WO2021008472A1

WO2021008472A1 - Cell sheet transfer device and transport apparatus, and method for transferring cell sheet

Info

Publication number: WO2021008472A1
Application number: PCT/CN2020/101540
Authority: WO
Inventors: 高爽; 杜志宏; 靳新; 吴峥; 常德华
Original assignee: 京东方科技集团股份有限公司
Priority date: 2019-07-15
Filing date: 2020-07-13
Publication date: 2021-01-21
Also published as: CN112221543A; CN112221543B

Abstract

A cell sheet transfer device (20), a cell sheet transport apparatus (30), and a method for transferring a cell sheet (11) by using the cell sheet transport apparatus (30). The cell sheet transfer device (20) comprises: a bottom plate (201) and a lifting portion (202) provided at the edge of the bottom plate (201), wherein the bottom plate (201) is configured to carry the cell sheet (11). The bottom plate (201) is provided with a liquid channel (203), and the liquid channel (203) is configured to penetrate through the bottom plate (201) along the thickness direction of the bottom plate (201). The cell sheet transfer device (20) is provided in the cell sheet transport apparatus (30). The cell sheet transfer device (20) can ensure that the cell sheet (11) is not damaged during the process of transporting the cell sheet (11); moreover, the cell sheet (11) can be quickly and accurately transferred and attached to the surface of an organ or tissue to be repaired.

Description

Cell sheet layer transfer device, transport device and method for transferring cell sheet layer

This application claims the priority of the Chinese patent application No. 201910637375.1 filed on July 15, 2019, and the content of the above-mentioned Chinese patent application is quoted here in full as a part of this application.

Technical field

The embodiments of the present disclosure relate to a cell sheet transfer device, a cell sheet transport device, and a method for transferring a cell sheet using the cell sheet transport device.

Background technique

Cell sheet (cell membrane) is a research hotspot in the field of tissue engineering, and has a wide range of applications in the treatment of skin, cornea, heart, liver, periodontal, bone marrow and other related diseases. The formation of cell sheets by in vitro culture of primary cells, for example, the use of nerve cells, bone marrow stromal stem cells, etc. to form cell sheets has become a hot spot in the field of regenerative medicine, and there are already mature methods for preparing cell sheets.

Summary of the invention

At least one embodiment of the present disclosure provides a cell sheet transfer device. The cell sheet transfer device includes: a bottom plate and a lifting part arranged at an edge of the bottom plate, wherein the bottom plate is configured to carry the cell sheet; The bottom plate has a liquid channel, and the liquid channel is configured to penetrate the bottom plate along a thickness direction of the bottom plate.

For example, in the cell sheet transfer device provided by at least one embodiment of the present disclosure, the lifting part and the bottom plate are movably connected at the connection point, so that the angle between the lifting part and the main surface of the bottom plate is Adjustable.

For example, in the cell sheet transfer device provided by at least one embodiment of the present disclosure, the lifting part is provided at two positions opposite to each other at the edge of the bottom plate.

For example, in the cell sheet transfer device provided by at least one embodiment of the present disclosure, the planar shape of the bottom plate is rectangular or circular.

For example, in the cell sheet transfer device provided by at least one embodiment of the present disclosure, the planar shape of the liquid channel is at least one of a circle, a rectangle, a square, a triangle, an ellipse, a diamond, or a sector.

For example, in the cell sheet transfer device provided by at least one embodiment of the present disclosure, the materials of the bottom plate and the lifting part are both biocompatible materials.

For example, in the cell sheet transfer device provided by at least one embodiment of the present disclosure, the biocompatible material includes titanium, titanium alloy, polycaprolactone, polylactic acid, polyethylene, polypropylene, polyethylene glycol, Among polystyrene, nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethyleneimine, polysulfone, polymethacrylate, polyurethane, polyterephthalic acid, sodium silicate, glass or alumina At least one.

At least one embodiment of the present disclosure further provides a cell sheet transport device. The cell sheet transport device includes a storage container, a cover layer, and the cell sheet transfer device according to any one of the above, wherein the storage container includes Groove, the groove has a side wall and a bottom surface; the cell sheet transfer device is arranged in the groove; the covering layer is arranged on the storage container, and the cell sheet transfer device is in the Between the storage container and the cover layer, there is a gap between the cover layer and the bottom plate of the cell sheet transfer device in a direction perpendicular to the bottom surface.

For example, in the cell sheet transport device provided by at least one embodiment of the present disclosure, a support column is arranged in the groove, and the support column protrudes toward a side away from the bottom surface.

For example, in the cell sheet transport device provided by at least one embodiment of the present disclosure, the cell sheet transfer device is arranged on a side of the support column close to the covering layer, and the size of the gap is 0.1 mm~ 0.5mm.

For example, in the cell sheet transport device provided by at least one embodiment of the present disclosure, the support column penetrates the cell sheet transfer device at the liquid channel, and in a direction perpendicular to the bottom surface, the support column The distance between the surface away from the bottom surface and the covering layer is 0.1 mm to 0.5 mm.

For example, in the cell sheet transport device provided by at least one embodiment of the present disclosure, the cover layer is detachably combined with the storage container.

