CN112221543A

CN112221543A - Cell sheet transfer device, transport apparatus, and method of transferring cell sheet

Info

Publication number: CN112221543A
Application number: CN201910637375.1A
Authority: CN
Inventors: 高爽; 杜志宏; 靳新; 吴峥; 常德华
Original assignee: BOE Technology Group Co Ltd; BOE Regenerative Medicine Technology Co Ltd
Current assignee: BOE Technology Group Co Ltd; BOE Regenerative Medicine Technology Co Ltd
Priority date: 2019-07-15
Filing date: 2019-07-15
Publication date: 2021-01-15
Also published as: WO2021008472A1

Abstract

A cell sheet transfer device, a cell sheet transporter and a method of transferring a cell sheet using the cell sheet transporter, the cell sheet transfer device comprising: a bottom plate and a lift portion disposed at an edge of the bottom plate, wherein the bottom plate is configured to carry the cell sheet layer; the bottom plate has a liquid passage configured to penetrate the bottom plate in a thickness direction of the bottom plate. The cell sheet layer transfer device can ensure that the cell sheet layer is not damaged in the process of transporting the cell sheet layer, and can quickly and accurately transfer and attach the cell sheet layer to the surface of an organ or tissue to be repaired.

Description

Cell sheet transfer device, transport apparatus, and method of transferring cell sheet

Technical Field

Embodiments of the present disclosure relate to a cell sheet transfer device, a cell sheet transport apparatus, and a method of transferring a cell sheet using the cell sheet transport apparatus.

Background

Cell sheets (cell patches) are a research hotspot in the field of tissue engineering and have wide application in the treatment of diseases related to skin, cornea, heart, liver, periodontal, bone marrow and the like. Cell sheets are formed by in vitro culture of primary cells, for example, cell sheets formed by nerve cells, bone marrow stromal stem cells and the like have become hot spots in the field of regenerative medicine, and a set of mature methods are available for preparing cell sheets.

BRIEF SUMMARY OF THE PRESENT DISCLOSURE

At least one embodiment of the present disclosure provides a cell sheet transfer device including: a bottom plate and a lift portion disposed at an edge of the bottom plate, wherein the bottom plate is configured to carry the cell sheet layer; the bottom plate has a liquid passage configured to penetrate the bottom plate in a thickness direction of the bottom plate.

For example, in the cell sheet transfer device provided in at least one embodiment of the present disclosure, the lift portion and the bottom plate are movably connected at a connection point such that an angle between the lift portion and a main surface of the bottom plate is adjustable.

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

For example, in the cell sheet transfer device provided in at least one embodiment of the present disclosure, the planar shape of the base plate is a rectangle or a circle.

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

For example, in at least one embodiment of the present disclosure, the biocompatible material includes at least one of titanium, titanium alloy, polycaprolactone, polylactic acid, polyethylene, polypropylene, polyethylene glycol, polystyrene, nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethyleneimine, polysulfone, polymethacrylate, polyurethane, poly (terephthalic acid), sodium borosilicate, glass, or alumina.

At least one embodiment of the present disclosure also provides a cell sheet transport device, including: a storage container, a cover layer and the cell sheet transfer device of any one of the above, wherein the storage container comprises a recess having a side wall and a bottom surface; the cell sheet layer transfer device is arranged in the groove; the cover layer is disposed on the storage container, and the cell sheet transfer device is between the storage container and the cover layer such that 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 in at least one embodiment of the present disclosure, a support pillar is disposed in the groove, and the support pillar 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 disposed on one side of the support pillar near the cover layer, and the size of the gap is 0.1mm to 0.5 mm.

For example, in the cell sheet transport device provided in at least one embodiment of the present disclosure, the support columns penetrate the cell sheet transfer device at the liquid channels, and a distance between a surface of the support columns away from the bottom surface and the cover layer in a direction perpendicular to the bottom surface is 0.1mm to 0.5 mm.

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

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

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

For example, at least one embodiment of the present disclosure provides a cell sheet transport device, further comprising: a carrier layer disposed on the cell sheet transfer device, wherein a bending strength of a material of the carrier layer is less than a bending strength of the cell sheet transfer device.

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

At least one embodiment of the present disclosure also provides a method for transferring a cell sheet using the cell sheet transport device described in any one of the above, the method for transferring a cell sheet including: placing the cell sheet in the cell sheet transport device, wherein the cell sheet is positioned between the cover layer and the cell sheet transfer device; removing the cover layer, and taking out the cell sheet layer and the cell sheet layer transfer device by extracting the extraction part; transferring the cell sheet to a tissue or organ to be repaired.

