TIL cell separation container for cell therapy

Abstract

The invention relates to the technical field of TIL cell separation instruments, and particularly discloses a TIL cell separation container for cell therapy, which is technically characterized by comprising a tumor sample chopping device, and a separation container temperature control mechanism is fixedly connected to the outer ring surface of the tumor sample chopping device; the tumor sample chopping device comprises a cutting cavity and a driving motor bin fixedly connected to the end face of the bottom of the cutting cavity. The electric tumor sample chopping and separating container is arranged, so that the granularity difference of chopped samples is small; the cell filter is arranged in the container, and after chopping is completed, a sample passes through the filter through electric extrusion, so that a relatively efficient separation process is obtained. A temperature control structure is arranged at the bottom or on the periphery of the separation container, so that the temperature for chopping and filtering in the container is controlled to be 18-20 DEG C, and the influence of the temperature on the activity of cells is avoided.

Description

Technical Field

[0001] The patent of this invention relates to the technical field of TIL cell separation equipment, specifically, to a TIL cell separation container for cell therapy. Background Art

[0002] TIL cells are infiltrating lymphocytes isolated from tumor tissue. In 1986, the Rosenberg group first reported the presence of infiltrating lymphocytes, or TILs, in the tumor tissue of melanoma patients. These cells, isolated from the tumor and activated with IL-2, can proliferate in large numbers and have highly specific anti-tumor activity.

[0003] Currently, TIL cells are typically isolated from tumor samples using a single-edged scraper to mince the sample. However, the resulting sample has a large particle size discrepancy, hindering subsequent TIL cell extraction. Furthermore, high temperatures can affect TIL cell activity. Failure to maintain a stable temperature during the mincing and filtration process can negatively impact TIL cell activity. Therefore, researchers in this field have proposed a TIL cell separation container for cell therapy. Summary of the Invention

[0004] The present invention aims to solve the problem that when TIL cells are currently isolated from tumor samples, a single-edged scraper is used to chop human tumor samples, resulting in large differences in the particle size of the samples after chopping; and to solve the problem that high temperatures during the chopping and filtration process affect the activity of TIL cells.

[0005] The present invention is achieved as follows: a TIL cell separation container for cell therapy includes a tumor sample chopper, and a separation container temperature control mechanism is fixedly connected to the outer surface of the tumor sample chopper;

[0006] The tumor sample chopper includes a cutting chamber and a driving motor compartment fixedly connected to the bottom end surface of the cutting chamber; a cell filter is placed in the inner cavity of the cutting chamber, a rotating shaft is rotatably arranged in the inner cavity of the cell filter, the top end of the rotating shaft is connected to a screw, and a crushing paddle is arranged on the outer ring surface of the screw, and an end cover is hingedly connected to the top port of the cutting chamber, a servo electric cylinder is installed on the top surface of the end cover, and the telescopic shaft of the servo electric cylinder passes through the interior of the cell filter and is connected to a lower pressure plate; a servo motor is installed at the bottom of the inner cavity of the driving motor compartment, and the output shaft of the servo motor is connected to a transmission shaft passing through the interior of the cutting chamber through a coupling, and the top end of the transmission shaft is fixedly connected to the bottom end of the rotating shaft; wherein, a material storage tank is provided on the left surface of the driving motor compartment, and the top end of the material storage tank is connected to a discharge pipe passing through the inner cavity of the cutting chamber;

[0007] Specifically, the tumor sample is placed inside the cell filter, the crushing paddle is passed through the outer ring of the screw, and the crushing paddle is compressed by tightening the internal threaded cap and the screw thread segment. It should be noted that the loosening direction of the internal threaded cap and the screw thread is opposite to the axial rotation direction of the servo motor. The cell filter is placed inside the cutting chamber by means of the placement frame. After closing the end cover, the screw is passed through the block and the nut is tightened. The servo motor rotates the transmission shaft to drive the shaft to rotate. The crushing paddle cuts and crushes the tumor sample under the action of the rotational force, making it into small particles. Then, the end cover is opened, the crushing paddle on the screw is removed, and the tumor sample particles inside the cell filter are observed. After the end cover is closed again, the telescopic shaft of the servo electric cylinder drives the lower pressure plate downward to suppress the granular sample inside the cell filter and force the sample to pass through filtration. The filtered sample enters the storage tank along the discharge pipe for storage.

