Cell and Tissue Lamina Forming Packaging and Cell Perfusion Equipment

Abstract

The present invention discloses a cell and tissue sheet forming, packaging and cell perfusion device. The cell and tissue sheet forming and packaging includes a bottom plate, a diaphragm, a top plate and a sealing film. The top plate is slidably disposed on the top of the bottom plate along the horizontal plane to cover or expose the diaphragm. The top plate has a hole and a passive magnetic attraction component. The cell perfusion device includes a stage, a perfusion mechanism and a driving mechanism. The cell and tissue sheet forming and packaging is carried by the stage. The stage and the perfusion mechanism are driven by the driving mechanism to move, so that the perfusion mechanism injects a solution into the cell and tissue sheet forming and packaging through the hole. The diaphragm and the solution are heated by a heating element of the stage, so that the solution forms a colloid and adheres to the diaphragm to form a cell and tissue sheet. Then, the active magnetic attraction component adsorbed with the passive magnetic attraction component is driven to move to drive the top plate to slide, so as to expose the cell and tissue sheet.

Description

Technical Field

[0001] The present invention relates to a cell and tissue sheet forming, packaging and cell perfusion device. Background Art

[0002] Cell and tissue sheets (or simply dressings) are widely used in the medical field. Covering the wound with cell and tissue sheets can accelerate the wound healing speed.

[0003] Currently, the existing production process of cell and tissue sheets is generally as follows: First, cell collection is carried out, then cell culture (this step is extremely time-consuming), and then the cultured cells are transported and stored for subsequent surgical use. However, the cell culture step is extremely time-consuming and costly because it must be completed in a laboratory culture dish with special production processes and equipment. As for the transportation process, if the temperature, humidity and other conditions are not properly controlled, there is a risk of damage and contamination.

[0004] Therefore, how to develop a "cell and tissue sheet forming, packaging and cell perfusion device" to simplify the cell treatment operation process, eliminate the lengthy operations of culturing cells in large quantities and fabricating cell membranes in the laboratory, avoid the risk of difficult temperature control during cell transportation, and enable the on-site fabrication of cell membranes in the clinical field through the packaging and cell perfusion device is an urgent issue for those in the relevant technical fields. Summary of the Invention

[0005] In one embodiment, the present invention provides a cell and tissue sheet forming and packaging, which includes: a bottom plate having a groove; a membrane sheet disposed in the groove, the membrane sheet being made of a hydrophilic material; a top plate parallel to the horizontal plane and parallel to a first direction, the top plate being slidably disposed on the top of the bottom plate between a first position and a second position, when the top plate is in the first position, it can cover the groove and the membrane sheet, when the top plate is in the second position, it can expose the groove and the membrane sheet, the top plate includes: a hole penetrating from the top surface of the top plate to the bottom surface of the top plate, when the top plate is in the first position, the hole is located above the groove and the membrane sheet, and the hole provides an injection of a solution from the top surface of the top plate into the groove; a passive magnetic attraction assembly disposed on the top plate, adapted to be magnetically attracted to an active magnetic attraction assembly, and the top plate is driven to slide by the active magnetic attraction assembly; a sealing film covering the upper surfaces of the top plate and the bottom plate to seal the top plate and the membrane sheet in the sealing film.

[0006] In another embodiment, the present case proposes a cell perfusion device suitable for the above-mentioned cell and tissue sheet forming and packaging. The cell perfusion device includes a stage, which includes: a base suitable for carrying the cell and tissue sheet forming and packaging; an upper cover movably arranged above the base in an openable or closable manner to position the cell and tissue sheet forming and packaging within the base. The upper cover has a perfusion hole. When the upper cover is closed on the base, the projection range of the perfusion hole overlaps with the projection range of the holes on the top plate of the cell and tissue sheet forming and packaging; a heating element arranged on the base to provide heat energy to the diaphragm and the solution; an active magnetic attraction component slidably arranged on the top of the upper cover between a third position and a fourth position parallel to the horizontal plane and parallel to the first direction. The active magnetic attraction component is suitable for magnetic attraction with the passive magnetic attraction component. When the active magnetic attraction component slides to the fourth position, it can synchronously drive the top plate to slide to the second position; a perfusion mechanism, which includes: a fixed seat arranged on a track, and the extending direction of the track is perpendicular to the horizontal plane; a syringe, which includes: a barrel in a long cylindrical shape suitable for accommodating the solution, and the barrel is arranged on the fixed seat with its axis perpendicular to the horizontal plane; a needle coaxially arranged at the bottom end of the barrel, and the tip of the needle faces the horizontal plane; a piston coaxially arranged within the barrel; a driving mechanism, which includes: a first driving component suitable for driving the stage to reciprocate between a fifth position and a sixth position parallel to the horizontal plane and parallel to the first direction. When the stage is at the fifth position, the projection range of the needle is misaligned with the projection range of the perfusion hole on the upper cover. When the stage is at the sixth position, the projection range of the needle overlaps with the projection range of the perfusion hole on the upper cover and the projection range of the holes on the top plate; a second driving component suitable for synchronously driving the fixed seat and the syringe to reciprocate between a seventh position and an eighth position perpendicular to the horizontal plane on the track. When the fixed seat and the syringe are at the seventh position, the horizontal position of the tip of the needle is higher than the horizontal position of the top surface of the upper cover of the stage. When the fixed seat and the syringe are at the eighth position, the horizontal position of the tip of the needle is lower than the horizontal position of the sealing film at the top of the hole on the top plate; a third driving component suitable for driving the piston to move perpendicular to the horizontal plane within the barrel to push the solution in the barrel out of the needle. Description of the Drawings