Drawings

To more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings of the embodiments will be briefly introduced below, and it is apparent that the drawings in the following description relate only to some embodiments of the present disclosure and are not limiting to the present disclosure.

FIG. 1 is a schematic illustration of a cell sheet transfer process;

fig. 2 is a schematic plan structure view of a cell sheet layer transfer device according to an embodiment of the present disclosure;

FIG. 3 is a schematic plan view of a cell sheet transfer device according to still another embodiment of the present disclosure;

FIG. 4 is a schematic plan view of a cell sheet transfer device according to another embodiment of the present disclosure;

FIG. 5 is a schematic plan view of a cell sheet transfer device according to another embodiment of the present disclosure;

FIG. 6 is a schematic plan view of the lift portion of the cell sheet transfer device of FIG. 5 after it has been flattened;

FIG. 7 is a schematic plan view of a cell sheet transfer device according to another embodiment of the present disclosure;

FIG. 8 is a schematic cross-sectional view of a cell sheet transport device according to an embodiment of the present disclosure;

FIG. 9 is a schematic cross-sectional view of a cell sheet transporter according to still another embodiment of the present disclosure;

FIG. 10 is a schematic plan view of the cell sheet layer transfer device in FIG. 9 with a carrier layer disposed thereon;

FIG. 11 is a schematic plan view of a cell sheet transport device according to an embodiment of the present disclosure;

FIG. 12 is a schematic cross-sectional view of a cell sheet transport device according to yet another embodiment of the present disclosure; and

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

Reference numerals:

11-cell sheet; 12-a layer of carrier material; 20-a cell sheet transfer device; 201-a backplane; 202-a lift-off portion; 203-a liquid channel; 204-a handle; 205-a first connection; 206-a second connection; 207-a carrier layer; 30-a cell sheet transport device; 31-a storage container; 32-a cover layer; 311-a groove; 3111-side walls; 3112-bottom surface; 33-clearance; 34-support column.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present disclosure more apparent, the technical solutions of the embodiments of the present disclosure will be described clearly and completely with reference to the drawings of the embodiments of the present disclosure. It is to be understood that the described embodiments are only a few embodiments of the present disclosure, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the disclosure without any inventive step, are within the scope of protection of the disclosure.

Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this disclosure belongs. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another. The word "comprising" or "comprises", and the like, means that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items. The terms "connected" or "coupled" and the like are not restricted to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "upper", "lower", "left", "right", and the like are used merely to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships may also be changed accordingly.

All terms (including technical or scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs unless specifically defined otherwise. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

For example, the preparation process of the cell sheet is generally complicated, the preparation period is long, and the preparation cost is high. The cell sheet layer is very thin and fragile, has a three-dimensional structure, and is easy to tear, fold or break in the processes of culturing, peeling, washing, storing, transporting and the like, so that the use of the subsequent cell sheet layer is influenced, and great difficulty is brought to the application of the cell sheet layer in clinical medicine. For example, FIG. 1 is a schematic illustration of a cell sheet transfer process. As shown in FIG. 1, before the cell sheet 11 is transferred from the support material layer 12, the cell sheet 11 is laid on the support material layer 12, and the cell sheet 11 maintains a complete circular shape, after the cell sheet 11 is separated from the support material layer 12, the edge of the cell sheet 11 becomes non-flat, and the cell sheet 11 is damaged or has wrinkles.

The inventor of the present disclosure finds that, the carrier material layer 12 shown in fig. 1 is not provided with a channel for liquid to flow through, when the cell sheet layer 11 and the carrier material layer 12 are taken out of the culture solution after the transportation process of the cell sheet layer is completed, the carrier material layer 12 needs to be inclined to pour out the culture solution thereon, which easily causes the cell sheet layer 11 to slide off the carrier material layer 12, thereby damaging the cell sheet layer. Even if the cell sheet 11 does not slip off, in the process of collecting the cell sheet 11, for example, the cell sheet 11 and the support material layer 12 are changed into a state of being easily separated by lowering the temperature, and then the cell sheet 11 is scooped up by a cell scoop or the cell sheet 11 is clamped by a special forceps to peel the cell sheet 11 off the support material layer 12, so that the cell sheet 11 is easily damaged when the cell sheet 11 is transferred.

