Sample clean-up enrichment tube

Abstract

The utility model provides a kind of sample cleaning enrichment tube, including tube body, the tube body is formed with accommodating space, the accommodating space is built-in filter membrane, the filter membrane separates the accommodating space into cleaning enrichment cavity and waste liquid discharge cavity, the bottom of the cleaning enrichment cavity has enrichment groove, the top opening of the accommodating space is blocked with upper cover, the upper cover is equipped with cleaning liquid introduction pipe and cell suction pipe, the end port of cleaning liquid introduction pipe and cell suction pipe close to the accommodating space is all in the cleaning enrichment cavity, the bottom of the accommodating space also has waste liquid lead-out pipe, the inlet end of waste liquid lead-out pipe is in the waste liquid discharge cavity. The utility model effectively avoids the potential damage to cell integrity and activity caused by shear force and local heating in the prior art using centrifugal enrichment method, and significantly reduces the sample enrichment processing cost.

Description

Technical Field

[0001] This utility model belongs to the field of automated production equipment design technology for cell and gene therapy (CGT) products, and specifically relates to a sample cleaning and enrichment tube. Background Technology

[0002] Cell therapies, exemplified by chimeric antigen receptor T-cell (CAR-T) therapy, have achieved significant breakthroughs in treating malignant tumors, but their manufacturing remains a major bottleneck for commercialization. Traditional production models heavily rely on manual, open operations within high-level cleanrooms. This model is not only labor-intensive and costly, but also struggles to guarantee batch-to-batch consistency and production success rates, and carries the risk of microbial contamination. Furthermore, workshop-style production has fundamental deficiencies in scalability, failing to meet the demands of large-scale commercialization. To address these issues, the industry is shifting towards automated, closed-loop production systems aimed at improving production efficiency, standardizing processes, reducing costs, and enhancing product safety; however, existing automation solutions still have limitations.

[0003] Current automated cell production technologies for cell enrichment often involve placing centrifuge tubes containing cell samples (such as whole blood samples) into large centrifuges for centrifugation and enrichment. However, since the core of cell enrichment in a centrifuge is the centrifugation caused by high-speed rotation, mechanical shearing forces are easily generated during high-speed centrifugation. This can damage the structural integrity of cells to some extent. Localized heating may also occur during centrifugation, which may damage the activity of heat-sensitive samples and thus affect the accuracy of test results. In addition, the configuration of centrifuges results in high costs for cell enrichment. Summary of the Invention

[0004] Therefore, the technical problem to be solved by this invention is to provide a sample washing and enrichment tube that can eliminate the potential risk of damage to cell integrity and activity caused by centrifugation enrichment, while achieving low cost.

[0005] To address the aforementioned problems, this utility model provides a sample cleaning and enrichment tube, comprising a tube body with a accommodating space formed within it. A filter membrane is embedded within the accommodating space, dividing it into a cleaning and enrichment chamber and a waste liquid discharge chamber. The bottom of the cleaning and enrichment chamber has an enrichment groove. The top opening of the accommodating space is sealed with a top cover. The top cover is equipped with a cleaning solution inlet tube and a cell aspiration tube. The ends of both the cleaning solution inlet tube and the cell aspiration tube near the accommodating space are located within the cleaning and enrichment chamber. The bottom of the accommodating space also has a waste liquid outlet tube, the inlet of which is located within the waste liquid discharge chamber.

[0006] In some embodiments, one end of the cleaning fluid inlet pipe near the accommodating space is located within the opening of the enrichment groove.

[0007] In some embodiments, the end of the cell aspiration tube near the accommodating space is located within the opening of the enrichment groove and is at a lower height than the end of the cleaning fluid inlet tube near the accommodating space.

[0008] In some embodiments, the upper cover is further provided with a target cell introduction tube, and one end of the target cell introduction tube near the accommodating space is located in the cleaning and enrichment chamber.

[0009] In some embodiments, the upper cover is also provided with a waste liquid discharge pipe, and one end of the waste liquid discharge pipe near the accommodating space is located in the waste liquid discharge cavity.

[0010] In some embodiments, the filter membrane is cylindrical, and the cylindrical filter membrane surrounds the opening of the enrichment groove to divide the accommodating space into a cleaning enrichment chamber and a waste liquid discharge chamber that are concentrically arranged inside and out.