For example, in the cell sheet transport device provided by at least one embodiment of the present disclosure, the covering layer is a water-blocking and gas-permeable layer.

For example, in the cell sheet transport device provided by at least one embodiment of the present disclosure, the material of the covering layer includes polyurethane rubber or silica gel.

For example, the cell sheet transport device provided by at least one embodiment of the present disclosure further includes: a bearing layer provided on the cell sheet transfer device, wherein the material of the bearing layer has a lower bending strength than the cell sheet Transfer the bending strength of the device.

For example, in the cell sheet transport device provided by at least one embodiment of the present disclosure, the storage container includes a plurality of the grooves, and each of the grooves is provided with the cell sheet transfer device.

At least one embodiment of the present disclosure further provides a method for transferring a cell sheet using the cell sheet transport device described in any one of the above, and the method for transferring the cell sheet includes: placing the cell sheet on the cell In the sheet transport device, wherein the cell sheet is located between the covering layer and the cell sheet transfer device; the covering layer is removed, and the cell sheet and the cell sheet are taken out by the extracting part. The cell sheet layer transfer device; the cell sheet layer is transferred to the tissue or organ to be repaired.

Description of the drawings

In order to explain the technical solutions of the embodiments of the present disclosure more clearly, the following will briefly introduce the drawings of the embodiments. Obviously, the drawings in the following description only relate to some embodiments of the present disclosure, rather than limit the present disclosure. .

Figure 1 is a schematic diagram of a cell sheet transfer process;

2 is a schematic diagram of a planar structure of a cell sheet transfer device provided by an embodiment of the disclosure;

3 is a schematic diagram of a planar structure of a cell sheet transfer device provided by still another embodiment of the present disclosure;

4 is a schematic plan view of a cell sheet transfer device provided by another embodiment of the present disclosure;

5 is a schematic diagram of a planar structure of a cell sheet transfer device provided by another embodiment of the present disclosure;

6 is a schematic diagram of the planar structure of the lifting portion of the cell sheet transfer device in FIG. 5 after being flattened;

FIG. 7 is a schematic diagram of a planar structure of a cell sheet transfer device provided by another embodiment of the present disclosure;

FIG. 8 is a schematic cross-sectional structure diagram of a cell sheet transport device provided by an embodiment of the present disclosure;

Fig. 9 is a schematic diagram of a cross-sectional structure of a cell sheet transport device provided by still another embodiment of the present disclosure;

10 is a schematic diagram of a planar structure of the cell sheet transfer device in FIG. 9 provided with a carrier layer;

11 is a schematic diagram of a planar structure of a cell sheet transport device provided by an embodiment of the disclosure;

12 is a schematic cross-sectional structure diagram of a cell sheet transport device provided by another embodiment of the present disclosure; and

FIG. 13 is a flowchart of a method for transferring a cell sheet by a cell sheet transport device according to an embodiment of the disclosure.

Reference signs:

11-cell sheet layer; 12-carrying material layer; 20-cell sheet layer transfer device; 201-bottom plate; 202-lifting part; 203-liquid channel; 204-handle; 205-first connection part; 206-second connection Section; 207-carrying layer; 30-cell sheet transport device; 31-preservation container; 32-covering layer; 311-groove; 3111-side wall; 3112-bottom; 33-gap; 34-support column.

Detailed ways

In order to make the objectives, technical solutions, and advantages of the embodiments of the present disclosure clearer, the technical solutions of the embodiments of the present disclosure will be described clearly and completely in conjunction with the accompanying drawings of the embodiments of the present disclosure. Obviously, the described embodiments are part of the embodiments of the present disclosure, rather than all of the embodiments. Based on the described embodiments of the present disclosure, all other embodiments obtained by those of ordinary skill in the art without creative labor are within the protection scope of the present disclosure.

Unless otherwise defined, the technical terms or scientific terms used in the present disclosure shall have the usual meanings understood by those with ordinary skills in the field to which this disclosure belongs. The "first", "second" and similar words used in the present disclosure do not indicate any order, quantity, or importance, but are only used to distinguish different components. "Include" or "include" and other similar words mean that the element or item appearing before the word encompasses the element or item listed after the word and its equivalents, but does not exclude other elements or items. Similar words such as "connected" or "connected" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "Up", "Down", "Left", "Right", etc. are only used to indicate the relative position relationship. When the absolute position of the described object changes, the relative position relationship may also change accordingly.

All terms (including technical or scientific terms) used in the present disclosure have the same meanings as understood by those of ordinary skill in the art to which the present disclosure belongs, unless specifically defined otherwise. It should also be understood that terms defined in, for example, general-purpose dictionaries should be interpreted as having meanings consistent with their meanings in the context of the relevant technology, and should not be interpreted using idealized or extremely formal definitions, unless explicitly so. definition.

