TWI858845B - Automatic cell freezing and thawing equipment - Google Patents

Abstract

This invention is an automatic cell freezing and thawing device and a freezing storage box, wherein the freezing storage box includes a frame and a plurality of freezing trays. The frame includes a plurality of mounting walls, and a plurality of tray racks are formed between any two mounting walls. The freezing trays can be detachably arranged on the tray racks, and each freezing tray has a plurality of freezing tube insertion holes for storing frozen tubes. By designing the freezing magazine to include a frame and a detachable freezing tray, the freezing magazine can be first moved out of the freezing bucket by the magazine transfer mechanism, and then any freezing tray can be taken out from the frame by the freezing tray picker, and then the robot arm can perform the operation of inserting or removing the frozen tube. This can avoid the robot arm from operating directly in an ultra-low temperature environment, and can more efficiently take and put the frozen tube in the freezing magazine.

Description

Automatic cell freezing and thawing equipment

This work involves a biochemical experimental device, especially an automatic cell freezing and thawing device.

In the cell preparation process, after a large number of cells have been cultured and processed, they will first be dispensed into cryovials, and then they need to be frozen and stored. Usually, the cryovials are placed in a cryostat (liquid or gaseous nitrogen barrel) for long-term cryopreservation of cells. Specifically, the process of freezing cells is as follows: the cryovials containing cells will first be placed in a gradual freezing device, and after its temperature slowly drops to -80°C, the cryovials containing cells that have been cooled to -80°C will be moved to a cryovial rack, and then the cryovial rack containing the cryovials will be placed in a cryostat for long-term freezing. Once the cells need to be thawed for use, specifically, the procedure for thawing cells is as follows: first, take out the freezer rack containing the frozen tubes of cells to be thawed from the freezing bucket, then take out the frozen tubes containing cells to be thawed from the freezer rack and put them into a warming device. After the cell fluid in the frozen tube slowly thaws, transfer it from the frozen tube to a culture container containing culture fluid for culture, completing the procedure for thawing cells.

However, whether cells are frozen or thawed, the entire cryopreservation rack must be removed from the cryopreservation barrel first. The cryopreservation rack in the prior art is an integrated multi-layer rack, so that it is difficult for the robot arm to directly grab the cryopreservation tubes in the middle layer or near the inner side, so it can only be performed manually. Therefore, when placing or removing the cryopreservation tubes in a specific position, the steps are cumbersome and time-consuming. As a result, when a specific cryopreservation tube is taken out or placed separately, other cryopreservation tubes are left in the cryopreservation barrel for a longer time, which may cause unnecessary temperature rise, thereby affecting the cryopreservation quality of other cryopreservation tubes.

In view of the shortcomings and deficiencies of the aforementioned prior art, this invention provides an automatic cell freezing and thawing device and a freezing magazine thereof, wherein the freezing magazine has a separable frame and freezing tray, so that any specific freezing tray can be taken out of the frame by a claw and then any specific frozen tube on the freezing tray can be grabbed by a robotic arm, thereby making it more convenient for the robotic arm to put in or take out the frozen tube, thereby achieving the purpose of automated cell freezing and thawing.

In order to achieve the above-mentioned creative purpose, the technical means adopted by this creation is to design a kind of automatic cell freezing and thawing equipment, which includes: an access part, which can provide a cryotube or a cell culture container to enter and exit; a robot arm; a gradual freezer, the robot arm can move the cryotube in the access part to the gradual freezer, and the gradual freezer can reduce the temperature of the cryotube; a freezing box, which includes a frame, which includes a plurality of mounting walls, any two of which are A plurality of tray racks are formed between the mounting walls; a plurality of freezing trays can be detachably arranged on the tray racks; each of the freezing trays has a plurality of freezing tube insertion holes, each of which is used to temporarily place the freezing tube; the robot arm can move the freezing tube to the freezing tube insertion hole for storage; a freezing barrel having a freezing space inside; a magazine moving mechanism, which can move the freezing magazine out of or into the freezing space of the freezing barrel; a freezing tray picking claw, which moves the freezing tray out of or into the freezing space of the freezing barrel; After the magazine transfer mechanism moves the freezing storage magazine out of the freezing space, the freezing tray picker can take out one of the freezing trays or put it into one of the tray racks; a dry bath, the robot arm can move one of the frozen tubes in the freezing tray on the freezing tray picker to the dry bath, and the dry bath can increase the temperature of one of the frozen tubes; a cell culture container temporary storage rack, the robot arm can move the cell culture container in the access part to the cell culture rack; The cell culture container temporary storage rack is used to store the cell culture container; a cover opening and closing machine, the robot arm can move the frozen tube in the dry bath to the cover opening and closing machine, and the robot arm can move the cell culture container in the cell culture container temporary storage rack to the cover opening and closing machine; the cover opening and closing machine can open and close the cover of the frozen tube, and the cover opening and closing machine can open and close the cover of the cell culture container.