The inventor of the present disclosure also finds that the carrier material layer 12 shown in fig. 1 is usually disposed on two opposite side walls of the groove to ensure that the nutrient solution in the groove flows and the nutrient solution passes through the carrier material layer 12 to provide nutrition for the cell sheet layer 11, but the groove has a wider opening, the carrier material layer 12 has a certain bending capability, which may cause the cell sheet layer 11 and the carrier material layer 12 to leak into the groove during transportation of the cell sheet layer 11, and the shearing force of the liquid in the nutrient solution may cause damage to the cell sheet layer 11. Therefore, the method for transferring the cell sheet as shown in fig. 1 cannot ensure that the cell sheet is not damaged during the transportation of the cell sheet, and cannot transfer and attach the cell sheet to the surface of the organ or tissue to be repaired quickly and accurately. Therefore, a special cell sheet transportation device is needed to ensure that the cell sheet is in a smooth environment, the damage of liquid shearing force to the cell sheet is reduced, and meanwhile, a certain amount of cell culture solution (including transportation protection solution) needs to be contained in the cell sheet transportation device to provide nutrients needed in the transportation process and in a certain storage time for the cell sheet.

At least one embodiment of the present disclosure provides a cell sheet transfer device including: a bottom plate and a lifting part arranged at the edge of the bottom plate, wherein the bottom plate is configured to bear the cell sheet layer; the bottom plate has a liquid passage configured to penetrate the bottom plate in a thickness direction of the bottom plate. The lifting part and the liquid channel in the cell sheet layer transfer device are matched with each other, so that the cell sheet layer can be ensured not to be damaged in the process of transporting the cell sheet layer, and meanwhile, the cell sheet layer can be quickly and accurately transferred and attached to the surface of an organ or tissue to be repaired.

For example, fig. 2 is a schematic plan structure diagram of a cell sheet layer transfer device according to an embodiment of the present disclosure. As shown in fig. 2, the cell sheet transfer device 20 includes: a base plate 201 and a lift-off portion 202 disposed at an edge of the base plate 201, the base plate 201 being configured to carry a cell sheet (the cell sheet is not shown in FIG. 2); the bottom plate 201 has a liquid passage 203, and the liquid passage 203 is disposed to penetrate the bottom plate 201 in a thickness direction of the bottom plate 201. When shifting the cell sheet, the cell sheet is located bottom plate 201, can guarantee like this that the cell sheet tiling is in order to avoid the cell sheet fold to appear, and the portion 202 of mentioning at bottom plate 201 edge can guarantee that the cell sheet shifts out from the culture solution steadily, has liquid channel 203 on the bottom plate 201 and makes and to spill the culture solution with the tilting floor.

For example, in FIG. 2, the number of the lifting portions 202 is two, and the two lifting portions 202 are disposed at two positions opposite to each other at the edge of the bottom plate 201, which ensures that the cell sheet is removed from the culture solution more smoothly. The cell sheet layer transfer device can be directly attached to the surface of the tissue or organ to be repaired at one side provided with the cell sheet layer, so that the cell sheet layer 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 the lifting portions 202 may be more or 1, and is not limited herein.

For example, fig. 3 is a schematic plan view of a cell sheet layer transfer device according to still another embodiment of the present disclosure. As shown in FIG. 3, the number of the lifting parts 202 is 1, and the lifting parts 202 are provided only at one position on the edge of the bottom plate 201, which simplifies the structure of the cell sheet transfer device 20 while ensuring that the cell sheet can be smoothly removed from the culture solution.

For example, the planar shape of the bottom plate 201 is a rectangle or a circle, and both the shapes of the bottom plate 201 are circles in fig. 2 and 3. The planar shape of the bottom plate 201 is rectangular or circular, which ensures that the bottom plate 201 is more stably fixed in the area defined by the groove in the cell sheet transport device concerned later, thereby enabling the cell sheet to be more stably preserved in the culture solution.

For example, fig. 4 is a schematic plan view of a cell sheet transfer device according to still another embodiment of the disclosure, and as shown in fig. 4, the bottom plate 201 is rectangular in shape to better match the cross-sectional shape of the groove in the cell sheet transport device. For example, the lifting portions 202 are symmetrically provided on opposite sides of the rectangular bottom plate 201.

For example, fig. 5 is a schematic plan view of a cell sheet transfer device according to still another embodiment of the present disclosure, as shown in fig. 5, a lifting part 202 and a bottom plate 201 are movably connected at a connection point, so that an angle between main surfaces of the lifting part 202 and the bottom plate 201 can be adjusted, thereby enabling a subsequently placed cell sheet (not shown in the figure) to be better transferred to a repaired tissue or organ. For example, the angle between the lift-off 202 and the main surface of the bottom plate 201 is adjustable in the range of 90 ° to 180 °. The adjustable angular range is continuous and can be accurate to 0.1 °.

