Tangential flow filtering device

Abstract

The utility model relates to a tangential flow filtering device. The tangential flow filtering device comprises a filtering cabin, the filtering cabin is provided with a cavity for containing filtrate, the two ends of the filtering cabin are provided with a filtrate inlet and a concentrated solution outlet respectively, the connecting line direction of the filtrate inlet and the concentrated solution outlet is consistent with the flowing direction of the filtrate, and the filtering cabin is further provided with a permeate outlet communicated with the cavity; the filtering column is arranged in the filtering cabin, the tangential direction of the filtering column is consistent with the flowing direction of filtrate, the filtering column is distributed in a hollow shape, the two ends of the filtering column are communicated with the filtrate inlet and the concentrated solution outlet respectively, the filtering column is provided with a plurality of membrane holes, and the membrane holes are communicated with the filtering cabin. The inner cavity of the filter column is communicated with the chamber through the membrane holes, and the membrane holes are 0.2-8 microns. According to the scheme provided by the invention, the tangential flow filtering device is not easy to cause system blockage, and can realize efficient separation of high-throughput culture solution.

Description

Technical Field

[0001] The present application relates to the field of devices and apparatuses used in biopharmaceuticals and biotechnology, and in particular to a tangential flow filtration device. Background Art

[0002] The rapid development of biotechnology has led to a diverse range of biopharmaceutical products and the emergence of a host of new equipment and process methods for their application. In fields such as cell culture and antibody production, tangential flow filtration (TFF) devices are frequently used to separate and purify macromolecules or large particles from small molecules or small particles.

[0003] TFF devices apply pressure to force fluid flow tangentially along the membrane. During this process, smaller molecules and solvents are able to pass through the membrane's micropores, including cell fragments, forming the permeate, while retained intact cells and larger molecules and particles form the concentrate, achieving the return, concentration, and purification of biomolecules. Due to the tangential flow of the fluid, contaminants on the membrane surface are repeatedly washed away, reducing the risk of membrane fouling and clogging.

[0004] Among them, Alternating Tangential Flow (ATF) is a special tangential flow filtration technology, mainly used in cell culture and production of biological products in the biopharmaceutical field. It can reduce the shear force on the cells on the membrane surface by alternating the flow direction of the fluid, thereby protecting the cells from damage. ATF technology uses hollow fiber filters to achieve the separation and purification of substances in biopharmaceutical processes. However, because the membrane material itself can only allow a maximum pore size of 0.65 microns, when it is used to process culture fluids containing high concentrations of cells or cell fragments, the product easily forms complexes with cells and cell fragments, and the membrane clogging problem occurs frequently. Utility Model Content

[0005] To solve or partially solve the problems existing in the related art, the present application provides a tangential flow filtration device. On the one hand, the filter can solve the problem of product and cell clogging of the filter column during the continuous flow production of antibodies, thereby achieving efficient separation of cells and cell products; on the other hand, it can solve the problems of high cost and high transportation fragility of hollow fiber columns; and for the first time, it solves the problem of filters required for MF (macro filtration), greatly promoting the large-scale production and application of disposable filters in industries such as biopharmaceuticals.

[0006] The present application provides a tangential flow filtration device, comprising:

[0007] A filter cabin, wherein the filter cabin has a chamber for accommodating filtrate, and a filtrate inlet and a concentrate outlet are respectively provided at both ends of the filter cabin, wherein the direction of the line connecting the filtrate inlet and the concentrate outlet is consistent with the flow direction of the filtrate, and the filter cabin further has a permeate outlet communicating with the chamber;

[0008] A filter column is placed in the filter cabin, the tangential direction of the filter column is consistent with the flow direction of the filtrate, the filter column is hollow, and the two ends of the filter column are respectively connected to the filtrate inlet and the concentrate outlet, the filter column has a plurality of membrane pores, the internal cavity of the filter column is connected to the chamber through the membrane pores, and the membrane pores are 0.2-8μm.

[0009] In some optional embodiments, the height of the filter cabin is 0.5 inches to 1 meter, and the diameter of the filter cabin is 1 to 40 inches.

[0010] In some optional embodiments, the filter column includes a hollow support column and a filter membrane, the ends of the hollow support column are respectively connected to the filtrate inlet and the concentrate outlet, the filter membrane is fixed on the outer side of the hollow support column, and the side wall of the hollow support column is provided with filter holes for the filtrate to pass through, and the pore size of the filter holes is larger than the pore size of the membrane holes.

[0011] In some optional embodiments, the filter membrane has a thickness of 0.5-3 mm.

[0012] In some optional embodiments, the filter membrane is a hydrophilic membrane material.

