A filtration concentration system based on pipe quantification of tangential flow filtration

Abstract

This invention proposes a filtration and concentration system based on pipeline-based quantitative tangential flow filtration. It includes a main inlet pipe with a circulation pump. A filter is installed on the main inlet pipe at the outlet end of the circulation pump. The outlet end of the main inlet pipe is connected to the inlet end of a tangential flow filtration membrane pack. The return end of the tangential flow filtration membrane pack is connected to the inlet end of an outlet main pipe. The outlet end of the outlet main pipe is connected to the inlet end of a tubular container. The outlet end of the tubular container is connected to the main inlet pipe via pipes. The connection point is located on the main inlet pipe on the side of the filter's outlet end. The permeate end of the tangential flow filtration membrane pack is connected to a drain pipe. In use, the filter can be used for filtration, and the tubular container replaces part of the product tank's function as a circulation tank. This invention has the advantages of increased membrane flux and improved processing efficiency of biological products.

Description

Technical Field

[0001] This utility model relates to filtration systems in the fields of biopharmaceutical production, chemical industry and food, and particularly to a filtration and concentration system based on pipeline quantitative tangential flow filtration. Background Technology

[0002] The processing of biological products involves multiple steps, such as filtration, concentration, and displacement. During filtration, viruses in the biological product need to be filtered out to achieve safety. Current virus removal methods rely on physical interception, using virus-removing filtration membrane technology to achieve sanitary standards. Therefore, virus removal filtration and concentration are separate processing units in the process. The applicant's prior patent application, titled "A Tangential Flow Filtration System for Quantitative Flow Without Stirring Pipes," application number 202411554280.0, eliminates the need for the tank container to function as a circulation tank, removing the need for stirring and weighing devices at the bottom of the tank, resulting in a compact structure; it also prevents reverse mixing, achieving smooth fluid flow and increasing throughput.

[0003] The drawback of existing technology is that filtering and concentration, such as those for viruses, are handled by separate modules. Utility Model Content

[0004] To overcome the shortcomings of the prior art, this utility model provides a filtration and concentration system based on pipeline quantitative tangential flow filtration, which can realize virus filtration and concentration replacement processes, and improve the efficiency of biological product processing.

[0005] To achieve the above objectives, the technical solution adopted by this utility model is as follows:

[0006] To address the aforementioned technical problems, the first aspect of this utility model discloses a filtration and concentration system based on pipeline quantitative tangential flow filtration, comprising a main inlet pipe, a circulation pump installed on the main inlet pipe, a filter installed on the main inlet pipe at the outlet end of the circulation pump, the outlet end of the main inlet pipe connected to the inlet end of a tangential flow filter membrane, the return end of the tangential flow filter membrane connected to the inlet end of an outlet main pipe, the outlet end of the outlet main pipe connected to the inlet end of a tubular container, the outlet end of the tubular container connected to the main inlet pipe via pipes, the connection point being located on the main inlet pipe on the side of the outlet end of the filter, and the permeation end of the tangential flow filter membrane connected to a drain pipe.

[0007] In some embodiments, the tubular container is a coiled or folded tube or pipe.

[0008] In some embodiments, the diameter of the tubular container is no more than twice the diameter of the main outlet pipe.

[0009] In some embodiments, a regulating pump is provided on the liquid outlet pipe.

[0010] In some embodiments, the inlet end of the tubular container is connected to a branch pipe, and a valve is installed on the pipe.

[0011] In some embodiments, the outlet end of the tubular container is connected to the collection end via a pipe.

[0012] In some embodiments, a mixer is provided on the main inlet pipe, and the mixer is located between the outlet end of the tubular container and the connection point of the main inlet pipe and the outlet end of the main outlet pipe.

[0013] The beneficial effects of this utility model are:

[0014] This invention features a filter installed on one side of the circulating pump for filtration, which can intercept substances larger than the membrane pore size (such as virus particles). At the same time, a tubular container is used to replace the product tank as part of the circulating tank, which also brings about reverse mixing in the circulating tank. This increases the membrane flux, allowing the system to complete concentration more quickly. This combines filtration (except for virus filtration) with quantitative tangential flow filtration in pipelines, improving the processing efficiency of biological products. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of the structure of this utility model.

[0016] Figure 2 This is a schematic diagram of the structure of Embodiment 1 of this utility model.