[0011] In some embodiments, the top cover is detachably connected to the top opening of the accommodating space, and a first sealing ring is provided between the top cover and the tube body.

[0012] In some embodiments, a lower cover is detachably connected to the bottom opening of the accommodating space, and the enrichment groove is formed on the top surface of the lower cover.

[0013] In some embodiments, a second sealing ring is provided between the lower cover and the tube body.

[0014] In some embodiments, the diameter of the enrichment groove decreases as it moves away from the top cover.

[0015] This invention provides a sample washing and enrichment tube. A filter membrane within the tube body divides the space into a washing and enrichment chamber and a waste liquid discharge chamber. A washing solution inlet tube and a cell aspiration tube are located on the top cover. The washing solution inlet tube introduces external washing solution into the washing and enrichment chamber to wash the sample solution within, ultimately enriching and storing target cells in the enrichment grooves. The cell aspiration tube then aspirates the enriched target cells and transfers them to a target container. During the washing process, waste liquid (excluding target cells) passes through the filter membrane into the waste liquid discharge chamber and is discharged through the waste liquid discharge tube into a waste liquid storage component, thus completing the washing, screening, and enrichment of target cells. The structure is simple. It is easy to operate; due to the use of membrane filtration for cleaning, the target cells can be efficiently cleaned by the amount of cleaning solution introduced. Theoretically, the cleaning effect can be ensured by controlling the amount of cleaning solution introduced. Moreover, since the cleaning solution can be discharged synchronously in real time through the waste liquid discharge chamber, sample enrichment can be achieved with a smaller structure. Since the sample cleaning and enrichment tube in this utility model does not require a large centrifuge to generate centrifugal force, the target cells can be efficiently enriched through the cleaning of the cleaning solution and the filtration of the membrane. This effectively avoids the potential damage to cell integrity and activity caused by the shear force and local heating generated by the centrifugal enrichment method in the prior art, and significantly reduces the sample enrichment processing cost. Attached Figure Description

[0016] Figure 1 This is a three-dimensional structural schematic diagram of the sample cleaning and enrichment tube in an embodiment of this utility model; Figure 2 yes Figure 1 A top view of the sample cleaning enrichment tube; Figure 3 yes Figure 2 A cross-sectional schematic diagram of AA.

[0017] The reference numerals in the attached figures are as follows: 1. Tube body; 11. Cleaning and enrichment chamber; 12. Waste liquid discharge chamber; 13. Enrichment groove; 2. Filter membrane; 3. Top cover; 31. Cleaning solution inlet tube; 32. Cell aspiration tube; 33. Waste liquid outlet tube; 34. Target cell inlet tube; 35. Waste liquid discharge tube; 41. First sealing ring; 42. Second sealing ring; 5. Bottom cover. Detailed Implementation

[0018] See also Figures 1 to 3As shown, according to an embodiment of the present invention, a sample washing and enrichment tube is provided, including a tube body 1. A receiving space (not indicated in the figure) is formed within the tube body 1. A filter membrane 2 is built into the receiving space, dividing the receiving space into a washing and enrichment chamber 11 and a waste liquid discharge chamber 12. The bottom of the washing and enrichment chamber 11 has an enrichment groove 13 for collecting washed and screened target cells. A top cover 3 seals the top opening of the receiving space. A washing liquid inlet tube 31 and a cell aspiration tube 32 are provided on the top cover 3. The washing liquid inlet tube 31 and the cell aspiration tube 32 are located near one end of the receiving space (as shown in the figure). Figure 3 The orientation shown is for reference, i.e., the bottom port) is located within the washing and enrichment chamber 11. The washing solution inlet tube 31 is used to introduce external washing solution into the washing and enrichment chamber 11 to wash the sample solution within the washing and enrichment chamber 11. The cell aspiration tube 32 can aspirate the washed and enriched target cells from the enrichment groove 13 and transport them to the corresponding container (e.g., a cell product bag). The bottom of the accommodating space also has a waste liquid outlet tube 33, the inlet end of which is located within the waste liquid discharge chamber 12, so as to discharge the waste liquid entering the waste liquid discharge chamber 12 (such as the waste liquid flowing in after being filtered through the filter membrane 2 from the washing and enrichment chamber 11). In some embodiments, the material of the aforementioned filter membrane 2 can be PET or PC, and the pore size of the filter membrane ranges from 3 to 30 μm.

