CN116331644A - Cell and tissue layer sheet forming packaging and cell perfusion equipment - Google Patents

Abstract

The invention discloses a cell and tissue lamellar forming package and cell perfusion equipment, the cell and tissue lamellar forming package comprises a bottom plate, a diaphragm, a top plate and a sealing film, wherein the top plate is slidably arranged at the top of the bottom plate along a horizontal plane so as to cover or expose the diaphragm, and the top plate is provided with a hole and a passive magnetic component. The cell perfusion equipment comprises a carrier, a perfusion mechanism and a driving mechanism, wherein the carrier is used for carrying cell and tissue lamellar forming package, the driving mechanism is used for driving the carrier and the perfusion mechanism to move, so that the perfusion mechanism injects solution into the cell and tissue lamellar forming package through holes, a heating element of the carrier is used for heating a diaphragm and the solution, so that the solution forms colloid to be attached to the diaphragm to form the cell and tissue lamellar, and then the driving magnetic component adsorbed with the driven magnetic component is driven to move to drive a top plate to slide so as to expose the cell and tissue lamellar.

Description

Cell and tissue layer forming packaging and cell perfusion equipment

technical field

The invention relates to a cell and tissue layer forming packaging and cell perfusion equipment.

Background technique

Cell and tissue sheets (or dressings for short) are commonly used in the medical field. Covering the wound with a layer of cells and tissues can increase the speed of wound healing.

At present, the existing production process of cell and tissue slices is roughly as follows: first, cell collection is performed, followed by cell culture (this step is extremely time-consuming), and then the cultured cells are transported and stored for use in subsequent operations. However, the steps of cell culture are extremely time-consuming and costly because they must be completed in a petri dish in a laboratory with special manufacturing techniques and equipment. As for the transportation process, if the temperature, humidity and other conditions are not properly controlled, there will be a risk of damage and contamination.

Based on this, how to develop a "cell and tissue layer forming packaging and cell perfusion equipment" to simplify the operation process of cell therapy, without the need to enter the laboratory to culture cells in large quantities and make cell membranes. Not easy risk, through packaging and cell perfusion equipment, cell membranes can be manufactured on-site in the clinical field, which is an urgent problem to be solved by people in the related technical field.

Contents of the invention

In one embodiment, this case proposes a cell and tissue layer forming package, which includes: a bottom plate with a groove; a membrane, which is arranged in the groove, and the membrane is made of a hydrophilic material ; a top plate, parallel to the horizontal plane and parallel to the first direction, the top plate is slidably arranged on the top of the bottom plate between a first position and a second position, the top plate can cover the groove and the membrane when it is in the first position, When the top plate is in the second position, the groove and the diaphragm can be exposed. The top plate includes: a hole, the top surface of the top plate penetrates 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 the hole provides The solution is injected into the groove from the top surface of the top plate; a passive magnetic attraction component is arranged on the top plate, which is suitable for magnetic attraction with an active magnetic attraction component, and the active magnetic attraction component drives the top plate to slide; a sealing film is coated on the The upper surfaces of the top plate and the bottom plate are used to seal the top plate and the diaphragm in the sealing film.

In another embodiment, this case proposes a cell perfusion device, which is suitable for forming and packaging the above-mentioned cell and tissue sheets. The cell perfusion device includes a carrier, which includes: a base, suitable for carrying cells and tissue sheets for forming Packaging; an upper cover, which can be set above the base in an open or closed manner, so as to position the cell and tissue layer forming package in the base. The upper cover has a perfusion hole. When the upper cover is closed on the base, the perfusion The projection range of the hole overlaps with the projection range of the top plate of the cell and tissue layer forming package; a heating element is arranged on the base to provide heat energy to the membrane and the solution; an active magnetic attraction component is parallel to the horizontal plane and The first direction is slidably arranged on the top of the upper cover between a third position and a fourth position. The active magnetic attraction component is suitable for magnetically attracting the passive magnetic attraction component. When the active magnetic attraction component slides to the fourth position , the top plate can be synchronously driven to slide to the second position; a filling 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 cylinder body, which is long Cylindrical, suitable for containing solution, the cylinder is installed on the fixed seat with its axial direction perpendicular to the horizontal plane; a needle is coaxially arranged at the bottom of the cylinder, and the tip of the needle faces the horizontal plane; a piston is coaxially arranged In the barrel; a drive mechanism, which includes: a first drive assembly, 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 When it is in the fifth position, the projection range of the needle head and the projection range of the perfusion hole of the upper cover are misaligned. When the carrier is in the sixth position, the projection range of the needle head is the projection range of the perfusion hole of the upper cover and the projection of the hole on the top plate. Range overlapping; a second driving assembly, suitable for synchronously driving the fixing base and the needle cylinder to reciprocate on the track perpendicular to the horizontal plane between a seventh position and an eighth position, when the fixing base and the needle cylinder are in the seventh position , the horizontal position of the needle point is higher than the horizontal position of the top surface of the upper cover of the stage, when the fixing seat and the syringe are in the eighth position, the horizontal position of the needle point is lower than the horizontal position of the sealing film on the top of the hole on the top plate; The third drive assembly is suitable for driving the piston to move vertically to the horizontal plane in the cylinder so as to push the solution in the cylinder out from the needle.

