that each support body 30, which deforms due to the shrinkage of the cell aggregate 15, comes into contact with the contact body 70. The contact body 70 illustrated in Figure 5 is attached to the substrate 20 so as to hang down from the substrate 20 toward the cell aggregate 15 in the region between the pair of support bodies 30. Note that the contact body 70 may be attached to a location other than the substrate 20, as long as it is provided in the region on the substrate 20 side between the pair of support bodies 30. Also, one contact body 70 does not have to contact both of the pair of support bodies 30. For example, a pair of contact bodies 70 may be provided, and each contact body 70 may contact a different support body 30.
[0058] The pair of support structures 30 undergo elastic deformation due to the contraction of the cell aggregates 15, with the lower ends of each support structure 30 moving closer together, starting from the portion of each support structure 30 on the substrate 20 side. Due to the deformation of the support structures 30 caused by the contraction of the cell aggregates 15, the contact body 70 comes into contact with each of the pair of support structures 30. The contact body 70 suppresses the deformation of the pair of support structures 30 as they deform due to the contraction of the cell aggregates 15. Therefore, the contact body 70 acts as resistance to the contraction of the cell aggregates 15. As a result, for example, when a healthy strain is used, the resistance to the contracting cell aggregates 15 leads to strong growth of the cell aggregates 15. On the other hand, when a diseased strain is used, the resistance to the contracting cell aggregates 15 leads to weak growth of the cell aggregates 15.
[0059] It is preferable that the contact body 70 is detachable from the substrate 20. In this case, when resistance is not required for the shrinking cell aggregate 15, the contact body 70 can be removed, and the shrinking cell aggregate 15 will not be subjected to resistance. Therefore, the presence or absence of resistance for the shrinking cell aggregate 15 can be switched depending on the degree of culture of the cell aggregate 15.
[0060] It is preferable that there are multiple contact bodies 70 that can be detachably attached to the substrate 20. In addition, it is preferable that the lengths of the multiple contact bodies 70 from the substrate 20 are different from each other. The length of the contact 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 contact body 70. The longer the length from the substrate 20, the further the support 30 will come into contact with the contact body 70 at a position away from the substrate 20 (i.e., closer to the cell aggregate 15) when the cell aggregate 15 contracts. Therefore, the resistance that the contact body 70 imparts to the contracting cell aggregate 15 varies depending on the length of the contact body 70, and increases as the length of the contact body 70 increases. As a result, by attaching contact bodies 70 of a length appropriate to the culture conditions of the cell aggregate 15 to the substrate 20, it is possible to impart an appropriate amount of resistance to the contracting cell aggregate 15 according to the culture conditions of the cell aggregate 15.
[0061] Specifically, Figure 6 shows a contact body 70 in which the length L3 from the substrate 20 is longer than the length L2 from the substrate 20 of the contact body 70 shown in Figure 5. As shown in Figure 6, when the length L3 from the substrate 20 of the contact body 70 is longer than the length L2 from the substrate 20 of the contact body 70 shown in Figure 5, the contact body 70 shown in Figure 6 contacts each support 30 at a position closer to the cell aggregate 15 than the contact body 70 shown in Figure 5 when the cell aggregate 15 contracts. Therefore, the contact body 70 shown in Figure 6 provides greater resistance to the contracting cell aggregate 15 than the contact body 70 shown in Figure 5.
[0062] When culturing the cell aggregates 15, gradually increasing the resistance applied when the cell aggregates 15 contract allows them to grow more strongly or weakly in a shorter time. Therefore, when culturing the cell aggregates 15, by sequentially replacing the contact elements 70 with shorter lengths from the substrate 20 to longer lengths from the substrate 20, strong or weak cell aggregates 15 can be efficiently cultured.
[0063] 4. Other Embodiments (1) In the first embodiment described above (see Figure 3), a configuration was described in which the displacement amount ΔW of the support 30 is measured from below the transparent or translucent container 50 using an optical microscope 60. However, the invention is not limited to such an example, and for example, the optical microscope 60 may measure the displacement amount ΔW from the side of the transparent container 50. Also, for example, the measuring instrument for detecting the displacement amount ΔW may be a measuring instrument other than an optical microscope. Also, for example, the displacement amount ΔW of the support 30 may be detectable from the outside by connecting a strain gauge to the support 30. Furthermore, the container 50 does not have to be light-transmitting; any cell characteristic detection set 100 that can detect the displacement amount ΔW from the outside is sufficient.
[0064] (2) In the first embodiment described above (see Figure 1), the pair of support bodies 30 were described as a pair of film bodies arranged opposite each other. However, the configuration is not limited to such an example, and for example, the shape of the support body 30 may be cylindrical or prismatic.