[0008] The separation container temperature control mechanism includes a heat-conducting sleeve wrapped and fixed on the outer ring surface of the cutting chamber, 8-10 semiconductor heating plates attached to the outer ring surface of the heat-conducting sleeve in a ring array, the outer ring surface of the semiconductor heating plate is fixedly connected to the heat dissipation sleeve, and the inner surface of the semiconductor heating plate is the cooling surface, and the outer surface of the semiconductor heating plate is the heating surface.

[0009] Specifically, during the cutting process, the cooling surface of the semiconductor heater transfers the low temperature to the thermal sleeve, which then transfers the low temperature to the interior of the cutting chamber. A thermostat on the outer surface of the heat dissipation sleeve controls the operation of the semiconductor heater, keeping the cutting chamber within a reasonable range of -°C during the cutting process, thereby maintaining cell activity. Heat from the heating surface of the semiconductor heater is released to the outside world through the heat dissipation sleeve and fins.

[0010] In the above technical solution, preferably: a placement frame is fixed on the inner side wall of the cutting chamber, the top edge of the outer ring of the cell filter is engaged with the top surface of the placement frame, and the bottom of the cell filter is provided with a circular hole for the rotating shaft to pass through and rotate.

[0011] In the above technical solution, preferably: the left and right surfaces of the cutting chamber are fixedly connected with a U-shaped seat, a block is fixed inside the left U-shaped seat, and an L-shaped rod is rotatably connected inside the right U-shaped seat, and the other end of the L-shaped rod is connected to the right side surface of the end cover.

[0012] In the above technical solution, preferably: the left end face of the end cover is rotatably connected to a screw, the end of the screw passes through the block inside the U-shaped seat on the left surface of the cutting chamber, and a nut is screwed on the section where the screw passes through the block.

[0013] In the above technical solution, preferably: the bottom end surface of the end cover and the top end surface of the cutting chamber are both fixed with a circle of sealing gasket by adhesive, the outer shell of the servo electric cylinder is fixed on the top surface of the end cover, and the top surface of the end cover is provided with a through hole for the telescopic shaft of the servo electric cylinder to pass through and telescope, and a sliding bearing is installed inside the through hole.

[0014] In the above technical solution, preferably: the diameter of the lower pressure plate is consistent with the inner diameter of the upper port of the cell filter, and the crushing paddle is located in the middle area of the inner cavity of the cell filter, and the outer ring and bottom surface of the cell filter are spaced 3.0 cm to 6.0 cm from the inner cavity side wall of the cutting chamber.

[0015] In the above technical solution, preferably: the shaft diameter of the rotating shaft is larger than the shaft diameter of the screw, the bottom end face of the crushing paddle contacts the top end face of the rotating shaft, an internal threaded cover is screwed on the outer threaded section of the screw, and the bottom end face of the internal threaded cover contacts the top surface of the crushing paddle.

[0016] In the above technical solution, preferably: the positions where the drive motor compartment and the cutting chamber are connected to each other are provided with holes for the transmission shaft to pass through and rotate, and sealed bearings adapted to the transmission shaft are provided inside the holes.

[0017] In the above technical solution, preferably: the bottom surface of the inner cavity of the drive motor compartment is connected to a support plate, the outer shell side wall of the servo motor is connected to the surface of the support plate, and the output shaft of the servo motor is coaxially arranged with the axis of the drive motor compartment and the cutting chamber.

[0018] In the above technical solution, preferably: thermal grease is coated between the inner ring surface of the heat-conducting sleeve and the outer ring surface of the cutting chamber, and 80-110 heat-conducting fins are fixed in an annular array on the outer ring surface of the heat-dissipating sleeve.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] This invention utilizes a motorized tumor sample mincing and separation container to minimize particle size variation in the minced sample. A cell filter is placed inside the container, and after mincing, the sample is electrically squeezed through the filter, resulting in a more efficient separation process. A temperature control mechanism is installed at the bottom or periphery of the separation container to maintain a constant temperature of 18-20°C during mincing and filtration, preventing temperature from affecting cell activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a diagram showing the overall appearance of a cell separation container according to an embodiment of the present invention;

[0022] Figure 2This is a structural diagram of a cell separation container in a longitudinal section according to an embodiment of the present invention;

[0023] Figure 3 is an exploded view of the upper half of a cell separation container according to an embodiment of the present invention;

[0024] Figure 4 is an exploded view of the lower half of a cell separation container according to an embodiment of the present invention;

[0025] Figure 5 Schematic diagram of the temperature control mechanism around the cell separation container in an embodiment of the present invention.