[0007] Figure 1 Combined structural schematic diagram of an embodiment of the cell and tissue sheet forming and packaging in the present case;

[0008] Figure 2 For Figure 1 Exploded structural schematic diagram of the embodiment removing the sealing film;

[0009] Figure 3 For Figure 1 Combined structural schematic diagram of the embodiment removing the sealing film and the top plate at the second position;

[0010] Figure 3A ForFigure 3 Schematic diagram of the enlarged structure of the 3A-3A section;

[0011] Figure 4 is Figure 1 Schematic diagram of the combined structure of the embodiment with the sealing film removed and the top plate in the first position;

[0012] Figure 4A is Figure 4 Schematic diagram of the enlarged structure of the 4A-4A section;

[0013] Figure 5 and Figure 5A is Figure 1 Schematic diagram of the structure of the embodiment with a snap ring;

[0014] Figure 6 Schematic diagram of the combined structure of the cell perfusion device in this case;

[0015] Figure 7 Schematic diagram of the structure of the cell and tissue layer forming and packaging device in this case placed in the base of the stage with the upper cover open;

[0016] Figure 8 Schematic diagram of the sectional structure of the stage in this case at the fifth position where the projection range of the needle is misaligned with the projection range of the perfusion hole of the upper cover;

[0017] Figure 8A Schematic diagram of the sectional structure of the stage in this case at the sixth position where the projection range of the needle 622 overlaps with the projection range of the perfusion hole of the upper cover and the projection range of the hole of the upper cover;

[0018] Figure 9 Schematic diagram of the state of the syringe barrel of the perfusion device in this case descending to the eighth position;

[0019] Figure 9A Schematic diagram of the sectional structure of the perfusion device in this case where the horizontal position of the tip of the needle is lower than the horizontal position of the bottom surface of the top plate;

[0020] Figure 10 Schematic diagram of the state of the syringe barrel of the perfusion device in this case ascending to the seventh position and the heating element heating;

[0021] Figure 11 Schematic diagram of the state of the perfusion device in this case when the active magnetic attraction assembly slides to the fourth position;

[0022] Figure 12 Schematic diagram of the perfusion device in this case with the upper cover open and ready to remove the cell and tissue layer forming package;

[0023] Figure 13 Schematic diagram of removing the cell and tissue layer from the cell and tissue layer forming package in this case;

[0024] Figure 14 Schematic diagram of removing the cell and tissue layer sheet when a buckle is provided for the cell and tissue layer sheet forming package in this case.

[0025] Symbol description

[0026] 100: Cell and tissue layer sheet forming package

[0027] 10: Bottom plate

[0028] 11: Groove

[0029] 12: Recess

[0030] 13: Depressed area

[0031] 14: Slide groove

[0032] 15: Buckle

[0033] 20: Diaphragm

[0034] 30: Top plate

[0035] 31: Hole

[0036] 32: Passive magnetic attraction component

[0037] 321: Passive magnetic attraction element

[0038] 33: Top surface

[0039] 34: Bottom surface

[0040] 40: Sealing film

[0041] 200: Cell perfusion device

[0042] 50: Carrier platform

[0043] 51: Base

[0044] 52: Upper cover

[0045] 521: Perfusion hole

[0046] 53: Heating element

[0047] 54: Active magnetic attraction component

[0048] 541: Active magnetic attraction element

[0049] 542: Pushing member

[0050] 55: Hinge

[0051] 56: Magnetic buckle

[0052] 60: Perfusion mechanism

[0053] 61: Fixed seat

[0054] 62: Syringe barrel

[0055] 63: Track

[0056] 621: Barrel body

[0057] 622: Needle

[0058] 623: Piston

[0059] 70: First drive assembly

[0060] 71: First screw

[0061] 72: First motor

[0062] 80: Second drive assembly

[0063] 81: Turntable

[0064] 82: Connecting rod

[0065] 90: Third drive assembly

[0066] 91: Second screw

[0067] 92: Pressing seat

[0068] 93: Second motor

[0069] D1: First sensing element

[0070] D2: Second sensing element

[0071] D3: Third sensing element

[0072] D4: Fourth sensing element

[0073] F1: First direction

[0074] H: Depth

[0075] h: Thickness

[0076] H1, H2, H3, H4: Horizontal position

[0077] S1: First sensor

[0078] S2: Second sensor

[0079] S3: Third sensor

[0080] S4: Fourth sensor

[0081] SL: Solution Detailed implementation manners

[0082] In one embodiment of this case, through the design of the cell and tissue sheet forming package and the cell perfusion device, the cell membrane sheet can be fabricated on-site in the clinical field, which can simplify the operation process of cell therapy. There is no need for pre-operation to enter the laboratory to culture and amplify cells and fabricate the cell membrane sheet, eliminating the risk of difficult temperature control during cell transportation.