Description of drawings

Fig. 1 is the combined structure schematic diagram of the embodiment of the cell and tissue ply forming packaging of this case;

Fig. 2 is the schematic diagram of the disassembled structure of Fig. 1 embodiment removing sealing film;

Fig. 3 is a schematic diagram of the combined structure of the embodiment of Fig. 1 with the sealing film removed and the top plate in the second position;

FIG. 3A is a schematic diagram of the enlarged structure of the 3A-3A section of FIG. 3;

Fig. 4 is a schematic diagram of the combined structure of the embodiment of Fig. 1 with the sealing film removed and the top plate at the first position;

Fig. 4A is a schematic diagram of the enlarged structure of the section 4A-4A of Fig. 4;

Fig. 5 and Fig. 5 A are the structural schematic diagrams of the embodiment of Fig. 1 provided with buckles;

Figure 6 is a schematic diagram of the combined structure of the cell perfusion device in this case;

Fig. 7 is a structural schematic diagram of the cell and tissue layer forming package device placed in the base of the carrier and the upper cover opened;

Fig. 8 is a cross-sectional schematic diagram of the present case where the stage is located at the fifth position and the projected range of the needle and the projected range of the perfusion hole of the upper cover are misaligned;

FIG. 8A is a schematic cross-sectional structure diagram of the present case where the stage is located at the sixth position and 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;

Fig. 9 is a schematic diagram of the state in which the syringe of the perfusion device in this case is lowered to the eighth position;

FIG. 9A is a schematic cross-sectional structural view of the perfusion device where the horizontal position of the needle tip is lower than the horizontal position of the bottom surface of the top plate;

Fig. 10 is a schematic diagram of the state in which the syringe of the perfusion device in this case is raised to the seventh position and the heating element is heated;

Fig. 11 is a schematic diagram of the state when the active magnetic attraction component of the perfusion device in this case slides to the fourth position;

Fig. 12 is a schematic structural view of the perfusion device in this case with the upper cover opened and the cell and tissue layer forming package ready to be taken out;

Fig. 13 is a schematic diagram of taking out the cell and tissue layer from the packaging of the cell and tissue layer in this case;

Fig. 14 is a schematic diagram of taking out the cell and tissue layer when the forming package of the cell and tissue layer is provided with a buckle.

Symbol Description

100: Forming and packaging of cell and tissue layers

10: Bottom plate

11: Groove

12: Concave

13: Depressed area

14: Chute

15: Buckle

20: Diaphragm

30: top plate

31: hole

32:Passive magnetic components

321: Passive magnetic element

33: top surface

34: bottom surface

40: sealing film

200: cell perfusion equipment

50: carrier

51: base

52: Upper cover

521: perfusion hole

53: Heating element

54:Active magnetic components

541:Active magnetic element

542: Pusher

55:Hinge

56: Magnetic buckle

60: Perfusion mechanism

61: fixed seat

62: Syringe

63: track

621: barrel

622: Needle

623: Piston

70: The first drive assembly

71: the first screw

72: The first motor

80: Second drive assembly

81: turntable

82: Connecting rod

90: The third driving component

91: second screw

92: Press seat

93:Second motor

D1: the first sensor

D2: The second sensor

D3: The third sensor

D4: The fourth sensor

F1: first direction

H: Depth

h: thickness

H1, H2, H3, H4: Horizontal position

S1: first sensor

S2: Second sensor

S3: Third sensor

S4: Fourth sensor

SL: solution

Detailed ways

In one embodiment of this case, through the design of cell and tissue sheet forming packaging and cell perfusion equipment, the cell membrane can be manufactured on-site in the clinical field, which can simplify the cell therapy operation process and require no pre-work to enter The laboratory scales up cell culture and makes cell membranes, eliminating the risk of difficult temperature control for cell transportation.