[0017] Figure 3 This is a structural schematic diagram of Embodiment 2 of the present invention. Detailed Implementation

[0018] The present invention will now be further described with reference to the accompanying drawings.

[0019] The technical content of this utility model is illustrated below through specific embodiments. Those skilled in the art can easily understand other advantages and effects of this utility model from the content disclosed in this specification. This utility model can also be implemented or applied through other different specific embodiments. Those skilled in the art can make various modifications and changes without departing from the spirit of this utility model.

[0020] Before detailing the specific embodiments of this disclosure, some terms used in this disclosure will be explained first.

[0021] Unless otherwise defined below, all technical and scientific terms used herein are intended to have the same meaning as commonly understood by one of ordinary skill in the art. References to technical terms herein refer to techniques commonly understood in the art, including variations or equivalent substitutions of techniques obvious to one of ordinary skill in the art. While it is believed that the following terms will be well understood by one of ordinary skill in the art, the following definitions are set forth to better explain this utility model. When trade names appear herein, they are intended to refer to the corresponding goods or services. All patents, published patent applications, and publications cited herein are incorporated herein by reference.

[0022] Terms such as “connection,” “linked,” “connected,” or “coupled” used in this article are not limited to direct connections; they also include indirect connections.

[0023] As described in this article, "biological products" refer to biological macromolecules, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids and their derivatives.

[0024] As used herein, "online monitoring" or "real-time monitoring" refers to the real-time detection of certain parameters or properties of the buffer solution, reaction fluid, or fluid exiting the flow reactor during the use of the chromatography system, such as pH, pressure, flow rate, and conductivity. Unlike offline detection or analysis, online or real-time monitoring provides immediate feedback on the detection results.

[0025] The positional terms "up," "down," "left," "right," "front," and "back" used in this article are determined based on the layout direction of the accompanying drawings in the specification. They are only used to indicate relative positional relationships. When the absolute position of the object being described changes, the relative positional relationship may also change accordingly.

[0026] This patent is applicable to laboratory-scale, pilot-scale, intermediate-scale, and large-scale production, and is suitable for the biopharmaceutical industry, which requires high value, high sensitivity, and strict aseptic conditions.

[0027] Reference Figure 1As shown, a tangential flow filtration and concentration system based on pipeline quantitative filtration includes a main inlet pipe 1, a circulation pump 2 installed on the main inlet pipe 1, and a filter 3 installed on the main inlet pipe 1 at the outlet end of the circulation pump 2. The filter membrane in the filter 3 can use a nano-sized pore size to physically filter virus particles. Substances larger than the membrane pore size are throttled, while proteins and small molecules smaller than the membrane pore size can pass through the membrane to downstream processes. A mixer 4 is installed on the main inlet pipe 1, located at the outlet end of the filter 3. The outlet end of the main inlet pipe 1 is connected to the inlet end of the tangential flow filtration membrane pack 5. The return end of the tangential flow filtration membrane pack 5 is connected to the inlet end of the main outlet pipe 6. The outlet end of the main outlet pipe 6 is connected to the inlet end of the tubular container 7. A regulating pump 13 is installed on the main outlet pipe 6. The inlet end of the tubular container 7 is connected to a branch pipe 8, and a valve 9 is installed on the branch pipe 8. The tubular container 7 is a coiled or folded tube or pipe. The diameter of the tubular container 7 is no more than twice that of the main outlet pipe. The volume of the tubular container 7 is determined based on the volume of the product in the product tank. The outlet of the tubular container 7 is connected to the main inlet pipe 1 via pipes. The connection points are located between the filter 3 and the mixer 4, and at the collection end 10. Valves 11 and 12 are respectively installed on the connecting pipes. The permeation end of the tangential flow filter membrane 5 is connected to the drain pipe 17.

