System for tangential flow control, chromatography system and filtration system

Abstract

The invention provides a system for tangential flow control, a chromatography system and a filtering system thereof, the system comprises a first liquid inlet main pipeline, a liquid inlet pump is arranged on the first liquid inlet main pipeline, and the outlet end of the first liquid inlet main pipeline is connected with an inlet pipeline of a mounting module through a valve; a first outlet pipeline of the mounting module is connected with the inlet end of a second liquid inlet main pipeline, an adjusting pump is arranged on the second liquid inlet main pipeline, and the outlet end of the second liquid inlet main pipeline is communicated with a first liquid inlet main pipeline through a valve; a second outlet pipeline of the mounting module is connected with the inlet end of the first liquid outlet main pipeline through a valve; a tangential flow chromatographic column and a tangential flow filtering membrane bag can be replaced in the mounting module; during use, the suction force is increased through the adjusting pump arranged on the second liquid inlet main pipeline; the method has the advantages that the flow speed of tangential flow can be actively controlled, and the sensitivity of tangential flow control is improved.

Description

Technical Field

[0001] The invention relates to the technical fields of biology, medicine and food, and in particular to a system for tangential flow control, a chromatography system and a filtering system thereof. Background Art

[0002] Existing separation technologies for downstream biopharmaceuticals involve chromatography and filtration, and tangential flow filtration is often used for material concentration, buffering, and displacement. Therefore, the tangential flow filtration in the prior art includes a tangential flow filtration membrane package, a circulation pump, and a circulation tank. The bottom outlet of the circulation tank is connected to the inlet of the tangential flow filtration membrane package through a circulation pump, the reflux end of the membrane package is connected to the inlet of the circulation tank through a regulating valve, and the permeate end of the membrane package is connected to the collection pipe. Therefore, there are the following disadvantages: first, a higher pressure drop will be generated at both ends of the regulating valve; second, the flow rate at the reflux end cannot be effectively controlled; third, the flow rate is only provided by the circulation pump for tangential flow. Since the requirement of TMP requires the circulation pump to provide a higher pressure, a higher head is required. Summary of the invention

[0003] In order to overcome the deficiencies of the prior art, the present invention provides a system for tangential flow control, a chromatography system and a filtration system thereof, which can actively control the tangential flow velocity, improve sensitivity, and avoid the pressure drop caused by the use of a regulating valve.

[0004] In order to meet the above requirements, the technical solution adopted by the present invention is:

[0005] In response to the above technical problems, the first aspect of the present invention discloses a system for tangential flow control, comprising a first liquid inlet main pipeline, on which a liquid inlet pump is provided, the outlet end of the first liquid inlet main pipeline is connected to the inlet pipeline of the installation module through a valve, the first outlet pipeline of the installation module is connected to the inlet end of the second liquid inlet main pipeline, the second liquid inlet main pipeline is provided with a regulating pump, the outlet end of the second liquid inlet main pipeline is connected to the first liquid inlet main pipeline through a valve; the second outlet pipeline of the installation module is connected to the inlet end of the first liquid outlet main pipeline through a valve.

[0006] Furthermore, a filter module is provided on the second liquid inlet main pipe, one end of the second liquid inlet main pipe is connected to the filter via a connecting pipe, and the other end of the filter is connected via a connecting pipe.

[0007] Furthermore, the outlet end of the second liquid inlet main pipeline is connected to a bypass liquid outlet pipeline through a valve.

[0008] Furthermore, the outlet end of the first liquid inlet main pipeline is connected to the inlet end of the first liquid outlet main pipeline through a connecting pipeline, and a valve is provided on the connecting pipeline.

[0009] Furthermore, the first liquid inlet main pipeline and / or the second liquid inlet main pipeline are provided with a pressure sensor and / or a flow sensor.

[0010] Furthermore, the first liquid outlet main pipeline is provided with a UV sensor and / or a conductivity transmitter and / or a pH sensor.