[0083] Please refer to Figure 1 and Figure 2 As shown, a cell and tissue sheet forming package 100 provided in this case includes a bottom plate 10, a membrane sheet 20, a top plate 30, and a sealing film 40.

[0084] The materials of the bottom plate 10 and the top plate 30 can be, for example, one of polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyethylene (PE), polycarbonate (PC), acrylonitrile butadiene styrene (ABS), and polytetrafluoroethylene (PTFE).

[0085] The membrane sheet 20 is made of a hydrophilic material. The materials of the membrane sheet 20 can be, for example, one of polylactic acid (PLA), polycaprolactone (PCL), and collagen.

[0086] The materials of the sealing film 40 can be, for example, one of Tyvek, aluminum foil, and nylon.

[0087] Please refer to Figure 2 , Figure 3 and Figure 3A As shown, the bottom plate 10 has a groove 11, and a recess 12 is provided on one side of the groove 11. The recess 12 communicates with the groove 11.

[0088] The membrane sheet 20 is disposed in the groove 11. After the membrane sheet 20 is placed in the groove 11, a part of the edge of the membrane sheet 20 can be exposed in the recess 12 to create a gap between the membrane sheet 20 and the recess 12, which is beneficial for taking the membrane sheet 20.

[0089] The bottom plate 10 is provided with a recessed area 13, and the groove 11 is disposed in the recessed area 13. On the opposite inner sides of the recessed area 13 corresponding to the position of the groove 11, a sliding groove 14 is respectively provided, and the length directions of the two sliding grooves 14 are parallel to the first direction F1.

[0090] Please refer to Figure 3 , Figure 3A , Figure 4 and Figure 4AAs shown, the top plate 30 is disposed within the chute 14. The top plate 30 is parallel to the horizontal plane and parallel to the first direction F1. The top plate 30 can be slidably disposed at the top of the bottom plate 10 between a first position and a second position parallel to the first direction F1. Herein and hereinafter, the horizontal plane refers to the plane formed by the X-axis and the Y-axis.

[0091] When the top plate 30 is at the second position, the groove 11 and the diaphragm 20 can be exposed, as Figure 3 shown. When the top plate 30 is at the first position, the groove 11 and the diaphragm 20 can be covered, as Figure 4 shown.

[0092] Please refer to Figure 3 、 Figure 3A 、 Figure 4 and Figure 4A shown. The top plate 30 includes a hole 31 and a passive magnetic attraction assembly 32.

[0093] The hole 31 penetrates from the top surface 33 of the top plate 30 to the bottom surface 34 of the top plate 30. When the top plate 30 is at the first position shown in Fig. 4, the hole 31 is located above the groove 11 and the diaphragm 20. The hole 31 can provide for injecting a solution (not shown in the figure) from the top surface 33 of the top plate 30 into the groove 11. Please refer to Figure 4A shown. In this embodiment, when the top plate 30 is at the first position, the projection range of the hole 31 is located at the center of the groove 11 and the diaphragm 20, so that the distribution of the solution can be more uniform.

[0094] The solution used in this case is a mixed solution of a biocompatible polymer material and cells. Among them, the polymer material is one of collagen, gelatin, hyaluronic acid, alginate, and polyethylene glycol (PEG) copolymer polymers. The cells are one of fibroblasts, myoblasts, epithelial cells, endothelial cells, progenitor cells, tendon cells, stem cells, mesenchymal stem cells, bone marrow stem cells, or adipose stem cells.

[0095] The passive magnetic attraction assembly 32 is adapted to be magnetically attracted to an active magnetic attraction assembly (not shown in the figure), and the top plate 30 is driven by the active magnetic attraction assembly to slide between a first position and a second position parallel to the horizontal plane and parallel to the first direction F1. In this embodiment, the passive magnetic attraction assembly 32 has two passive magnetic attraction elements 321. The two passive magnetic attraction elements 321 are distributed parallel to the horizontal plane, and the distribution direction is parallel to the horizontal plane and perpendicular to the first direction F1.

[0096] Please refer to Figure 4AAs shown, the groove 11 is parallel to the Z-axis direction and perpendicular to the horizontal plane with a depth H. The diaphragm 20 is parallel to the Z-axis direction and perpendicular to the horizontal plane with a thickness h. The depth H is greater than the thickness h, and the groove 11 has an area A (i.e., the bottom area) along the horizontal plane. Therefore, the maximum volume of the solution injected into the groove 11 can be (H - h)×A. Usually, the thickness h of the diaphragm 20 ranges from 10 to 100 micrometers (μm). For a diaphragm 20 with dimensions of 30×30×0.02 millimeters (mm), the required volume of the solution is approximately 0.9 to 1.1 milliliters (ml). According to the above formula, (H - h)×A, the required depth H of the groove 11 can be deduced as a reference for the design.