[0026] Reference numerals in the above drawings:

[0027] 1. Tumor sample chopper; 11. Cutting chamber; 12. End cap; 13. Servo electric cylinder; 14. Cell filter; 15. Discharge tube; 16. Storage tank; 17. Drive motor compartment; 18. Servo motor; 19. Lower pressure plate; 110. Placement frame; 111. Sealed bearing; 112. Drive shaft; 113. Internal threaded cap; 114. Crushing paddle; 115. Screw; 116. Rotating shaft; 2. Separation container temperature control mechanism; 21. Thermal sleeve; 22. Semiconductor heating plate; 23. Heat dissipation sleeve. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0029] The implementation of the present invention is described in detail below with reference to specific embodiments.

[0030] The same or similar numbers in the drawings of this embodiment correspond to the same or similar parts; in the description of the present invention, it should be understood that if the terms "upper", "lower", "left", "right", etc. indicate the orientation or position relationship, they are based on the orientation or position relationship shown in the drawings. This is only for the convenience of describing the present invention and simplifying the description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operate in a specific orientation. Therefore, the terms describing the position relationship in the drawings are only used for illustrative purposes and cannot be understood as limiting this patent. For ordinary technicians in this field, the specific meanings of the above terms can be understood according to specific circumstances.

[0031] As shown in the drawings, there is provided a preferred embodiment of the present invention.

[0032] Example:

[0033] See attached Figure 1As shown: It includes a tumor sample chopper 1, and a separation container temperature control mechanism 2 is fixedly connected to the outer surface of the tumor sample chopper 1; Figure 2 As shown: the tumor sample chopper 1 includes a cutting chamber 11, a drive motor compartment 17 fixedly connected to the bottom end surface of the cutting chamber 11; Figure 3 and attached Figure 4 As shown: a cell filter 14 is placed in the inner cavity of the cutting chamber 11, a rotating shaft 116 is rotatably set in the inner cavity of the cell filter 14, the top of the rotating shaft 116 is connected to a screw rod 115, and a crushing paddle 114 is set on the outer ring surface of the screw rod 115, and the top port of the cutting chamber 11 is hinged with an end cover 12, and a servo electric cylinder 13 is installed on the top surface of the end cover 12, and the telescopic shaft of the servo electric cylinder 13 passes through the interior of the cell filter 14 and is connected to the lower pressure plate 19; a servo motor 18 is installed at the bottom of the inner cavity of the driving motor compartment 17, and the output shaft of the servo motor 18 is connected to a transmission shaft 112 passing through the interior of the cutting chamber 11 through a coupling, and the top of the transmission shaft 112 is fixedly connected to the bottom end of the rotating shaft 116; wherein, a material storage tank 16 is provided on the left surface of the driving motor compartment 17, and the top of the material storage tank 16 is connected to a discharge pipe 15 passing through the inner cavity of the cutting chamber 11;

[0034] See attached Figure 5 As shown: the separation container temperature control mechanism 2 includes a heat-conducting sleeve 21 wrapped and fixed on the outer ring surface of the cutting chamber 11, 8-10 semiconductor heating plates 22 attached to the outer ring surface of the heat-conducting sleeve 21 in a ring array, and the outer ring surface of the semiconductor heating plate 22 is fixedly connected to the heat dissipation sleeve 23, and the inner surface of the semiconductor heating plate 22 is the cooling surface, and the outer surface of the semiconductor heating plate 22 is the heating surface.

[0035] See attached Figure 3 As shown: a placement frame 110 is fixed to the inner side wall of the cutting chamber 11, the outer top edge of the cell filter 14 is engaged with the top surface of the placement frame 110, and a circular hole is provided at the bottom of the cell filter 14 for the rotation shaft 116 to pass through and rotate; the left and right surfaces of the cutting chamber 11 are fixedly connected to U-shaped seats, a block is fixed inside the U-shaped seat on the left, and an L-shaped rod is rotatably connected inside the U-shaped seat on the right, and the other end of the L-shaped rod is connected to the right surface of the end cover 12.

[0036] See attached Figure 3As shown: the left end face of the end cover 12 is rotatably connected to a screw, the end of the screw passes through the block inside the U-shaped seat on the left surface of the cutting chamber 11, and a nut is screwed on the section where the screw passes through the block; the bottom end face of the end cover 12 and the top end face of the cutting chamber 11 are both fixed with a circle of sealing gasket by adhesive, the outer shell of the servo electric cylinder 13 is fixed to the top surface of the end cover 12, and the top surface of the end cover 12 is provided with a through hole for the telescopic shaft of the servo electric cylinder 13 to pass through and extend, and a sliding bearing is installed inside the through hole.