Please refer to Fig. 1 and Fig. 2, a kind of cell and tissue sheet forming package 100 provided in this case includes a bottom plate 10, a diaphragm 20, a top plate 30 and a sealing film 40.

The material of the bottom plate 10 and the top plate 30 can be, for example, polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyethylene (PE), polyethylene One of carbonate (PC), acrylonitrile butadiene styrene (ABS), polytetrafluoroethylene (PTFE).

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

The material of the sealing film 40 can be one of Tyvek, aluminum foil and nylon, for example.

Referring to FIG. 2 , FIG. 3 and FIG. 3A , the bottom plate 10 has a groove 11 , and a concave portion 12 is formed on one side of the groove 11 , and the concave portion 12 communicates with the groove 11 .

The diaphragm 20 is disposed in the groove 11 . After the membrane 20 is put into the groove 11 , part of the edge of the membrane 20 can be exposed in the recess 12 , so as to create a gap between the membrane 20 and the recess 12 , which is convenient for taking the membrane 20 .

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

Please refer to Fig. 3, Fig. 3A, Fig. 4 and Fig. 4A, the top plate 30 is arranged in 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 parallel to the first direction F1 in a first The position and a second position are slidably disposed on the top of the bottom plate 10 . The horizontal plane referred to here and below refers to the plane formed by the X axis and the Y axis.

When the top plate 30 is at the second position, the groove 11 and the diaphragm 20 can be exposed, as shown in FIG. 3 . When the top plate 30 is at the first position, it can cover the groove 11 and the diaphragm 20 , as shown in FIG. 4 .

Referring to FIG. 3 , FIG. 3A , FIG. 4 and FIG. 4A , the top plate 30 includes a hole 31 and a passive magnetic attraction component 32 .

The hole 31 passes through the bottom surface 34 of the top plate 30 from the top surface 33 of the top plate 30 . When the top plate 30 is in the first position shown in FIG. 4, the hole 31 is located above the groove 11 and the diaphragm 20, and the hole 31 can provide a solution (not shown) injected into the groove by the top surface 33 of the top plate 30. within 11. 4A, 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 solution can be distributed more evenly.

The solution used in this case is a mixed solution of biocompatible polymer materials and cells. Wherein, 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, precursor cells, tenocytes, stem cells, mesenchymal stem cells, bone marrow stem cells or adipose stem cells.

The passive magnetic attraction assembly 32 is suitable for magnetic attraction with an active magnetic attraction assembly (not shown in the figure), and the top plate 30 is driven by the active magnetic attraction assembly to be parallel to the horizontal plane and parallel to the first direction F1 at the first position and the second Swipe between locations. In this embodiment, the passive magnetic assembly 32 has two passive magnetic elements 321 , the two passive magnetic 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 .

Please refer to FIG. 4A, the groove 11 is parallel to the Z-axis direction and has a depth H in the vertical horizontal plane, the diaphragm 20 is parallel to the Z-axis direction and has a thickness h in the vertical horizontal plane, the depth H is greater than the thickness h, and the groove 11 is along the The horizontal plane has an area A (ie the area of the bottom). Therefore, the volume of the solution injected into the groove 11 can be at most (H-h)×A. Usually, the thickness h of the diaphragm 20 is in the range of 10-100 microns (μm). For a diaphragm 20 with a size of 30×30×0.02 mm (mm), the required solution volume is about 0.9 to 1.1 milliliters (ml). According to the above formula, (H-h)×A, the groove can be calculated The required depth H of 11 is used as a reference for design.

Please refer to Fig. 5 and shown in Fig. 5A, in this embodiment, a clasp 15 is provided in the groove 11, and the clasp 15 is suitable for tight fitting with the groove 11 so that the diaphragm 20 is fixed on the clasp 15 and the groove. Between the slots 11 , a buckle 15 is pressed against the top peripheral edge of the diaphragm 20 to limit the position of the diaphragm 20 and prevent movement.

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

Please refer to Fig. 1, Fig. 3 and Fig. 4, as shown in Fig. 3, the diaphragm 20 and the top plate 30 are arranged in the bottom plate 10; then, as shown in Fig. 4, the top plate 30 is slid to the first position to cover the diaphragm 20 Then wrap the upper surface of the top plate 30 and the bottom plate 10 with the sealing film 40, so that the top plate 30 and the diaphragm 20 are sealed in the sealing film 40 to form a sealed cell and tissue layer molding package 100 as shown in FIG. 1 .

