System for forming a reinforcing layer, method for forming a reinforcing layer, and program

Abstract

To provide a system for forming a reinforcing layer that enables the reinforcing layer to be formed with a uniform thickness. [Solution] The formation system 100 has a processing unit 110 for forming a reinforcing layer 30 made of fibrin gel on a sheet-shaped cell culture 10, a detection unit 121 for detecting the thickness of the reinforcing layer, a calculation unit 123 for calculating the amount of additional fibrin gel 30A to be formed in an area 30H where the thickness of the reinforcing layer is below a predetermined value, and a control unit 120 for controlling the operation of the processing unit so that the amount of fibrin gel calculated by the calculation unit is formed in the area where the thickness of the reinforcing layer is below the predetermined value.

Description

[Technical Field]

[0001] The present invention relates to a system for forming a reinforcing layer, a method for forming a reinforcing layer, and a program. [Background technology]

[0002] Sheet-shaped cell cultures (cell sheets) are widely known for use in fields such as regenerative medicine. Sheet-shaped cell cultures are produced by storing and culturing cells collected from humans or non-human animals in a culture substrate (culture vessel) containing a culture medium, and allowing them to adhere and aggregate into a sheet.

[0003] Because the sheet-shaped cell culture is constructed in the form of a thin film sheet, it is physically fragile and therefore requires careful handling, as it is prone to wrinkling and tearing during isolation from the culture substrate, transportation and storage of the sheet-shaped cell culture, and actual transplantation into a patient's body.

[0004] To solve the above problems, a method (fibrin treatment) has been proposed in which a fibrinogen solution and a thrombin solution are applied to a sheet-shaped cell culture, a reinforcing layer made of fibrin gel is formed on the sheet-shaped cell culture, and a laminate consisting of the sheet-shaped cell culture and the reinforcing layer is produced (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 2014-179151 Summary of the Invention [Problem to be solved by the invention]

[0006] On the other hand, when forming a reinforcing layer made of fibrin gel on a sheet-shaped cell culture and producing a laminate consisting of the sheet-shaped cell culture and the reinforcing layer, areas where the thickness of the laminate is below a predetermined value may unintentionally occur, resulting in uneven thickness of the laminate.

[0007] When there are regions where the thickness of the laminate is uneven, the laminate is difficult to handle, and the sheet-shaped cell culture may be damaged or may be difficult to transplant into the target location.

[0008] An object of the present invention is to provide a system for forming a reinforcing layer, a method for forming a reinforcing layer, and a program for forming the reinforcing layer, which enable the reinforcing layer to be formed with a uniform thickness. [Means for solving the problem]

[0009] The present invention is achieved by any one of the following means (1) to (5).

[0010] (1) a processing unit for forming a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a detection unit that detects the thickness of the reinforcing layer; a calculation unit that identifies an area where the thickness of the reinforcing layer is equal to or less than a predetermined value and calculates an amount of the fibrin gel to be additionally formed; A system for forming a reinforcing layer, comprising: a control unit that controls the operation of the processing unit so that the amount of fibrin gel calculated by the calculation unit is formed in an area where the thickness of the reinforcing layer is below a predetermined value.

[0011] (2) an imaging unit for imaging the sheet-shaped cell culture and the reinforcing layer, The system for forming a reinforcing layer according to (1), wherein the detection unit detects the thickness of the reinforcing layer based on image information acquired by the imaging unit.

[0012] (3) a light irradiation unit that irradiates the sheet-shaped cell culture and the reinforcing layer with an inspection light; The system for forming a reinforcing layer described in (1) or (2), wherein the detection unit detects the thickness of the reinforcing layer based on the optical transmittance of the inspection light through the sheet-shaped cell culture and the reinforcing layer.

[0013] (4) a step in which a processing unit forms a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a detecting unit detecting a thickness of the reinforcing layer; a calculation unit specifying an area where the thickness of the reinforcing layer is equal to or less than a predetermined value and calculating an amount of the fibrin gel to be additionally formed; A method for forming a reinforcing layer, comprising a step in which a processing unit forms the amount of fibrin gel calculated by the calculation unit in an area where the thickness of the reinforcing layer is less than a predetermined value.