[0019] In this technical solution, a filter membrane 2 is installed within the accommodating space of the tube body 1, dividing the accommodating space into a cleaning and enrichment chamber 11 and a waste liquid discharge chamber 12. A cleaning solution inlet tube 31 and a cell aspiration tube 32 are installed on the upper cover 3. The external cleaning solution is introduced into the cleaning and enrichment chamber 11 through the cleaning solution inlet tube 31 to clean the sample solution inside, and finally to enrich and store the target cells in the enrichment groove 13. Then, the enriched target cells are aspirated and transferred to the target container using the cell aspiration tube 32. During the cleaning process, the waste liquid other than the target cells enters the waste liquid discharge chamber 12 through the filter membrane 2 and is discharged into the waste liquid storage component through the waste liquid discharge tube 33, thereby completing the cleaning, screening and enrichment of the target cells. The structure is simple and easy to operate. Due to the use of filter membrane 2 for filtration and cleaning, the target cells can be efficiently cleaned by the amount of cleaning solution introduced. Theoretically, the cleaning effect can be ensured by controlling the amount of cleaning solution introduced. Since the cleaning solution can be discharged synchronously in real time through the waste liquid discharge chamber 12, sample enrichment can be achieved with a smaller structure. Since the sample cleaning and enrichment tube in this utility model does not require a large centrifuge to generate centrifugal force, the target cells can be efficiently enriched by the cleaning effect of the cleaning solution and the filtration effect of filter membrane 2. This effectively avoids the potential damage to cell integrity and activity caused by the shear force and local heating generated by the centrifugal enrichment method in the prior art, and significantly reduces the sample enrichment processing cost.

[0020] The volume of the aforementioned enrichment groove 13 can be reasonably selected according to the actual enrichment needs.

[0021] In some embodiments, the end of the cleaning fluid inlet pipe 31 near the accommodating space is located within the opening of the enrichment groove 13, see [reference]. Figure 3 As shown, the cleaning fluid inlet pipe 31 extends into the accommodating space and downwards along the depth direction of the accommodating space to a position close to the bottom area of ​​the enrichment groove 13. This allows the cleaning fluid to flow back upwards from the bottom area of ​​the sample liquid when it is introduced, thereby achieving an upward throwing effect on the sample liquid. This ensures that the cleaning fluid thoroughly cleans the sample liquid and improves the cleaning and filtration efficiency.

[0022] In some embodiments, the end of the cell aspiration tube 32 near the accommodating space is located inside the opening of the enrichment groove 13 and its height is lower than the height of the end of the cleaning solution inlet tube 31 near the accommodating space. That is, the cell aspiration tube 32 is closer to the bottom wall of the enrichment groove 13 than the bottom of the cleaning solution inlet tube 31, which can ensure more efficient and thorough aspiration, transfer and storage of the enriched target cells after cleaning.

[0023] The target cells can be introduced, for example, by opening the aforementioned cover 3 and adding them in. However, this method is not conducive to automated cleaning and enrichment. As a preferred embodiment, the cover 3 is also provided with a target cell introduction tube 34. The end of the target cell introduction tube 34 near the accommodating space is located in the cleaning and enrichment chamber 11. In this way, in specific use, the target cells obtained after processing (e.g., positive or negative sorting of the sample solution) can be controllably introduced into the cleaning and enrichment chamber 11 through the target cell introduction tube 34, so that the sample cleaning and enrichment tube of this invention can be applied to automated processing equipment to further improve the cleaning and enrichment efficiency.

[0024] In some embodiments, the upper cover 3 is further provided with a waste liquid discharge pipe 35. The end of the waste liquid discharge pipe 35 near the accommodating space is located in the waste liquid discharge chamber 12. In this technical solution, by further providing a waste liquid discharge pipe 35 on the upper cover 3, it can form a synergy with the upstream target cell sorting process. In this way, the waste liquid generated in the target cell sorting process can be discharged to the corresponding waste liquid storage component through the waste liquid discharge chamber 12 and the waste liquid discharge pipe 33.

[0025] In some embodiments, the filter membrane 2 is cylindrical, and the cylindrical filter membrane 2 surrounds the groove of the enrichment groove 13 to divide the accommodating space into the cleaning enrichment chamber 11 and the waste liquid discharge chamber 12, which are arranged concentrically inside and outside.