For example, the lifting part 202 of the cell sheet layer transfer device 20 and the bottom plate 201 are movably connected at the connection part, so that the cell sheet layer can be conveniently turned over after being subsequently fished, and the cell sheet layer can be attached to the tissue or organ to be repaired, namely, the cell sheet layer transfer device can be used as a transplantation tool of the cell sheet layer.

For example, as shown in fig. 5, the lift-off portion 202 and the bottom plate 201 are provided with a first connection portion 205 at the connection, and the first connection portion 205 may allow the angle between the main surfaces of the lift-off portion 202 and the bottom plate 201 to be adjustable.

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

For example, fig. 7 is a schematic plan structure view of a cell sheet layer transfer device according to still another embodiment of the present disclosure. As shown in fig. 7, a handle 204 is further provided on a 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, which is inconvenient for lifting the cell sheet, the arrangement of the handle 204 is equivalent to increasing the accessible area of the lifting part 202, which makes it easier to smoothly remove the cell sheet from the culture solution.

In one example, the handle 204 may be configured with a rugged surface that may increase the roughness of the handle to facilitate removal of the cell sheet transfer device 20.

For example, a movable connection may be provided between the handle 204 and the lifting portion 202, as shown in FIG. 7, and a second connection 206 may be provided between the handle 204 and the lifting portion 202 to facilitate operation in a limited space.

For example, the planar shape of the liquid passage 203 is at least one of a circle, a rectangle, a square, a triangle, an ellipse, a diamond, or a fan. The liquid channel 203 is designed into the regular shape, so that the bottom plate 201 can better penetrate through the support columns in the cell sheet layer conveying device, and the sizes of the liquid channel and the support columns can be designed more conveniently.

In the above fig. 2, fig. 3, and fig. 5 to fig. 7, the planar shape of the liquid passage 203 is described as an example of a fan shape. The area of each sector is equal, i.e. the area of each liquid channel 203 is equal. In the above-described fig. 4, the planar shape of the liquid passage 203 is described as a right triangle as an example, and the area of each right triangle is equal, that is, the area of each liquid passage 203 is equal. The equal area of each liquid channel 203 in fig. 2-7 can make the bottom plate 201 divided more uniformly, and the equal area of each liquid channel 203 is more beneficial to the uniformity of the culture solution distribution.

For example, in some embodiments of the present disclosure, the material of the base plate 201 and the lift 202 are both biocompatible materials. By using a biocompatible material, adverse effects on the cell sheet can be reduced during and before transfer of the cell sheet.

For example, the material of the bottom plate 201 and the lifting portion 202 is hard material, which is advantageous for structural stability.

For example, the biocompatible material includes a metal having good biocompatibility, such as titanium or a titanium alloy; biocompatible materials include non-metals that are well biocompatible, such as at least one of polycaprolactone, polylactic acid, polyethylene, polypropylene, polyethylene glycol, polystyrene, nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethyleneimine, polysulfone, polymethacrylate, polyurethane, poly (terephthalic acid), sodium silicoborate, or glass; the biocompatible material also includes metal oxides with good biocompatibility, such as aluminum oxide and the like.

For example, embodiments of the present disclosure provide a cell sheet transfer device that can facilitate removal of a cell sheet. Cell lamella shifts device has fluid passage, both had mechanical support to the cell lamella when taking out the cell lamella, can make liquid flow through from fluid passage simultaneously, and surface tension is acted on to the suction force of cell lamella when avoiding the cell lamella to break away from liquid, makes the cell lamella more easily by the use of shifting to the harm that the cell lamella brought has been got to the sharp apparatus clamp of stereoplasm such as having avoided with tweezers.

For example, the handle of the cell sheet layer transfer device can be held by hand to take out the cell sheet layer and turn the base plate so that the side of the base plate carrying the cell sheet layer faces the position where the cell membrane sheet needs to be attached, so that the cell sheet layer carried by the cell sheet layer transfer device can be accurately attached to the tissue or organ where the cell sheet layer needs to be attached, and the operation of performing the operation is convenient.