[0011] In view of the above technical problems, the second aspect of the present invention discloses a chromatography system for tangential flow control, comprising a liquid inlet main pipeline, a liquid inlet pump and a bubble trap are arranged on the first liquid inlet main pipeline, the outlet end of the first liquid inlet main pipeline is connected to the inlet end of the tangential flow chromatography column through a valve, the reflux end of the tangential flow chromatography column is connected to the inlet end of the second liquid inlet main pipeline through a pipeline, the second liquid inlet main pipeline is provided with a regulating pump, the outlet end of the second liquid inlet main pipeline is respectively connected to the first liquid inlet main pipeline and the bypass liquid outlet pipeline through a valve; the outlet end of the tangential flow chromatography column is connected to the inlet end of the first liquid outlet main pipeline through a valve.

[0012] Furthermore, the outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline are connected through a connecting pipeline, and a valve is provided on the connecting pipeline.

[0013] Furthermore, a rectangular valve array is arranged between the outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline, and the rectangular valve array is composed of four valves connected in the first position. The outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline are connected to a group of opposite sides of the rectangular valve array, and the other group of opposite sides of the rectangular valve array are respectively connected to the inlet end and the top outlet end of the tangential flow chromatography column.

[0014] Furthermore, a rectangular valve array is provided on the second liquid inlet main pipeline, and the rectangular valve array is composed of four valves connected in the first position. The second liquid inlet main pipeline is connected to a group of opposite sides of the rectangular valve array, and valves are provided on the second liquid inlet main pipeline between the group of opposite sides. The other group of opposite sides of the rectangular valve array are respectively connected to the inlet and outlet at both ends of the filter.

[0015] Furthermore, the first liquid inlet main pipeline and / or the second liquid inlet main pipeline are provided with a pressure sensor and / or a flow sensor.

[0016] Furthermore, the first liquid outlet main pipeline is provided with a UV sensor and / or a conductivity transmitter and / or a pH sensor.

[0017] In response to the above technical problems, the third aspect of the present invention discloses a filtration system for tangential flow control, comprising a liquid inlet main pipeline, a liquid inlet pump is arranged on the first liquid inlet main pipeline, the outlet end of the first liquid inlet main pipeline is connected to the inlet end of the tangential flow filtration membrane package through a valve, the reflux port of the tangential flow filtration membrane package is connected to the inlet end of the second liquid inlet main pipeline through a connecting pipeline, the second liquid inlet main pipeline is provided with a regulating pump, the outlet end of the second liquid inlet main pipeline is respectively connected to the first liquid inlet main pipeline and the bypass liquid outlet pipeline through a valve; the permeation port of the tangential flow filtration membrane package is connected to the inlet end of the first liquid outlet main pipeline through a connecting pipeline.

[0018] Furthermore, the outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline are connected through a connecting pipeline, and a valve is provided on the connecting pipeline.

[0019] Furthermore, a rectangular valve array is arranged between the outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline, and the rectangular valve array is composed of four valves connected in the first position. The outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline are connected to a group of opposite sides of the rectangular valve array, and the other group of opposite sides of the rectangular valve array are respectively connected to the inlet end and the top outlet end of the tangential flow chromatography column.

[0020] Furthermore, the first liquid inlet main pipeline and / or the second liquid inlet main pipeline are provided with a pressure sensor and / or a flow sensor.

[0021] Furthermore, the first liquid outlet main pipeline is provided with a UV sensor and / or a conductivity transmitter and / or a pH sensor.

[0022] Beneficial effects of the present invention:

[0023] The second liquid inlet main pipeline connected to the reflux end of the present invention is provided with a regulating pump. The suction force is increased by the regulating pump, so that the flow rate of the tangential flow can be actively controlled, thereby improving the sensitivity of the tangential flow control.

[0024] Instruction Manual

[0025] Figure 1 Schematic diagram of the structure of embodiment 1 of the tangential flow control system of the present invention

[0026] Figure 2 It is a schematic structural diagram of the tangential flow chromatography system of the present invention.

[0027] Figure 3 It is a schematic structural diagram of the tangential flow filtration system of the present invention. DETAILED DESCRIPTION

[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 the name of a top grade appears in this article, it is intended to refer to its corresponding top grade. All patents, published patent applications and publications cited herein are incorporated herein by reference.