Similarly, the embodiment shown in FIG. 5 and FIG. 5A can also be covered with a sealing film 40 on the upper surface of the top plate 30 and the bottom plate 10 in the manner shown in FIG. 3 and FIG. 4 to form a sealed shape as shown in FIG. Cell and tissue ply forming package 100.

Please refer to FIG. 6 , a cell perfusion device 200 provided in this case, which is used to perfuse the cell and tissue layer forming package 100 shown in FIG. 1 with a solution.

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

Referring to FIG. 6 , FIG. 7 and FIG. 8 , the stage 50 includes a base 51 , an upper cover 52 , two heating elements 53 and an active magnetic attraction component 54 .

The base 51 is suitable for carrying the cell and tissue ply forming package 100 as shown in FIG. 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 can be fixed by a magnetic buckle 56 on the opposite side. Or separate on the base 51. The upper cover 52 is movably disposed above the base 51 in an open or closed manner. When the upper cover 52 is disposed above the base 51 in a closed manner, the cell and tissue ply forming package 100 can be positioned in the base 51. Since the top plate 30 and other components of the cell and tissue layer forming package 100 are sealed in the sealing film 40 , they are indicated by dotted lines in FIG. 7 . The upper cover 52 has a filling hole 521 . When the upper cover 52 is closed on the base 51 , the projected range of the perfusion hole 521 overlaps with the projected range of the hole 31 of the top plate 30 of the cell and tissue layer forming package 100 , as shown in FIG. 8 .

The heating element 53 is disposed on the base 51 . In this embodiment, two heating elements 53 are disposed on opposite sides 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 element 53 is not limited. As shown in FIG. 7 , the heating element 53 is in the shape of a long tube, but it is not limited thereto.

The active magnetic attraction component 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 assembly 54 includes two active magnetic elements 541 , and the two active magnetic elements 541 are connected to a pusher 542 . When the upper cover 52 is disposed above the base 51 in a closed manner, the two active magnetic elements 541 in the active magnetic assembly 54 are suitable for matching with the two passive magnetic elements 32 of the passive magnetic assembly 32 of the cell and tissue ply forming package 100. The attracting element 321 is magnetically attracted, therefore, by pushing the position of the push piece 542 connected with the active magnetically attracting element 541, the active magnetically attracting assembly 54 can slide between the third position and the fourth position (see the active magnetically attracting component 54 shown in FIG. 11 ). The position of the magnetic attraction assembly 54), so that the top plate 30 of the cell and tissue ply forming package 100 can be synchronously driven to slide between the first position and the second position (refer to the position of the top plate 30 shown in FIG. 3 ).

That is, the cell and tissue ply forming package 100 is arranged inside the carrier 50, and the active magnetic attraction component 54 and the passive magnetic component 32 are magnetically attracted to control the cell and tissue ply forming package 100 outside the carrier 50. The top plate 30 moves. In one embodiment, the active magnetic assembly 54 can be moved by the user manually moving the pusher 542 , or the position of the active magnetic assembly 54 can be changed by mechanically or electrically driving the pusher 542 .

Please refer to FIG. 6 , the filling mechanism 60 includes a fixing base 61 and a syringe 62 . The fixing seat 61 is disposed on a track 63, and the track 63 extends parallel to the Z-axis direction and perpendicular to the horizontal plane.

The syringe 62 includes a barrel 621 , a needle 622 and a piston 623 . The barrel 621 is elongated and suitable for accommodating the solution. The barrel 621 is arranged on the fixing seat 61 with its axis parallel to the Z-axis and perpendicular to the horizontal plane. The needle 622 is coaxially arranged at the bottom end of the barrel 621 , and the needle tip 6221 of the needle 622 faces the horizontal plane. The piston 623 is coaxially disposed in the barrel 621 , and the piston 623 is adapted to move along the Z-axis in the barrel 621 , so that the solution in the barrel 621 can be pushed to flow out from the needle tip 6221 of the needle 622 .

The operation modes of the first driving assembly 70 , the second driving assembly 80 and the third driving assembly 90 included in the driving mechanism will be described below.

Please refer to FIG. 6 , FIG. 8 and FIG. 8A , the first driving component 70 is suitable for driving the stage 50 to move, for example, to move parallel to the horizontal plane and parallel to the first direction F1 . The first driving assembly 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 in the forward and reverse direction and synchronously drives the stage 50 to reciprocate between a fifth position and a sixth position.