[0014] (5) A system having a processing unit for performing a process to form a reinforcing layer made of fibrin gel on a sheet-shaped cell culture, forming the reinforcing layer made of the fibrin gel on the sheet-shaped cell culture; detecting a thickness of the reinforcing layer; a step of identifying an area where the thickness of the reinforcing layer is equal to or less than a predetermined value and calculating an amount of the fibrin gel to be additionally formed; a step of controlling the operation of the processing unit so that a calculated amount of fibrin gel is formed in an area where the thickness of the reinforcing layer is equal to or less than a predetermined value. [Effects of the Invention]

[0015] In the system, method, and program for forming a reinforcing layer according to the present invention, the detection unit detects the thickness of the reinforcing layer, the calculation unit identifies areas where the thickness of the reinforcing layer is equal to or less than a predetermined value and calculates the amount of additional fibrin gel to form, and the processing unit forms the amount of fibrin gel calculated by the calculation unit in the areas where the thickness of the reinforcing layer is equal to or less than the predetermined value. As a result, it is possible to eliminate areas where the thickness of the reinforcing layer is equal to or less than the predetermined value and form a reinforcing layer with a uniform thickness. [Brief explanation of the drawings]

[0016] [Figure 1] FIG. 1 is a block diagram illustrating a system for forming a reinforcement layer, according to an embodiment. [Figure 2] 4 is a flowchart illustrating steps in a method for forming a reinforcement layer, according to an embodiment. [Figure 3] FIG. 10 is a cross-sectional view illustrating a method for forming a reinforcing layer according to an embodiment, showing the state before fibrin gel is added. [Figure 4] FIG. 10 is a cross-sectional view illustrating a method for forming a reinforcing layer according to an embodiment, showing the state after fibrin gel has been added. DETAILED DESCRIPTION OF THE INVENTION

[0017] Hereinafter, embodiments of the present invention will be described with reference to the drawings. Note that the dimensional proportions in the drawings are exaggerated for the sake of explanation and may differ from the actual proportions.

[0018] FIG. 1 is a simplified block diagram showing the overall configuration of a system 100 (hereinafter also referred to as "forming system 100") for forming a reinforcing layer 30 according to this embodiment. FIG. 2 is a flowchart showing each step of a method (hereinafter also referred to as "forming method") for forming a reinforcing layer 30 according to this embodiment. FIG. 3 is a cross-sectional view for explaining the method for forming a reinforcing layer 30 according to this embodiment, showing the state before fibrin gel 30A is added. FIG. 4 is a cross-sectional view for explaining the method for forming a reinforcing layer 30 according to this embodiment, showing the state after fibrin gel 30A has been added.

[0019] Arrows X1 and X2 in each figure indicate directions parallel to the surface direction of the sheet-shaped cell culture 10, and arrows Z1 and Z2 indicate the thickness direction perpendicular to the surface direction of the sheet-shaped cell culture 10 and the laminate 20.

[0020] <Sheet-shaped cell culture 10> The sheet-shaped cell culture 10 used in this embodiment can contain any cells capable of forming the sheet-shaped cell culture 10. The specific types of such cells are not particularly limited, but include, for example, somatic stem cells (adult stem cells), mesenchymal stem cells, or iPS cell (induced pluripotent stem cell)-derived cardiomyocytes, fibroblasts, synovial cells, epithelial cells, and endothelial cells. Somatic stem cells preferably include skeletal myoblasts (myoblast cells). Furthermore, the term "sheet-shaped cell culture" as used herein refers to a sheet-like (thin film-like) structure in which cells are interconnected.

[0021] The sheet-shaped cell culture 10 may be configured to have, for example, a substantially circular planar shape in its natural state when no external force is applied. The planar shape of the sheet-shaped cell culture 10 is not limited to a circle, and may be, for example, a rectangle, a triangle, an oval, or any other geometric shape. There are also no particular limitations on the specific size or thickness of the sheet-shaped cell culture 10.