[0065] (3) In the second embodiment described above (see Figure 4), a support 30 having a recess 36 and a bent end 34 was described. However, as shown in Figure 7, the support 30 may have a support body portion 32 formed on a flat surface and a notch portion 37 in the support body portion 32. The notch portion 37 is formed on the side surface of the support body portion 32 in the width direction. With this configuration, the portion of the support body portion 32 closer to the tip of the notch portion 37 is easily bent, and a bent portion corresponding to the bent end 34 described in the second embodiment can be easily formed afterward. By bending the portion of the support body portion 32 closer to the tip of the notch portion 37, the cell aggregates 15 are held in the bent portion. Preferably, in support body portions 32 facing each other, the portion of each support body portion 32 closer to the tip of the notch portion 37 is bent perpendicular to the direction in which they approach each other. This makes it possible to stably hold the cell aggregates 15, similar to the second embodiment. In this case, it is preferable that the notch portion 37 is formed at a position 0.5 mm to 2.0 mm from the tip of the support body portion 32.
[0066] The support 30 illustrated in Figure 7 includes a recess 36 and a notch 37. The recess 36 shown in Figure 7 is formed on both sides in the width direction of the support body 32, similar to the recess 36 shown in Figure 4. On the other hand, the longitudinal length of the recess 36 shown in Figure 7 is shorter than the longitudinal length of the recess 36 shown in Figure 4. The notch 37 is formed by cutting out a triangular shape on both sides in the width direction of the support body 32, closer to the tip of the recess 36. The position, size, and shape of the recess 36 and the notch 37 may be appropriately determined depending on the type of cell aggregate 15.
[0067] (4) In the first embodiment described above (see Figure 1), the cell aggregate 15 was described as a skeletal muscle cell aggregate, cardiomyocyte aggregate, or smooth muscle cell aggregate produced by differentiation induction from induced pluripotent stem cells (iPS cells). However, the invention is not limited to such examples, and for example, the cell aggregate 15 may be a muscle cell aggregate, adipocyte aggregate, osteocyte aggregate, nerve cell aggregate, epithelial cell aggregate, chondrocyte aggregate, or tendon tissue differentiated from embryonic stem cells (ES cells), nuclear transfer embryonic stem cells (ntES cells), somatic stem cells, umbilical cord blood stem cells, etc. Furthermore, for example, the cell aggregate 15 may be produced by a method other than differentiation induction.
[0068] (5) The configurations disclosed in each of the embodiments described above can be applied in combination with configurations disclosed in other embodiments, as long as no inconsistencies arise. With regard to other configurations, the embodiments disclosed herein are merely illustrative in all respects. Therefore, various modifications can be made as appropriate without departing from the spirit of this disclosure. [Industrial applicability]
[0069] The technology described herein can be used, for example, in a cell characteristic detection device for detecting the contractile characteristics of cardiomyocyte aggregates. [Explanation of Symbols]
[0070] 10: Devices for detecting cell characteristics 15: Cell aggregates 20: Circuit board 30:Support 32: Support main body part 34: Bent end 50: Container 52a: Inner surface 70: Contact body ΔW: Displacement
Claims
1. circuit board and The system comprises a pair of resin supports that are elastically deformable and suspended from the substrate, The pair of supports are a pair of opposing film bodies suspended downward from the substrate, The pair of film bodies are made of a resin material with a Young's modulus of 100 MPa or more and 4500 MPa or less, and have a thickness of 5 μm or more and 400 μm or less. Each of the support members has a support body portion extending downward from the substrate, and a bent end portion formed by bending the lower ends of the support body portions toward each other. A cell characteristic detection device capable of detecting the displacement of a pair of supports from the outside, while a cell aggregate is held between the bent ends of a pair of supports by the pair of supports.
2. The cell characteristic detection device according to claim 1, wherein the support body portion of the pair of supports is provided with recesses on both sides in the width direction of the film body.
3. The cell characteristic detection device according to claim 1, wherein the pair of supports are made of a polystyrene resin, a polypropylene resin, or a polyethylene resin.
4. The cell characteristic detection device according to claim 1, wherein the cell aggregate is a skeletal muscle cell aggregate, a cardiomyocyte aggregate, or a smooth muscle cell aggregate.
5. A contact body is provided in the substrate-side region between the pair of supports, which can contact the pair of supports from the inside when the cell aggregate contracts. The cell characteristic detection device according to claim 1, wherein the contact body is provided between a pair of supports so as to hang down from the substrate toward the cell aggregate, and the length hanging down from the substrate is shorter than the support body.
6. The cell characteristic detection device according to claim 5, wherein at least one of the contact bodies selected from a plurality of contact bodies having different lengths hanging from the substrate is detachably provided on the substrate.
7. A cell characteristic detection device according to any one of claims 1 to 6, Equipped with a container, A cell characteristic detection set, wherein the inner surface of the container is treated to suppress non-specific adsorption of cells.
Citation Information
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