For example, the preparation process of the cell sheet is generally complicated, the preparation cycle is longer, and the preparation cost is higher. The cell sheet is very thin, fragile, and has a three-dimensional structure. During the process of culturing, peeling, washing, storing and transporting the cell sheet, it is easy to cause the cell sheet to tear, fold or break, thereby affecting the subsequent cell sheet The use of layers brings great difficulties to the application of cell sheets in clinical medicine. For example, Figure 1 is a schematic diagram of a cell sheet transfer process. As shown in Figure 1, before the cell sheet 11 is transferred from the carrier material layer 12, the cell sheet 11 is laid flat on the carrier material layer 12, and the cell sheet 11 maintains a complete circle; After 11 is separated from the carrier material layer 12, the edge of the cell sheet 11 becomes no longer flat, and the cell sheet 11 is damaged or wrinkled.

The inventors of the present disclosure found that the carrier material layer 12 shown in FIG. 1 is not provided with a channel for liquid circulation. After the cell sheet is transported, the cell sheet 11 and the carrier material layer 12 are removed from the culture solution. When taking it out, the carrier material layer 12 needs to be tilted to pour out the culture solution on it, which easily causes the cell sheet 11 to slip off the carrier material layer 12, thereby causing damage to the cell sheet. Even if the cell sheet 11 does not slip off, in the process of collecting the cell sheet 11, for example, by cooling the cell sheet 11 and the carrier material layer 12 into an easily detached state, then use a cell shovel to scoop up the cell sheet 11 Or use special tweezers to clamp the cell sheet 11 to peel the cell sheet 11 from the carrier material layer 12 to transfer the cell sheet 11, the cell sheet 11 is also easily damaged.

The inventor of the present disclosure also found that the carrier material layer 12 shown in FIG. 1 is usually laid on two opposite side walls of the groove to ensure that the nutrient solution in the groove flows and the nutrient solution does not pass the carrier material layer 12 Thereby providing nutrition for the cell sheet 11, but the opening of the groove is wider, and the bearing material layer 12 has a certain bending ability. This will cause the cell sheet 11 and the bearing material layer 12 to be transported during the cell sheet 11 transportation. Leaking into the groove, and the shear force of the liquid in the nutrient solution will also damage the cell sheet 11. Therefore, the method of transferring the cell sheet shown in Figure 1 cannot guarantee that the cell sheet will not be damaged during the process of transporting the cell sheet, nor can the cell sheet be quickly and accurately transferred and attached to the organ to be repaired. Or the surface of the organization. Therefore, a specific cell sheet transport device is required to ensure that the cell sheet is in a flat environment and reduce the damage to the cell sheet by the liquid shearing force. At the same time, the cell sheet transport device also needs to be able to hold a certain amount of cells. The culture solution (including the transportation protection solution) provides the nutrient materials needed during the transportation process and a certain storage period for the cell sheet.

At least one embodiment of the present disclosure provides a cell sheet transfer device. The cell sheet transfer device includes: a bottom plate and a lifting part arranged on the edge of the bottom plate, the bottom plate is configured to carry the cell sheet; the bottom plate has a liquid channel, and the liquid channel is configured To penetrate the bottom plate along the thickness direction of the bottom plate. The lifting part and the liquid channel in the cell sheet transfer device cooperate with each other to ensure that the cell sheet is not damaged during the process of transporting the cell sheet, and at the same time, the cell sheet can be quickly and accurately transferred and attached to the cell sheet. The surface of the repaired organ or tissue.

For example, FIG. 2 is a schematic diagram of a planar structure of a cell sheet transfer device provided by an embodiment of the present disclosure. As shown in FIG. 2, the cell sheet transfer device 20 includes: a bottom plate 201 and a lifting portion 202 provided on the edge of the bottom plate 201, the bottom plate 201 is configured to carry the cell sheet (the cell sheet is not shown in FIG. 2); 201 has a liquid channel 203 which is configured to penetrate the bottom plate 201 along the thickness direction of the bottom plate 201. When transferring the cell sheet, the cell sheet is located on the bottom plate 201, which can ensure that the cell sheet is flat to avoid the cell sheet from wrinkling. The lifting part 202 at the edge of the bottom plate 201 can ensure that the cell sheet is smoothly removed from the culture. The liquid is removed, and the bottom plate 201 has a liquid channel 203 so that the culture liquid can leak out without tilting the bottom plate.

For example, the lifting portion 202 may be a linear or rod-shaped member, and its material may be the same as or different from that of the bottom plate. However, the embodiment according to the present disclosure is not limited to this, and it may also have other shapes as long as the bottom plate can be lifted by the lifting part.

For example, in FIG. 2, the number of lifting parts 202 is two, and the two lifting parts 202 are arranged at two positions opposite to each other on the edge of the bottom plate 201, which can ensure that the cell sheet is more smoothly removed from the culture solution. . The cell sheet transfer device can be directly attached to the surface of the tissue or organ to be repaired on the side where the cell sheet is provided to ensure that the cell sheet is more stably transferred to the surface of the tissue or organ to be repaired. In other embodiments of the present disclosure, the number of lifting parts 202 can also be more or one, which is not limited here.

For example, FIG. 3 is a schematic diagram of a planar structure of a cell sheet transfer device provided by still another embodiment of the present disclosure. As shown in Figure 3, the number of the lifting part 202 is one, and the lifting part 202 is only provided at one position on the edge of the bottom plate 201, so as to ensure that the cell sheet can be smoothly removed from the culture solution while simplifying The structure of the cell sheet transfer device 20.