[0022] As shown in Figure 3, the sheet-shaped cell culture 10 has a surface 10a, a back surface 10b located opposite the surface 10a and facing the bottom 223 of the container 220, and a peripheral portion 10c having a circular outer shape.

[0023] The formation method described below can be carried out with the sheet-shaped cell culture 10 contained in a predetermined container 220. The target sheet-shaped cell culture 10 is generally in a state after being detached from the container. The target sheet-shaped cell culture 10 may be a single layer or a laminate of multiple sheets. The target sheet-shaped cell culture 10 may have a nonuniform thickness.

[0024] The container 220 is, for example, a culture substrate used for culturing the sheet-shaped cell culture 10. When the container 220 is a culture substrate, the container 220 can be made of a material that is impermeable to liquids such as liquid culture media. When the container 220 is a culture substrate, the solution (liquid culture media, etc.) used for culturing is discharged from the container 220 before starting the formation method.

[0025] As shown in Figures 3 and 4, the container 220 has an opening 221 that opens upward, a bottom 223 on which the back surface 10b of the sheet-shaped cell culture 10 is placed, and a side wall 225 that surrounds the bottom 223.

[0026] The container 220 has a substantially circular planar shape. The bottom 223 of the container 220 has a size (inner diameter) that is the same as or larger than that of the sheet-shaped cell culture 10.

[0027] There are no particular restrictions on the specific form of the sheet-shaped cell culture 10 (e.g., manufacturing method, physical properties, function, etc.) and the specific form of the culture substrate (e.g., material, function, structure and shape, type of liquid medium used, etc.), and publicly known content (e.g., Patent Publication No. 2011-155869, Patent Publication No. 2022-106986, Patent Publication No. 2021-106609, etc.) can be taken into consideration as appropriate.

[0028] <Forming system 100> To summarize with reference to Figure 1, the formation system 100 comprises a processing unit 110 that performs processing to form a reinforcing layer 30 made of fibrin gel on the sheet-shaped cell culture 10, a detection unit 121 that detects the thickness of the reinforcing layer 30, a calculation unit 123 that identifies areas 30H where the thickness of the reinforcing layer 30 is below a predetermined value and calculates the amount of additional fibrin gel 30A to be formed, and a control unit 120 that controls the operation of the processing unit 110 so that the amount of fibrin gel 30A calculated by the calculation unit 123 is formed in the areas 30H where the thickness of the reinforcing layer 30 is below the predetermined value.

[0029] As shown in FIG. 1, the formation system 100 may further include an imaging unit 130 that photographs the sheet-shaped cell culture 10 and the reinforcing layer 30, a stage 210 on which a container 220 containing the sheet-shaped cell culture 10 can be placed, an image display unit 140 that can display an image generated from image information (image data) acquired by the imaging unit 130, and a light irradiation unit 150 that irradiates the laminate 20 with inspection light f.

[0030] As shown in Figure 1, the processing unit 110 can be configured to have a first application unit 111 that applies fibrinogen liquid (liquid containing fibrinogen) L1 to the sheet-shaped cell culture 10, and a second application unit 112 that applies thrombin liquid (liquid containing thrombin) L2 to the sheet-shaped cell culture 10.

[0031] The first applicator 111 can be configured to include, for example, a mechanism for dripping the fibrinogen liquid L1 onto the sheet-shaped cell culture 10. Examples of the mechanism for dripping the fibrinogen liquid L1 include a known syringe or pipette.

[0032] The second applicator 112 can be configured to include, for example, a mechanism for spraying the thrombin solution L2 onto the sheet-shaped cell culture 10. The mechanism for spraying the thrombin solution L2 can be, for example, a known spray.

[0033] The fibrinogen solution L1 and the thrombin solution L2 are not particularly limited as long as they react with each other and solidify to form a fibrin gel. There are also no particular limitations on the concentrations and volume ratios of the respective solutions L1 and L2, the amount applied per unit time, the application pressure, etc. The specific forms of the respective solutions L1 and L2 used in this embodiment can be determined by referring to known information (e.g., JP 2014-179151 A, etc.).