The advantage of this invention is that by designing the freezing storage box to include a frame and a detachable freezing tray, after the box transfer mechanism moves the freezing storage box out of the freezing bucket, the freezing tray picker can first take out one of the freezing trays from the frame, and then the robot arm can perform the operation of inserting or removing the frozen tube. This makes it easier for the robot arm to insert or remove the frozen tube in the middle layer or near the inside, and during the process, the freezing storage box can also be moved into the freezing bucket first to prevent it from being exposed outside the freezing bucket for too long.

Furthermore, the automatic cell freezing and thawing device includes a cold storage room, the temperature inside the cold storage room is lower than the temperature outside the cold storage room; the freezing storage box, the freezing bucket and the box transfer mechanism are located in the cold storage room; the freezing plate retrieval claw is located outside the cold storage room and can extend into the cold storage room to take out one of the freezing plates or put it into one of the plate racks.

Furthermore, the automatic cell freezing and thawing device includes a cold storage tunnel connected to the cold storage room; an arm opening is formed on the wall of the cold storage tunnel; an insulation cover is arranged on the arm opening and selectively opens the arm opening; the freezing tray retrieval claw is located in the cold storage tunnel; the robot arm can contact and take out one of the frozen tubes in the freezing tray on the freezing tray retrieval claw through the arm opening after the insulation cover opens the arm opening, or insert any frozen tube into the frozen tube insertion hole of the freezing tray on the freezing tray retrieval claw.

A: Frozen tube

B: Frozen tube tray

C: Cell culture container

1: Entry and exit department

2:Robotic arm

21: First clamping claw

22: Second clamping claw

23: RFID reader 23

3: Gradual Freezing Machine

4: Freezing storage box

41:Frame

411:Erection of wall

412: Rack Department

413: ribs

414: Fastening convex part

415:Center axis

42: Frozen disk

421: Frozen tube jack

422: Fixing recess

5: Freezing bucket

6: Box moving mechanism

7: Frozen plate claw removal

71: Slide rail

72: Clamping claws

8: Dry bath

9: Cell culture container temporary storage rack

10: Opening and closing lid machine

11: Refrigerator

12: Refrigerated Tunnel

121: Arm opening

13: Insulation cover

14: Abandon the bucket

Figure 1 is a three-dimensional appearance diagram of this work.

Figure 2 is a schematic diagram of the interior of one side of the refrigerator compartment of this creation.

Figure 3 is a schematic diagram of the interior of one side of the cold storage tunnel of this creation.

Figure 4A is a top view of the cross-section of this creation, in which the access part contains a frozen tube tray.

Figure 4B is another top view of the present invention, in which the access portion contains a cell culture container. Figure 5 is a diagram showing the positional relationship between the freezing storage box and the freezing plate claw of the present invention.

Figure 6 is an exploded view of the frozen storage disk and the frame of this creation.

Figure 7 is a three-dimensional appearance diagram of the frozen plate claw in this creation.

Figure 8 is a three-dimensional appearance diagram of the robot arm of this creation.

Figure 9 is a partial enlarged view of the robot arm of this creation.

Figure 10 is a schematic diagram of the cell cryopreservation process of this work.

Figure 11 is a schematic diagram of the cell thawing process of this work.

The following is a diagram and a preferred embodiment of this creation to further explain the technical means adopted by this creation to achieve the intended creation purpose.

Please refer to Figures 1, 4A, 4B and 10. The automatic cell freezing equipment of this invention includes an access part 1, a robot arm 2, a gradual freezer 3, a freezing storage box 4, a freezing bucket 5, a box transfer mechanism 6, a freezing plate picking claw 7, a dry bath 8, a cell culture container temporary storage rack 9, an opening and closing cover machine 10, a cold storage room 11, a cold storage tunnel 12 and a heat preservation cover 13.

