Quantitative tangential flow filtering system without stirring pipeline

Abstract

The invention provides a quantitative tangential flow filtering system without a stirring pipeline, which comprises a product tank, a bottom outlet of the product tank is connected with a liquid inlet main pipeline through a pipeline, a circulating pump is arranged on the liquid inlet main pipeline, and an outlet end of the liquid inlet main pipeline is connected with a liquid inlet end of a tangential flow filtering membrane bag. A backflow end of the tangential flow filtering membrane bag is connected with a liquid outlet main pipeline, the liquid outlet main pipeline is connected with a liquid inlet end of a tubular container, a liquid outlet end of the tubular container is respectively connected with the liquid inlet main pipeline and a collection end through pipelines, and a permeation end of the tangential flow filtering membrane bag is connected with a liquid discharge pipeline; during use, the tubular container replaces a product tank to serve as a part of functions of a circulation tank, and meanwhile reverse mixing of the circulation tank is brought about; the membrane has the advantages that the flux of the membrane is improved, and concentration and re-filtration can be completed more quickly.

Description

Technical Field

[0001] The invention relates to a filtering system in the fields of biomedicine production, chemical industry and food, and in particular to a tangential flow filtering system without the need for stirring pipeline quantitative filtering. Background Art

[0002] The most common filtration in downstream biopharmaceuticals is tangential flow filtration or TFF, which is mainly used for clarification, product concentration and buffer filtration. Figure 1 The existing tangential flow filtration system mainly includes a tank container, and the bottom of the tank container is provided with an agitator and a weighing device. The bottom of the tank container is connected to the inlet of the tangential flow module through a pump, and the reflux end of the tangential flow module is connected to the inlet of the tank container through a pipeline, and the permeate end is connected to the collection container. Therefore, in the above components, the tank container plays the role of a circulation tank, and the product liquid enters the tangential flow filtration module through the circulation pump, and then returns to the tank body through the reflux end, thereby achieving the purpose of concentration and filtration.

[0003] The defects of the tangential flow filtration system in the prior art are: it is necessary to add a stirring device and a weighing device at the bottom of the tank container; when the tank container is used as a circulation tank, serious reverse mixing will occur when the liquid at the reflux end enters the tank, which is not conducive to the flux of the tangential flow filtration module; since the overall structure of the system is not compact, it is not conducive to cleaning and sterilization; the product yield is low. Summary of the invention

[0004] In order to overcome the deficiencies of the above-mentioned prior art, the present invention provides a tangential flow filtration system that does not require a stirring pipeline for quantitative filtering, which can make the tank container no longer serve as a circulation tank, and there is no need to add a stirring device and a weighing device at the bottom of the tank, so that the structure is compact; there will be no reverse mixing, and the fluid can be pushed horizontally, thereby improving the flux.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] In view of the above technical problems, the first aspect of the present invention discloses a quantitative tangential flow filtration system without stirring pipeline, comprising a product tank, the bottom outlet of the product tank is connected to the liquid inlet main pipeline through a pipeline, the liquid inlet main pipeline is provided with a circulation pump, the outlet end of the liquid inlet main pipeline is connected to the liquid inlet end of the tangential flow filtration membrane package, the reflux end of the tangential flow filtration membrane package is connected to the liquid outlet main pipeline, the liquid outlet main pipeline is connected to the liquid inlet end of the tubular container, the liquid outlet end of the tubular container is respectively connected to the liquid inlet main pipeline and the collecting end through pipelines, and the permeate end of the tangential flow filtration membrane package is connected to the discharge pipeline.

[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 greater than twice the diameter of the liquid outlet main pipe and / or the liquid inlet main pipe.

[0009] In some embodiments, a mixer is provided on the liquid inlet main pipeline, and the connecting end between the liquid outlet end of the tubular container and the liquid inlet main pipeline is located between the circulation pump and the mixer.

[0010] In some embodiments, a regulating pump is provided on the liquid outlet pipeline.

[0011] In some embodiments, the liquid inlet end of the tubular container is connected to a bypass pipeline, and a valve is provided on the pipeline.