[0097] Please refer to Figure 5 and Figure 5A As shown, in this embodiment, a snap ring 15 is provided in the groove 11. The snap ring 15 is adapted to be in a tight fit with the groove 11 to fix the diaphragm 20 between the snap ring 15 and the groove 11. The snap ring 15 presses on the peripheral edge of the top surface of the diaphragm 20 to limit the position of the diaphragm 20 and prevent it from moving.

[0098] The material of the snap ring 15 can be, for example, one of polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyethylene (PE), polycarbonate (PC), acrylonitrile butadiene styrene (ABS), polytetrafluoroethylene (PTFE), rubber, and silicon carbide (Silicon).

[0099] Please refer to Figure 1 , Figure 3 and Figure 4 As shown, as Figure 3 shown, the diaphragm 20 and the top plate 30 are arranged in the bottom plate 10; again, as Figure 4 shown, the top plate 30 is slid to the first position to cover the diaphragm 20; then, the sealing film 40 is wrapped around the upper surfaces of the top plate 30 and the bottom plate 10 to seal the top plate 30 and the diaphragm 20 within the sealing film 40, forming a sealed cell and tissue laminate forming package 100 as Figure 1 shown.

[0100] Similarly, Figure 5 and Figure 5A The embodiments shown can also be wrapped with the sealing film 40 around the upper surfaces of the top plate 30 and the bottom plate 10 in the manner as Figure 3 , Figure 4 shown, forming a sealed cell and tissue laminate forming package 100 with the outer shape as Figure 1 shown.

[0101] Please refer to Figure 6 As shown, a cell perfusion device 200 provided in this case is used for Figure 1The cells and tissue layer forming package 100 shown are perfused with a solution.

[0102] The cell perfusion device 200 includes a stage 50 and a perfusion mechanism 60, and the stage 50 and the perfusion mechanism 60 are actuated by a drive mechanism composed of a first drive assembly 70, a second drive assembly 80, and a third drive assembly 90.

[0103] Please refer to Figure 6 , Figure 7 and Figure 8 As shown, the stage 50 includes a base 51, an upper cover 52, two heating elements 53, and an active magnetic attraction assembly 54.

[0104] The base 51 is adapted to carry the cell and tissue layer forming package 100 as shown in Figure 1 . The upper cover 52 is connected to the base 51. In this embodiment, one side between the upper cover 52 and the base 51 can be pivotally connected by a hinge 55, and the upper cover 52 is fixed or separated from the base 51 by a magnetic buckle 56 on the opposite side. The upper cover 52 is movably arranged above the base 51 in an open or closed manner. When the upper cover 52 is arranged above the base 51 in a closed manner, the cell and tissue layer forming package 100 can be positioned within the base 51. Since the top plate 30 of the cell and tissue layer forming package 100 and other components are sealed within the sealing film 40, it is shown in Figure 7 by a dotted line. The upper cover 52 has a perfusion hole 521. When the upper cover 52 is closed on the base 51, the projection range of the perfusion hole 521 overlaps with the projection range of the hole 31 of the top plate 30 of the cell and tissue layer forming package 100, as shown in Figure 8 .

[0105] The heating elements 53 are arranged on the base 51. In this embodiment, two heating elements 53 are arranged on opposite side edges of the base 51 to provide heat energy to the membrane 20 and the solution of the cell and tissue layer forming package 100. The form of the heating elements 53 is not limited. As shown in Figure 7 , the heating elements 53 are in the form of long tubular shapes, but are not limited thereto.

[0106] The active magnetic attraction assembly 54 is slidably disposed on the top of the upper cover 52 between a third position and a fourth position parallel to the horizontal plane and parallel to the first direction F1. The active magnetic attraction assembly 54 includes two active magnetic attraction elements 541, and the two active magnetic attraction elements 541 are connected to a pushing member 542. When the upper cover 52 is disposed above the base 51 in a closed manner, the two active magnetic attraction elements 541 in the active magnetic attraction assembly 54 are adapted to magnetically attract the two passive magnetic attraction elements 321 of the passive magnetic attraction assembly 32 of the cell and tissue laminate forming package 100. Therefore, by pushing the position of the pushing member 542 connected to the active magnetic attraction element 541, the active magnetic attraction assembly 54 can slide between the third position and the fourth position (refer to Figure 11 for the position of the active magnetic attraction assembly 54 shown), so that the top plate 30 of the cell and tissue laminate forming package 100 can be synchronously driven to slide between the first position and the second position (refer to Figure 3 for the position of the top plate 30 shown).

[0107] That is, the cell and tissue laminate forming package 100 is disposed inside the stage 50. By magnetically attracting the active magnetic attraction assembly 54 and the passive magnetic attraction assembly 32, the movement of the top plate 30 of the cell and tissue laminate forming package 100 can be controlled outside the stage 50. In an embodiment, the active magnetic attraction assembly 54 can be moved by manually moving the pushing member 542 by the user, or the position of the active magnetic attraction assembly 54 can be changed by mechanically or electrically driving the pushing member 542.

[0108] Please refer to Figure 6 shown. The perfusion mechanism 60 includes a fixed seat 61 and a syringe 62. The fixed seat 61 is disposed on a track 63, and the track 63 extends in a direction parallel to the Z axis and is perpendicular to the horizontal plane.