Please refer to Figure 3, Figure 4A and Figure 4B. The access portion 1 can allow a frozen tube tray B or a cell culture container C to enter and exit.

Please refer to Figures 10 and 11. The robot arm 2 can move a cryotube A in the access part 1 to the gradual freezer 3, and the gradual freezer 3 can gradually reduce the temperature of the cryotube A. Specifically, please refer to Figures 8 and 9. The robot arm 2 has a first clamping claw 21 and a second clamping claw 22 for clamping the cryotube A and the cell culture container C in the access part 1 respectively.

Please refer to Figures 5 and 6. The freezing storage box 4 includes a frame 41 and a plurality of freezing storage trays 42. The frame 41 includes a plurality of mounting walls 411. A plurality of tray racks 412 are formed between any two mounting walls 411. The freezing storage trays 42 can be detachably arranged on the tray racks 412. Each freezing storage tray 42 has a plurality of freezing tube insertion holes 421, each freezing tube insertion hole 421 is used to store freezing tubes A, and the robot arm 2 can move freezing tubes A to the freezing tube insertion holes 421 for storage.

Specifically, in this embodiment, a plurality of mounting ribs 413 are provided on each mounting wall 411, and the mounting ribs 413 on any mounting wall 411 respectively form the tray rack parts 412 with the mounting ribs 413 on another mounting wall 411, and each freezing tray 42 can be detachably provided on the mounting ribs 413 of any two mounting walls 411. In addition, each mounting rib 413 is formed with a locking convex part 414, and each freezing tray 42 is formed with two locking concave parts 422, and the two locking concave parts 422 can be mutually engaged with the locking convex parts 414 of the two mounting ribs 413 to prevent the freezing tray 42 from being arbitrarily frozen relative to the mounting ribs 413 and detached from the frame 41. Furthermore, in this embodiment, the frame 41 includes a central axis 415. The mounting walls 411 are arranged around the central axis 415 at intervals and extend radially along the central axis 415. Each freezing disk 42 is a fan-shaped disk. However, the specific structure of the frame 41 and the freezing disk 42 is not limited to the above, as long as the freezing disk 42 can be separated from the frame 41.

The freezing barrel 5 has a freezing space inside.

The box transfer mechanism 6 can move the freezing storage box 4 out of or into the freezing space of the freezing barrel 5.

The plate picking claw 7 can take out or put one of the frozen disks 42 into one of the tray racks 412 after the tray shifting mechanism 6 moves the frozen storage tray 4 out of the freezing space. Specifically, please refer to Figures 5 and 7. The plate picking claw 7 has a slide rail 71 and a clamping claw 72. The clamping claw 72 can move along the slide rail 71 toward the frozen storage tray 4 after the tray shifting mechanism 6 moves out of the freezing space, and after clamping one of the frozen disks 42, it returns to its original position along the slide rail 71, thereby taking out or putting the frozen disk 42 into the tray rack 412. However, the specific structure of the plate picking claw 7 is not limited to this.

The dry bath 8 can gradually increase the temperature of one of the cryotubes A, and the robot arm 2 can move one of the cryotubes A in the cryo tray 42 on the cryo tray claw 7 to the dry bath 8.

The cell culture container temporary storage rack 9 is used to store the cell culture container C, and the robot arm 2 can move the cell culture container C in the access portion 1 to the cell culture container temporary storage rack 9.

The cover opening and closing machine 10 can open and close the cover of the frozen tube A, and the cover opening and closing machine 10 can open and close the cover of the cell culture container C. The robot arm 2 can move the frozen tube A in the dry bath 8 to the cover opening and closing machine 10, and the robot arm 2 can move the cell culture container C in the cell culture container temporary rack 9 to the cover opening and closing machine 10.

Please refer to Figures 1, 2, 3, 4A and 4B. Specifically, in this embodiment, the automatic cell freezing and thawing device is equipped with a cold storage room 11, a cold storage tunnel 12 and a heat preservation cover 13. The temperature inside the cold storage room 11 is lower than the temperature outside the cold storage room 11. Preferably, the cold storage room 11 is a cold storage space of approximately 4 degrees Celsius. The cold storage tunnel 12 is connected to the cold storage room 11, thereby extending the cold storage effect of the cold storage space of 4 degrees Celsius. An arm opening 121 is formed on the wall of the cold storage tunnel 12. The heat preservation cover 13 is arranged on the arm opening 121, and the arm opening 121 is selectively opened.

