System for determining the solidification state of fibrin gel, method for determining the solidification state of fibrin gel, and program

Abstract

Provided are a system for determining the solidification state of a fibrin gel, a method for determining the solidification state of a fibrin gel, and a program for determining the solidification state of a fibrin gel, which enable accurate determination of the solidification state of a fibrin gel formed in a sheet-shaped cell culture. [Solution] The determination system 100 includes a processing unit 110 that performs processing to form a reinforcing layer 30 made of fibrin gel on a sheet-shaped cell culture 10, a light irradiation unit 120 that irradiates test light f1 onto a laminate 20 in which fibrin gel is laminated on a sheet-shaped cell culture, a detection unit 131 that detects the light transmittance of the test light through the laminate, and a determination unit 132 that determines the solidification state of the fibrin gel based on the change in light transmittance detected by the detection unit.

Description

[Technical Field]

[0001] The present invention relates to a system for determining the solidification state of a fibrin gel, a method for determining the solidification state of a fibrin gel, 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 then 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 transplantation into a patient's body.

[0004] To solve the above problems, a method 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. 2016-52272 Summary of the Invention [Problem to be solved by the invention]

[0006] The laminate produced by the method of Patent Document 1 has the physical strength of part or all of the sheet-shaped cell culture reinforced by the reinforcing layer, which effectively prevents wrinkling and tearing when handled by workers.

[0007] In the method of Patent Document 1, after performing fibrin treatment (application of fibrinogen solution and application of thrombin solution) to form a reinforcing layer, the sheet-shaped cell culture is left to stand in a specified container while the fibrinogen solution and thrombin solution react and solidify to form a fibrin gel. The worker producing the laminate determines whether the fibrin gel has sufficiently solidified by visual inspection or the like, and if solidification is deemed complete, the formation of the reinforcing layer (manufacturing of the laminate) is completed.

[0008] When the solidification state of the fibrin gel is determined by visual inspection by an operator as described above, the burden on the operator increases. Furthermore, there is a possibility that the production of the laminate may be completed with the fibrin gel in an unsolidified state, which would result in a decrease in the product quality of the laminate.

[0009] The present invention aims to provide a system for determining the solidification state of a fibrin gel, a method for determining the solidification state of a fibrin gel, and a program that enable accurate determination of the solidification state of a fibrin gel formed in a sheet-shaped cell culture. [Means for solving the problem]

[0010] The present invention is achieved by any one of the following means (1) to (6).

[0011] (1) a processing unit that performs a process to form a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a light irradiation unit that irradiates an inspection light onto a laminate in which the fibrin gel is laminated on the sheet-shaped cell culture; a detection unit that detects the light transmittance of the inspection light through the laminate; a determination unit that determines the solidification state of the fibrin gel based on the change in light transmittance detected by the detection unit.

[0012] (2) The system for determining the solidification state of a fibrin gel according to (1), further comprising a calculation unit that predicts the time until the fibrin gel solidifies based on the change in light transmittance detected by the detection unit.

[0013] (3) the light irradiating unit irradiates the laminate with the inspection light when the determining unit determines that the fibrin gel is in a solidified state; the detection unit detects a portion where the thickness of the fibrin gel is equal to or less than a predetermined value based on the light transmittance of the inspection light irradiated onto the laminated body in a state where the fibrin gel has solidified; The system for determining the solidification state of fibrin gel according to (1) or (2), wherein the determination unit determines whether or not to form additional fibrin gel in areas where the thickness of the fibrin gel is below a predetermined value.

[0014] (4) an imaging unit for imaging the sheet-shaped cell culture and the fibrin gel; The system for determining the solidification state of a fibrin gel according to any one of (1) to (3), wherein the detection unit detects the light transmittance based on image information acquired by the imaging unit.

[0015] (5) a step in which a processing unit forms a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a step in which a light irradiation unit irradiates an inspection light onto a laminate in which the fibrin gel is laminated on the sheet-shaped cell culture; a detection unit detecting the light transmittance of the inspection light through the laminate; a determining unit determining the solidification state of the fibrin gel based on the change in light transmittance detected by the detecting unit.