[0034] The control unit 120 is configured to comprehensively control each unit of the forming system 100. The control unit 120 is configured with a CPU (Central Processing Unit), memories such as RAM (Random Access Memory) and ROM (Read Only Memory), and a storage unit, and controls each of the above units and performs various arithmetic processing according to a program.

[0035] The storage unit is configured with an HDD (Hard Disk Drive) or an SSD (Solid State Drive) and stores various programs and data. The storage unit can store a series of programs necessary for controlling the operation of the forming system 100. The above programs can incorporate algorithms for causing the control unit 120 to function as a detection unit 121, a determination unit 122, and a calculation unit 123.

[0036] The operational control executed by the control unit 120 includes the operation of forming the reinforcing layer 30 by the formation system 100. In carrying out the above operation, the control unit 120 controls the operation of the formation system 100 to execute the following steps: a step in which the detection unit 121 detects the thickness of the reinforcing layer 30; a step in which the calculation unit 123 identifies regions 30H of the reinforcing layer 30 where the thickness is equal to or less than a predetermined value and calculates the amount of fibrin gel 30A to be formed; and a step in which the processing unit 110 forms the amount of fibrin gel 30A calculated by the calculation unit 123 in the regions 30H of the reinforcing layer 30 where the thickness is equal to or less than the predetermined value. Specific steps of the formation method will be described later. The predetermined value of the thickness of the reinforcing layer 30 is not particularly limited, but is 1000 μm to 5000 μm.

[0037] The detection unit 121 is configured to detect the thickness of the reinforcing layer 30 based on the image information acquired by the imaging unit 130. Specifically, the detection unit 121 detects the thickness of the reinforcing layer 30 based on the image information of the sheet-shaped cell culture 10 and the image information of the laminate 20 acquired by the imaging unit 130. For this purpose, as shown in FIG. 1, the imaging unit 130 is disposed on the front side of the sheet-shaped cell culture 10 and captures images along the horizontal direction. In this case, it is also possible to capture images of the 360° periphery of the sheet-shaped cell culture 10. The detection unit 121 detects a region 30H of the reinforcing layer 30 where the thickness is equal to or less than a predetermined value. Here, the region 30H is a space (gap) occurring in the thickness direction from the top surface of the formed reinforcing layer 30 to the predetermined thickness of the reinforcing layer 30 (see the two-dot chain line in FIGS. 3 and 4). A plurality of regions 30H may exist in the laminate 20 consisting of the sheet-shaped cell culture 10 and the reinforcing layer 30.

[0038] Based on the thickness data of the reinforcing layer 30 detected by the detection unit 121, the determination unit 122 determines the region 30H where the thickness of the reinforcing layer 30 is equal to or less than a predetermined value.

[0039] The calculation unit 123 is programmed to calculate the amount of fibrin gel 30A to be additionally formed in the region 30H where the thickness of the reinforcing layer 30 is equal to or less than a predetermined value. Specifically, the calculation unit 123 refers to pre-stored reference data (data related to the thickness of the reinforcing layer and the amount of fibrin gel required to be formed), and calculates the amount of fibrin gel 30A (fibrinogen solution L1 and thrombin solution L2) required to be additionally formed based on the thickness of the reinforcing layer 30 detected by the detection unit 121. The calculation unit 123 calculates the thickness of the reinforcing layer 30 by subtracting the thickness of the sheet-shaped cell culture 10 based on the image information of the sheet-shaped cell culture 10 from the thickness of the laminate 20 based on the image information of the laminate 20.

[0040] The control unit 120 controls the operation of the processing unit 110 to form the amount of fibrin gel 30A calculated by the calculation unit 123 in the region 30H where the thickness of the reinforcing layer 30 is equal to or less than a predetermined value. Here, the required amount of fibrin gel 30A calculated by the calculation unit 123 corresponds to the volume of the region 30H. When there are multiple regions 30H, the required amount corresponding to each region 30H is calculated.