At least one embodiment of this 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 according to an embodiment of the present disclosure. The cell sheet transport device 30 includes: the storage container 31, the cover 32 and the cell sheet transfer device 20 of any of the above embodiments, wherein the storage container 31 includes a recess 311, the recess 311 having a side wall 3111 and a bottom surface 3112; the cell sheet transfer device 20 is disposed in the recess 311; the cover layer 32 is provided on the storage container 31, and the cell sheet transfer device 20 has a gap between the storage container 31 and the cover layer 32 in a direction perpendicular to the bottom surface 3112 between the cover layer 32 and the bottom plate 201 of the cell sheet transfer device 20.

For example, the cell sheet conveying device can maintain the flatness of the surface of the cell sheet and reduce the damage of liquid shearing force to the cell sheet. Meanwhile, the cell sheet layer conveying device can contain a certain amount of nutrient solution (such as conveying protection solution) to provide a stable storage environment for the cell sheet layer, maintain the acid-base balance and osmotic pressure balance of the surrounding environment of the cell sheet layer, and provide required nutrient substances for the cell sheet layer. And the cell sheet layer conveying device comprises a detachable cell sheet layer transfer device which can conveniently take out the cell sheet layer and transfer the cell sheet layer to the tissue or organ to be repaired.

For example, as shown in fig. 8, support posts 34 are disposed in recesses 311, and support posts 34 protrude toward a side facing away from floor 3112. For example, the support pillars 34 provide mechanical support for the cell sheet, so that the support pillars 34 can make the cell sheet exist more stably in the cell sheet transportation device than the case without the support pillars 34 having only the side walls 3111 of the grooves 311, and the cell sheet does not slip into the grooves 311 by its own weight to form folds or be damaged.

For example, the embodiments of the present disclosure do not have any particular limitation on the size of the bottom 3112 of the recess 311, as long as it is satisfied that the size of the bottom 3112 of the recess 311 is adapted to the size of the cell sheet to be contained.

For example, the cell sheet layer comprises one or more living cells, and a culture solution (comprising a transportation protection solution) is required to maintain the stability of the growth environment of the cell sheet layer during the transportation of the cell sheet layer, and a certain supply of the culture solution (comprising the transportation protection solution) is provided. Set up the condition of support column in the recess, the bottom surface of preserving the container is intercommunication each other, and the design that should communicate each other has improved the capacity of preserving the container culture solution (including transportation protection liquid) in finite space, is favorable to the circulation of culture solution simultaneously, makes things convenient for culture solution and cell lamella to carry out the nutrient substance exchange, provides stable environment and nourishment for the cell lamella and supplies with. In addition, the circulation of the culture solution can make nutrient components at all positions uniform, so that nutrient substances and oxygen in the culture solution are fully utilized.

For example, buffer solutions for pH equilibration in culture fluids include: 4-hydroxyethyl piperazine ethanesulfonic acid (HEPE) and phosphate buffer solution.

For example, the main components of transportation protection solutions are human blood proteins and human alpha, beta, sodium pyruvate, sodium chloride, magnesium sulfate, Ethylene Diamine Tetraacetic Acid (EDTA), glucose, and various amino acids.

For example, as shown in FIG. 8, support columns 34 penetrate cell-sheet transfer device 20 at liquid channels (not shown in FIG. 8), and the spacing between the surface of support columns 34 remote from bottom surface 3112 and cover layer 34 in a direction perpendicular to bottom surface 3112 is 0.1mm to 0.5mm so that cell-sheet transfer device 20 is more stably present in recess 311. Thus, during the transportation of the cell sheet layer, the cell sheet layer is located on the support column, and the distance between the surface of the support column 34 far from the bottom surface 3112 and the covering layer 34 is just as large as the thickness of the cell sheet layer, so that the space for the cell sheet layer to move is small, and the probability of the cell sheet layer being wrinkled can be reduced. When the cell sheet needs to be fished out of the culture solution, the cell sheet transfer device 20 can be vertically taken out, 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 covering layer 32, the cell sheet falls onto the bottom plate 201 of the cell sheet transfer device 20, and the cell sheet transfer device 20 can be conveniently taken out through the extraction part 202.

For example, fig. 9 is a schematic cross-sectional structure diagram of a cell sheet transportation apparatus according to still another embodiment of the present disclosure, a cell sheet transfer device 20 is disposed on a side of a support pillar 34 close to a cover layer 32, the cell sheet transfer device 20 is disposed on the support pillar 34, a bottom plate 201 of the cell sheet transfer device 20 does not pass through the support pillar 34, a gap 33 between the bottom plate 201 of the cell sheet transfer device 20 and the cover layer 32 is 0.1mm to 0.5mm, and the size of the gap is approximately equal to the thickness of the cell sheet, so that a space for movement of the cell sheet can be reduced, and a probability of wrinkles occurring on the cell sheet is reduced.