[0016] (6) 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, irradiating an inspection light onto a laminate in which the fibrin gel is laminated on the sheet-shaped cell culture; detecting the optical transmittance of the inspection light through the laminate; determining a solidification state of the fibrin gel based on the detected change in light transmittance. [Effects of the Invention]

[0017] According to the system, method, and program for determining the solidification state of a fibrin gel of the present invention, a laminate in which fibrin gel is layered on a sheet-shaped cell culture is irradiated with test light, a detection unit detects the light transmittance of the test light and changes in the light transmittance over time, and a determination unit determines the solidification state of the fibrin gel based on the detection results of the detection unit. This reduces the workload of workers manufacturing the laminate and prevents a decrease in product quality of the laminate due to the formation of unsolidified fibrin gel. [Brief explanation of the drawings]

[0018] [Figure 1] FIG. 1 is a block diagram showing a system for determining the solidification state of a fibrin gel according to an embodiment. [Figure 2] 1 is a flowchart showing steps of a method for determining the solidification state of a fibrin gel according to an embodiment. [Figure 3] 10A and 10B are cross-sectional views for explaining a method for determining the solidification state of fibrin gel according to an embodiment. [Figure 4] 10A and 10B are cross-sectional views for explaining a method for determining the solidification state of fibrin gel according to an embodiment. [Figure 5] 10A and 10B are cross-sectional views for explaining a method for determining the solidification state of fibrin gel according to an embodiment. [Figure 6] 10A and 10B are cross-sectional views for explaining a method for determining the solidification state of fibrin gel according to an embodiment. [Figure 7]10 is a flowchart showing steps of a method for determining the solidification state of fibrin gel according to a modified example. DETAILED DESCRIPTION OF THE INVENTION

[0019] 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.

[0020] Fig. 1 is a simplified block diagram showing the overall configuration of a system 100 for determining the solidification state of a fibrin gel according to this embodiment (hereinafter also referred to as "determination system 100"). Fig. 2 is a flowchart showing each step of a method for determining the solidification state of a fibrin gel according to this embodiment (hereinafter also referred to as "determination method").

[0021] 3 to 6 are diagrams for explaining the determination method. Figures 3 to 6 are cross-sectional views taken along the thickness direction (height direction of the container 220) of the sheet-shaped cell culture 10 and the laminate 20. Arrows X1 and X2 in each figure indicate a direction parallel to the surface direction of the sheet-shaped cell culture 10, and arrows Z1 and Z2 indicate a thickness direction perpendicular to the surface direction of the sheet-shaped cell culture 10 (laminate 20).

[0022] <Sheet-shaped cell culture 10> The sheet-shaped cell culture 10 used in this embodiment can contain any cells capable of constituting the sheet-shaped cell culture 10. Cells constituting the sheet-shaped cell culture 10 include, for example, somatic stem cells (adult stem cells), mesenchymal stem cells, or cardiomyocytes derived from iPS cells (induced pluripotent stem cells). Somatic stem cells preferably include skeletal myoblasts (myoblast cells), fibroblasts, synovial cells, epithelial cells, endothelial cells, etc. Furthermore, the term "sheet-shaped cell culture" as used herein refers to a sheet-like (thin film-like) structure in which cells are interconnected.

[0023] The sheet-shaped cell culture 10 can be configured to have, for example, a substantially circular planar shape (the shape when viewed from the front surface 10a and the back surface 10b) 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, thickness, etc. of the sheet-shaped cell culture 10.

[0024] The sheet-shaped cell culture 10 has a surface 10a, a back surface 10b located opposite the surface 10a and arranged to face the bottom 223 of the container 220, and a peripheral edge 13 having a circular outer shape.

[0025] In this embodiment, the laminate in which the reinforcing layer 30 is formed in a position overlapping at least a portion of the sheet-shaped cell culture 10 is defined as a laminate 20 (see FIGS. 5 and 6).

[0026] The determination method described below can be carried out in a state where the sheet-shaped cell culture 10 is housed in a predetermined container 220 (see FIGS. 3 to 6).

[0027] The container 220 that houses the sheet-shaped cell culture 10 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. Furthermore, when the container 220 is a culture substrate, the solution (liquid culture medium, etc.) used for the culture is appropriately discharged from the container 220 before starting the determination method.

[0028] As shown in FIG. 3, 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 sidewall 225 that surrounds the periphery of the bottom 223.

[0029] The container 220 has a substantially circular planar shape. The bottom 223 of the container 220 has a size (inner diameter) larger than the outer shape of the sheet-shaped cell culture 10 before the reinforcing layer 30 is formed.