[0109] The syringe 62 includes a barrel 621, a needle 622, and a piston 623. The barrel 621 is in the shape of a long cylinder and is adapted to accommodate a solution. The barrel 621 is disposed on the fixed seat 61 with its axial direction parallel to the Z axis and perpendicular to the horizontal plane. The needle 622 is coaxially disposed at the bottom end of the barrel 621, and the tip 6221 of the needle 622 faces the horizontal plane. The piston 623 is coaxially disposed inside the barrel 621, and the piston 623 is adapted to move inside the barrel 621 along the Z axis so that the solution inside the barrel 621 can be pushed out from the tip 6221 of the needle 622.

[0110] The following describes the actuation modes of the first drive assembly 70, the second drive assembly 80, and the third drive assembly 90 included in the drive mechanism.

[0111] Please refer to Figure 6 、 Figure 8 and Figure 8AAs shown, the first driving component 70 is adapted to drive the stage 50 to move, for example, to move parallel to the horizontal plane and parallel to the first direction F1. The first driving component 70 includes a first screw 71 and a first motor 72. The axial direction of the first screw 71 is parallel to the horizontal plane, and the stage 50 is disposed on the first screw 71. The first motor 72 drives the first screw 71 to rotate forward and backward and synchronously drives the stage 50 to reciprocate between a fifth position and a sixth position.

[0112] A first sensor S1 and a second sensor S2 are provided on one side of the stage 50. On the same side of the base 51 of the stage 50 and the first sensor S1 and the second sensor S2, a first sensing member D1 and a second sensing member D2 are provided. The first sensing member D1 and the second sensing member D2 are respectively adapted to be sensed by the first sensor S1 and the second sensor S2 to obtain the position information of the stage 50. Specifically, when the first driving component 70 drives the stage 50 to move, the first sensing member D1 and the second sensing member D2 can move synchronously and respectively enter the sensing ranges of the first sensor S1 and the second sensor S1 to control the stage 50 to stop at the fifth position or the sixth position.

[0113] When the first sensor S1 senses the first sensing member D1, the first driving component 70 is controlled to stop operating, so that the stage 50 stops at the fifth position, as Figure 6 shown. At this time, the projection range of the needle 622 and the projection range of the perfusion hole 521 of the upper cover 52 are misaligned with each other, as Figure 8 shown.

[0114] Please refer to Figure 6 shown. When the first driving component 70 drives the stage 50 to move toward the side where the perfusion mechanism 60 is provided, so that the second sensor S2 senses the second sensing member D2, the first driving component 70 is controlled to stop operating, so that the stage 50 stops at the sixth position. At this time, the projection range of the needle 622, the projection range of the perfusion hole 521 of the upper cover 52, and the projection range of the hole 31 of the top plate 30 overlap with each other, as Figure 8A shown. Then, the second driving component 80 can be controlled to drive the fixing base 61 and the syringe 62 to move.

[0115] Please refer to Figure 6As shown, the second driving assembly 80 is adapted to drive the movement of the fixed seat 61 and the syringe barrel 62. The second driving assembly 80 includes a turntable 81, a connecting rod 82, and a driving element (not shown in the figure), and the driving element can be a motor. The turntable 81 is disposed below the fixed seat 61. One end of the connecting rod 82 is pivotally connected to the fixed seat 61, and the opposite end thereof is pivotally connected to an eccentric position of the turntable 81. When the driving element drives the turntable 81 to rotate, the connecting rod 82 will be synchronously driven to move the fixed seat 61, and the fixed seat 61 and the syringe barrel 62 will reciprocally move on the track 63 between a seventh position and an eighth position in a direction parallel to the Z-axis and perpendicular to the horizontal plane.

[0116] A third sensor S3 is provided on one side of the perfusion mechanism 60. A third sensing member D3 is provided on the same side of the fixed seat 61 and the third sensor S3, and the third sensing member D3 is adapted to be sensed by the third sensor S3 to obtain the position information of the fixed seat 61 and the syringe barrel 62 of the perfusion device 60. Specifically, when the second driving assembly 80 drives the fixed seat 61 and the syringe barrel 62 to move, the third sensing member D3 can move synchronously and enter the sensing range of the third sensor S3. When the third sensor S3 senses the third sensing member D3, the second driving assembly 80 is controlled to stop operating, so that the fixed seat 61 stops at the seventh position, as Figure 6 shown. At this time, as Figure 8A shown, the horizontal position H1 of the needle tip 6221 is higher than the horizontal position H2 of the top surface 522 of the upper cover 52 of the stage 50.

[0117] Please refer to Figure 6 , Figure 9 and Figure 9A shown. When the fixed seat 61 and the syringe barrel 62 are driven downward to the eighth position, the needle 622 enters the perfusion hole 521. The horizontal position H3 of the needle tip 6221 is lower than the horizontal position H4 of the sealing film 40 at the top of the hole 31, and the projection range of the needle 622 overlaps with the projection range of the perfusion hole 521 of the upper cover 52. That is, the needle tip 6221 can pierce the sealing film 40 and extend into the hole 31. Then, the third driving assembly 90 can be driven to press the piston 623 of the syringe barrel 62.