[0012] In some embodiments, the liquid inlet port of the liquid inlet main pipeline is connected to the displacement tank through a pipeline.

[0013] In some embodiments, valves are respectively provided on the liquid outlet of the product tank and the connecting pipeline.

[0014] In some embodiments, valves are respectively provided on the liquid port of the displacement tank and the connecting pipeline.

[0015] Beneficial effects of the present invention:

[0016] 1. A tubular container is connected between the liquid inlet and reflux ends of the tangential flow filtration membrane package of the present invention, which replaces the product tank as part of the function of the circulation tank and brings about reverse mixing in the circulation tank, which will increase the flux of the membrane, so that the system can complete concentration and re-filtration faster.

[0017] 2. Compared with tubular containers and tank circulation, the consumption and time of cleaning and sterilization are greatly reduced.

[0018] 3. The product tank is only used to fill the product liquid, and does not need to have bottom stirring and weighing functions, making the overall structure compact.

[0019] 4. The volume of the tubular container is quantified according to the volume of the product in the product tank, so different pipeline quantifications can be configured to improve the flexibility and convenience of the process.

[0020] 5. The product concentration at the liquid inlet end of the tubular container is greater than the concentration at the liquid outlet end of the tubular container. The solution is pushed flat in the tubular container, which is more conducive to the filtration of the product.

[0021] Instruction Manual

[0022] Figure 1 It is a structural schematic diagram of a tangential flow filtration system in the prior art.

[0023] Figure 2 This is a schematic diagram of the structure of Example 1 of the present invention.

[0024] Figure 3 This is a schematic diagram of the structure of Example 2 of the present invention.

[0025] Figure 4 This is a schematic diagram of the structure of Example 3 of the present invention.

[0026] Figure 5 This is a schematic diagram of the structure of Example 4 of the present invention. DETAILED DESCRIPTION

[0027] The present invention will be further described below in conjunction with the accompanying drawings.

[0028] The technical content of the present invention is described below by specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention 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 the present invention.

[0029] Before describing the specific embodiments of the present disclosure in detail, some terms used in the present disclosure are first explained.

[0030] Unless otherwise defined below, the meaning of all technical terms and scientific terms used herein is intended to be the same as those commonly understood by those skilled in the art. Mentioning the technology used in this article is intended to refer to the technology commonly understood in the art, including those changes in technology that are obvious to those skilled in the art or the replacement of equivalent technology. Although it is believed that the following terms are well understood by those skilled in the art, the following definitions are still set forth to better explain the present invention. When a trade name appears in this article, it is intended to refer to the corresponding commodity. All patents, published patent applications and publications cited herein are incorporated herein by reference.

[0031] As used herein, the terms “connected”, “connected”, “connected” or “coupled” and the like are not limited to direct connections but also include indirect connections.

[0032] As used herein, "products" are biomolecules, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids and their derivatives.

[0033] As used herein, the term "online monitoring" or "real-time monitoring" refers to real-time detection of certain parameters or properties of buffers, reaction fluids, and fluids flowing out of flow reactors during use of the chromatography system, such as pH, pressure, flow rate, conductivity, etc. Unlike offline detection or analysis, online monitoring or real-time monitoring can provide real-time feedback of the detection results.

[0034] The position relationship words "up", "down", "left", "right", "front", "back", etc. involved in this article are determined according to the layout direction of the drawings in the specification. They are only used to indicate relative position relationships. When the absolute position of the object being described changes, the relative position relationship may also change accordingly.

[0035] The application scenarios of this patent are laboratory scale, small-scale trials, pilot tests and large-scale production, and are suitable for the biopharmaceutical industry with high value, high sensitivity and strict sterility requirements.