[0030] There are no particular limitations on the specific form of the sheet-shaped cell culture 10 (e.g., manufacturing method, physical properties, functions, etc.) and the specific form of the culture substrate (e.g., material, functions, structure and shape, type of liquid medium used, etc.), and known content (e.g., JP 2011-155869 A, JP 2022-106986 A, JP 2021-106609 A, etc.) can be appropriately referred to. Note that the sheet-shaped cell culture 10 used in this embodiment is detached from the culture substrate and placed in the container 220, but is not firmly adhered to the container 220.

[0031] <Determination system 100> To give an overview with reference to Figures 1 and 3 to 5, the determination 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 light irradiation unit 120 that irradiates test light f1 onto a laminate 20 in which fibrin gel is laminated on the sheet-shaped cell culture 10, a detection unit 131 that detects the light transmittance of the test light f1 through the laminate 20, and a determination unit 132 that determines the solidification state of the fibrin gel based on the change in light transmittance detected by the detection unit 131.

[0032] As shown in Figures 1, 3, and 4, 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.

[0033] 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.

[0034] 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.

[0035] 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 of the solutions L1 and L2, the amounts applied per unit time, the volume ratio of the solutions L1 and L2, the application pressure, etc. The specific forms of the solutions L1 and L2 used in this embodiment can be determined by referring to known information (e.g., JP 2016-52272 A, etc.).

[0036] As shown in Figures 3 to 6, the light irradiating unit 120 can be configured with a light source (for example, a known lamp) that irradiates the sheet-shaped cell culture 10 and the laminate 20 contained in the container 220 with inspection light f1 of a predetermined wavelength. There are no particular limitations on the inspection light f1 irradiated by the light irradiating unit 120, but for example, visible light of a predetermined wavelength can be used. The transmittance wavelength can be set to a detection sensitivity of, for example, 400 to 800 nm.

[0037] As shown in Fig. 1, the light irradiating unit 120 can be laid out above the stage 210 on which the container 220 containing the sheet-shaped cell culture 10 is placed. Also, as shown in Figs. 5 and 6, the light irradiating unit 120 can be laid out so as to irradiate the inspection light f1 over the entire range in the planar direction of the sheet-shaped cell culture 10 constituting the laminate 20 (the entire range of the front surface 10a). Note that the light irradiating unit 120 can also be arranged below the stage 210 (the rear surface 10b side of the sheet-shaped cell culture 10) and configured to irradiate the sheet-shaped cell culture 10 with the inspection light f1.

[0038] The control unit 130 is configured to comprehensively control each unit of the determination system 100. The control unit 130 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.

[0039] The storage unit is configured with an HDD (Hard Disc Drive) or an SSD (Solid State Drive) and stores various programs and various data. The storage unit can store a series of programs required for controlling the operation of the determination system 100. The above programs can incorporate algorithms for causing the control unit 130 to function as a detection unit 131, a determination unit 132, and a calculation unit 133.

[0040] The operational control executed by the control unit 130 includes the operation of forming the reinforcing layer 30 by the determination system 100. In carrying out the above operations, the control unit 130 controls the operation of the determination system 100 to execute the following steps: the processing unit 110 forms the reinforcing layer 30 made of fibrin gel on the sheet-shaped cell culture 10; the light irradiation unit 120 irradiates the laminate 20 in which fibrin gel is laminated on the sheet-shaped cell culture 10 with the test light f1; the detection unit 131 detects the light transmittance of the test light f1 through the laminate 20; and the determination unit 132 determines the solidification state of the fibrin gel based on the change in light transmittance detected by the detection unit 131. Specific steps of the determination method will be described later.

[0041] The detection unit 131 is configured to detect the light transmittance based on the image information acquired by the imaging unit 140. Specifically, the detection unit 131 is configured to analyze the image information (image data of the optical image) acquired by the imaging unit 140 and detect the light transmittance as well as the change in the light transmittance over time over a predetermined period of time while the light irradiation unit 120 is irradiating the inspection light f1. The detection of the light transmittance by the detection unit 131 may be performed over the entire range in the planar direction of the sheet-shaped cell culture 10, or may be configured to detect only a predetermined location. In this case, the predetermined location may be the center position o1 of the sheet-shaped cell culture 10 where the thickness of the laminate 20 is likely to increase, the peripheral portion 13 of the sheet-shaped cell culture 10 that can be grasped during transplantation, etc.