For example, the planar shape of the bottom plate 201 is rectangular or circular, and the shape of the bottom plate 201 in FIGS. 2 and 3 is both circular. The planar shape of the bottom plate 201 is rectangular or circular, which can ensure that the bottom plate 201 is more stably fixed in the area defined by the groove in the cell sheet transport device involved, so that the cell sheet can be more stably stored in the culture medium. in.

For example, FIG. 4 is a schematic diagram of a planar structure of a cell sheet transfer device provided by another embodiment of the present disclosure. As shown in FIG. 4, the shape of the bottom plate 201 is rectangular for better and subsequent cell sheet transportation. The cross-sectional shape of the groove in the device matches. For example, two opposite sides of the rectangular bottom plate 201 are symmetrically provided with lifting parts 202.

For example, FIG. 5 is a schematic diagram of a plan structure of a cell sheet transfer device provided by another embodiment of the present disclosure. As shown in FIG. 5, the lifting portion 202 and the bottom plate 201 are movably connected at the joint, so that the lifting portion 202 and The angle between the main surfaces of the bottom plate 201 can be adjusted, so that the subsequently placed cell sheet (not shown in the figure) is better transferred to the tissue or organ to be repaired. For example, the adjustable range of the angle between the lifting portion 202 and the main surface of the bottom plate 201 is 90° to 180°. The adjustable angle range is continuous and can be accurate to 0.1°.

For example, the lifting portion 202 of the cell sheet transfer device 20 and the bottom plate 201 are movably connected at the joint, which facilitates the subsequent reversal of the cell sheet after the subsequent harvesting of the cell sheet, so as to realize the attachment of the cell sheet to the tissue or organ to be repaired. That is, the cell sheet transfer device can be used as a cell sheet transplantation tool.

For example, as shown in FIG. 5, the lifting part 202 and the bottom plate 201 are provided with a first connecting part 205 at the connection position, and the first connecting part 205 can make the angle between the lifting part 202 and the main surface of the bottom plate 201 adjustable.

For example, the first connection portion 205 may be an articulated connection structure, as long as the relative angle adjustment between the lifting portion 202 and the bottom plate 201 can be satisfied, the specific structure of the first connection portion 205 is not particularly limited in the embodiment of the present disclosure.

For example, FIG. 6 is a schematic plan view of the lifting portion 202 of the cell sheet transfer device in FIG. 5 after being flattened. As shown in FIG. 6, by adjusting the angle between the lifting portion 202 and the main surface of the bottom plate 201 to 180°, the turning process can be performed more conveniently, and the cell sheet can be more stably attached to the tissue or organ to be repaired. According to different application scenarios, the angle between the lifting portion 202 and the main surface of the bottom plate 201 can be adjusted to other suitable angles.

For example, FIG. 7 is a schematic plan view of a cell sheet transfer device provided by another embodiment of the present disclosure. As shown in FIG. 7, a handle 204 is also provided on the side of the lifting portion 202 away from the bottom plate 201. Since the side of the lifting part 202 close to the bottom plate is too thin, it is inconvenient to lift the cell sheet. By setting the handle 204, the contact area of the lifting part 202 is increased, which makes it easier to remove the cell sheet smoothly. Remove from the culture medium.

In an example, the handle 204 may be provided with an uneven surface, which can increase the roughness of the handle, and is more conducive to taking out the cell sheet transfer device 20.

For example, the handle 204 and the lifting portion 202 can also be movably connected. As shown in FIG. 7, a second connecting portion 206 is provided between the handle 204 and the lifting portion 202, which facilitates the operation in a limited space. operating.

For example, the second connecting portion 206 may be an articulating connection structure, as long as the relative angle adjustment between the lifting portion 202 and the handle 204 can be satisfied, the specific structure of the second connecting portion 206 is not particularly limited in the embodiment of the present disclosure.

For example, the planar shape of the liquid channel 203 is at least one of a circle, a rectangle, a square, a triangle, an ellipse, a rhombus, or a fan shape. Designing the liquid channel 203 into the above-mentioned regular shape can better realize that the bottom plate 201 can pass through the supporting columns in the cell sheet transport device mentioned later, so that the sizes of the liquid channels and supporting columns can be designed more conveniently.

In the above-mentioned FIG. 2, FIG. 3, and FIG. 5 to FIG. 7, the planar shape of the liquid channel 203 is described as an example. The area of each sector is equal, that is, the area of each liquid channel 203 is equal. In the above FIG. 4, the planar shape of the liquid channel 203 is a right-angled triangle as an example for illustration. The area of each right-angled triangle is equal, that is, the area of each liquid channel 203 is equal. The area of each liquid channel 203 in FIGS. 2-7 is equal, so that the bottom plate 201 can be divided more evenly, and the area of each liquid channel 203 is equal, which is more conducive to the uniformity of the distribution of the culture solution.

For example, in some embodiments of the present disclosure, the materials of the bottom plate 201 and the lifting portion 202 are both biocompatible materials. By using biocompatible materials, the adverse effects on the cell sheet can be reduced during the process of transferring the cell sheet and before the cell sheet is transferred.