For example, the gap 33 provides space for subsequent placement of the cell sheet, and is designed to be small enough so that there is no excess space for the cell sheet to fold or wrinkle, given that the cell sheet is flexible and susceptible to folding or creasing.

For example, in the schematic cross-sectional structure of the cell sheet transport device shown in fig. 8 and 9, a snap or lock part may be designed at a position of the storage container 31 corresponding to the lifting part 202 of the cell sheet transfer device 20, so that the cell sheet transfer device 20 and the cell sheet transport device 30 can be firmly combined, thereby preventing the cell sheet transfer device 20 from moving and damaging the cell sheet during the transport of the cell sheet.

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

For example, the cover layer 32 and the storage container 31 may be coupled by a simple mechanical engagement, and the cover layer 32 and the storage container 31 may be coupled by other means, such as a screw connection, a snap connection, or a hinge connection.

For example, the material of the cover layer 32 is a soft material or a hard material. When the material of the cover layer 32 is a hard material, better protection can be provided for the cell sheet transporter 30. When the covering layer 32 is made of a soft material, the soft material can deform to a certain extent, so that more bubbles can be eliminated as much as possible, and the damage of liquid shearing force to cell sheets in the transportation process is reduced.

For example, when the cover layer 32 is coupled to the holding container 31 by means such as a screw, snap or hinge connection, different portions of the cover layer 32 may be formed of different materials. For example, a hard material is used for the threaded fastener portion and a soft material is used for the cover portion. This can satisfy both the stability of the connecting portion and the minimization of the gap between the cover portion holding container 31 and the cover layer 32, so that the space for the movement of the cell sheet becomes small.

For example, the cover layer 32 is a water-blocking breathable layer. The waterproof breathable layer can prevent the transportation protection liquid from flowing out while not blocking air flow. For example, the material of this ventilative layer that blocks water is polytetrafluoroethylene, and this overburden 32 that is formed by the material that has the ventilative performance that blocks water can make things convenient for the cell piece layer to carry out gas exchange with external environment, and the cell piece layer can realize carrying out the exchange of oxygen and carbon dioxide with the external world in the long-time transportation storage's in-process promptly to help maintaining the balance of oxygen concentration in the cell piece layer conveyer, in order to do benefit to the storage of cell piece layer.

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

For example, when the transported cell sheet is formed of relatively fragile cells such as nerve cells, the cell sheet transport device 30 may further include: a carrier layer provided on the cell sheet transfer device 20 (the carrier layer is not shown in fig. 8 and 9 because it is too thin). In the configuration shown in FIG. 8, during transport of the cell sheet, the carrier layer is disposed directly on support posts 34 and not directly on cell sheet transfer device 20. When the cell sheet is scooped up, the carrier layer is directly on the cell sheet transfer device 20. In the configuration shown in FIG. 9, the cell sheet may also be disposed directly on a carrier layer disposed on the side of the cell sheet transfer device 20 adjacent to the cover layer 34.

For example, fig. 10 is a schematic plan view of the cell sheet layer transfer device in fig. 9 with a carrier layer disposed thereon. As shown in fig. 10, the bearing layer 207 is disposed on the cell sheet transfer device 20, and the bearing layer 207 may cover the entire bottom plate 201 of the cell sheet transfer device 20 or may cover a part of the bottom plate 201 of the cell sheet transfer device 20.

For example, the flexural strength of the material of the carrier layer is less than the flexural strength of the cell sheet transfer device 20. Therefore, the cell sheet layer can be attached to the bearing layer with low bending strength for transportation, and the integrity of the cell sheet layer can be ensured.

The bending strength refers to the maximum stress that a material can bear when the material is broken under the action of bending load or reaches a specified bending moment, the maximum stress is the maximum positive stress when the material is bent, the maximum positive stress is expressed in MPa (megapascal), the bending resistance of the material is reflected, the bending performance of the material is measured, and the higher the bending strength is, the stronger the rigidity of the material is; the smaller the bending strength, the more flexible the material.

Alternatively, the material of the carrier layer has a modulus of elasticity that is less than the modulus of elasticity of the cell sheet layer transfer device. The elastic modulus is an index for measuring the degree of difficulty of the material in elastic deformation, and the larger the value, the larger the stress for causing the material to elastically deform to a certain extent, that is, the higher the rigidity of the material, that is, the smaller the elastic deformation under a certain stress.