[0118] Please refer to Figure 6 shown. The third driving assembly 90 is adapted to drive the movement of the piston 623. The third driving assembly 90 includes a second screw 91, a pressing seat 92, and a second motor 93. The axial direction of the second screw 91 is parallel to the Z-axis direction and perpendicular to the horizontal plane. The pressing seat 92 is disposed on the second screw 91. One side of the pressing seat 92 is located above the top surface of the piston 623 and is adapted to press the piston 623. The second motor 93 drives the second screw 91 to rotate forward and backward to synchronously drive the pressing seat 92 to reciprocally move between a ninth position and a tenth position in a direction parallel to the Z-axis and perpendicular to the horizontal plane.

[0119] On one side of the cell perfusion device 200, a fourth sensor S4 is provided. On the same side of the pressing seat 92 of the third driving assembly 90 and the fourth sensor S4, a fourth sensing member D4 is provided, and the fourth sensing member D4 is adapted to be sensed by the fourth sensor S4 to obtain the position information of the pressing seat 92. Specifically, when the third driving assembly 90 drives the pressing seat 92 to move, the fourth sensing member D4 can move synchronously and enter the sensing range of the fourth sensor S4. Figure 6 It is shown that the pressing seat 92 is located at the ninth position. The fourth sensor S4 can sense the fourth sensing member D4 and control the third driving assembly 90 to stop operating. At this time, the pressing seat 92 does not contact the piston 623, and the fixing seat 61 is located at the seventh position.

[0120] Please refer to Figure 9 and Figure 9A As shown, when the second driving assembly 80 drives the fixing seat 61 and the syringe 62 to move downward to Figure 9 and Figure 9A the eighth position shown, the third driving assembly 90 will drive the pressing seat 92 to descend in a direction parallel to the Z-axis and perpendicular to the horizontal plane, so that the pressing seat 92 contacts the piston 623, and the pressing seat 92 continues to descend to the tenth position to push out the solution SL in the cylinder body 621 from the needle 622, so that the solution SL enters the space between the top plate 30 and the diaphragm 20, as Figure 9A shown.

[0121] Please refer to Figure 6 , Figure 9A and Figure 10 As shown, when the solution SL is completely perfused into the space between the top plate 30 and the diaphragm 20, the third driving assembly 90 drives the pressing seat 92 to rise to disengage from the piston 623, and when the pressing seat 92 rises to Figure 6 the ninth position shown, the fourth sensor S4 senses the fourth sensing member D4 and controls the third driving assembly 90 to stop operating.

[0122] Then, control the second driving assembly 80 to drive the fixing seat 61 and the syringe 62 to rise to Figure 6 the seventh position shown. When the third sensor S3 senses the third sensing member D3, control the second driving assembly 80 to stop operating, so that the fixing seat 61 stops at the seventh position, as Figure 6 shown.

[0123] Subsequently, the heating element 53 provides thermal energy to the diaphragm 20 and the solution SL of the cell and tissue laminate forming package 100, causing the solution SL to form a colloid 21 and adsorb onto the diaphragm 20. In one embodiment, for a diaphragm 20 with dimensions of 30×30×0.02 millimeters (mm) and a solution SL volume of approximately 0.9 to 1.1 milliliters (ml), heating with the heating element 53 to 37 to 40 degrees Celsius for about 10 minutes can cause the solution SL to form a colloid 21 and adsorb onto the diaphragm 20.

[0124] Subsequently, as Figure 11 shown, the pusher 542 is moved in parallel to the first direction F1 to slide the active magnetic attraction assembly 54 to the fourth position. Since the two active magnetic attraction elements 541 in the active magnetic attraction assembly 54 can magnetically attract the two passive magnetic attraction elements 321 of the passive magnetic attraction assembly 32 of the cell and tissue laminate forming package 100, the top plate 30 can be synchronously driven to slide to the second position (refer to the position of the top plate 30 shown in Figure 3 ). Since the top plate 30 is pushed open in a sliding manner, it will not stick to the diaphragm 20 with the colloid 21 attached.

[0125] Subsequently, as Figure 12 shown, the upper cover 52 is opened to remove the cell and tissue laminate forming package 100 from the base 51, and the sealing film 40 on the outer layer of the cell and tissue laminate forming package 100 is torn off.

[0126] Subsequently, as Figure 13 shown, the diaphragm 20 with the colloid 21 attached (i.e., the cell and tissue laminate) is taken out from the bottom plate 10 and can be covered on the affected part for use.

[0127] If a buckle 15 is provided on the diaphragm 20 as shown in Figure 5 and Figure 5A shown, then as shown in Figure 14 the diaphragm 20 with the colloid 21 attached is taken out from the bottom plate 10 together with the buckle 15, and then the buckle 15 is separated from the diaphragm 20 with the colloid 21 attached, and the diaphragm 20 with the colloid 21 attached (i.e., the cell and tissue laminate) can be covered on the affected part for use.