[0042] Furthermore, the detection unit 131 is configured to be able to detect locations where the thickness of the fibrin gel is equal to or less than a predetermined value (for example, locations where the thickness of the fibrin gel is equal to or less than 500 μm and the thickness of the laminate 20 is equal to or less than 1 mm) based on the light transmittance of the inspection light f1 irradiated onto the laminate 20 in a state where the fibrin gel has solidified. As shown in FIG. 5, the detection unit 131 irradiates each portion of the laminate 20 with the inspection light f1 in a state where the solidification of the fibrin gel has progressed sufficiently, and detects the light transmittance of each portion of the laminate 20. When the detection unit 131 detects a location in the laminate 20 where the light transmittance is high (a location exceeding a predetermined threshold), it identifies that location as a location in the laminate 20 that does not have a predetermined thickness (a location where a sufficient thickness of fibrin gel has not been formed).

[0043] The determination unit 132 determines the solidification state of the fibrin gel based on the change in light transmittance detected by the detection unit 131. In this case, the determination of the solidification state by the determination unit 132 may be performed over the entire range in the planar direction of the sheet-shaped cell culture 10, or may be performed only at predetermined locations. When the above determination is performed over the entire range in the planar direction of the sheet-shaped cell culture 10, it is possible to identify the distribution of areas where solidification has been completed and areas where solidification has not been completed.

[0044] Generally, the fibrinogen solution L1 and the thrombin solution L2 are colorless and transparent. On the other hand, the fibrin gel has a translucent color with low light transmittance compared to the fibrinogen solution L1 and the thrombin solution L2. Therefore, as the solidification of the fibrin gel progresses, the light transmittance of the fibrin gel gradually decreases. The determination unit 132 determines that the solidification of the fibrin gel is incomplete when the change in the light transmittance within a predetermined time exceeds a preset threshold (i.e., when the decrease in the light transmittance within a predetermined time exceeds a threshold during the gelation of the fibrinogen solution L1 and the thrombin solution L2). Conversely, the determination unit 132 determines that the gelation and solidification of the fibrin gel are complete when the change in the light transmittance within a predetermined time is equal to or less than the preset threshold.

[0045] Furthermore, when the detecting unit 131 identifies a location where the thickness of the fibrin gel is equal to or less than a predetermined value, the determining unit 132 determines whether or not to form additional fibrin gel at the location where the thickness is equal to or less than the predetermined value.

[0046] The calculation unit 133 is programmed to predict the time until the fibrin gel solidifies, based on the change in light transmittance detected by the detection unit 131. Specifically, the calculation unit 133 refers to pre-stored reference data (data relating to light transmittance and the time until solidification), and predicts the time until the fibrin gel solidifies, based on the change in light transmittance detected by the detection unit 131.

[0047] The determination system 100 can notify the time calculated by the calculation unit 133 by voice or display it on the image display unit 150.

[0048] As shown in FIG. 1, the determination system 100 may further include an imaging unit 140 that photographs the sheet-shaped cell culture 10 and fibrin gel, a stage 210 on which a container 220 containing the sheet-shaped cell culture 10 can be placed, and an image display unit 150 that can display an image generated from image information (image data) acquired by the imaging unit 140.

[0049] The image capturing unit 140 can be configured with a known camera device capable of acquiring still image data and / or video data.

[0050] 1, the imaging unit 140 can be laid out above the stage 210 on which the container 220 containing the sheet-shaped cell culture 10 is placed. By laying out the imaging unit 140 in this manner, it becomes possible to capture the entire sheet-shaped cell culture 10 within the imaging field of view from above the stage 210. The placement of the imaging unit 140 is not particularly limited as long as it is possible to photograph the sheet-shaped cell culture 10, and it can also be laid out below the container 220, for example.

[0051] In the determination system 100 according to this embodiment, the detection unit 131 is configured to detect the light transmittance and the change in light transmittance for the stack 20 based on image information acquired by the imaging unit 140. However, the detection unit 131 only needs to be configured to be able to detect the light transmittance and the change in light transmittance for the stack 20 based on the inspection light f1 irradiated onto the stack 20. For example, the determination system 100 can be configured to include a light receiving element capable of receiving the inspection light f1 that has passed through the stack 20, and to detect the light transmittance and the change in light transmittance for the stack 20 based on the inspection light f1 detected by the light receiving element.