For example, the bottom plate 201 and the lifting portion 202 are made of hard materials, which is beneficial to the stability of the structure.

For example, the biocompatible material includes metals with good biocompatibility, such as titanium or titanium alloys, and the biocompatible materials include nonmetals with good biocompatibility, such as polycaprolactone, polylactic acid, Polyethylene, polypropylene, polyethylene glycol, polystyrene, nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethyleneimine, polysulfone, polymethacrylate, polyurethane, polyterephthalic acid , At least one of sodium silicoborate or glass; biocompatible materials also include metal oxides with good biocompatibility, such as alumina.

For example, the cell sheet transfer device provided by the embodiment of the present disclosure can conveniently take out the cell sheet. The cell sheet transfer device has a liquid channel, which can not only mechanically support the cell sheet when the cell sheet is taken out, but also allow liquid to flow through the liquid channel, avoiding the attraction of the cell sheet by the surface tension when the cell sheet is detached from the liquid The effect of force makes the cell sheet easier to be transferred and used, thereby avoiding the damage to the cell sheet caused by gripping the cell sheet with tweezers and other hard sharp instruments.

For example, you can hold the handle of the cell sheet transfer device to take out the cell sheet and turn the bottom plate so that the side of the bottom plate carrying the cell sheet faces the position where the cell sheet needs to be attached, so that the cell sheet transfer device can be transferred. The loaded cell sheet is accurately attached to the tissue or organ to which the cell sheet needs to be attached to facilitate the operation of the operation.

At least one embodiment of the present disclosure also provides a cell sheet transport device. For example, FIG. 8 is a schematic cross-sectional structure diagram of a cell sheet transport device provided by an embodiment of the disclosure. The cell sheet transport device 30 includes: a storage container 31, a cover layer 32, and the cell sheet transfer device 20 in any of the above embodiments, wherein the storage container 31 includes a groove 311, and the groove 311 has side walls 3111 and The bottom surface 3112; the cell sheet layer transfer device 20 is arranged in the groove 311; the covering layer 32 is arranged on the storage container 31, and the cell sheet layer transfer device 20 is located between the storage container 31 and the covering layer 32, at a position perpendicular to the bottom surface 3112 In the direction, there is a gap between the cover layer 32 and the bottom plate 201 of the cell sheet transfer device 20.

For example, the cell sheet transport device can maintain the flatness of the cell sheet surface and reduce the damage to the cell sheet by the liquid shearing force. At the same time, the cell sheet transport device can contain a certain amount of nutrient solution (such as transport protection solution) to provide a stable storage environment for the cell sheet, maintain the acid-base balance and osmotic pressure balance of the surrounding environment of the cell sheet, and help The cell sheet provides the required nutrients. In addition, the detachable cell sheet transfer device included in the cell sheet transport device can conveniently take out the cell sheet and transfer it to the tissue or organ to be repaired.

For example, as shown in FIG. 8, a supporting column 34 is provided in the groove 311, and the supporting column 34 protrudes toward a side away from the bottom surface 3112. For example, the support column 34 provides mechanical support for the cell sheet. In this way, compared to the case where the support column 34 only has the sidewall 3111 of the groove 311, the support column 34 can make the cell sheet more effective in the cell sheet transport device. It is stable, and will not fall into the groove 311 due to its own gravity to form wrinkles or be damaged.

For example, the embodiment of the present disclosure has no special limitation on the size of the bottom surface 3112 of the groove 311, as long as the size of the bottom surface 3112 of the groove 311 is compatible with the size of the cell sheet contained.

For example, the cell sheet includes one or more living cells. During the process of transporting the cell sheet, it is necessary to maintain the stability of the cell sheet growth environment by the culture medium (including the transportation protection liquid) and provide a certain culture medium (including the transportation Protection liquid) supply. In the case of the support column provided in the groove, the bottom surface of the storage container is connected to each other. This interconnected design improves the capacity of the storage container in the limited space of the culture solution (including the transportation protection solution), and at the same time facilitates the growth of the culture solution Circulation facilitates nutrient exchange between the culture medium and the cell sheet, and provides a stable environment and nutrient supply for the cell sheet. In addition, the circulation of the culture fluid can make the nutrients everywhere uniform, so that the nutrients and oxygen in the culture fluid can be fully utilized.

For example, the buffer solution used to balance the pH in the culture medium includes: 4-hydroxyethylpiperazine ethanesulfonic acid (HEPE) and phosphate buffer solution.

For example, the main components of the transport protection solution are human blood protein, human alpha globulin, beta globulin, sodium pyruvate, sodium chloride, magnesium sulfate, ethylenediaminetetraacetic acid (EDTA), glucose, and various amino acids.