[0037] See attached Figure 3 and attached Figure 4 As shown: the diameter of the lower pressure plate 19 is consistent with the inner diameter of the upper port of the cell filter 14, and the crushing paddle 114 is located in the middle area of the inner cavity of the cell filter 14. The outer ring and the bottom surface of the cell filter 14 are all separated by a distance of 3.0 cm to 6.0 cm from the inner cavity side wall of the cutting chamber 11; the shaft diameter of the rotating shaft 116 is larger than the shaft diameter of the screw rod 115, the bottom end surface of the crushing paddle 114 contacts the top end surface of the rotating shaft 116, and an internal threaded cap 113 is screwed onto the outer threaded section of the screw rod 115, and the bottom end surface of the internal threaded cap 113 contacts the top surface of the crushing paddle 114.

[0038] See attached Figure 4 As shown: The positions where the drive motor compartment 17 and the cutting chamber 11 are connected to each other are provided with holes for the transmission shaft 112 to pass through and rotate, and the holes are provided with sealed bearings 111 adapted to the transmission shaft 112. The bottom surface of the inner cavity of the drive motor compartment 17 is connected to a support plate, the side wall of the housing of the servo motor 18 is connected to the surface of the support plate, and the output shaft of the servo motor 18 is coaxially arranged with the axis of the drive motor compartment 17 and the cutting chamber 11. Figure 5 As shown, thermal grease is coated between the inner surface of the heat-conducting sleeve 21 and the outer surface of the cutting chamber 11, and 80-110 heat-conducting fins are fixed in an annular array on the outer surface of the heat-dissipating sleeve 23.

[0039] Working principle:

[0040] A tumor sample is placed into the cell filter 14. The pulverizing paddle 114 is threaded onto the outer ring of the screw 115. The paddle 114 is compressed by tightening the internally threaded cap 113 and the threaded section of the screw 115. It is important to note that the direction of loosening the threads of the internally threaded cap 113 and screw 115 is opposite to the axial rotation direction of the servo motor 18. The cell filter 14 is placed within the cutting chamber 11 by means of the mounting frame 110. After closing the end cap 12, the screw is passed through the block and the nut is tightened. The servo motor 18 rotates the drive shaft 112, driving the rotating shaft 116. The pulverizing paddle 114, under the action of the rotational force, cuts and pulverizes the tumor sample into small particles. The end cap 12 is then opened, and the pulverizing paddle 114 is removed from the screw 115. The tumor sample particles within the cell filter 14 are observed. After reclosing the end cap 12, the telescopic shaft of the servo cylinder 13 presses downward, driving the lower pressure plate 19 downward, compressing the granular sample within the cell filter 14 and forcing the sample through filtration. The filtered sample flows along the discharge pipe 15 into the storage tank 16 for storage.

[0041] During the sample cutting process, the cooling surface of the semiconductor heater 22 transfers the low temperature to the thermal sleeve 21, which then transfers the low temperature to the interior of the cutting chamber 11. The temperature controller on the outer surface of the heat dissipation sleeve 23 controls the operation of the semiconductor heater 22, maintaining the cutting chamber 11 within a reasonable range of 18-20°C during the cutting process, thereby maintaining cell activity. The heat from the heating surface of the semiconductor heater 22 is released to the outside through the heat dissipation sleeve 23 and fins.