[0013] In some optional embodiments, the filter membrane is folded and distributed in a pleated shape, and the filter membrane is fixed to the outer side of the hollow support column through the troughs of each pleat.

[0014] In some optional embodiments, the pleats of the filter membrane are evenly distributed.

[0015] In some optional embodiments, the filter column further includes a plurality of flexible support wires, and the support wires are fixed on the filter membrane.

[0016] In some optional embodiments, the support wires are located at the peaks and troughs of each pleat of the filter membrane.

[0017] In some optional embodiments, the filter membrane is fixed to the outer side of the hollow support column by bonding.

[0018] The technical solution provided by the present application may include the following beneficial effects: The technical solution provided by the present application may include the following beneficial effects: Through the large-pore tangential flow filtration device of 0.2-8μm, on the one hand, it can solve the problem of products and cells clogging the filter column of the ATF filter during the continuous flow production of antibodies, and realize the efficient separation of cells and cell products; on the other hand, it can solve the problems of high cost and high transportation fragility of hollow fiber columns, which is conducive to large-scale production and application in industries such as biopharmaceuticals; on the other hand, the MF (macro filtration) disposable filter is designed and manufactured, providing a powerful solution for the fields of biopharmaceuticals, food processing industry, environmental protection, etc.

[0019] It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The above and other objects, features and advantages of the present application will become more apparent by describing in more detail exemplary embodiments of the present application in conjunction with the accompanying drawings, wherein the same reference numerals generally represent the same components in the exemplary embodiments of the present application.

[0021] Figure 1 Schematic diagram of the structure of the tangential flow filtration device shown in the embodiment of the present application;

[0022] Figure 2 is a longitudinal cross-sectional view of a tangential flow filtration device shown in an embodiment of the present application;

[0023] Figure 3 It is a transverse cross-sectional view of a tangential flow filtration device shown in an embodiment of the present application.

[0024] Reference numerals:

[0025] 10. Filter cabin; 11. Filtrate inlet; 12. Concentrate outlet; 13. Permeate outlet; 14. Chamber;

[0026] 20. Filter column; 21. Hollow support column; 211. Filter hole; 22. Filter membrane; 221. Membrane hole; 23. Support wire; 24. Ring. DETAILED DESCRIPTION

[0027] The following describes embodiments of the present application in more detail with reference to the accompanying drawings. Although the accompanying drawings illustrate embodiments of the present application, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments described herein. Rather, these embodiments are provided to make the present application more thorough and complete, and to fully convey the scope of the present application to those skilled in the art.

[0028] It should be understood that although the terms "first", "second", "third", etc. may be used in this application to describe various information, this information should not be limited to these terms. These terms are only used to distinguish information of the same type from each other. For example, without departing from the scope of this application, the first information may also be referred to as the second information, and similarly, the second information may also be referred to as the first information. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0029] In the description of this application, it should be understood that the terms "length", "width", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on this application.

[0030] Unless otherwise expressly specified or limited, the terms "mounted," "connected," "connect," "fixed," and the like should be interpreted broadly. For example, they may refer to fixed connection, detachable connection, or integration; mechanical connection or electrical connection; direct connection or indirect connection through an intermediate medium; and internal communication between two components or interaction between two components. Those skilled in the art will understand the specific meanings of the above terms in this application based on the specific circumstances.

[0031] ATF technology uses hollow fiber filters to separate and purify substances in biopharmaceutical processes. However, when it is used to process culture fluids containing high concentrations of cells or cell fragments, membrane clogging is very likely to occur.

[0032] In response to the above problems, the embodiments of the present application provide a tangential flow filtration device that can solve the problem of products and cells clogging the filter column of the ATF filter during the continuous flow production of antibodies, thereby achieving efficient separation of cells and cell products. At the same time, it can solve the problems of high cost and high transportation fragility of hollow fiber columns, which is conducive to large-scale production and application in industries such as biopharmaceuticals.

[0033] The technical solutions of the embodiments of the present application are described in detail below with reference to the accompanying drawings.

[0034] Figure 1 It is a schematic diagram of the overall structure of the tangential flow filtration device shown in the embodiment of the present application.

[0035] See also Figure 1The tangential flow filtration device includes a filter cabin 10, and a filtrate inlet 11 and a concentrate outlet 12 are respectively provided at both ends of the filter cabin 10. The flow direction of the filtrate is from the filtrate inlet 11 to the concentrate outlet 12, so the direction of the line connecting the filtrate inlet 11 and the concentrate outlet 12 is consistent with the flow direction of the filtrate. The filtrate inlet 11 is located at the lower end of the filter cabin 10, and the concentrate outlet 12 is located at the upper end of the filter cabin 10. The filtrate inlet 11 is connected to the filtrate transport pipeline, and the concentrate outlet 12 is connected to the concentrate transport pipeline. The filtrate enters the filter cabin 10 from the filtrate inlet 11 for filtration, thereby achieving separation and purification of large and small molecules in the filtrate. The filtrate that cannot be filtered out is concentrated and enters the concentrate transport pipeline from the concentrate outlet 12.