[0028] Reference Figure 2As shown, Example 1 illustrates a filtration and concentration system based on tangential flow filtration with pipeline metering. This system includes a main inlet pipe 21. The inlet end of the main inlet pipe 21 is connected to a product tank 214 via a pipeline. The product tank 214 holds the biological products to be processed. A valve 215 is installed at the bottom outlet of the product tank 214. The outlet of the main inlet pipe 21 is connected to a pipeline connected to the product tank 214 via a valve 216. A circulation pump 22 is installed on the main inlet pipe 21. A filter 23 is installed on the main inlet pipe 21 at the outlet end of the circulation pump 22. The filter membrane in the filter 23 can use a nanometer-sized pore size to physically filter viral particles. Substances larger than the membrane pore size are throttled, while proteins and small molecules smaller than the membrane pore size can pass through the membrane to downstream processes. A mixer 24 is installed on the main inlet pipe 21, located at the outlet end of the filter 23. The outlet end of the main inlet pipe 21 is connected to the inlet end of the tangential flow filter membrane pack 25. The return end of the tangential flow filter membrane pack 25 is connected to the inlet end of the main outlet pipe 26. The outlet end of the main outlet pipe 26 is connected to the inlet end of the tubular container 27. A regulating pump 213 is installed on the main outlet pipe 26. The inlet end of the tubular container 27 is connected to a branch pipe 28, and a valve 29 is installed on the branch pipe 28. The tubular container 27 is a coiled or folded tube or pipe. The diameter of the tubular container 27 is no more than 22 times that of the main outlet pipe. The volume of the tubular container 27 is determined according to the volume of the product in the product tank. The outlet of the tubular container 27 is connected to the main inlet pipe 21 via pipes. The connection points are located between the filter 23 and the mixer 24, and at the collection end 210. Valves 211 and 212 are installed on the connecting pipes. The permeate end of the tangential flow filter membrane pack 25 is connected to the drain pipe 217.

[0029] In this embodiment 1, the bottom valves 215, 216, 22, 213, and 211 of the product tank 214 are opened. The biological product to be processed passes through the main inlet pipe 21 and is processed by the filter 23. Substances larger than the membrane pore size (such as virus particles) are trapped by the filter membrane, while substances smaller than the membrane pore size can pass through the membrane pores to the downstream of the filter membrane and enter the tangential flow filter membrane package 25. Some small molecule solutions permeate through the filter membrane and enter the drain pipe 217 through the permeate end of the tangential flow filter membrane package 25. Most of the biological products to be processed enter the tubular container 27 through the return port of the tangential flow filter membrane pack 25 and the main outlet pipe 26, and finally flow into the main inlet pipe 21 through the outlet end of the tubular container 27. Simultaneously, the biological products to be processed in the product tank 214 continue to output solution under the action of the circulation pump 22. This solution mixes with the biological solution in the tubular container 27 under the action of the mixer 24 and then enters the tangential flow filter membrane pack 25. Thus, a loop is formed between the tangential flow filter membrane pack 25 and the tubular container 27. The circulation pump 22 provides the tangential flow rate, and its speed is adjusted according to the set flow rate requirements to reach a steady state. The regulating pump 213 is used to increase suction to actively control the tangential flow rate, providing suction on the membrane of the tangential flow filter membrane pack 25 for sensitive and active control of the tangential flow. When the product liquid reaches the end of the concentration process, the circulation pump 22 and the regulating pump 213 are stopped, and the bottom valves 215, 216, and 211 of the product tank 214 are closed. The product is concentrated using a pipeline quantitative method for product recovery. At this time, valves 29 and 212 are opened, and pressure is applied to allow the product to flow from the tubular container 27 into the collection end 210 for collection.

[0030] Reference Figure 3As shown, Example 2 is a filtration and concentration system based on tangential flow filtration with pipeline metering. It includes a main inlet pipe 31, whose inlet end is connected to the outlet ends of a product tank 314 and a replacement tank 318 via pipes. A valve 315 is installed at the bottom outlet of the product tank 314, and the outlet of the main inlet pipe 31 is connected to the pipe connected to the product tank 314 via a valve 316. A valve 319 is installed at the bottom outlet of the replacement tank 318, and the outlet of the main inlet pipe 31 is connected to the pipe connected to the replacement tank 318 via a valve 320. A circulation pump 32 is installed on the main inlet pipe 31, and a filter 33 is installed at the outlet end of the main inlet pipe 31 of the circulation pump 32. The filter membrane in the filter 33 can use a nano-sized pore size to physically filter virus particles. Substances larger than the membrane pore size are throttled, while proteins and small molecules smaller than the membrane pore size can pass through the membrane to downstream processes. A mixer 34 is installed on the main inlet pipe 31, located at the outlet end of the filter 33. The outlet end of the main inlet pipe 31 is connected to the inlet end of the tangential flow filter membrane pack 35. The return end of the tangential flow filter membrane pack 35 is connected to the inlet end of the main outlet pipe 36. The outlet end of the main outlet pipe 36 is connected to the inlet end of the tubular container 37. A regulating pump 313 is installed on the main outlet pipe 36. The inlet end of the tubular container 37 is connected to a branch pipe 38, and a valve 39 is installed on the branch pipe 38. The tubular container 37 is a coiled or folded tube or pipe. The diameter of the tubular container 37 is no more than 32 times that of the main outlet pipe. The volume of the tubular container 37 is quantitatively determined according to the volume of the product in the product tank. The outlet of the tubular container 37 is connected to the main inlet pipe 31 via pipes, with the connection points located between the filter 33 and the mixer 34, and at the collection end 310. Valves 311 and 312 are respectively installed on the connecting pipes. The permeate end of the tangential flow filter membrane pack 25 is connected to the drain pipe 317.