[0042] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A TIL cell separation container for cell therapy, comprising a tumor sample chopper (1), characterized in that: A separation container temperature control mechanism (2) is fixedly connected to the outer ring surface of the tumor sample chopper (1); The tumor sample chopper (1) includes a cutting chamber (11), a driving motor compartment (17) fixedly connected to the bottom end surface of the cutting chamber (11); a cell filter (14) is placed in the inner cavity of the cutting chamber (11), a rotating shaft (116) is rotatably arranged in the inner cavity of the cell filter (14), the top end of the rotating shaft (116) is connected to a screw (115), and a crushing paddle (114) is arranged on the outer ring surface of the screw (115); and the top port of the cutting chamber (11) is hinged with an end cover (12), and a servo electric cylinder (13) is installed on the top surface of the end cover (12), and the telescopic shaft of the servo electric cylinder (13) penetrates the interior of the cell filter (14) and is connected to a lower pressure plate (19); A servo motor (18) is installed at the bottom of the inner cavity of the driving motor bin (17), and the output shaft of the servo motor (18) is connected to a transmission shaft (112) that penetrates into the interior of the cutting chamber (11) through a coupling, and the top end of the transmission shaft (112) is fixedly connected to the bottom end of the rotating shaft (116); wherein, a material storage tank (16) is provided on the left surface of the driving motor bin (17), and the top end of the material storage tank (16) is connected to a discharge pipe (15) that penetrates into the inner cavity of the cutting chamber (11); The separation container temperature control mechanism (2) comprises a heat-conducting sleeve (21) wrapped and fixed on the outer surface of the cutting chamber (11), 8-10 semiconductor heating plates (22) attached to the outer surface of the heat-conducting sleeve (21) in a ring array, the outer surface of the semiconductor heating plate (22) is fixedly connected to the heat dissipation sleeve (23), and the inner surface of the semiconductor heating plate (22) is a cooling surface, and the outer surface of the semiconductor heating plate (22) is a heating surface.

2. A TIL cell separation container for cell therapy according to claim 1, characterized in that: A placement frame (110) is fixed on the inner cavity side wall of the cutting chamber (11), the outer ring top edge of the cell filter (14) is snap-fitted to the top surface of the placement frame (110), and the bottom of the cell filter (14) is provided with a circular hole for the rotating shaft (116) to penetrate and rotate.

3. A TIL cell separation container for cell therapy according to claim 1, characterized in that: The left and right surfaces of the cutting chamber (11) are both fixedly connected to a U-shaped seat, a block is fixed inside the left U-shaped seat, and an L-shaped rod is rotatably connected inside the right U-shaped seat, and the other end of the L-shaped rod is connected to the right side surface of the end cover (12).

4. A TIL cell separation container for cell therapy according to claim 1, characterized in that: The left end face of the end cover (12) is rotatably connected with a screw rod, the end of which passes through a block inside a U-shaped seat on the left side surface of the cutting chamber (11), and a nut is screwed on the section where the screw rod passes through the block.

5. A TIL cell separation container for cell therapy according to claim 4, characterized in that: The bottom end surface of the end cover (12) and the top end surface of the cutting chamber (11) are both fixed with a circle of sealing gasket by adhesive. The shell of the servo electric cylinder (13) is fixed on the top surface of the end cover (12), and the top surface of the end cover (12) is provided with a through hole for the telescopic shaft of the servo electric cylinder (13) to pass through and telescope, and a sliding bearing is installed inside the through hole.

6. A TIL cell separation container for cell therapy according to claim 1, characterized in that: The diameter of the lower pressure plate (19) is consistent with the inner diameter of the upper port of the cell filter (14), and the crushing paddle (114) is located in the middle area of the inner cavity of the cell filter (14). The outer ring and bottom surface of the cell filter (14) are spaced 3.0 cm to 6.0 cm from the inner cavity side wall of the cutting chamber (11).

7. A TIL cell separation container for cell therapy according to claim 1, characterized in that: The shaft diameter of the rotating shaft (116) is larger than the shaft diameter of the screw rod (115); the bottom end surface of the crushing paddle (114) contacts the top end surface of the rotating shaft (116); an internal thread cover (113) is screwed onto the outer thread section of the screw rod (115); and the bottom end surface of the internal thread cover (113) contacts the top surface of the crushing paddle (114).

8. A TIL cell separation container for cell therapy according to claim 1, characterized in that: The positions where the driving motor compartment (17) and the cutting chamber (11) are connected to each other are both provided with holes for the transmission shaft (112) to pass through and rotate, and a sealed bearing (111) adapted to the transmission shaft (112) is provided inside the hole.

9. A TIL cell separation container for cell therapy according to claim 1, characterized in that: The bottom surface of the inner cavity of the driving motor compartment (17) is connected to a support plate, the side wall of the outer shell of the servo motor (18) is connected to the surface of the support plate, and the output shaft of the servo motor (18) is coaxially arranged with the axis of the driving motor compartment (17) and the cutting chamber (11).

10. The TIL cell separation container for cell therapy according to claim 1, characterized in that: Thermal grease is coated between the inner surface of the heat-conducting sleeve (21) and the outer surface of the cutting chamber (11), and 80-110 heat-conducting fins are fixed in an annular array on the outer surface of the heat-dissipating sleeve (23).

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