For example, as shown in FIG. 8, the support column 34 penetrates the cell sheet transfer device 20 at the liquid channel (not shown in FIG. 8). In the direction perpendicular to the bottom surface 3112, the surface of the support column 34 away from the bottom surface 3112 and covers The spacing between the layers 34 is 0.1 mm˜0.5 mm, so that the cell sheet layer transfer device 20 is more stable in the groove 311. In this way, in the process of transporting the cell sheet, the cell sheet is located on the support column, and the distance between the surface of the support column 34 away from the bottom surface 3112 and the covering layer 34 is exactly the thickness of the cell sheet. The space for movement is small, which can reduce the chance of folds in the cell sheet. When it is necessary to fish the cell sheet from the culture solution, the cell sheet transfer device 20 can be taken out vertically, so that when the bottom plate 201 of the cell sheet transfer device 20 moves to the end of the support column 34 close to the cover layer 32, the cells The sheet falls onto the bottom plate 201 of the cell sheet transfer device 20, so that the cell sheet and the cell sheet transfer device 20 can be easily taken out through the extraction part 202.

For example, FIG. 9 is a schematic cross-sectional structure diagram of a cell sheet transport device provided by another embodiment of the present disclosure. The cell sheet transfer device 20 is arranged on the side of the support column 34 close to the cover layer 32. The cell sheet transfer device 20 is placed on the support column 34, the bottom plate 201 of the cell sheet transfer device 20 does not pass through the support column 34, and the size of the gap 33 between the bottom plate 201 of the cell sheet transfer device 20 and the cover layer 32 is 0.1 mm ~ 0.5 mm, The size of the gap is roughly the thickness of the cell sheet, which can reduce the space for the cell sheet to move, thereby reducing the probability of wrinkling of the cell sheet.

For example, the gap 33 provides space for subsequent placement of the cell sheet, and considering that the cell sheet is soft and prone to folds and folds, the gap is designed to be small enough so that there is no extra space for the cell sheet to fold or fold.

For example, in the schematic cross-sectional structure diagrams of the cell sheet transport device shown in FIGS. 8 and 9, a buckle or locking part may be designed at the position of the storage container 31 corresponding to the lifting part 202 of the cell sheet transfer device 20, The cell sheet transfer device 20 can be more firmly combined with the cell sheet transport device 30, thereby preventing the cell sheet transfer device 20 from moving during the process of transporting the cell sheet, causing damage to the cell sheet.

For example, in the schematic cross-sectional structure diagrams of the cell sheet transport device shown in FIGS. 8 and 9, the covering layer 32 is detachably combined with the storage container 31, so that the covering layer 32 can be easily removed from the storage container 31.

For example, the covering layer 32 and the storage container 31 can be combined by simple mechanical fastening, and the covering layer 32 and the storage container 31 can also be combined in other ways, such as threaded connection, snap connection or hinge connection.

For example, the material of the cover layer 32 is a soft material or a hard material. When the material of the covering layer 32 is a hard material, it can provide better protection for the cell sheet transport device 30. When the material of the covering layer 32 is a soft material, the soft material can be deformed to a certain extent, so as to eliminate as many bubbles as possible and reduce the damage to the cell sheet by the liquid shearing force during transportation.

For example, when the cover layer 32 is combined with the storage container 31 in a manner such as screw connection, snap connection or hinge connection, different parts of the cover layer 32 may be formed of different materials. For example, the threaded fixing part uses a hard material, and the covering part uses a soft material. In this way, the stability of the connecting part can be satisfied at the same time, and the gap between the covering part storage container 31 and the covering layer 32 can be reduced as much as possible, so that the space for the cell sheet to move becomes smaller.

For example, the cover layer 32 is a water-blocking and breathable layer. The water-blocking and air-permeable layer can prevent the transportation protection liquid from flowing out while not blocking the air flow. For example, the material of the water-blocking and gas-permeable layer is polytetrafluoroethylene, and the covering layer 32 formed of a material with water-blocking and gas-permeable properties can facilitate gas exchange between the cell sheet and the external environment, that is, the cell sheet is transported and stored for a long time. During the process, oxygen and carbon dioxide can be exchanged with the outside world, which helps to maintain the balance of oxygen concentration in the cell sheet transport device and facilitates the preservation of the cell sheet.

For example, when the material of the covering layer 32 is a soft material, the material of the covering layer 32 includes urethane rubber or silicone.

For example, when the cell sheet to be transported is formed by relatively fragile cells such as nerve cells, the cell sheet transport device 30 may further include: a carrier layer arranged on the cell sheet transfer device 20 (due to the carrier layer being too thin in the figure The carrier layer is not shown in 8 and 9). In the structure shown in FIG. 8, in the process of transporting the cell sheet, the bearing layer is directly arranged on the supporting column 34 and not directly arranged on the cell sheet transfer device 20. When the cell sheet is picked up, the carrier layer is directly located on the cell sheet transfer device 20. In the structure shown in FIG. 9, the cell sheet layer may also be directly disposed on the carrier layer, which is disposed on the side of the cell sheet layer transfer device 20 close to the cover layer 34.

For example, FIG. 10 is a schematic diagram of a planar structure of the cell sheet transfer device in FIG. 9 provided with a carrier layer. As shown in FIG. 10, the carrier layer 207 is disposed on the cell sheet transfer device 20. The carrier layer 207 can cover the entire bottom plate 201 of the cell sheet transfer device 20 or cover a part of the bottom plate 201 of the cell sheet transfer device 20. .

For example, the bending strength of the material of the supporting layer is less than the bending strength of the cell sheet transfer device 20. In this way, the cell sheet can be attached to a bearing layer with lower bending strength for transportation, thereby ensuring the integrity of the cell sheet.