A first sensor S1 and a second sensor S2 are provided on one side of the stage 50, and a first sensor D1 and a first sensor D1 are arranged on the same side of the base 51 of the stage 50 as the first sensor S1 and the second sensor S2. Two sensing elements D2. The first sensing element D1 and the second sensing element D2 are adapted to be sensed by the first sensor S1 and the second sensor S2 respectively, so as to obtain position information of the stage 50 . In detail, when the first driving assembly 70 drives the stage 50 to move, the first sensing element D1 and the second sensing element D2 can move synchronously and enter the sensing ranges of the first sensor S1 and the second sensor S1 respectively. In order to control the carrier 50 to stop at the fifth position or the sixth position.

When the first sensor S1 senses the first sensor D1, the first driving assembly 70 is controlled to stop, so that the stage 50 stops at the fifth position, as shown in FIG. 6 . At this time, the projection range of the needle head 622 and the projection range of the perfusion hole 521 of the upper cover 52 are misaligned, as shown in FIG. 8 .

Please refer to FIG. 6 , when the first drive assembly 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 sensor D2, the first drive assembly 70 is controlled. Stop the operation and stop the stage 50 at the sixth position. At this time, the projection range of the needle head 622 overlaps with the projection range of the filling hole 521 of the upper cover 52 and the projection range of the hole 31 of the top plate 30, as shown in FIG. 8A , Then, the second driving assembly 80 can be controlled to drive the fixing seat 61 and the syringe 62 to move.

Please refer to FIG. 6 , the second driving assembly 80 is suitable for driving the movement of the fixing base 61 and the syringe 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 under the fixing seat 61 . One end of the connecting rod 82 is pivotally connected to the fixing base 61 , and the opposite end thereof is pivotally connected to the eccentric portion of the turntable 81 . When the driving element drives the turntable 81 to rotate, it will synchronously drive the connecting rod 82 to move the fixed seat 61, and the fixed seat 61 and the syringe 62 will be parallel to the Z-axis direction and perpendicular to the horizontal plane on the track 63 at a seventh position and - move back and forth between the eighth position.

One side of the perfusion mechanism 60 is provided with a third sensor S3, and a third sensor D3 is provided on the same side S3 of the fixing base 61 and the third sensor, and the third sensor D3 is suitable for being sensed by the third sensor S3 , to obtain the position information of the fixing seat 61 and the syringe 62 of the perfusion device 60 . In detail, when the second driving assembly 80 drives the fixing base 61 and the syringe 62 to move, the third sensing element D3 can move synchronously and enter the sensing range of the third sensor S3. When the third sensor S3 senses the third sensing element D3, the second driving assembly 80 is controlled to stop, so that the fixing seat 61 stops at the seventh position, as shown in FIG. 6 . At this time, as shown in FIG. 8A , the horizontal position H1 of the needle point 6221 is higher than the horizontal position H2 of the top surface 522 of the upper cover 52 of the stage 50.

Please refer to Fig. 6, Fig. 9 and Fig. 9A, when the fixing base 61 and the syringe 62 are driven downward to the eighth position, the needle head 622 enters the perfusion hole 521, and the horizontal position H3 of the needle point 6221 is lower than the top of the hole 31. The horizontal position H4 of the sealing film 40 , and the projected range of the needle 622 overlaps with the projected range of the perfusion hole 521 of the upper cover 52 , that is, the needle point 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 62 .

Please refer to FIG. 6 , 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 axis 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 , and one side of the pressing seat 92 is located above the top surface of the piston 623 and is suitable for pressing the piston 623 . The second motor 93 drives the second screw rod 91 to rotate forward and reverse to synchronously drive the pressing base 92 to reciprocate between a ninth position and a tenth position parallel to the Z-axis direction and perpendicular to the horizontal plane.

One side of the cell perfusion device 200 is provided with a fourth sensor S4, and a fourth sensor D4 is provided on the same side of the pressing seat 92 of the third drive assembly 90 as the fourth sensor S4, and the fourth sensor D4 is suitable for It is sensed by the fourth sensor S4 to obtain the position information of the pressing seat 92 . In detail, when the third driving assembly 90 drives the pressing seat 92 to move, the fourth sensing element D4 can move synchronously and enter the sensing range of the fourth sensor S4. Figure 6 shows that the pressing seat 92 is in the ninth position, the fourth sensor S4 can sense the fourth sensor D4, and control the third drive assembly 90 to stop, at this time, the pressing seat 92 is not in contact with the piston 623, and is fixed Seat 61 is in the seventh position.