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

[0032] As used herein, a "sample" is a biomolecule, 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 RTF chromatography column (tangential flow chromatography column) mentioned in this article is a patented chromatography column independently developed by our company, with patent number: 202220697921.8; it has a radial and tangential flow structure, and can be loaded through the tangential flow at the bottom of the column, while the upper part of the column head can be flushed and eluted at the same time, cyclic loading and cleaning mode with equilibrium liquid can be achieved, thereby achieving high linear flow rate and overload loading, and achieving extremely high dynamic loading capacity.

[0036] The application scenarios of this patent are laboratory scale and pilot scale, and the maximum flow range of a single pump is 1000ml / min.

[0037] Reference Figure 1 The system for tangential flow control shown in the figure comprises a first liquid inlet main pipeline 1, on which a liquid inlet pump 3, a first pressure sensor 10 and a first flow sensor 11 are arranged, the outlet end of the first liquid inlet main pipeline 1 is connected to the inlet pipeline 8 of the installation module 5, on which a valve is arranged, and the return end pipeline 7 of the installation module 5 is connected to the inlet end of the second liquid inlet main pipeline 2 through the valve, and the second liquid inlet main pipeline 2 is respectively provided with a regulating pump 4, a second pressure sensor 12 and a second flow sensor 13; the second liquid inlet main pipeline 2 is provided with a filter 17, and both ends of the filter 17 are respectively connected to the second liquid inlet main pipeline 2 through connecting pipelines, and valves are respectively arranged on the connecting pipelines, and a valve is arranged on the second liquid inlet main pipeline 2 between the two ends of the filter 17. The outlet end of the second liquid inlet main pipeline 2 is respectively connected to the first liquid inlet main pipeline 1 and the bypass liquid outlet pipeline 18 through connecting pipelines, and a valve is arranged on the connecting pipeline, and a valve is also arranged at the outlet end of the second liquid inlet main pipeline 2. The permeation end pipeline 9 of the installation module 5 is connected to the first liquid outlet main pipeline 6, and valves are respectively provided at the permeation end pipeline 9 and the inlet end of the first liquid outlet main pipeline 6. The first liquid outlet main pipeline 6 is provided with a UV sensor 14, a conductivity transmitter 15 and a pH sensor 16. The outlet end of the first liquid outlet main pipeline 6 is connected to multiple collection pipelines through valves. This embodiment uses six collection ports. Similarly, the inlet ends of the first liquid inlet main pipeline 1 and the second liquid inlet main pipeline 2 are respectively provided with three entry ports.

[0038] Reference Figure 2As shown, the chromatography system for tangential flow control includes a first liquid inlet main pipeline 21, on which a liquid inlet pump 23, a first pressure sensor 210, a first flow sensor 211 and a bubble trap 20 are arranged. The inlet and outlet of the bubble trap 20 are connected to the first liquid inlet main pipeline 21 through connecting pipelines, respectively, and valves are arranged on the connecting pipelines. A valve is arranged on the first liquid inlet main pipeline 21 between the inlet and outlet of the bubble trap 20. The outlet end of the first liquid inlet main pipeline 21 is connected to the inlet end of the first liquid outlet main pipeline 26 through a connecting pipeline, and a valve is arranged on the connecting pipeline. At the same time, a rectangular valve array is also arranged between the first liquid inlet main pipeline 21 and the first liquid outlet main pipeline 26, and the rectangular valve array is composed of four valves connected at the end, and the outlet end of the first liquid inlet main pipeline 21 is connected to the inlet end of the first liquid outlet main pipeline 26, and the corresponding one group of opposite sides of the rectangular valve array, and the other group of opposite sides of the rectangular valve array are respectively connected to the connecting pipelines of the bottom inlet and outlet ends 28 and the top inlet 29 of the tangential flow chromatography column 25. The reflux end connecting pipeline of the tangential flow chromatography column 25 is connected to the second liquid inlet main pipeline 22 through a valve. The second liquid inlet main pipeline 22 is respectively provided with a regulating pump 24, a second pressure sensor 212 and a second flow sensor 213; the second liquid inlet main pipeline 2 is provided with a filter 217, and a rectangular valve array is provided on the second liquid inlet main pipeline 22. The rectangular valve array is composed of four valves connected in the first position. The second liquid inlet main pipeline 22 is connected to a group of opposite sides of the rectangular valve array, and a valve is provided on the second liquid inlet main pipeline between the two opposite sides. The other group of opposite sides of the rectangular valve array is respectively connected to the inlet and outlet of the filter 217, and a valve is provided on the connecting pipeline at the top of the filter 217. The outlet end of the second liquid inlet main pipeline 22 is respectively connected to the first liquid inlet main pipeline 21 and the bypass liquid outlet pipeline 218 through a connecting pipeline, and a valve is provided on the connecting pipeline. The first liquid outlet main pipeline 26 is provided with a UV sensor 214, a conductivity transmitter 215 and a pH sensor 216. The outlet end of the first liquid outlet main pipeline 26 is connected to a plurality of collection pipelines through valves. Six collection ports are used in this embodiment. Similarly, the inlet ends of the first liquid inlet main pipeline 21 and the second liquid inlet main pipeline 22 are respectively provided with three inlet ports.