It should be noted that bending strength refers to the maximum stress that a material can withstand when it ruptures or reaches a specified bending moment under a bending load. The maximum stress is the maximum normal stress when the material is bent, in MPa (megapascals) as the unit. It reflects the ability of the material to resist bending and is used to measure the bending performance of the material. The greater the bending strength, the stronger the rigidity of the material; the smaller the bending strength, the stronger the flexibility of the material.

Alternatively, the elastic modulus of the material of the supporting layer is smaller than the elastic modulus of the cell sheet transfer device. It should be noted that the modulus of elasticity is an index that measures the difficulty of elastic deformation of a material. The larger the value, the greater the stress that causes the material to undergo a certain elastic deformation, that is, the greater the stiffness of the material, that is, the greater the stiffness of the material, that is, when a certain stress acts Bottom, the less elastic deformation occurs.

For example, the material of the supporting layer is a film or sheet material with good biocompatibility, and the material of the supporting layer can be processed by surface treatment to improve the attachment ability of the cell sheet thereon. For example, the surface treatment process includes cationic treatment or grafting of organic functional groups.

For example, using a carrier layer to carry the cell sheet can make the cell sheet closely adhere to the carrier layer without any external force. In addition, due to the soft texture and smooth surface of the carrier layer, not only the cell sheet is easy to be laid on the carrier layer in a flat and wrinkle-free form, but the carrier layer also functions as a protective pad and cushion for the cell sheet.

For example, the material of the supporting layer includes at least one temperature-sensitive material selected from poly-N-isopropylacrylamide (PIPAAm), a complex of N-isopropylacrylamide and methacrylic acid, and lysine peptide. By adjusting the temperature, when the temperature felt by the carrier layer reaches a specific condition, for example, when the temperature is increased/decreased to a specific temperature, the cell sheet changes from a state close to the temperature-sensitive material to an easily detached state, thereby facilitating the harvest of the cell sheet And collection.

For example, FIG. 11 is a schematic diagram of a planar structure of a cell sheet transport device provided by an embodiment of the present disclosure. As shown in FIG. 11, the cell sheet transfer device 20 in the cell sheet transport device 30 is overlapped on the side wall 3111 of the groove 311, and the storage container 31 is the external body of the cell sheet transport device 30.

For example, FIG. 12 is a schematic cross-sectional structure diagram of a cell sheet transport device provided by another embodiment of the present disclosure. As shown in FIG. 12, one storage container 31 in a cell sheet transport device 30 may include a plurality of grooves 311, and each groove 311 is provided with a cell sheet transfer device 20. A cover layer 32 is provided in the interior.

For example, in FIGS. 8, 9 and 12, the cover layer 32 may also be provided with a sealing ring to seal the protection container 31 when the cover layer 32 is placed on the protection container 31 to prevent leakage of the protective transport liquid.

For example, in FIGS. 8, 9 and 12, a handle can also be provided on the protective container 31 to facilitate the user to carry the large-volume cell sheet transport device 30.

For example, the cell sheet transport device is formed by an additive manufacturing (AM) method, that is, a 3D printing method. The cell sheet transport device can also be formed by casting.

The embodiment of the present disclosure also provides a method for transferring cells by using the cell sheet transport device in any of the above embodiments. For example, FIG. 13 is a cell sheet transport device provided by an embodiment of the present disclosure to transfer cells Flow chart of the slice method. As shown in Figure 13, the method for transferring cell sheets includes:

S101: Place the cell sheet in the cell sheet transport device, wherein the cell sheet is located between the cover layer and the cell sheet transfer device;

S102: Remove the covering layer, and take out the cell sheet and the cell sheet transfer device through the extracting part;

S103: Transfer the cell sheet to the tissue or organ to be repaired.

For example, before transferring the cell sheet to the tissue or organ to be repaired, the angle between the extraction part and the bottom plate may be adjusted to make the cell sheet easier to be transferred to the tissue or organ to be repaired.

For example, before transferring the cell sheet, it also includes the use of a detection device, such as an optical detection device. The optical detection device detects the condition of the cell sheet, for example, detecting the shape, area, thickness, uniformity, flatness, and flatness of the cell sheet. Distribution density, survival status, etc.

The embodiments of the present disclosure provide a cell sheet transfer device, a cell sheet transport device, and a method for transferring a cell sheet using the cell sheet transport device, having at least one of the following beneficial effects:

(1) The cell sheet transport device provided by at least one embodiment of the present disclosure can ensure that the cell sheet is not damaged during the process of transporting the cell sheet.

(2) The cell sheet transport device provided by at least one embodiment of the present disclosure can quickly and accurately transfer and attach the cell sheet to the surface of the organ or tissue to be repaired.

(3) The cell sheet transport device provided by at least one embodiment of the present disclosure can realize the exchange of oxygen and carbon dioxide with the outside during the long-term transportation and storage of the cell sheet, which helps maintain oxygen in the cell sheet transport device. The balance of concentration is conducive to the preservation of cell sheets.