Please refer to FIG. 9 and FIG. 9A, when the second driving assembly 80 drives the fixing seat 61 and the syringe 62 to move down to the eighth position shown in FIG. 9 and FIG. 9A, the third driving assembly 90 will drive the pressing seat 92 descends parallel to the Z-axis direction 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, so that the solution SL in the barrel 621 is pushed out from the needle 622, and the solution SL Enter the space between the top plate 30 and the diaphragm 20, as shown in FIG. 9A.

Please refer to FIG. 6, FIG. 9A and FIG. 10, when the solution SL is completely poured into the space between the top plate 30 and the diaphragm 20, the third drive assembly 90 drives the pressing seat 92 to rise to break away from the contact with the piston 623, and When the pressing seat 92 rises to the ninth position shown in FIG. 6 , the fourth sensor S4 senses the fourth sensing element D4 and controls the third driving assembly 90 to stop.

Then, the second driving assembly 80 is controlled to drive the fixing seat 61 and the syringe 62 to rise to the seventh position shown in FIG. 6 , and when the third sensor S3 senses the third sensor D3, the second driving assembly 80 is controlled to stop actuate to make the fixing seat 61 stop at the seventh position, as shown in FIG. 6 .

Then, the heating element 53 provides heat energy to the membrane 20 and the solution SL of the cell and tissue layer forming package 100, so that the solution SL forms a colloid 21 and is adsorbed on the membrane 20. In one embodiment, for a membrane 20 with a size of 30×30×0.02 millimeters (mm), the volume of the solution SL is about 0.9-1.1 milliliters (ml), and the heating element 53 is heated to 37-40 degrees Celsius, It takes about 10 minutes for the solution SL to form a colloid 21 and adsorb on the membrane 20 .

Then, as shown in FIG. 11 , the pusher 542 is moved in parallel to the first direction F1, and the active magnetic attraction assembly 54 is slid to the fourth position. Since the two active magnetic attraction elements 541 in the active magnetic attraction assembly 54 can be connected with the cells and The two passive magnetic elements 321 of the passive magnetic assembly 32 of the tissue ply forming package 100 are magnetically attracted to each other, so 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 FIG. 3 ). Since the top plate 30 is pushed away in a sliding manner, it will not stick to the membrane 20 attached with the colloid 21 .

Then, as shown in FIG. 12 , the upper cover 52 is opened to take out the cell and tissue layer forming package 100 from the base 51 , and the outer sealing film 40 of the cell and tissue layer forming package 100 is torn off.

Then, as shown in FIG. 13 , the membrane 20 (that is, the layer of cells and tissues) attached with the colloid 21 is taken out from the bottom plate 10 and can be used to cover the affected part.

If the diaphragm 20 is provided with a buckle 15 as shown in Figure 5 and Figure 5A, then as shown in Figure 14, the diaphragm 20 with the colloid 21 attached and the buckle 15 are taken out from the bottom plate 10 together, and then the The clasp 15 is separated from the membrane 20 attached with the colloid 21 , so that the membrane 20 attached with the colloid 21 (that is, the layer of cells and tissues) can be covered on the affected part for use.

To sum up, for the cell and tissue layer forming packaging and cell perfusion equipment provided in this case, the pre-work is to seal the membrane in the cell and tissue layer forming packaging. When the cell and tissue layer needs to be used, A cell perfusion equipment is prepared, and the doctors or nurses in the clinical field will pack the cells and tissue layers into the stage of the cell perfusion equipment, and install the syringe with the mixed solution of cells and polymer materials on the cell perfusion On the perfusion mechanism of the equipment, then start the cell perfusion equipment, move the stage to the bottom of the perfusion mechanism, and then lower the syringe to inject the solution into the cell and tissue layer forming package. After heating, the magnetic attraction component slides Pushing away the top plate of the cell and tissue layer forming package, the membrane sheet with colloid attached (that is, the cell and tissue layer sheet) can be taken out and covered on the affected part for use.

As mentioned above, it has been verified by experiments that for a membrane with a size of 30×30×0.02 millimeters (mm), the volume of the solution is about 0.9-1.1 milliliters (ml), and the heating element is heated to 37-40 degrees Celsius. It takes about 10 minutes for the solution to form a colloid and adsorb on the membrane. This case can simplify the operation process of cell therapy, without the need to enter the laboratory to culture cells in large quantities and make cell membranes, and avoid the risk of cell transportation temperature control, and cell membranes can be manufactured on-site in the clinical field through packaging and cell perfusion equipment piece. After unsealing the aseptic package, the cells and tissue layers can be taken out directly and covered on the affected area for use. There is no need to wait during treatment, and the work is easy.