[0036] Reference Figure 2 As shown, Example 1 is a tangential flow filtration system that does not require a stirring pipeline for quantitative measurement, comprising a product tank 1, a valve one 2 is arranged at the bottom of the product tank, the outlet end of the product tank 1 is connected to a liquid inlet main pipeline 3 through a connecting pipeline, a valve two 4 is arranged on the connecting pipeline, a circulation pump 5 and a mixer 6 are arranged on the liquid inlet main pipeline 3, the liquid outlet end of the liquid inlet main pipeline 3 is connected to the liquid inlet end of a tangential flow filtration membrane package 7, the reflux end of the tangential flow filtration membrane package 7 is connected to the liquid inlet end of a tubular container 10 through a liquid outlet main pipeline 8, a regulating pump 9 is arranged on the liquid outlet main pipeline 8, the liquid outlet ends of the tubular containers 10 are respectively connected to the liquid inlet main pipeline 3 through connecting pipes, the connection points are located between the circulation pump 5 and the mixer 6, and are connected to the collecting end 12, and valve three 13 and valve four 11 are respectively arranged on the connecting pipelines. The liquid inlet end of the tubular container 10 is also connected to the branch pipe 14, and a valve 5 15 is provided on the branch pipe 14. The tubular container 10 is a coiled or folded tube or pipe, and the coiling and folding direction is horizontal. The diameter of the tubular container is not more than twice the main liquid outlet pipe, and the volume of the tubular container is quantitatively determined according to the volume of the product in the product tank. The permeation end of the tangential flow filtration membrane package 7 is connected to the discharge pipe 16.

[0037] When the present embodiment 1 is used, the valve 1 2, the valve 2 4, the circulation pump 5, the regulating pump 9 and the valve 3 13 at the bottom of the product tank 1 are opened, and the product liquid enters the tangential flow filtration membrane package 7 after passing through the liquid inlet main pipeline 3, and part of the small molecule solution passes through the filter membrane and enters the liquid discharge pipeline 16, and the remaining material passes through the reflux port of the tangential flow filtration membrane package 7 through the liquid outlet main pipeline 8 and enters the canned container 10, and then merges into the bamboo liquid inlet main pipeline 3; then the product liquid in the product tank 1 outputs the solution through the circulation pump 5, and enters the tangential flow filtration membrane package 7 again under the mixing action of the material in the tubular container by the mixer 6, so that a loop is formed between the tangential flow filtration membrane package 7 and the tubular container, and the circulation pump 2 provides the tangential flow velocity. According to the set flow rate requirement, the speed of the circulation pump 2 is adjusted to achieve the set flow rate and reach a steady state, and the regulating pump 9 is used to increase the suction to actively control the tangential flow velocity, which can provide the suction on the membrane of the tangential flow filtration membrane package 7 and sensitively actively control the tangential flow. When the product liquid reaches the end point of the concentration process, the circulation pump 2 and the regulating pump 9 are stopped, and the tank bottom valve 1 2, valve 2 4, circulation and valve 3 13 are closed. The product is concentrated in a pipeline quantitative manner and the product is recovered. At this time, valve 5 15 and valve 4 11 are opened to pressurize the product so that it flows from the tubular container 10 into the collection end 12 for collection.

[0038] Reference Figure 3 As shown, Example 2 is a tangential flow filtration system that does not require a stirring pipeline for quantitative filtering, including a product tank 21, a valve one 22 is arranged at the bottom of the product tank, the outlet end of the product tank 21 is connected to a liquid inlet main pipeline 23 through a connecting pipeline, a valve two 24 is arranged on the connecting pipeline, a circulation pump 25 and a mixer 26 are arranged on the liquid inlet main pipeline 23, the liquid outlet end of the liquid inlet main pipeline 23 is connected to the liquid inlet end of a tangential flow filtration membrane package 27, the reflux end of the tangential flow filtration membrane package 27 is connected to the liquid inlet end of a tubular container 210 through a liquid outlet main pipeline 28, a regulating pump 29 is arranged on the liquid outlet main pipeline 28, the liquid outlet ends of the tubular containers 210 are respectively connected to the liquid inlet main pipeline 23 through connecting pipes, the connection points are located between the circulation pump 25 and the mixer 26, and are connected to the collecting end 212, and valve three 213 and valve four 211 are respectively arranged on the connecting pipelines. The liquid inlet end of the tubular container 210 is also connected to a branch pipe 214, and a valve 5 215 is provided on the branch pipe 214. The tubular container 210 is a coiled or folded tube or pipe, and the coiling and folding direction is vertical. The diameter of the tubular container is not more than twice the main liquid outlet pipe, and the volume of the tubular container is quantitatively determined according to the volume of the product in the product tank. The permeation end of the tangential flow filtration membrane package 27 is connected to the discharge pipe 216.