[0039] Reference Figure 2The filtration system for tangential flow control shown in the figure includes a first liquid inlet main pipeline 31, on which a liquid inlet pump 33, a first pressure sensor 310, and a first flow sensor 311 are arranged. The outlet end of the first liquid inlet main pipeline 31 is connected to the inlet end of the first liquid outlet main pipeline 36 through a connecting pipeline, and a valve is arranged on the connecting pipeline. At the same time, a rectangular valve array is also arranged between the first liquid inlet main pipeline 31 and the first liquid outlet main pipeline 36, and the rectangular valve array is composed of four valves connected at the end, and the outlet end of the first liquid inlet main pipeline 31 is connected to the inlet end of the first liquid outlet main pipeline 36. A group of opposite sides of the corresponding rectangular valve array, and the other group of opposite sides of the rectangular valve array are respectively connected to the connecting pipelines of the inlet end pipeline 38 of the tangential flow filtration membrane package 35 and the permeate end inlet pipeline 39. The return end pipeline 27 of the tangential flow filtration membrane package 35 is connected to the second liquid inlet main pipeline 32 through a valve. The second liquid inlet main pipeline 32 is respectively provided with a regulating pump 34, a second pressure sensor 312 and a second flow sensor 313; a valve is provided on the second liquid inlet main pipeline 32. The outlet end of the second liquid inlet main pipeline 22 is respectively connected to the first liquid inlet main pipeline 31 and the bypass liquid outlet pipeline 318 through a connecting pipeline, and a valve is provided on the connecting pipeline. A UV sensor 314, a conductivity transmitter 315 and a pH sensor 316 are provided on the first liquid outlet main pipeline 36. The outlet end of the first liquid outlet main pipeline 36 is respectively connected to multiple collection pipelines through a valve. This embodiment adopts six collection ports. Similarly, the inlet ends of the first liquid inlet main pipeline 31 and the second liquid inlet main pipeline 32 are respectively provided with three entry ports.

Claims

1. A system for tangential flow control, characterized in that It includes a first liquid inlet main pipeline, on which a liquid inlet pump is arranged, the outlet end of the first liquid inlet main pipeline is connected to the inlet pipeline of the installation module through a valve, the first outlet pipeline of the installation module is connected to the inlet end of the second liquid inlet main pipeline, the second liquid inlet main pipeline is provided with a regulating pump, the outlet end of the second liquid inlet main pipeline is connected to the first liquid inlet main pipeline through a valve; the second outlet pipeline of the installation module is connected to the inlet end of the first liquid outlet main pipeline through a valve.

2. The system for tangential flow control according to claim 1, characterized in that: The second liquid inlet main pipeline is provided with a filter module, and the second liquid inlet main pipeline is connected to one end of the filter through a connecting pipeline, and the other end of the filter is connected through a connecting pipeline.

3. A system for tangential flow control according to claims 1 and 2, characterized in that The outlet end of the second liquid inlet main pipeline is connected to the bypass liquid outlet pipeline through a valve.

4. The system for tangential flow control according to claim 1, characterized in that: The outlet end of the first liquid inlet main pipeline is communicated with the inlet end of the first liquid outlet main pipeline through a connecting pipeline, and a valve is arranged on the connecting pipeline.