[0041] The imaging unit 130 can be configured with a known camera device capable of acquiring still image data and / or video data. As shown in Fig. 1, the imaging unit 130 is placed on the front side of the sheet-shaped cell culture 10 to detect the thickness of the reinforcing layer 30.

[0042] In the forming system 100 according to this embodiment, the detection unit 121 detects the thickness of the laminate 20 based on image information acquired by the imaging unit 130. However, the detection unit 121 may also detect the thickness of the laminate 20 based on the light transmittance of the inspection light f irradiated by the light irradiation unit 150. The configuration of the light irradiation unit 150 will be described below.

[0043] As shown in FIG. 1, the light irradiating unit 150 can be configured with a light source (e.g., a known lamp) that irradiates the laminate 20 contained in the container 220 with inspection light f of a predetermined wavelength. There are no particular limitations on the inspection light f irradiated by the light irradiating unit 150. Measurement of light transmittance may be performed using a transmission type in which a light source is provided on the back surface of the sheet-shaped cell culture 10 as viewed from the light receiver, or a reflection type in which an illumination light source is provided on the light receiver side and a reflective surface is provided on the back surface of the sheet-shaped cell culture 10. Furthermore, in both transmission and reflection types, ambient light may be used as the light source without providing a special light source, and the intensity of light transmitted through the sheet-shaped cell culture 10 may be measured. When targeting the sheet-shaped cell culture 10, visible light is typically used; however, any radiation whose transmittance varies depending on the thickness of the sheet-shaped cell culture 10 can also be used. A transmittance wavelength of 400 to 800 nanometers is optimal for detection sensitivity.

[0044] As shown in Fig. 1, the light irradiation unit 150 can be laid out above a stage 210 on which a container 220 containing a sheet-shaped cell culture 10 is placed. It is also possible to irradiate the sheet-shaped cell culture 10 with inspection light f from below and detect light transmittance on the upper surface of the sheet-shaped cell culture 10. As shown in Fig. 3, the light irradiation unit 150 can be laid out so as to irradiate the inspection light f over the entire range in the planar direction of the sheet-shaped cell culture 10 constituting the laminate 20 (the entire range of the surface 10a).

[0045] The detection unit 121 is configured to be able to detect the thickness based on the light transmittance of the inspection light f irradiated onto the laminate 20. The detection unit 121 irradiates each portion of the laminate 20 with the inspection light f when the fibrin gel has sufficiently solidified, and detects the light transmittance of each portion of the laminate 20. The detection unit 121 can detect the thickness by converting the light transmittance of each portion of the laminate 20 into the thickness of the laminate 20, taking into consideration pre-stored reference data (data relating to the relationship between light transmittance and thickness). In this case, the calculation unit 123 calculates the thickness of the reinforcing layer 30 by subtracting the thickness of the sheet-shaped cell culture 10 detected based on the image information of the sheet-shaped cell culture 10 acquired by the imaging unit 130 from the thickness of the laminate 20 detected based on the light transmittance of the inspection light f.

[0046] The image display unit 140 can be configured, for example, by a known liquid crystal display or the like.

[0047] The forming system 100 can also be configured as a portable or non-portable information terminal device in which the control unit 120, the imaging unit 130, and the image display unit 140 are integrally incorporated.

[0048] <Formation method> Next, a forming method according to this embodiment will be described.

[0049] The specific work content of each step will be described below with reference to the flowchart shown in Fig. 2 and Fig. 3 and Fig. 4. The following description will also explain an example in which the forming system 100 shown in Fig. 1 automatically performs steps S10 to S16 of the forming method.

[0050] To start the formation method, a container 220 is prepared, which contains a sheet-shaped cell culture 10 before the formation of the reinforcing layer 30 made of fibrin gel. The container 220 is placed on a stage 210 (see FIG. 1).

[0051] Next, the detection unit 121 detects the thickness of the sheet-shaped cell culture 10 (step S10). As a method for detecting the thickness of the sheet-shaped cell culture 10, detection is performed based on image information captured by the imaging unit 130, as described above.