[0039] Reference Figure 4As shown, Example 3 is a tangential flow filtration system that does not require a stirring pipeline for quantitative filtering, including a product tank 31, a valve one 32 is arranged at the bottom of the product tank, the outlet end of the product tank 31 is connected to the liquid inlet main pipeline 23 through a connecting pipeline, a valve two 34 is arranged on the connecting pipeline, a circulation pump 35 and a mixer 36 are arranged on the liquid inlet main pipeline 33, the liquid outlet end of the liquid inlet main pipeline 33 is connected to the liquid inlet end of the tangential flow filtration membrane package 37, the reflux end of the tangential flow filtration membrane package 37 is connected to the liquid inlet end of the tubular container 310 through the liquid outlet main pipeline 38, a regulating pump 39 is arranged on the liquid outlet main pipeline 38, the liquid outlet ends of the tubular containers 310 are respectively connected to the liquid inlet main pipeline 33 through connecting pipes, the connection points are located between the circulation pump 35 and the mixer 36, and are connected to the collecting end 312, and valve three 313 and valve four 31 are respectively arranged on the connecting pipelines. The liquid inlet end of the tubular container 310 is also connected to a branch pipe 314, and a valve 5 315 is provided on the branch pipe 314. The tubular container 310 is a coiled or folded tube or pipe, and the coiling and folding direction has a certain angle with the horizontal direction. The diameter of the tubular container is not more than twice the main liquid outlet pipe, and the volume of the tubular container is quantitatively determined according to the volume of the product in the product tank. The permeation end of the tangential flow filtration membrane package 37 is connected to the discharge pipe 316.

[0040] Reference Figure 5 As shown, Example 4 is a tangential flow filtration system that does not require a stirring pipeline for quantitative flow, including a product tank 41 and a displacement tank 417, a valve one 42 is provided at the bottom of the product tank, the outlet end of the product tank 41 is connected to the liquid inlet main pipeline 43 through a connecting pipeline, and a valve two 44 is provided on the connecting pipeline; a valve six 418 is provided at the bottom of the displacement tank 417, the outlet end of the displacement tank 417 is connected to the liquid inlet main pipeline 43 through a connecting pipeline, and a valve seven 419 is provided on the connecting pipeline. The main liquid inlet pipe 43 is provided with a circulation pump 45, a mixer 46, a pressure sensor 420 and a flow meter 421. The liquid outlet end of the main liquid inlet pipe 43 is connected to the liquid inlet end of the tangential flow filtration membrane package 47. The reflux end of the tangential flow filtration membrane package 47 is connected to the liquid inlet end of the tubular container 410 through the main liquid outlet pipe 48. The main liquid outlet pipe 48 is provided with a regulating pump 49. The liquid outlet end of the tubular container 410 is respectively connected to the main liquid inlet pipe 43 through a connecting pipe, and the connection point is located between the circulation pump 45 and the mixer 46, and connected to the collecting end 412. The connecting pipes are respectively provided with valves 3 413 and 4 41. The liquid inlet end of the tubular container 410 is also connected to the side branch pipe 414, and the side branch pipe 414 is provided with valve 5 415. The tubular container 410 adopts a coiled or folded tube or pipe. The diameter of the tubular container is not more than twice that of the main liquid outlet pipe. The volume of the tubular container is quantitatively determined according to the volume of the product in the product tank. The permeate end of the tangential flow filtration membrane package 47 is connected to the drainage pipe 416 .