5. The system for tangential flow control according to claim 1, characterized in that: The first liquid inlet main pipeline and / or the second liquid inlet main pipeline are provided with a pressure sensor and / or a flow sensor.

6. The system for tangential flow control according to claim 1, characterized in that: The first liquid outlet main pipeline is provided with a UV sensor and / or a conductivity transmitter and / or a pH sensor.

7. A chromatography system for tangential flow control, characterized in that The invention comprises a liquid inlet main pipeline, a liquid inlet pump and a bubble trap are arranged on the first liquid inlet main pipeline, the outlet end of the first liquid inlet main pipeline is connected to the inlet end of the tangential flow chromatography column through a valve, the reflux end of the tangential flow chromatography column is connected to the inlet end of the second liquid inlet main pipeline through a pipeline, the second liquid inlet main pipeline is provided with a regulating pump, the outlet end of the second liquid inlet main pipeline is respectively connected to the first liquid inlet main pipeline and the bypass liquid outlet pipeline through a valve; the outlet end of the tangential flow chromatography column is connected to the inlet end of the first liquid outlet main pipeline through a valve.

8. The tangential flow controlled chromatography system according to claim 7, characterized in that: The outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline are communicated with each other through a connecting pipeline, and a valve is arranged on the connecting pipeline.

9. The tangential flow controlled chromatography system according to claim 8, characterized in that: A rectangular valve array is arranged between the outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline. The rectangular valve array is composed of four valves connected in the first position. The outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline are connected to a group of opposite sides of the rectangular valve array, and the other group of opposite sides of the rectangular valve array are respectively connected to the inlet end and the top outlet end of the tangential flow chromatography column.

10. The tangential flow controlled chromatography system according to claim 7, characterized in that: A rectangular valve array is arranged on the second liquid inlet main pipeline, and the rectangular valve array is composed of four valves connected in the first position. The second liquid inlet main pipeline is connected to a group of opposite sides of the rectangular valve array, and valves are arranged on the second liquid inlet main pipeline between the group of opposite sides. The other group of opposite sides of the rectangular valve array are respectively connected to the inlet and outlet at both ends of the filter.

11. The tangential flow controlled chromatography system according to claim 7, characterized in that: The first liquid inlet main pipeline and / or the second liquid inlet main pipeline are provided with a pressure sensor and / or a flow sensor.

12. The tangential flow controlled chromatography system according to claim 7, characterized in that: The first liquid outlet main pipeline is provided with a UV sensor and / or a conductivity transmitter and / or a pH sensor.

13. A filtration system for tangential flow control, characterized in that It comprises a liquid inlet main pipeline, a liquid inlet pump is arranged on the first liquid inlet main pipeline, the outlet end of the first liquid inlet main pipeline is connected to the inlet end of the tangential flow filtration membrane package through a valve, the reflux port of the tangential flow filtration membrane package is connected to the inlet end of the second liquid inlet main pipeline through a connecting pipeline, the second liquid inlet main pipeline is provided with a regulating pump, the outlet end of the second liquid inlet main pipeline is respectively connected to the first liquid inlet main pipeline and the bypass liquid outlet pipeline through a valve; the permeation port of the tangential flow filtration membrane package is connected to the inlet end of the first liquid outlet main pipeline through a connecting pipeline.

14. The tangential flow control filtration system according to claim 13, characterized in that: The outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline are communicated with each other through a connecting pipeline, and a valve is arranged on the connecting pipeline.

15. The tangential flow control filtration system according to claim 14, characterized in that: A rectangular valve array is arranged between the outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline. The rectangular valve array is composed of four valves connected in the first position. The outlet end of the first liquid outlet main pipeline and the inlet end of the first liquid outlet main pipeline are connected to a group of opposite sides of the rectangular valve array, and the other group of opposite sides of the rectangular valve array are respectively connected to the inlet end and the top outlet end of the tangential flow chromatography column.

16. The tangential flow control filtration system according to claim 13, characterized in that: The first liquid inlet main pipeline and / or the second liquid inlet main pipeline are provided with a pressure sensor and / or a flow sensor.

17. The tangential flow control filtration system according to claim 13, characterized in that: The first liquid outlet main pipeline is provided with a UV sensor and / or a conductivity transmitter and / or a pH sensor.

Images