(4) The cell sheet transfer device provided by at least one embodiment of the present disclosure has a liquid channel, which can mechanically support the cell sheet when the cell sheet is taken out, while allowing liquid to flow from the liquid channel. However, there is no need to tilt the bottom plate to leak the culture solution, thereby avoiding the attraction of the surface tension on the cell sheet when the cell sheet is separated from the liquid, making the cell sheet easier to transfer and using, avoiding the use of tweezers and other hard sharp instruments to clamp Take the damage caused by the cell sheet.

(5) At least one embodiment of the present disclosure provides a cell sheet transfer device. After taking out the cell sheet, hold the handle of the cell sheet transfer device, and by turning it over, the cell sheet loaded on it can be accurately attached to the desired attachment. On the tissues or organs of the cell sheet, it is convenient to perform the operation.

The following points need to be explained:

(1) The drawings of the embodiments of the present disclosure only refer to the structures related to the embodiments of the present disclosure, and other structures can refer to the usual design.

(2) For the sake of clarity, in the drawings used to describe the embodiments of the present disclosure, the thickness of layers or regions is enlarged or reduced, that is, these drawings are not drawn according to actual scale. It will be understood that when an element such as a layer, film, region or substrate is referred to as being "on" or "under" another element, the element can be "directly" on or "under" the other element. Or there may be intermediate elements.

(3) In the case of no conflict, the embodiments of the present disclosure and the features in the embodiments can be combined with each other to obtain new embodiments.

The above are only specific implementations of the present disclosure, but the protection scope of the present disclosure is not limited thereto, and the protection scope of the present disclosure should be subject to the protection scope of the claims.

Claims

A cell sheet transfer device, comprising: a bottom plate and a lifting part arranged on the edge of the bottom plate, wherein:

The bottom plate is configured to carry the cell sheet;

The bottom plate has a liquid channel, and the liquid channel is configured to penetrate the bottom plate along a thickness direction of the bottom plate.
The cell sheet transfer device according to claim 1, wherein the lifting part and the bottom plate are movably connected at a connection point, so that the angle between the lifting part and the main surface of the bottom plate can be adjusted.
The cell sheet transfer device according to claim 2, wherein the lifting part is provided at two positions opposite to each other at the edge of the bottom plate.
The cell sheet transfer device according to any one of claims 1 to 3, wherein the planar shape of the bottom plate is rectangular or circular.
The cell sheet transfer device according to any one of claims 1 to 4, wherein the planar shape of the liquid channel is at least one of a circle, a rectangle, a square, a triangle, an ellipse, a diamond, or a sector.
The cell sheet transfer device according to any one of claims 1 to 5, wherein the materials of the bottom plate and the lifting part are both biocompatible materials.
The cell sheet transfer device according to claim 6, wherein the biocompatible material comprises titanium, titanium alloy, polycaprolactone, polylactic acid, polyethylene, polypropylene, polyethylene glycol, polystyrene , Nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethyleneimine, polysulfone, polymethacrylate, polyurethane, polyterephthalic acid, sodium silicoborate, glass or at least one of alumina .
A cell sheet transport device, comprising: a storage container, a covering layer and the cell sheet transfer device according to any one of claims 1-7, wherein:

The storage container includes a groove, the groove having a side wall and a bottom surface;

The cell sheet transfer device is arranged in the groove;

The covering layer is arranged on the storage container, and the cell sheet transfer device is between the storage container and the covering layer, and the covering layer and the cells are perpendicular to the bottom surface. There are gaps between the bottom plates of the sheet transfer device.
The cell sheet transport device according to claim 8, wherein a support column is arranged in the groove, and the support column protrudes toward a side away from the bottom surface.
The cell sheet transport device according to claim 9, wherein the cell sheet transfer device is arranged on a side of the support column close to the covering layer, and the size of the gap is 0.1 mm to 0.5 mm.
The cell sheet transport device according to claim 9, wherein the support column penetrates the cell sheet transfer device at the liquid channel, and in a direction perpendicular to the bottom surface, the support column is far away from the cell sheet transfer device. The distance between the surface of the bottom surface and the covering layer is 0.1 mm to 0.5 mm.
The cell sheet transport device according to any one of claims 8-11, wherein the covering layer is detachably combined with the storage container.
The cell sheet transport device according to any one of claims 8-12, wherein the covering layer is a water-blocking and gas-permeable layer.
The cell sheet transport device according to claim 13, wherein the material of the covering layer comprises urethane rubber or silica gel.
The cell sheet transport device according to any one of claims 8-14, further comprising: a bearing layer provided on the cell sheet transfer device, wherein the bending strength of the material of the bearing layer is less than that of the The bending strength of the cell sheet transfer device.
The cell sheet transport device according to any one of claims 8-15, wherein the storage container comprises a plurality of the grooves, and each of the grooves is provided with the cell sheet transfer device .
A method for transferring cell sheets using the cell sheet transport device according to any one of claims 8-16, comprising:

Placing the cell sheet in the cell sheet transport device, wherein the cell sheet is located between the covering layer and the cell sheet transfer device;

Remove the covering layer, and take out the cell sheet and the cell sheet transfer device through the extracting part;

The cell sheet is transferred to the tissue or organ to be repaired.