[0041] When this embodiment 4 is used, valve 1 42, valve 2 44, circulation pump 45, regulating pump 49 and valve 3 413 at the bottom of product tank 1 are opened, and the product liquid enters into the tangential flow filtration membrane package 47 after passing through the liquid inlet main pipeline 43, and part of the small molecule solution passes through the filter membrane and enters into the liquid discharge pipeline 416, and the remaining material passes through the reflux port of the tangential flow filtration membrane package 47 through the liquid outlet main pipeline 48 and enters into the canned container 410, and then merges into the bamboo liquid inlet main pipeline 43; then the product liquid in the product tank 41 passes through the bamboo liquid inlet main pipeline 43; The solution is outputted through the circulation pump 45, and then enters the tangential flow filtration membrane package 47 under the mixing action of the material in the tubular container in the mixer 46, so that a loop is formed between the tangential flow filtration membrane package 47 and the tubular container. The circulation pump 42 provides the tangential flow velocity. According to the set flow rate requirement, the speed of the circulation pump 2 is adjusted to achieve the set flow rate and reach a steady state. The regulating pump 49 is used to increase the suction to actively control the tangential flow velocity, which can provide suction on the membrane of the tangential flow filtration membrane package 47 and sensitively actively control the tangential flow. When fresh buffer needs to be added, the valve six 418 and the valve seven 419 at the bottom of the displacement tank 417 are opened, and the buffer enters the main liquid inlet pipeline 43.

[0042] The main liquid inlet pipeline 43 is provided with a pressure sensor 420 and a flow meter 421 for real-time monitoring of pressure and fluid flow, and adjusting the suction force of the regulating pump 49 by the actual transmembrane pressure difference, so as to achieve the required transmembrane pressure difference.

[0043] When the product liquid reaches the end point of the concentration process, the circulation pump 42 and the regulating pump 49 are stopped, and the tank bottom valve 1 42, valve 2 44, valve 3 43, valve 6 418 and valve 7 419 are closed. The product is concentrated in a pipeline quantitative manner and the product is recovered. At this time, valve 5 45 and valve 41 are opened to pressurize the product so that it flows from the tubular container 410 into the collection end 412 for collection.

Claims

1. A tangential flow filtration system without stirring pipeline quantitative, characterized in that: It includes a product tank, the bottom outlet of the product tank is connected to the liquid inlet main pipeline through a pipeline, the liquid inlet main pipeline is provided with a circulation pump, the outlet end of the liquid inlet main pipeline is connected to the liquid inlet end of the tangential flow filtration membrane package, the reflux end of the tangential flow filtration membrane package is connected to the liquid outlet main pipeline, the liquid outlet main pipeline is connected to the liquid inlet end of the tubular container, the liquid outlet end of the tubular container is respectively connected to the liquid inlet main pipeline and the collecting end through pipelines, and the permeate end of the tangential flow filtration membrane package is connected to the discharge pipeline.

2. A tangential flow filtration system without stirring pipeline quantitative according to claim 1, characterized in that: The tubular container is a coiled or folded tube or pipe.

3. A tangential flow filtration system without stirring pipeline quantitative according to claim 2, characterized in that: The diameter of the tubular container is not greater than twice the diameter of the liquid outlet main pipeline and / or the liquid inlet main pipeline.

4. The tangential flow filtration system without stirring pipeline quantitative according to claim 1, characterized in that: The liquid inlet main pipeline is provided with a mixer, and the connecting end between the liquid outlet end of the tubular container and the liquid inlet main pipeline is located between the circulation pump and the mixer.

5. The tangential flow filtration system without stirring pipeline quantitative according to claim 1, characterized in that: A regulating pump is arranged on the liquid outlet pipeline.

6. The tangential flow filtration system without stirring pipeline quantitative according to claim 1, characterized in that: The liquid inlet end of the tubular container is connected with a side branch pipeline, and a valve is arranged on the pipeline.

7. The tangential flow filtration system without stirring pipeline quantitative according to claim 1, characterized in that: The liquid inlet port of the liquid inlet main pipeline is connected to the displacement tank through a pipeline.

8. The tangential flow filtration system without stirring pipeline quantitative according to claim 7, characterized in that: The liquid port of the displacement tank and the connecting pipeline are respectively provided with valves.

9. The tangential flow filtration system without stirring pipeline quantitative according to claim 1, characterized in that: The liquid outlet of the product tank and the connecting pipeline are respectively provided with valves.

Images