The freezing storage box 4, freezing barrel 5 and box transfer mechanism 6 are located in the cold storage room 11. The freezing plate picking claw 7 is located outside the cold storage room 11 and in the cold storage tunnel 12, and can extend into the cold storage room 11 through the connecting port between the cold storage tunnel 12 and the cold storage room 11 to take out one of the freezing plates 42 or put it into one of the plate racks 412. The robot arm 2 can contact and take out one of the freezing tubes A in the freezing plate 42 on the freezing plate picking claw 7 through the arm opening 121 after the insulation cover 13 opens the arm opening 121, or put any freezing tube A into the freezing tube insertion hole 421 of the freezing plate 42 on the freezing plate picking claw 7.

By means of the cold storage room 11, the cold storage tunnel 12 and the heat-insulating cover 13, the freezing storage box 4 and the freezing tray 42 and the freezing tube A thereon can be kept at a lower refrigeration temperature after being taken out of the freezing barrel 5, rather than being directly exposed to room temperature.

The automatic cell freezing and thawing equipment of this invention can automatically perform the following process actions:

First, the cell freezing process, please refer to Figure 4A, Figure 6 and Figure 10.

First, the cryotube A is written with a radio frequency identification code (RFID) and then placed on the cryotube tray B and placed in the access section 1. As shown in FIG9 and FIG10, the robot arm 2 then reads the radio frequency identification code (RFID) with its RFID reader 23 and removes the specific cryotube A and moves it to the gradual freezer 3 for the first cooling. After the cryotube A is removed, the cryotube tray B is discharged from the access section 1. After the first cooling of the cryotube A is completed, the cover of the freezing barrel 5 is opened, the magazine moving mechanism 6 lifts the freezing magazine 4 and moves it out of the freezing barrel 5, and the freezing plate picking claw 7 then takes one of the freezing plates 42 of the freezing magazine 4 off the frame 41 for use. Then, the robot arm 2 moves the cryotube A that has completed the first cooling to the freezing plate 42 on the freezing plate picking claw 7 for use. Next, the freezing tray claw 7 re-places the freezing tray 42 carrying the freezing tube A onto the tray portion 412 of the frame 41, and then the magazine transfer mechanism 6 lowers the freezing storage magazine 4 again into the freezing space of the freezing barrel 5, completing the cell freezing process.

Second, the cell thawing process, please refer to Figure 4B and Figure 11.

Before this process is performed, an empty cell culture container C is encoded with RFID and filled with cell culture solution by a dispenser (this mechanism is not within the scope of the present invention), and then moved by the robot arm 2 from the access portion 1 to the cell culture container temporary storage rack 9 for storage and standby. As shown in FIG11 , when executing the cell thawing process, the robot arm 2 first takes out the standby cell culture container C from the cell culture container temporary storage rack 9 to the lid opening and closing machine 10 to prepare for opening the lid. At the same time, the cover of the freezing barrel 5 is opened, the magazine transfer mechanism 6 lifts the freezing magazine 4 and moves it out of the freezing barrel 5, and the freezing plate picking claw 7 then takes the freezing plate 42 containing the frozen tube A on the freezing magazine 4 off the frame 41. Then, the robot arm 2 reads the RFID and moves the frozen tube A to the dry bath 8 to thaw and heat the frozen tube A. After the frozen tube A is moved to the dry bath 8, the freezing plate picking claw 7 immediately puts the freezing plate 42 back on the frame 41, and the magazine transfer mechanism 6 immediately puts the freezing magazine 4 back into the freezing barrel 5 and closes the cover. After the cell solution in the cryotube A is thawed, the robot arm 2 moves the thawed cryotube A to the capping machine 10 to prepare for opening. After the cell culture container C and the cryotube A are both opened, the thawed cell solution in the cryotube A is poured into the cell culture container C, and then the container is closed by the capping machine 10. Finally, the robot arm 2 sends the cell culture container C containing the cell solution to the access part 1 to read the RFID and then send it out, while the cryotube A is closed and discarded to the disposal bucket 14. The cell culture container C containing the cell solution is transported by a main conveyor to a culture mechanism (this mechanism is not within the scope of the present invention) for storage and culture, completing the cell thawing and culture process.