[0026] In this technical solution, the cylindrical shape of the filter membrane 2 makes the cleaning and enrichment chamber 11 and the waste liquid discharge chamber 12 objectively form a concentric structure, which can maximize the filtration area of ​​the filter membrane 2, increase the filtration flux per unit time, and improve production efficiency.

[0027] As mentioned above, the top cover 3 is detachably connected to the top opening of the accommodating space, so that the filter membrane 2 can be replaced according to the actual enrichment needs to achieve the washing, screening and enrichment of target cells of different particle sizes. A first sealing ring 41 is provided between the top cover 3 and the tube body 1 to prevent leakage of washing liquid, sample liquid, etc.

[0028] In some embodiments, a lower cover 5 is detachably connected to the bottom opening of the accommodating space, and the enrichment groove 13 is formed on the top surface of the lower cover 5. In order to prevent leakage of cleaning fluid and sample fluid, in some embodiments, a second sealing ring 42 is provided between the lower cover 5 and the tube body 1.

[0029] In some embodiments, the diameter of the enrichment groove 13 decreases along the direction away from the top cover 3, which can make the target cells more concentrated and facilitate their full absorption and transfer in the future.

[0030] It will be readily understood by those skilled in the art that the aforementioned advantageous methods can be freely combined and superimposed without conflict.

[0031] The above are merely preferred embodiments of this utility model and are not intended to limit the scope of this utility model. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this utility model should be included within the protection scope of this utility model. The above are only preferred embodiments of this utility model. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of this utility model, and these improvements and modifications should also be considered within the protection scope of this utility model.

Claims

1. A sample cleaning enrichment tube, characterized by, The device includes a tube body (1) with a accommodating space inside. The accommodating space is housed within a filter membrane (2), which divides the accommodating space into a washing and enrichment chamber (11) and a waste liquid discharge chamber (12). The bottom of the washing and enrichment chamber (11) has an enrichment groove (13). The top opening of the accommodating space is sealed with a top cover (3). The top cover (3) is provided with a washing liquid inlet tube (31) and a cell aspiration tube (32). The washing liquid inlet tube (31) and the cell aspiration tube (32) are located at one end of the accommodating space. All are located within the cleaning and enrichment chamber (11). The bottom of the accommodating space also has a waste liquid outlet pipe (33), and the inlet end of the waste liquid outlet pipe (33) is located within the waste liquid discharge chamber (12). The filter membrane (2) is cylindrical. The cylindrical filter membrane (2) surrounds the groove of the enrichment groove (13) to divide the accommodating space into the cleaning and enrichment chamber (11) and the waste liquid discharge chamber (12) which are concentrically arranged inside and outside. The end of the cleaning liquid inlet pipe (31) near the accommodating space is located within the groove of the enrichment groove (13).

2. The sample cleaning enrichment tube of claim 1, wherein, The end port of the cell aspiration tube (32) near the accommodating space is located in the groove of the enrichment groove (13) and its height is lower than the height of the end port of the cleaning fluid inlet tube (31) near the accommodating space.

3. The sample cleaning enrichment tube of claim 1, wherein, The upper cover (3) is also provided with a target cell introduction tube (34), and one end of the target cell introduction tube (34) near the accommodating space is located in the cleaning and enrichment chamber (11).

4. The sample cleaning and enrichment tube of claim 1, wherein, The upper cover (3) is also provided with a waste liquid discharge pipe (35), and one end of the waste liquid discharge pipe (35) near the accommodating space is located in the waste liquid discharge cavity (12).

5. The sample cleaning and enrichment tube of claim 1, wherein, The top cover (3) is detachably connected to the top opening of the accommodating space, and a first sealing ring (41) is provided between the top cover (3) and the tube body (1).

6. The sample cleaning and enrichment tube of claim 1, wherein, The bottom opening of the accommodating space is detachably connected to a lower cover (5), and the enrichment groove (13) is formed on the top surface of the lower cover (5).

7. The sample cleaning and enrichment tube according to claim 6, characterized in that, A second sealing ring (42) is provided between the lower cover (5) and the tube body (1).

8. The sample cleaning and enrichment tube of claim 1, wherein, The diameter of the enrichment groove (13) decreases in the direction away from the top cover (3).

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