[0052] Next, the fibrinogen solution L1 is supplied (applied) to the sheet-shaped cell culture 10 by the first applicator 111 of the processing unit 110 (step S11).

[0053] Next, the second applicator 112 of the processing unit 110 supplies (applies) the thrombin solution L2 to the sheet-shaped cell culture 10 (step S12). When the thrombin solution L2 is supplied to the sheet-shaped cell culture 10, the fibrinogen solution L1 and the thrombin solution L2 applied to the sheet-shaped cell culture 10 start to react, and solidification proceeds accordingly.

[0054] Next, the detection unit 121 detects the thickness of the laminate 20 (step S13). As described above, the method for detecting the thickness of the laminate 20 may be based on image information captured by the imaging unit 130, or may be based on the light transmittance of the inspection light f irradiated by the light irradiating unit 150.

[0055] Next, the calculation unit 123 calculates the thickness of the reinforcing layer 30 based on the thickness of the sheet-shaped cell culture 10 detected in step S10 and the thickness of the laminate 20 detected in step S13 (step S14). Specifically, the calculation unit 123 calculates the thickness of the reinforcing layer 30 by subtracting the thickness of the sheet-shaped cell culture 10 detected in step S10 from the thickness of the laminate 20 detected in step S13.

[0056] Next, the detection unit 121 detects regions 30H in the reinforcing layer 30 where the thickness is equal to or less than a predetermined value (step S15). If the detection unit 121 does not detect regions 30H in the reinforcing layer 30 where the thickness is equal to or less than a predetermined value (step S15: NO), the forming method ends.

[0057] On the other hand, as shown in Fig. 3, if the detection unit 121 detects a region 30H in the reinforcing layer 30 where the thickness is equal to or less than the predetermined value in step S15 (step S15: YES), the formation system 100 operates the processing unit 110 (first applicator 111 and second applicator 112) as shown in Fig. 4 to supply the amounts of fibrinogen solution L1 and thrombin solution L2 calculated by the calculation unit 123 to the region 30H in the reinforcing layer 30 where the thickness is equal to or less than the predetermined value (see, for example, Figs. 3 and 4), thereby forming additional fibrin gel 30A (step S16). This prevents the formation of a portion in the laminate 20 where the fibrin gel is extremely thin. This makes it possible to uniformly increase the strength of each portion of the laminate 20.

[0058] After step S16 is completed, return to step S13 to detect the thickness of the laminate 20, and perform steps S14 and S15 again. Step S16 is repeated until step S15 detects no region 30H where the thickness of the reinforcing layer 30 is below the predetermined value (step S15: NO).

[0059] As described above, the formation system 100 of this embodiment includes a processing unit 110 for forming a reinforcing layer 30 made of fibrin gel on the sheet-shaped cell culture 10, a detection unit 121 for detecting the thickness of the reinforcing layer 30, a calculation unit 123 for calculating the amount of additional fibrin gel 30A to be formed in regions 30H where the thickness of the reinforcing layer 30 is below a predetermined value, and a control unit 120 for controlling the operation of the processing unit 110 so that the amount of fibrin gel 30A calculated by the calculation unit 123 is formed in regions 30H where the thickness of the reinforcing layer 30 is below the predetermined value.

[0060] Furthermore, the forming method according to this embodiment includes the steps of: a processing unit 110 forming a reinforcing layer 30 made of fibrin gel on the sheet-shaped cell culture 10; a detection unit 121 detecting the thickness of the reinforcing layer 30; a calculation unit 123 identifying a region 30H where the thickness of the reinforcing layer 30 is equal to or less than a predetermined value and calculating the amount of additional fibrin gel 30A to be formed; and a processing unit 110 forming the amount of fibrin gel 30A calculated by the calculation unit 123 in the region 30H where the thickness of the reinforcing layer 30 is equal to or less than the predetermined value.