[0031] In this embodiment 2, the bottom valves 315, 316, 32, 313, and 311 of the product tank 314 are opened. The biological product to be processed passes through the main inlet pipe 31 and is processed by the filter 33. Substances larger than the membrane pore size (such as virus particles) are trapped by the filter membrane, while substances smaller than the membrane pore size can pass through the membrane pores to the downstream of the filter membrane and enter the tangential flow filter membrane package 35. Some small molecule solutions permeate through the filter membrane and enter the drain pipe 317 through the permeate end of the tangential flow filter membrane package 35. Most of the biological products to be processed enter the tubular container 37 through the return port of the tangential flow filter membrane pack 35 and the main outlet pipe 36, and finally flow into the main inlet pipe 31 through the outlet end of the tubular container 37. Simultaneously, the biological products to be processed in the product tank 314 continue to output solution under the action of the circulation pump 32. This solution mixes with the biological solution in the tubular container 37 under the action of the mixer 34 and then enters the tangential flow filter membrane pack 35. Thus, a loop is formed between the tangential flow filter membrane pack 35 and the tubular container 37. The circulation pump 32 provides the tangential flow rate, and its speed is adjusted according to the set flow rate requirements to reach a steady state. The regulating pump 313 is used to increase suction to actively control the tangential flow rate, providing suction on the membrane of the tangential flow filter membrane pack 35 for sensitive and active control of the tangential flow. When fresh buffer needs to be added, valves 6 (319) and 7 (320) at the bottom outlet of the replacement tank 318 are opened, allowing the buffer solution to enter the main inlet pipe 31. When the product liquid reaches the end of the replacement process, stop the circulation pump 32 and the regulating pump 313, and close the bottom valves 315, 316, 311, 319 and 320 of the product tank 314. At this time, open valves 39 and 312, and pressurize the product so that it flows from the tubular container 37 into the collection end 310 for collection.

Claims

1. A filtration and concentration system based on tangential flow filtration with quantitative pipeline measurement, characterized in that, The system includes a main inlet pipe, a circulation pump mounted on the main inlet pipe, a filter mounted on the main inlet pipe at the outlet end of the circulation pump, the outlet end of the main inlet pipe connected to the inlet end of a tangential flow filter membrane, the return end of the tangential flow filter membrane connected to the inlet end of the main outlet pipe, the outlet end of the main outlet pipe connected to the inlet end of a tubular container, the outlet end of the tubular container connected to the main inlet pipe via pipes, the connection point being located on the main inlet pipe on the side of the outlet end of the filter, and the permeation end of the tangential flow filter membrane connected to a drain pipe.

2. The filtration and concentration system based on tangential flow filtration with pipeline metering according to claim 1, characterized in that, The tubular container is made of coiled or folded tubing.

3. The filtration and concentration system based on tangential flow filtration with pipeline metering according to claim 2, characterized in that, The diameter of the tubular container is no more than twice that of the main outlet pipe.

4. The filtration and concentration system based on tangential flow filtration with pipeline metering according to claim 1, characterized in that, A regulating pump is installed on the drainage pipeline.

5. The filtration and concentration system based on tangential flow filtration with pipeline metering according to claim 1, characterized in that, The tubular container has a branch pipe connected to its inlet end, and a valve is installed on the pipe.

6. The filtration and concentration system based on tangential flow filtration with pipeline metering according to claim 1, characterized in that, The outlet end of the tubular container is connected to the collection end via a pipe.

7. The filtration and concentration system based on tangential flow filtration with pipeline metering according to claim 1, characterized in that, A mixer is installed on the main inlet pipe, and the mixer is located between the liquid outlet end of the tubular container and the connection point of the main inlet pipe and the outlet end of the main outlet pipe.

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