For example, the material of the carrier layer is a film or sheet material with good biocompatibility, and the material of the carrier layer can be processed by surface treatment to improve the adhesion capability of the cell sheet layer thereon. For example, the surface treatment process includes cationic treatment, grafting of an organic functional group, or the like.

For example, the cell sheet layer can be closely attached to the carrier layer without any external force by using the carrier layer to carry the cell sheet layer. In addition, because the bearing layer is soft and smooth in surface, the cell sheet layer is easy to lay on the bearing layer in a flat and wrinkle-free form, and the bearing layer also has the effects of a protective pad and a cushion pad for the cell sheet layer.

For example, the material of the bearing layer comprises at least one temperature-sensitive material selected from poly-N-isopropylacrylamide (PIPAAM), a compound of N-isopropylacrylamide and methacrylic acid, and lysine short peptide. By adjusting the temperature, when the temperature sensed by the bearing layer reaches a specific condition, such as temperature rise/drop to a specific temperature, the cell sheet layer is changed from a state of being tightly attached to the temperature-sensitive material to a state of being easily separated, so that the cell sheet layer is convenient to harvest and collect.

For example, fig. 11 is a schematic plan view of a cell sheet transport device according to an embodiment of the disclosure. As shown in FIG. 11, the cell-sheet transferring device 20 in the cell-sheet transporting device 30 is attached to the side wall 3111 of the recess 311, and the storage container 31 is the outer body of the cell-sheet transporting device 30.

For example, fig. 12 is a schematic cross-sectional structure diagram of a cell sheet transport device according to still another embodiment of the present disclosure. As shown in FIG. 12, a storage container 31 in a cell sheet transport device 30 may include a plurality of recesses 311, each recess 311 having a cell sheet transfer device 20 disposed therein, the cell sheet transport device 30 further having a cover layer 32 disposed therein.

For example, in fig. 8, 9 and 12, the cover layer 32 may be provided with a seal ring to seal the protective container 31 and prevent leakage of the protective infusion solution when the cover layer 32 is placed on the protective container 31.

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

For example, the cell sheet transport device is formed using an Additive Manufacturing (AM) method, that is, a 3D printing method. The cell sheet layer conveying device can also be formed by adopting a casting molding mode.

Embodiments of the present disclosure also provide a method for transferring a cell sheet using the cell sheet transport device in any of the above embodiments, for example, fig. 13 is a flowchart of a method for transferring a cell sheet using the cell sheet transport device provided in an embodiment of the present disclosure. As shown in fig. 13, the method for transferring a cell sheet includes:

s101: placing the cell sheet in a cell sheet transport device, wherein the cell sheet is positioned between the cover layer and the cell sheet transfer device;

s102: removing the covering layer, and taking out the cell sheet layer and the cell sheet layer transfer device by extracting the extraction part;

s103: the cell sheet is transferred to the tissue or organ to be repaired.

For example, the angle between the extraction part and the base plate may be adjusted before transferring the cell sheet onto the tissue or organ to be repaired, so that the cell sheet is more easily transferred onto the tissue or organ to be repaired.

For example, before the cell sheet is transferred, the method further comprises detecting the condition of the cell sheet by using a detection device, such as an optical detection device, for example, detecting the shape, area, thickness, uniformity, flatness, distribution density, survival status, etc. of the cell sheet.

The embodiment of the disclosure provides a cell sheet transfer device, a cell sheet transport device and a method for transferring a cell sheet by using the cell sheet transport device, which have at least one of the following beneficial effects:

(1) the cell sheet layer transportation device provided by at least one embodiment of the present disclosure can ensure that the cell sheet layer is not damaged in the cell sheet layer transportation process.

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

(3) The cell sheet layer transportation device provided by at least one embodiment of the disclosure can realize the exchange of oxygen and carbon dioxide between the cell sheet layer and the outside in the long-time transportation and storage process, and is favorable for maintaining the balance of oxygen concentration in the cell sheet layer transportation device, so as to be favorable for the storage of the cell sheet layer.

(4) The cell lamella that this at least embodiment of disclosure provided shifts device, cell lamella shifts device has fluid passage, both had mechanical support to the cell lamella when taking out the cell lamella, can make liquid flow through from fluid passage simultaneously, need not the inclined bottom plate spill the culture solution to surface tension is to the effect of the suction force of cell lamella when avoiding the cell lamella to break away from liquid, makes the cell lamella more easily by the use of shifting, has avoided getting the harm that the cell lamella brought to the cell lamella with sharp apparatus clamp of stereoplasm such as tweezers.

