3D (three-dimensional) hepatic conglomerate microflow culture device

Abstract

The utility model discloses a 3D (three-dimensional) hepatic conglomerate microflow culture device, which relates to the technical field of hepatic cell culture and comprises a test tube rack, a plurality of culture tubes are arranged in the test tube rack at intervals, stirring paddles are arranged in the culture tubes, and a plurality of stirring gears, a plurality of driving gears and a driving device are arranged on the test tube rack. One end of the stirring paddle extends into the culture tube, the other end of the stirring paddle is fixed with the stirring gears, the plurality of stirring gears are respectively meshed with the plurality of driving gears, the plurality of driving gears are mutually meshed, the driving device is connected with any one of the plurality of driving gears, and any one driving gear is driven by the driving device to rotate. All the driving gears are driven to rotate synchronously, and all the stirring gears are driven to rotate synchronously, so that all the stirring paddles are driven to rotate synchronously in the corresponding culture tubes. According to the 3D hepatic conglomerate microflow culture device provided by the utility model, the rotating speeds of the paddles are consistent, the difference of produced finished products is small, the operation is convenient and quick, the damage to cells is small, the structure is simple, the disassembly and assembly are easy, and the cost is low.

Description

Technical Field

[0001] The utility model relates to the technical field of liver cell culture, in particular to a 3D liver aggregate microfluidic culture device. Background Art

[0002] 3D hepatocytes are composed of cell aggregates produced by a single cell type or a mixture of multiple cells. They can be self-aggregated by immortalized cell lines or primary hepatocytes in scaffold-based and scaffold-free culture conditions to form a spherical 3D structure. Because they are spherical, they can show more physiological performance than 2D hepatocytes (suspension, adherence), and the test results are naturally more comprehensive and accurate.

[0003] There are five main ways to prepare 3D hepatospheres: centrifugation, suspension, microfluidics, rotation, and magnetic levitation. Among them, the microfluidics method is to place 2D hepatocytes in a culture dish with an automatic paddle device, and aggregate the cells through microflows caused by the paddles. The advantages are that it is convenient and fast, and causes little damage to cells. The disadvantage is that the different speeds of the paddles in different culture dishes may lead to differences in the performance of the finished product. Therefore, it is necessary to design a new microfluidics culture device to solve the problem that the different speeds of the paddles in different culture dishes may lead to differences in the finished product. Utility Model Content

[0004] In view of the above-mentioned shortcomings, the utility model provides a 3D liver spheroid microfluidic culture device with consistent blade speed and small difference in the output of finished products, convenient and quick operation, little damage to cells, simple structure, easy disassembly and assembly, and low cost.

[0005] In order to achieve the above object, the embodiment of the utility model adopts the following technical solution:

[0006] A 3D hepatosphere microfluidic culture device comprises a test tube rack, wherein a plurality of culture tubes are arranged at intervals in the test tube rack, a stirring paddle is arranged in the culture tube, and the test tube rack is provided with a plurality of stirring gears, a plurality of driving gears, and a driving device. One end of the stirring paddle extends into the culture tube and the other end is fixed to the stirring gear. The plurality of stirring gears are respectively meshed with a plurality of driving gears, and the plurality of driving gears are meshed with each other. The driving device is connected to any one of the plurality of driving gears, and any one of the driving gears is driven to rotate by the driving device, thereby driving all the driving gears to rotate synchronously, driving all the stirring gears to rotate synchronously, thereby driving all the stirring paddles to rotate synchronously in the corresponding culture tubes.

[0007] According to one aspect of the utility model, the radius of the stirring gear is smaller than the radius of the driving gear.

[0008] According to one aspect of the present invention, a plurality of driving gears are meshed with each other and arranged in a row.

[0009] According to one aspect of the utility model, the 3D hepatosphere microfluidic culture device further includes a bracket, and the driving device is connected to the bracket or a test tube rack.

[0010] According to one aspect of the utility model, the test tube rack is provided with a support cover plate, and a plurality of stirring gears and a plurality of driving gears are provided on the support cover plate.

[0011] According to one aspect of the utility model, the driving device includes a motor, and the motor is connected to any one of a plurality of driving gears.

[0012] According to one aspect of the utility model, the driving device further includes a battery pack, and the battery pack is connected to the motor.

[0013] According to one aspect of the utility model, a test tube cover is provided on the culture tube, and the stirring paddle passes through the test tube cover.

[0014] According to one aspect of the utility model, the bottom of the culture tube is U-shaped.