[0052] The image display unit 150 can be configured, for example, by a known liquid crystal display or the like.

[0053] The determination system 100 can also be configured as a portable or non-portable information terminal device in which the control unit 130, the imaging unit 140, and the image display unit 150 are integrally incorporated.

[0054] <Judgment method> Next, a forming method according to this embodiment will be described.

[0055] The specific work content of each step will be described below with reference to the flowchart shown in Fig. 2 and Fig. 3 to Fig. 6. In addition, the following description will explain an example in which the determination system 100 shown in Fig. 1 automatically performs steps S11 to S18 of the determination method.

[0056] To start the determination 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).

[0057] Next, the imaging unit 140 starts to capture an image of the sheet-shaped cell culture 10 (step S10).

[0058] Next, as shown in FIG. 3, the fibrinogen solution L1 is supplied (applied) to the sheet-shaped cell culture 10 from the first applicator 111 of the processing section 110 (step S11).

[0059] 3, the light irradiation unit 120 starts irradiating the test light f1 and the detection unit 131 starts detecting the light transmittance (step S12). Note that in the determination method according to this embodiment, the irradiation of the test light f1 and the detection of the light transmittance are continued until all steps are completed.

[0060] 4, a thrombin solution L2 is supplied (applied) to the sheet-shaped cell culture 10 from the second applicator 112 of the processing unit 110 (step S13). 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.

[0061] Next, as shown in FIG. 5, the detector 131 detects the light transmittance (step S14).

[0062] Next, the determination unit 132 determines the solidification state of the fibrin gel based on the light transmittance and the change in light transmittance detected by the detection unit 131 (step S15). If the determination unit 132 determines that the change in light transmittance is equal to or less than the threshold (step S15: NO), it is determined that the solidification of the fibrin gel has progressed sufficiently. In this case, the process proceeds to step S17.

[0063] On the other hand, if the determination unit 132 determines in step S15 that the change in light transmittance exceeds the threshold value (step S15: YES), it is determined that solidification of the fibrin gel is in progress. In this case, the process proceeds to step S16, where the process waits until solidification of the fibrin gel is complete. At this time, the worker manufacturing the laminate 20 can appropriately grasp the waiting time by appropriately checking the time until the fibrin gel solidifies as predicted by the calculation unit 133. This reduces the workload of the worker in manufacturing the laminate 20. Note that when solidification determination is performed over the entire range in the planar direction of the sheet-shaped cell culture 10, the distribution of solidified and incomplete portions can be identified, and the waiting time can be calculated based on the region requiring the longest time for solidification (the condition requiring the longest time for solidification).

[0064] Similarly, steps S14 to S16 are repeated until the determining unit 132 determines that the amount of change in light transmittance is equal to or less than the threshold value (step S15: NO).

[0065] If it is determined in step S15 that the amount of change in light transmittance is equal to or less than the threshold, the detection unit 131 detects a location where the thickness of the laminate 20 is equal to or less than a predetermined value, and the determination unit 132 determines whether or not it is necessary to add fibrin gel (step S17). If the detection unit 131 does not detect a location where the thickness of the laminate 20 is equal to or less than the predetermined value, and the determination unit 132 determines that it is not necessary to add fibrin gel (step S17: NO), the determination method ends.

[0066] If the determination unit 132 determines in step S17 that additional fibrin gel is required, the determination system 100 operates the processing unit 110 (first applicator 111 and second applicator 112) to supply fibrinogen solution L1 and thrombin solution L2 to portions 20a of the laminate 20 where the thickness is equal to or less than a predetermined value (see, for example, FIGS. 5 and 6), thereby forming additional fibrin gel 30A. This prevents the formation of portions of 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.

[0067] Similarly, steps S17 and S18 are repeated until the determining unit 132 determines that no additional fibrin gel needs to be formed (step S17: NO).

[0068] As described above, the determination system 100 according to this embodiment includes 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 light irradiation unit 120 that irradiates the laminate 20 in which fibrin gel is laminated on the sheet-shaped cell culture 10 with test light f1, a detection unit 131 that detects the light transmittance of the test light f1 through the laminate 20, and a determination unit 132 that determines the solidification state of the fibrin gel based on the change in light transmittance detected by the detection unit 131.