[0036] In order to achieve separation and purification of the filtrate, the tangential flow filtration device may further be provided with a flow control valve at the filtrate inlet 11 or at a position close to the filtrate inlet 11 of the filtrate transport pipeline, and at a position close to the concentrate outlet 12 of the concentrate transport pipeline, or a flow monitoring device may be provided at a position close to the filtrate inlet 11 of the filtrate transport pipeline, and at a position close to the concentrate outlet 12 of the concentrate transport pipeline, so as to regulate the filtrate flow or pressure in the filter cabin 10, thereby achieving normal input and filtration of the filtrate.

[0037] A permeate outlet 13 is further provided on the side wall of the filter cabin 10 , and the permeate which is the portion of the filtrate filtered out in the filter cabin 10 can be discharged from the permeate outlet 13 .

[0038] The height and size of the filter cabin 10 can be adjusted according to actual production, specifically, it can be 0.5 inches to 1 meter, and the diameter of the filter cabin can be 1-40 inches.

[0039] See also Figure 2 and Figure 3 The filter chamber 10 has a chamber 14 for holding filtrate. A permeate outlet 13 communicates with the chamber 14, allowing the filtered portion of the filtrate in the chamber 14, i.e., the permeate, to be discharged. A hollow filter column 20 is disposed within the chamber 14, with its ends communicating with the filtrate inlet 11 and the concentrate outlet 12, respectively. Therefore, the tangential direction of the filter column 20 aligns with the flow direction of the filtrate. The filtrate enters from the lower end of the filter column 20, and after filtration, the concentrate is discharged from the concentrate outlet 12. The permeate then enters the chamber 14 and flows to the permeate outlet 13 for discharge.

[0040] The filter column 20 comprises a hollow support column 21 and a filter membrane 22. The hollow support column 21 stands upright within the filter chamber 10, with its ends communicating with the filtrate inlet 11 and concentrate outlet 12, respectively, to secure the filter column 20 and allow for the input of filtrate. The filter membrane 22 is secured to the outer side of the hollow support column 21, providing support and securing the filter membrane 22.

[0041] The hollow support column 21 can be a continuous single complete support body, or multiple hollow support columns 21 can be stacked to form a continuous support body, or multiple hollow support columns 21 can be connected to form a support body through components such as connecting rods. In the embodiment of the present application, a continuous single complete support body is preferred.

[0042] The sidewalls of the hollow support column 21 are provided with filter pores 211 through which the filtrate can pass. The filter membrane 22 has multiple membrane pores 221. The pore size of the filter pores 211 is larger than the pore size of the membrane pores 221. The internal cavity of the filter column 20 is connected to the chamber 14 through the filter pores 211 and the membrane pores 221. After being filtered by the filter membrane 22, the filtrate enters the chamber 14. To prevent substances such as cells, cell debris, or cell products in the filtrate from being trapped by the hollow support column 21, the pore size of the filter pores 211 is preferably much larger than the pore size of the membrane pores 221.

[0043] The membrane pores 221 of the filter membrane 22 are 0.2-8 μm, and the membrane pores 221 on the filter membrane 22 are evenly distributed.

[0044] The thickness of the filter membrane 22 is 0.5-3 mm.

[0045] The filter membrane 22 is made of a hydrophilic membrane material, such as polyethersulfone (PES), modified polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), polyacrylonitrile (PAN), polyamide, or polyvinyl alcohol (PVA). The hydrophilic filter membrane 22 is less likely to react, adsorb, or bind to substances such as proteins, enabling a long-term operation of 60 days or more.

[0046] The filter membrane 22 is folded and distributed in a pleated pattern, with each pleat connected end to end to form an annular pleat surrounding the outer side of the hollow support column 21. The pleated filter membrane 22 is secured to the outer side of the hollow support column 21 by the troughs of each pleat. The pleats of the filter membrane 22 can be evenly distributed, i.e., all pleats are of uniform size and shape; or unevenly distributed. A uniform distribution of the pleats in the filter membrane 22 provides a substantially consistent filtrate flux at all locations on the filter membrane 22 at the same time, thereby increasing the service life of the filter membrane 22.