[0015] According to one aspect of the utility model, the stirring paddle includes a rotating shaft and a paddle. One end of the rotating shaft is fixed to the paddle, and the other end is fixed to the stirring gear. The paddle is arranged in the culture tube.

[0016] Advantages of the implementation of the utility model: by driving any one of the driving gears to rotate through the driving device, all the driving gears are driven to rotate synchronously, all the stirring gears are driven to rotate synchronously, and thus all the stirring paddles are driven to rotate synchronously in the corresponding culture tubes, thereby inducing microflows in the culture tubes, so that the 2D liver cells in the culture tubes aggregate to form 3D liver aggregates. By setting the driving device to be connected to any one of the several driving gears, etc., the device can make all the stirring paddles rotate synchronously, that is, keep the rotation speed approximately consistent, so that the difference in the output of the finished product is small, that is, the device can solve the problem that the different rotation speeds of the blades of different culture dishes in the existing microfluidic culture device may cause differences in the finished products. The device is easy and quick to operate, causes little damage to cells, has a simple overall structure, is easy to disassemble and assemble, and has low cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0018] Figure 1 It is a structural schematic diagram of the utility model.

[0019] The names corresponding to the serial numbers in the figure are as follows:

[0020] 1. Test tube rack; 2. Culture tube; 3. Stirring gear; 4. Driving gear; 5. Motor; 6. Battery pack; 7. Test tube cover; 8. Rotating shaft; 9. Paddle. DETAILED DESCRIPTION

[0021] The following will be combined with the drawings in the embodiments of the utility model to clearly and completely describe the technical solutions in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0022] like Figure 1As shown, a 3D hepatosphere microfluidic culture device is used to culture 3D hepatospheres, which includes a test tube rack 1, a plurality of U-shaped bottom culture tubes 2, a plurality of stirring paddles, a plurality of stirring gears 3, a plurality of driving gears 4, and a driving device. The test tube rack 1 is a square box structure, the top of which can be opened or provided with a square support cover that can be opened and closed on the top; the test tube rack 1 is used to support and fix the culture tube 2, and can also be used to support the entire device. A plurality of U-shaped bottom culture tubes 2 are arranged in a row in the test tube rack 1 at intervals, and a large number of 2D hepatocytes for aggregation are contained in the culture tube 2, and the U-shaped bottom of the culture tube 2 is a place for cell aggregation. A stirring paddle is provided in a culture tube 2; the stirring paddle includes a rotating shaft 8 and a paddle 9, wherein the bottom end of the rotating shaft 8 is fixed to the paddle 9, and the top end of the rotating shaft 8 is fixed to the stirring gear 3, and the fixing method is arbitrary, and the paddle 9 is provided in the culture tube 2 to trigger microflow in the culture tube 2. Several stirring gears 3 and several driving gears 4 are rotatably placed on the top of the test tube rack 1 or on the supporting cover; the stirring gear 3 is located directly above the culture tube 2; the driving gear 4 is meshed on the side of the stirring gear 3; each driving gear 4 is meshed with a corresponding stirring gear 3; several driving gears 4 are meshed adjacent to each other and arranged in a row, and several stirring gears 3 are also arranged in a row; the arrangement of the culture tube 2, the stirring gear 3, and the driving gear 4 is adapted. The driving device includes a motor 5 and a battery pack 6, which are connected; wherein the output shaft of the motor 5 is connected to any one of the several driving gears 4, and the motor 5 is used as a power source for the rotation of the blade 9; the tail base of the motor 5 or the outer shell of the motor 5 can be fixed to the top of the test tube rack 1 through a connecting frame of any structure, or the motor 5 can also be installed on the following bracket; the battery pack 6 is used to power the motor 5, and it is installed with the motor 5 for applicability. By driving any one of the driving gears 4 to rotate through the motor 5, all the driving gears 4 are driven to rotate synchronously, all the stirring gears 3 are driven to rotate synchronously, and thus all the stirring paddles are driven to rotate synchronously in the corresponding culture tubes 2 (that is, the blades 9 in each culture tube 2 can maintain a nearly consistent rotation speed to ensure that the output of the finished product is small), thereby inducing microflow in the culture tube 2, so that the 2D hepatocytes in the culture tube 2 are aggregated to form 3D hepatocyte aggregates.

[0023] In practical applications, the radius of the stirring gear 3 is smaller than that of the driving gear 4, and there is a gap between adjacent stirring gears 3; in this way, collision of the culture tube 2 located directly below the stirring gear 3 can be avoided, which facilitates the assembly of the entire structure.