[0061] Furthermore, the program for executing the formation method according to this embodiment is a program for causing a system having a processing unit 110 that performs processing to form a reinforcing layer 30 made of fibrin gel on a sheet-shaped cell culture 10 to execute the following steps: forming a reinforcing layer 30 made of fibrin gel on a sheet-shaped cell culture 10; detecting the thickness of the reinforcing layer 30; identifying regions 30H where the thickness of the reinforcing layer 30 is below a predetermined value and calculating the amount of additional fibrin gel 30A to be formed; and controlling the operation of the processing unit 110 so that the calculated amount of fibrin gel 30A is formed in the regions 30H where the thickness of the reinforcing layer 30 is below the predetermined value.

[0062] According to this embodiment, the detection unit 121 detects the thickness of the reinforcing layer 30, the calculation unit 123 identifies regions 30H of the reinforcing layer 30 where the thickness is equal to or less than a predetermined value and calculates the amount of additional fibrin gel 30A to be formed, and the processing unit 110 forms the amount of fibrin gel 30A calculated by the calculation unit 123 in the regions 30H of the reinforcing layer 30 where the thickness is equal to or less than the predetermined value. This makes it possible to eliminate regions 30H of the reinforcing layer 30 where the thickness is equal to or less than the predetermined value, thereby forming the reinforcing layer 30 with a uniform thickness. Note that "formed uniformly" here is not limited to a completely constant thickness.

[0063] Although the system for forming the reinforcing layer 30, the method for forming the reinforcing layer 30, and the program according to the present invention have been described through the embodiments, the present invention is not limited to the configurations described in the embodiments, and can be modified as appropriate based on the claims. [Explanation of symbols]

[0064] 10. Sheet-shaped cell culture 20 laminate 30 Reinforcement layer 30A Additional fibrin gel 30H Region where the thickness of the reinforcing layer is below a specified value 100 Formation System 110 Processing section 111 First application section 112 Second application section 120 control section 121 Detector 122 Judgment section 123 Calculation Unit 130 Imaging unit 140 Image display unit 150 Light irradiation unit 210 Stages 220 Container L1 fibrinogen liquid L2 thrombin solution f Inspection light

Claims

1. a processing unit for forming a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a detection unit that detects the thickness of the reinforcing layer; a calculation unit that calculates an amount of the fibrin gel to be additionally formed in an area where the thickness of the reinforcing layer is equal to or less than a predetermined value; A system for forming a reinforcing layer, comprising: a control unit that controls the operation of the processing unit so that the amount of fibrin gel calculated by the calculation unit is formed in an area where the thickness of the reinforcing layer is below a predetermined value.

2. an imaging unit for imaging the sheet-shaped cell culture and the reinforcing layer, The system for forming a reinforcing layer according to claim 1 , wherein the detection unit detects the thickness of the reinforcing layer based on image information acquired by the imaging unit.

3. a light irradiation unit that irradiates the sheet-shaped cell culture and the reinforcing layer with an inspection light; The system for forming a reinforcing layer according to claim 1 or 2, wherein the detection unit detects the thickness of the reinforcing layer based on the optical transmittance of the inspection light through the sheet-shaped cell culture and the reinforcing layer.

4. a step in which a processing unit forms a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a detecting unit detecting a thickness of the reinforcing layer; a calculation unit specifying an area where the thickness of the reinforcing layer is equal to or less than a predetermined value and calculating an amount of the fibrin gel to be additionally formed; A method for forming a reinforcing layer, comprising a step in which the processing unit forms the amount of fibrin gel calculated by the calculation unit in an area where the thickness of the reinforcing layer is below a predetermined value.

5. A system having a processing unit for performing a process to form a reinforcing layer made of fibrin gel on a sheet-shaped cell culture, forming the reinforcing layer made of the fibrin gel on the sheet-shaped cell culture; detecting a thickness of the reinforcing layer; a step of identifying an area where the thickness of the reinforcing layer is equal to or less than a predetermined value and calculating an amount of the fibrin gel to be additionally formed; a step of controlling the operation of the processing unit so that a calculated amount of fibrin gel is formed in an area where the thickness of the reinforcing layer is equal to or less than a predetermined value.

Images