By designing the freezing magazine 4 to include a frame 41 and a detachable freezing tray 42, after the magazine transfer mechanism 6 moves the freezing magazine 4 out of the freezing barrel 5, the freezing tray picking claw 7 can first take out one of the freezing trays 42 from the frame 41, and then the robot arm 2 can perform the operation of inserting or removing the freezing tube A, thereby facilitating the robot arm 2 to insert or remove the freezing tube A in the middle layer or near the inner side, and during the process, the freezing magazine 4 can also be first moved into the freezing barrel 5 to prevent it from being exposed outside the freezing barrel 5 for too long.

The above is only the best embodiment of this creation, and does not limit this creation in any form. Although this creation has been disclosed as the best embodiment, it is not used to limit this creation. Any person with ordinary knowledge in the relevant technical field can make some changes or modifications to the technical content disclosed above to make equivalent embodiments within the scope of the technical solution of this creation. However, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of this creation without departing from the content of the technical solution of this creation still falls within the scope of the technical solution of this creation.

B: Frozen tube tray

C: Cell culture container

1: Entry and exit department

2:Robotic arm

3: Gradual Freezing Machine

4: Freezing storage box

5: Freezing bucket

6: Box moving mechanism

8: Dry bath

9: Cell culture container temporary storage rack

10: Opening and closing lid machine

11: Refrigerator

12: Refrigerated Tunnel

121: Arm opening

13: Insulation cover

14: Abandon the bucket

Claims (3)

A cell automatic freezing and thawing device, comprising: an access portion, which can provide a cryotube or a cell culture container for access; a robot arm; a gradual freezer, the robot arm can move the cryotube in the access portion to the gradual freezer, the gradual freezer can reduce the temperature of the cryotube; a freezing storage box, which includes a frame, which includes a plurality of mounting walls, and a plurality of tray racks are formed between any two of the mounting walls; A plurality of freezing trays, which can be separately arranged on the tray racks; each of the freezing trays has a plurality of freezing tube insertion holes, each of which is used to store the freezing tube; the robot arm can move the freezing tube to the freezing tube insertion hole for storage; A freezing barrel, which has a freezing space inside; A magazine moving mechanism, which can move the freezing storage magazine out of or into the freezing space of the freezing barrel; A freezing tray picking claw, after the magazine moving mechanism moves the freezing storage magazine out of the freezing space, the freezing tray picking claw can take out one of the freezing trays or put it into one of the tray racks; A dry bath, the robot arm can move one of the frozen tubes in the freezing tray on the freezing tray claw to the dry bath, and the dry bath can increase the temperature of one of the frozen tubes; A cell culture container temporary storage rack, the robot arm can move the cell culture container in the access portion to the cell culture container temporary storage rack, and the cell culture container temporary storage rack is used to store the cell culture container; A cover opening and closing machine, the robot arm can move the frozen tube in the dry bath to the cover opening and closing machine, and the robot arm can move the cell culture container in the cell culture container temporary storage rack to the cover opening and closing machine; the cover opening and closing machine can open and close the cover of the frozen tube, and the cover opening and closing machine can open and close the cover of the cell culture container. The automatic cell freezing and thawing device as described in claim 1, wherein: The automatic cell freezing and thawing device comprises a cold storage room, the temperature in the cold storage room is lower than the temperature outside the cold storage room; The freezing storage box, the freezing bucket and the box transfer mechanism are located in the cold storage room; The freezing plate retrieval claw is located outside the cold storage room and can extend into the cold storage room to take out one of the freezing plates or put it into one of the plate racks. The automatic cell freezing and thawing device as described in claim 2, wherein, the automatic cell freezing and thawing device comprises a cold storage tunnel connected to the cold storage room; an arm opening is formed on the wall of the cold storage tunnel; an insulation cover is arranged on the arm opening and selectively opens the arm opening; the freezing tray retrieval claw is located in the cold storage tunnel; the robot arm can pass through the arm opening to contact one of the frozen tubes in the freezing tray on the freezing tray retrieval claw after the insulation cover opens the arm opening.