[0024] In practical applications, the 3D hepatosphere microfluidic culture device may further include a support of any structure, the support may be a door-shaped frame, in which case the test tube rack 1 is located in the middle of the support; the support may also be an inverted L-shaped frame, in which case the support is located on the side of the test tube rack 1. The support may be used to fix the motor 5.

[0025] In practical applications, the bracket can also be designed as a frame structure with a lifting form, which can also be used to adjust the installation height of the motor 5, making the device more applicable.

[0026] In practical applications, each culture tube 2 is provided with a test tube cover 7, and the structures and shapes of the two are adapted to each other; the test tube cover 7 is used to seal the culture tube 2 to facilitate cell culture in the culture tube 2. The rotating shaft 8 passes through the test tube cover 7, or the test tube cover 7 is provided with corresponding holes for the rotating shaft 8 to pass through.

[0027] Advantages of the implementation of the utility model: by driving any one of the driving gears 4 to rotate through the driving device, all the driving gears 4 are driven to rotate synchronously, all the stirring gears 3 are driven to rotate synchronously, and all the stirring paddles are driven to rotate synchronously in the corresponding culture tube 2, thereby inducing microflow in the culture tube 2, so that the 2D liver cells in the culture tube 2 are aggregated to form 3D liver aggregates. By setting the driving device to be connected to any one of the driving gears 4, etc., the device can make all the stirring paddles rotate synchronously, that is, keep the rotation speed approximately the same, so that the difference in the output of the finished product is small, that is, the device can solve the problem that the different rotation speeds of the blades 9 of different culture dishes in the existing microfluidic culture device may cause differences in the finished products. The device is easy and quick to operate, causes little damage to cells, has a simple overall structure, is easy to disassemble and assemble, and has low cost.

[0028] The above is only a specific implementation of the utility model, but the protection scope of the utility model is not limited thereto. Any changes or substitutions that can be easily thought of by any technician familiar with the technical field within the technical scope disclosed in the utility model should be included in the protection scope of the utility model. Therefore, the protection scope of the utility model shall be based on the protection scope of the claims.

Claims

1. A 3D hepatosphere microfluidic culture device, comprising a test tube rack (1), wherein a plurality of culture tubes (2) are arranged at intervals in the test tube rack (1), wherein a stirring paddle is arranged in the culture tube (2), characterized in that: The test tube rack (1) is provided with a plurality of stirring gears (3), a plurality of driving gears (4), and a driving device. One end of the stirring paddle extends into the culture tube (2), and the other end is fixed to the stirring gear (3). The plurality of stirring gears (3) are respectively meshed with the plurality of driving gears (4), and the plurality of driving gears (4) are meshed with each other. The driving device is connected to any one of the plurality of driving gears (4). The driving device drives any one of the driving gears (4) to rotate, thereby driving all the driving gears (4) to rotate synchronously, driving all the stirring gears (3) to rotate synchronously, and thus driving all the stirring paddles to rotate synchronously in the corresponding culture tube (2).

2. The 3D hepatosphere microfluidic culture device according to claim 1, characterized in that: The radius of the stirring gear (3) is smaller than the radius of the driving gear (4).

3. The 3D hepatosphere microfluidic culture device according to claim 2, characterized in that: A plurality of driving gears (4) are meshed with each other and arranged in a row.

4. The 3D hepatosphere microfluidic culture device according to claim 1, characterized in that: The 3D hepatosphere microfluidic culture device also includes a support, and the driving device is connected to the support or the test tube rack (1).

5. The 3D hepatosphere microfluidic culture device according to claim 4, characterized in that: The test tube rack (1) is provided with a support cover plate, and a plurality of stirring gears (3) and a plurality of driving gears (4) are all provided on the support cover plate.

6. The 3D hepatosphere microfluidic culture device according to claim 1, characterized in that: The driving device comprises a motor (5), and the motor (5) is connected to any one of a plurality of driving gears (4).

7. The 3D hepatosphere microfluidic culture device according to claim 6, characterized in that: The driving device further comprises a battery pack (6), and the battery pack (6) is connected to the motor (5).

8. The 3D hepatosphere microfluidic culture device according to claim 1, characterized in that: The culture tube (2) is provided with a test tube cover (7), and the stirring paddle passes through the test tube cover (7).

9. The 3D hepatosphere microfluidic culture device according to claim 8, characterized in that: The bottom of the culture tube (2) is U-shaped.

10. The 3D hepatosphere microfluidic culture device according to claim 1, characterized in that: The stirring paddle comprises a rotating shaft (8) and a paddle (9); one end of the rotating shaft (8) is fixed to the paddle (9) and the other end is fixed to the stirring gear (3); and the paddle (9) is arranged in the culture tube (2).

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