(5) According to the cell sheet layer transfer device provided by at least one embodiment of the disclosure, after the cell sheet layer is taken out, the handle of the cell sheet layer transfer device is held, and the cell sheet layer carried by the cell sheet layer transfer device can be accurately attached to the tissue or organ to which the cell sheet layer needs to be attached through overturning, so that the operation is conveniently carried out.

The following points need to be explained:

(1) the drawings of the embodiments of the disclosure only relate to the structures related to the embodiments of the disclosure, and other structures can refer to the common design.

(2) For purposes of clarity, the thickness of layers or regions in the figures used to describe embodiments of the present disclosure are exaggerated or reduced, i.e., the figures are not drawn on a true 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, it can be "directly on" or "under" the other element or intervening elements may be present.

(3) Without conflict, embodiments of the present disclosure and features of the embodiments may be combined with each other to arrive at new embodiments.

The above description is only a specific embodiment of the present disclosure, but the scope of the present disclosure is not limited thereto, and the scope of the present disclosure should be subject to the scope of the claims.

Claims

1. A cell sheet transfer device comprising: a bottom plate and a lift-off portion provided at an edge of the bottom plate, wherein,

the bottom plate is configured to carry the cell sheet;

the bottom plate has a liquid passage configured to penetrate the bottom plate in a thickness direction of the bottom plate.

2. The cell sheet transfer device of claim 1, wherein the lift and the bottom plate are movably connected at a connection such that an angle between the lift and a major surface of the bottom plate is adjustable.

3. The cell sheet transfer device according to claim 2, wherein the lift portions are provided at two positions opposing each other at the edge of the bottom plate.

4. The cell sheet transfer device according to any one of claims 1 to 3, wherein the planar shape of the base plate is a rectangle or a circle.

5. The cell sheet transfer device according to claim 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 fan.

6. The cell sheet transfer device of claim 5, wherein the bottom plate and the lift portion are both made of a biocompatible material.

7. The cell sheet transfer device of claim 6, wherein the biocompatible material comprises at least one of titanium, titanium alloy, polycaprolactone, polylactic acid, polyethylene, polypropylene, polyethylene glycol, polystyrene, nylon, polyacetal, polycarbonate, polyvinyl alcohol, polyethyleneimine, polysulfone, polymethacrylate, polyurethane, poly (terephthalic acid), sodium borosilicate, glass, or alumina.

8. A cell sheet transport device comprising: a storage container, a cover layer and the cell sheet transfer device according to any one of claims 1 to 7,

the holding container comprises a recess having a side wall and a bottom surface;

the cell sheet layer transfer device is arranged in the groove;

the cover layer is provided on the storage container, and the cell sheet transfer device is between the storage container and the cover layer with a gap between the cover layer and the bottom plate of the cell sheet transfer device in a direction perpendicular to the bottom surface.

9. The cell sheet transport device of claim 8 wherein support posts are disposed within the recess, the support posts projecting toward a side facing away from the floor.

10. The cell sheet conveying device according to claim 9, wherein the cell sheet transferring means is provided on a side of the support column close to the covering layer, and the size of the gap is 0.1mm to 0.5 mm.

11. The cell sheet transport device according to claim 9, wherein the support columns penetrate the cell sheet transfer means at the liquid channels, and a distance between a surface of the support columns remote from the bottom surface and the cover layer in a direction perpendicular to the bottom surface is 0.1mm to 0.5 mm.

12. The cell sheet transport device according to any one of claims 8 to 11, wherein the cover layer is detachably combined with the storage container.

13. The cell sheet transport device of claim 12 wherein the cover layer is a water-and gas-permeable layer.

14. The cell sheet transport device of claim 13, wherein the material of the cover layer comprises urethane rubber or silicone rubber.

15. The cell sheet transport device of claim 8 further comprising: a carrier layer disposed on the cell sheet transfer device, wherein a bending strength of a material of the carrier layer is less than a bending strength of the cell sheet transfer device.

16. The cell sheet transport device according to claim 8, wherein the preservation container includes a plurality of the recesses, each of which has the cell sheet transfer means disposed therein.

17. A method of transferring a cell sheet using the cell sheet transport device of any one of claims 8 to 16, comprising:

placing the cell sheet in the cell sheet transport device, wherein the cell sheet is positioned between the cover layer and the cell sheet transfer device;

removing the cover layer, and taking out the cell sheet layer and the cell sheet layer transfer device by extracting the extraction part;

transferring the cell sheet to a tissue or organ to be repaired.