[0047] The filter membrane 22 can be fixed to the outer surface of the hollow support column 21 by physical bonding (hot melt bonding) or chemical bonding (adhesive). For example, the troughs of the folds of the filter membrane 22 can be bonded to the outer surface of the hollow support column 21 by hot bonding or adhesive. In this case, the filter membrane 22 and the hollow support column 21 can be formed into an independent filter column 20. Alternatively, the filter membrane 22 and the outer surface of the hollow support column 21 can be fixed together by cold pressing. In this case, the filter membrane 22 and the hollow support column 21 can also be formed into an independent filter column 20. The number of troughs of the folds can be N, as long as the problem of the filtration process can be solved.

[0048] In addition, the filter membrane 22 can also be fixed to the surface of the hollow support column 21 by an external clamp or clip. For example, the troughs of each fold of the filter membrane 22 can be fixed to the outer side of the hollow support column 21 by using a clip, so that the filter membrane 22 can be replaced at any time.

[0049] The filter column 20 may further include a plurality of flexible support wires 23, the diameter of which may be greater than, equal to, or less than the thickness of the filter membrane 22. The support wires 23 may be adhered to the surface of the filter membrane 22 or embedded within the filter membrane 22 using an adhesive. The flexible support wires 23 not only provide support strength for the filter membrane 22, enabling it to maintain sufficient filtering effectiveness, but also possess a certain degree of bending and deformation capability, enabling the filter membrane 22 to fold.

[0050] The support wire 23 may be located at a trough, a peak, or a position between the trough and the peak of the filter membrane 22 .

[0051] The support wire 23 may be aligned with the flow direction of the filtrate, or may be perpendicular to or intersect the flow direction of the filtrate.

[0052] When the support wire 23 is consistent with the flow direction of the filtrate, the two ends of the support wire 23 can be connected to the hollow support column 21 respectively, or rings 24 can be added at both ends of the hollow support column 21 to sleeve the filter membrane 22 and the support wire 23 on the outer wall of the hollow support column 21 to achieve stable support of the filter membrane 22.

[0053] The support wire 23 can be made of flexible plastic, such as polyvinyl chloride (PVC), polyolefins (such as polyethylene PE and polypropylene PP), thermoplastic polyurethane (TPU), polyisobutylene (PIB), polyether ester (PBT), polycarbonate (PC), polyester (such as polyethylene terephthalate PET), etc.

[0054] The embodiments of the present application have been described above. The above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is selected to best explain the principles of the embodiments, their practical applications, or improvements to the technology in the market, or to enable other persons skilled in the art to understand the embodiments disclosed herein.

Claims

1. A tangential flow filtration device, characterized in that: include: A filter cabin, wherein the filter cabin has a chamber for accommodating filtrate, and a filtrate inlet and a concentrate outlet are respectively provided at both ends of the filter cabin, wherein the direction of the line connecting the filtrate inlet and the concentrate outlet is consistent with the flow direction of the filtrate, and the filter cabin further has a permeate outlet communicating with the chamber; A filter column is placed in the filter cabin, the tangential direction of the filter column is consistent with the flow direction of the filtrate, the filter column is hollow, and the two ends of the filter column are respectively connected to the filtrate inlet and the concentrate outlet, the filter column has a plurality of membrane pores, the internal cavity of the filter column is connected to the chamber through the membrane pores, and the membrane pores are 0.2-8μm.

2. The tangential flow filtration device according to claim 1, characterized in that The height of the filter cabin is 0.5 inches to 1 meter, and the diameter of the filter cabin is 1 to 40 inches.

3. The tangential flow filtration device according to claim 1 or 2, characterized in that: The filter column includes a hollow support column and a filter membrane. The ends of the hollow support column are respectively connected to the filtrate inlet and the concentrate outlet. The filter membrane is fixed on the outer side of the hollow support column, and the side wall of the hollow support column is provided with filter holes for the filtrate to pass through. The pore size of the filter holes is larger than the pore size of the membrane holes.

4. The tangential flow filtration device according to claim 3, characterized in that: The thickness of the filter membrane is 0.5-3 mm.

5. The tangential flow filtration device according to claim 3, characterized in that: The filter membrane is a hydrophilic membrane material.

6. The tangential flow filtration device according to claim 3, characterized in that: The filter membrane is folded and distributed in a pleated shape, and the filter membrane is fixed to the outer side surface of the hollow support column through the troughs of each pleat.

7. The tangential flow filtration device according to claim 6, characterized in that: The folds of the filter membrane are evenly distributed.

8. The tangential flow filtration device according to claim 6, characterized in that: The filter column further includes a plurality of flexible support wires, which are fixed on the filter membrane.

9. The tangential flow filtration device according to claim 8, characterized in that: The supporting wires are located at the peaks and valleys of each fold of the filter membrane.

10. The tangential flow filtration device according to claim 6, characterized in that: The filter membrane is fixed to the outer side of the hollow support column by bonding.

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