[0128] In summary, for the cell and tissue sheet forming packaging and cell perfusion device provided in this case, the preliminary operation is to seal the membrane in the cell and tissue sheet forming packaging. When the cell and tissue sheet is needed, a cell perfusion device is prepared. A physician or nurse in the clinical field places the cell and tissue sheet forming packaging in the stage of the cell perfusion device, installs a syringe containing a mixed solution of cells and polymer materials on the perfusion mechanism of the cell perfusion device, and then starts the cell perfusion device. The stage is moved below the perfusion mechanism, and then the syringe is lowered to inject the solution into the cell and tissue sheet forming packaging. After heating, the top plate of the cell and tissue sheet forming packaging is pushed open in a sliding manner by the magnetic attraction component, and the membrane attached with the colloid (i.e., the cell and tissue sheet) can be taken out and covered on the affected part for use.

[0129] As described above, through experimental verification, for a membrane with dimensions of 30×30×0.02 millimeters (mm) and a solution volume of approximately 0.9 to 1.1 milliliters (ml), when heated to 37 to 40 degrees Celsius by a heating element, it takes about 10 minutes for the solution to form a colloid and adsorb on the membrane. This case can simplify the cell therapy operation process, eliminating the lengthy operations of culturing cells in large quantities and fabricating cell membranes in the laboratory, and avoiding the risk of difficult temperature control during cell transportation. The cell membrane can be fabricated on-site in the clinical field through the packaging and cell perfusion device. After opening the sterile packaging, the cell and tissue sheet can be directly taken out and covered on the affected part for use. There is no need to wait during the treatment period, and the operation is simple.

[0130] Although the present invention is disclosed in combination with the above embodiments, it is not intended to limit this case. Any person of ordinary skill in the art can make some modifications and refinements without departing from the spirit and scope of this case. Therefore, the protection scope of this case shall be defined by the appended claims.

Claims

1. A cell and tissue laminate forming package, comprising: A bottom plate having a groove; A diaphragm disposed in the groove, the diaphragm being made of a hydrophilic material; A top plate parallel to the horizontal plane and parallel to the first direction, the top plate being slidably disposed on the top of the bottom plate between a first position and a second position, the top plate covering the groove and the diaphragm when in the first position, and exposing the groove and the diaphragm when in the second position, the top plate including: A hole penetrating from the top surface of the top plate to the bottom surface of the top plate, when the top plate is in the first position, the hole is located above the groove and the diaphragm, and a solution is injected into the groove through the hole; A passive magnetic attraction assembly disposed on the top plate, adapted to be magnetically attracted to an active magnetic attraction assembly, and the top plate is driven to slide by the active magnetic attraction assembly; A sealing film covering the upper surfaces of the top plate and the bottom plate to seal the top plate and the diaphragm within the sealing film, Wherein when the top plate is in the first position, the projection range of the hole is located at the center of the groove and the diaphragm, Wherein the passive magnetic attraction assembly has two passive magnetic attraction elements, the two passive magnetic attraction elements are distributed parallel to the horizontal plane, and the distribution direction is perpendicular to the first direction.

2. The cell and tissue laminate forming package according to claim 1, wherein a snap ring is provided in the groove, the snap ring is adapted to be in a tight fit with the groove, and the snap ring presses on the peripheral edge of the top surface of the diaphragm to limit the movement of the diaphragm.

3. The cell and tissue laminate forming package according to claim 1, wherein the depth of the groove is greater than the thickness of the diaphragm.

4. The cell and tissue laminate forming package according to claim 1, wherein the groove has a depth H perpendicular to the horizontal plane, the diaphragm has a thickness h perpendicular to the horizontal plane, the groove has an area A along the horizontal plane, and the volume of the solution is at most (H - h)×A.

5. The cell and tissue laminate forming package according to claim 1, wherein the bottom plate is provided with a recessed area, the groove is disposed in the recessed area, and sliding grooves are respectively provided on the opposite inner sides of the recessed area corresponding to the position of the groove, the length direction of the sliding grooves is parallel to the first direction, and the top plate is disposed in the sliding grooves.

6. The cell and tissue laminate forming package according to claim 1, wherein a recess is provided on one side of the groove, the recess communicates with the groove, and a part of the edge of the diaphragm is exposed in the recess to create a gap between the diaphragm and the recess.

7. The cell and tissue laminate forming package according to claim 1, wherein the solution is a mixed solution of a biocompatible polymer material and cells.

8. The cell and tissue laminate forming package according to claim 7, wherein the polymer material is one of collagen, gelatin, Hyaluronic acid, Alginate, and PEG copolymer polymer.

9. The cell and tissue laminate forming package according to claim 7, wherein the cell is one of fibroblast, myoblast, epithelial cell, endothelial cell, progenitor cell, tendon cell, stem cell, mesenchymal stem cell, bone marrow stem cell or adipose stem cell.