[0069] Furthermore, the determination 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 light irradiation unit 120 irradiating test light f1 onto a laminate 20 in which fibrin gel is laminated on the sheet-shaped cell culture 10; a detection unit 131 detecting the light transmittance of the test light f1 through the laminate 20; and a determination unit 132 determining the solidification state of the fibrin gel based on the change in light transmittance detected by the detection unit 131.

[0070] Furthermore, the program for executing the determination method according to this embodiment is a program for causing a determination system 100 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: irradiating test light f1 onto a laminate 20 in which fibrin gel is laminated on a sheet-shaped cell culture 10; detecting the light transmittance of the test light f1 through the laminate 20; and determining the solidification state of the fibrin gel based on the change in the detected light transmittance.

[0071] According to this embodiment, the laminate 20, in which fibrin gel is laminated on a sheet-shaped cell culture 10, is irradiated with the inspection light f1, the detection unit 131 detects the light transmittance of the inspection light f1 and the change in the light transmittance over time, and the determination unit 132 determines the solidification state of the fibrin gel based on the detection result of the detection unit 131. This reduces the workload of the worker manufacturing the laminate 20 and prevents a decrease in the product quality of the laminate 20 due to the formation of unsolidified fibrin gel.

[0072] The system for determining the solidification state of a fibrin gel, the method for determining the solidification state of a fibrin gel, and the program according to the present invention have been described through the embodiments, but the present invention is not limited to the configurations described in the embodiments, and can be modified as appropriate based on the claims.

[0073] For example, as shown in the flowchart of the modified determination method in Figure 7, the steps of adding fibrin gel 30A to areas where the thickness of the laminate 20 is below a predetermined value (steps S17 and S18 in Figure 2) can be omitted as appropriate. [Explanation of symbols]

[0074] 10. Sheet-shaped cell culture 20 laminate 20a Where the thickness of the laminated layer is below the specified value 30 Reinforcement layer 30A Additional fibrin gel 100 Judgment System 110 Processing section 111 First application section 112 Second application section 120 Light irradiation unit 130 control section 131 Detector 132 Judgment section 133 Calculation Unit 140 Imaging unit 150 Image display unit 210 Stages 220 Container L1 fibrinogen liquid L2 thrombin solution f1 inspection light

Claims

1. a processing unit that performs a process to form a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a light irradiation unit that irradiates an inspection light onto a laminate in which the fibrin gel is laminated on the sheet-shaped cell culture; a detection unit that detects the light transmittance of the inspection light through the laminate; a determination unit that determines the solidification state of the fibrin gel based on the change in light transmittance detected by the detection unit.

2. The system for determining the solidification state of a fibrin gel according to claim 1 , further comprising a calculation unit that predicts the time until the fibrin gel solidifies based on the change in light transmittance detected by the detection unit.

3. the light irradiating unit irradiates the laminate with the inspection light when the determining unit determines that the fibrin gel is in a solidified state; the detection unit detects a portion where the thickness of the fibrin gel is equal to or less than a predetermined value based on the light transmittance of the inspection light irradiated onto the laminated body in a state where the fibrin gel has solidified; The system for determining the solidification state of fibrin gel according to claim 1 , wherein the determination unit determines whether or not to form additional fibrin gel at a location where the thickness of the fibrin gel is equal to or less than a predetermined value.

4. an imaging unit for imaging the sheet-shaped cell culture and the fibrin gel; The system for determining the solidification state of a fibrin gel according to any one of claims 1 to 3, wherein the detection unit detects the light transmittance based on image information acquired by the imaging unit.

5. a step in which a processing unit forms a reinforcing layer made of fibrin gel on the sheet-shaped cell culture; a step in which a light irradiation unit irradiates an inspection light onto a laminate in which the fibrin gel is laminated on the sheet-shaped cell culture; a detection unit detecting the light transmittance of the inspection light through the laminate; a determining unit determining the solidification state of the fibrin gel based on the change in light transmittance detected by the detecting unit.

6. 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, irradiating an inspection light onto a laminate in which the fibrin gel is laminated on the sheet-shaped cell culture; detecting the optical transmittance of the inspection light through the laminate; determining a solidification state of the fibrin gel based on the detected change in light transmittance.

Images