Although the present invention is disclosed in conjunction with the above embodiments, it is not intended to limit the present case, and any ordinary skilled person in the technical field can make some changes and modifications without departing from the spirit and scope of the present case, so the protection of the present case The scope should be determined as defined by the appended claims.

Claims (19)

1. A cell and tissue ply forming package comprising:

a base plate having a recess;

the membrane is arranged in the groove and is made of hydrophilic materials;

a top plate parallel to a horizontal plane and parallel to a first direction, the top plate being slidably disposed on top of the bottom plate between a first position and a second position, the top plate being located at the first position to cover the recess and the diaphragm, the top plate being located at the second position to expose the recess and the diaphragm, the top plate comprising:

a hole penetrating the bottom surface of the top plate from the top surface of the top plate, the hole being located above the groove and the membrane when the top plate is located at the first position, the hole providing for injecting a solution into the groove from the top surface of the top plate;

the passive magnetic component is arranged on the top plate and is suitable for being magnetically attracted with the active magnetic component, and the active magnetic component drives the top plate to slide;

and the sealing film is coated on the upper surfaces of the top plate and the bottom plate so as to seal the top plate and the diaphragm in the sealing film.

2. The cell and tissue ply forming package of claim 1, wherein a retaining ring is disposed within the recess, the retaining ring adapted to be a tight fit with the recess, the retaining ring pressing against a top peripheral edge of the diaphragm to limit movement of the diaphragm.

3. The cell and tissue ply forming package of claim 1, wherein the depth of the groove is greater than the thickness of the membrane.

4. The cell and tissue ply forming package of claim 1, wherein the groove has a depth H perpendicular to the horizontal plane, the membrane 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) x a.

5. The molded package of cells and tissue sheets according to claim 1, wherein the bottom plate is provided with a concave area, the concave groove is arranged in the concave area, two opposite inner sides of the concave area corresponding to the position of the concave groove are respectively provided with a sliding groove, the length directions of the two sliding grooves are parallel to the first direction, and the top plate is arranged in the sliding grooves.

6. The cell and tissue ply forming package of claim 1, wherein one side of the recess is provided with a recess, the recess being in communication with the recess, a portion of the edge of the diaphragm being exposed to the recess to create a void between the diaphragm and the recess.

7. The cell and tissue ply forming package of claim 1, wherein the projection range of the aperture is centered between the recess and the diaphragm when the top panel is in the first position.

8. The cell and tissue sheet forming package according to claim 1, wherein the passive magnetic component has two passive magnetic elements, the two passive magnetic elements being distributed parallel to the horizontal plane and the distribution direction being perpendicular to the first direction.

9. The cell and tissue ply forming package of claim 1, wherein the solution is a mixed solution of biocompatible polymeric material and cells.

10. The cell and tissue ply forming package of claim 9, wherein the polymer material is one of collagen (collagen), gelatin (gelatin), hyaluronic acid (Hyaluronic acid), alginate (Alginate), polyethylene glycol (PEG) copolymer polymer.

11. The cell and tissue ply forming package of claim 9, wherein the cell is one of a fibroblast, myoblast, epithelial cell, endothelial cell, precursor cell, tenocyte, stem cell, mesenchymal stem cell, bone marrow stem cell, or adipose stem cell.

12. A cell perfusion apparatus suitable for use in the cell and tissue ply forming packaging of any one of claims 1 to 11, the cell perfusion apparatus comprising:

a carrier, comprising:

a base adapted to carry the cell and tissue ply shaped package;

the upper cover is movably arranged above the base in an opening or closing mode so as to position the cell and tissue layer sheet forming package in the base, and is provided with a pouring hole, when the upper cover is closed on the base, the projection range of the pouring hole is overlapped with the projection range of the hole of the top plate of the cell and tissue layer sheet forming package;

at least one heating element arranged on the base for providing heat energy for the membrane and the solution;

the driving magnetic component is parallel to the horizontal plane and is arranged on the top of the upper cover in a sliding manner between a third position and a fourth position in parallel to the first direction, and is suitable for magnetically attracting the driven magnetic component, and when the driving magnetic component slides to the fourth position, the top plate can be synchronously driven to slide to the second position;

a priming mechanism, comprising:

the fixed seat is arranged on the track, and the extending direction of the track is perpendicular to the horizontal plane;

a syringe, comprising:

the cylinder body is in a long cylinder shape and is suitable for accommodating the solution, and the cylinder body is perpendicular to the horizontal plane in the axial direction and is arranged on the fixing seat;

the needle head is coaxially arranged at the bottom end of the cylinder body, and the needle point of the needle head faces the horizontal plane;

the piston is coaxially arranged in the cylinder body;

a drive mechanism, comprising:

the first driving component is suitable for driving the carrying platform to reciprocate between a fifth position and a sixth position parallel to the horizontal plane and parallel to the first direction, when the carrying platform is positioned at the fifth position, the projection range of the needle head and the projection range of the filling hole of the upper cover are staggered, and when the carrying platform is positioned at the sixth position, the projection range of the needle head and the projection range of the filling hole of the upper cover and the projection range of the hole of the top plate are overlapped;

the second driving component is suitable for driving the fixed seat and the needle cylinder to reciprocate between a seventh position and an eighth position which are perpendicular to the horizontal plane on the track, when the fixed seat and the needle cylinder are positioned at the seventh position, the horizontal position of the needle point is higher than the horizontal position of the top surface of the upper cover of the carrier, and when the fixed seat and the needle cylinder are positioned at the eighth position, the horizontal position of the needle point is lower than the horizontal position of the sealing film at the top of the hole of the top plate;

and a third driving component which is suitable for driving the piston to move in the cylinder body perpendicular to the horizontal plane so as to push out the solution in the cylinder body from the needle head.

13. The cell perfusion apparatus of claim 12, wherein a first sensor and a second sensor are disposed on one side of the stage, and a first sensor and a second sensor are disposed on the base of the stage; when the first driving component drives the carrier to move, the first sensing piece and the second sensing piece can synchronously move and respectively enter the sensing ranges of the first sensor and the second sensor; when the first sensor senses the first sensing piece, the first driving component is controlled to stop acting, so that the carrier is stopped at the fifth position; when the second sensor senses the second sensing piece, the first driving component is controlled to stop acting, so that the carrier is stopped at the sixth position.

14. The cell perfusion apparatus of claim 12, wherein a third sensor is disposed on one side of the perfusion mechanism, a third sensor is disposed on the fixed seat, and the third sensor can move synchronously and enter a sensing range of the third sensor when the second driving assembly drives the fixed seat and the syringe to move; when the third sensor senses the third sensing piece, the second driving component is controlled to stop acting, so that the fixing seat is stopped at the seventh position.

15. The cell perfusion apparatus of claim 12, wherein the first drive assembly includes:

the axis direction of the first screw is parallel to the horizontal plane, and the carrying platform is arranged on the first screw; and

the first motor drives the first screw rod to rotate forward and backward and synchronously drives the carrying platform to reciprocate between the fifth position and the sixth position.

16. The cell perfusion apparatus of claim 12, wherein the second drive assembly includes:

the rotary disc is arranged below the fixed seat;

one end of the connecting rod is pivoted with the fixed seat, and the opposite end of the connecting rod is pivoted with the eccentric part of the turntable; and

the driving element drives the turntable to rotate and synchronously drives the connecting rod to enable the fixing seat to move, and the fixing seat and the needle cylinder can reciprocate on the track between the seventh position and the eighth position in a mode of being perpendicular to the horizontal plane.

17. The cell perfusion apparatus of claim 12, wherein the third drive assembly includes:

the axis direction of the second screw rod is perpendicular to the horizontal plane;

the pressing seat is arranged on the second screw rod, one side of the pressing seat is positioned above the top surface of the piston, and the pressing seat presses the piston; and

and the second motor drives the second screw rod to rotate forward and backward and synchronously drives the pressing seat to reciprocate between a ninth position and a tenth position perpendicular to the horizontal plane.

18. The cell perfusion apparatus of claim 17, wherein a fourth sensor is provided on one side of the cell perfusion apparatus and a fourth sensing member is provided on the pressing seat; when the third driving component drives the pressing seat to move, the fourth sensing piece can synchronously move and enter the sensing range of the fourth sensor; when the fourth sensor senses the fourth sensing piece, the third driving component is controlled to stop acting.

19. The cell perfusion apparatus of claim 12, wherein the passive magnetic component has two passive magnetic elements, the two passive magnetic elements being distributed parallel to the horizontal plane and a direction of distribution being disposed perpendicular to the first direction; the active magnetic component comprises two active magnetic elements, and the two active magnetic elements are suitable for magnetically attracting with the two passive magnetic elements.

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