10. A cell perfusion device applicable to the cell and tissue laminate forming package according to any one of claims 1 to 9, the cell perfusion device comprising: A stage, which includes: A base, adapted to carry the cell and tissue laminate forming package; An upper cover, movably arranged above the base in an openable or closable manner to position the cell and tissue laminate forming package within the base. The upper cover has a perfusion hole. When the upper cover is closed on the base, the projection range of the perfusion hole overlaps with the projection range of the hole on the top plate of the cell and tissue laminate forming package; At least one heating element, arranged on the base to provide heat energy to the diaphragm and the solution; A active magnetic attraction assembly, slidably arranged on the top of the upper cover between a third position and a fourth position parallel to the horizontal plane and parallel to a first direction. The active magnetic attraction assembly is adapted to magnetically attract with a passive magnetic attraction assembly. When the active magnetic attraction assembly slides to the fourth position, it can synchronously drive the top plate to slide to the second position; A perfusion mechanism, which includes: A fixed seat, arranged on a track, the extending direction of the track being perpendicular to the horizontal plane; A syringe, which includes: A barrel, in a long cylindrical shape, adapted to contain the solution. The barrel is arranged on the fixed seat with its axis perpendicular to the horizontal plane; A needle, coaxially arranged at the bottom end of the barrel, the tip of the needle facing the horizontal plane; A piston, coaxially arranged within the barrel; A driving mechanism, which includes: A first driving component, adapted to drive the stage to reciprocate between a fifth position and a sixth position parallel to the horizontal plane and parallel to the first direction. When the stage is at the fifth position, the projection range of the needle is misaligned with the projection range of the perfusion hole on the upper cover. When the stage is at the sixth position, the projection range of the needle overlaps with the projection range of the perfusion hole on the upper cover and the projection range of the hole on the top plate; A second driving component, adapted to drive the fixed seat and the syringe to reciprocate between a seventh position and an eighth position perpendicular to the horizontal plane on the track. When the fixed seat and the syringe are at the seventh position, the horizontal position of the tip of the needle is higher than the horizontal position of the top surface of the upper cover of the stage. When the fixed seat and the syringe are at the eighth position, the horizontal position of the tip of the needle is lower than the horizontal position of the sealing film at the top of the hole on the top plate; A third driving component, adapted to drive the piston to move perpendicular to the horizontal plane within the barrel to push out the solution in the barrel from the needle.

11. The cell perfusion device according to claim 10, wherein a first sensor and a second sensor are provided on one side of the stage, and a first sensing member and a second sensing member are provided on the base of the stage; when the first driving assembly drives the stage to move, the first sensing member and the second sensing member can move synchronously and respectively enter the sensing ranges of the first sensor and the second sensor; when the first sensor senses the first sensing member, the first driving assembly is controlled to stop operating, so that the stage stops at the fifth position; when the second sensor senses the second sensing member, the first driving assembly is controlled to stop operating, so that the stage stops at the sixth position.

12. The cell perfusion device according to claim 10, wherein a third sensor is provided on one side of the perfusion mechanism, and a third sensing member is provided on the fixed seat; when the second driving assembly drives the fixed seat and the syringe to move, the third sensing member can move synchronously and enter the sensing range of the third sensor; when the third sensor senses the third sensing member, the second driving assembly is controlled to stop operating, so that the fixed seat stops at the seventh position.

13. The cell perfusion device according to claim 10, wherein the first driving assembly includes: A first screw rod, the axis direction of which is parallel to the horizontal plane, and the stage is arranged on the first screw rod; And A first motor, which drives the first screw rod to rotate forward and backward and synchronously drives the stage to reciprocate between the fifth position and the sixth position.

14. The cell perfusion device according to claim 10, wherein the second driving assembly includes: A turntable, which is arranged below the fixed seat; A connecting rod, one end of which is pivotally connected to the fixed seat, and the opposite end of which is pivotally connected to an eccentric position of the turntable; and A driving element, which drives the turntable to rotate, synchronously drives the connecting rod and makes the fixed seat move, and the fixed seat and the syringe will reciprocate between the seventh position and the eighth position perpendicular to the horizontal plane on the track.

15. The cell perfusion device according to claim 10, wherein the third driving assembly includes: A second screw rod, the axis direction of which is perpendicular to the horizontal plane; A pressing seat, which is arranged on the second screw rod, one side of the pressing seat is above the top surface of the piston, and the pressing seat presses the piston; and A second motor, which drives the second screw rod to rotate forward and backward and synchronously drives the pressing seat to reciprocate between the ninth position and the tenth position perpendicular to the horizontal plane.

16. The cell perfusion device according to claim 15, wherein a fourth sensor is provided on one side of the cell perfusion device, and a fourth sensing member is provided on the pressing seat; when the third driving assembly drives the pressing seat to move, the fourth sensing member can move synchronously and enter the sensing range of the fourth sensor; when the fourth sensor senses the fourth sensing member, the third driving assembly is controlled to stop operating.

17. The cell perfusion device according to claim 10, wherein the passive magnetic attraction assembly has two passive magnetic attraction elements, the two passive magnetic attraction elements are distributed parallel to the horizontal plane, and the distribution direction is perpendicular to the first direction; the active magnetic attraction assembly includes two active magnetic attraction elements, and the two active magnetic attraction elements are adapted to be magnetically attracted to the two passive magnetic attraction elements.

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