Suspended feed liquid clarifying and concentrating system

Abstract

The utility model discloses a suspended feed liquid clarification and concentration system which comprises a suspended feed liquid storage tank, a disc centrifuge, a clarified feed liquid collecting bag and a tangential flow system which are connected in series, the disc centrifuge is used for primary filtration of feed liquid, the clarified feed liquid collecting bag is used for secondary filtration of the feed liquid, and the tangential flow system is used for secondary filtration of the feed liquid. The tangential flow system is used for concentrating, so that the concentration quality is improved; concentration uniformization and heat preservation are conducted on feed liquid through the suspended feed liquid storage tank, constant-speed driving is conducted on the feed liquid through the peristaltic pump between the suspended feed liquid storage tank and the disc type centrifugal machine and the diaphragm pump in the tangential flow system, the utilization efficiency of the feed liquid is guaranteed, and the peristaltic pump and the diaphragm pump are matched to rapidly and effectively clarify and concentrate a sample.

Description

Technical Field

[0001] This utility model relates to a clarification and concentration system, and more particularly to a clarification and concentration system for suspended liquids. Background Technology

[0002] Before downstream chromatographic purification of biological products, clarification and concentration steps are generally required to reduce sample turbidity and volume. Common clarification methods include dead-end filtration, such as using depth filters. Taking lentivirus packaged in suspension cells as an example, this method faces several challenges: controlling turbidity <10 NTU, ensuring high recovery rates ≥90%, guaranteeing high loading capacity, and being suitable for scale-up.

[0003] Patent publication number CN108883345A discloses a method for protein purification:

[0004] Molecule A is a humanized monoclonal IgG4P antibody expressed in a fed-batch bioreactor process in a CHO DG44 cell line and purified using a three-step chromatographic process. The theoretical intact mass of the complete glycosylated molecule was determined to be 147,460 Da, with the feed material derived from a 2000 L bioreactor grown for 14 days. The material was centrifuged using a diskstack centrifuge with settings optimized for product recovery and clarification. In Activity 2, the concentrate (or supernatant) was then deep filtered using Pall PDE2 and PDD1 filters (or equivalents), followed by sterile filtration. This was followed by a capture step using protein A (MabSelect SuRe LX, GE Healthcare) and subsequent purification steps: anion exchange (AEX, using Capto Q, GE Healthcare), cation exchange (CEX, using Capto SPImpRes), virus reduction filtration (VRF), and formulation. In Activity 3, an activated carbon filter was applied online between the depth filter and the disinfection filter (0.2μm pore size). However, this filtration method was not efficient and could not meet the conditions that required processing large amounts of liquid.

[0005] Currently, there is no suitable filter on the market that can efficiently clarify unlyslaughtered suspended cell solutions. Therefore, some companies use centrifugation. However, conventional centrifuges have limited single-cycle volume and require opening the container to remove sediment and collect the supernatant, a repetitive and time-consuming process that is not feasible for large-scale production. Secondly, the clarified lentivirus solution is concentrated using tangential flow ultrafiltration systems, such as flat-sheet membranes or hollow fiber columns. Both types of equipment use peristaltic pumps, and because their flow patterns inevitably cause some damage to the viral envelope, the longer the concentration time, the more severe the damage. Therefore, the key is to quickly and effectively clarify and concentrate large-scale samples. Utility Model Content

[0006] The purpose of this invention is to provide a suspension clarification and concentration system to solve the problem of how to effectively clarify and concentrate large-scale samples.

[0007] A suspension clarification and concentration system adopts the following technical solution:

[0008] A suspension clarification and concentration system includes a disc centrifuge, a suspension storage tank, a clarified liquid collection bag, and a tangential flow system. The disc centrifuge includes an inlet end, an outlet end, and a waste collection end. The disc centrifuge has a rotating drum inside, with several sets of disc-shaped parts inside the drum. The disc centrifuge is equipped with an adapter; the shaft of the adapter is hollow and connected to the inlet end; the top of the adapter is connected to the outlet end. The inlet end of the disc centrifuge is connected to the suspension storage tank via a first pipeline, and the outlet end of the disc centrifuge is connected to the clarified liquid collection bag via a second pipeline. The clarified liquid collection bag is connected in series with the tangential flow system.

[0009] Optionally, the disc centrifuge is provided with a rotating drum inside, a driving device is provided at the bottom of the rotating drum, a number of disc-shaped parts are nested together inside the rotating drum, the disc-shaped parts are evenly arranged inside the rotating drum, and a filter residue discharge channel is provided at the bottom of the rotating drum.

[0010] By adopting the above technical solution, the liquid to be concentrated enters the disc centrifuge from the suspension storage tank for centrifugation. After centrifugation, the liquid enters the clarified liquid collection bag for sedimentation. After sedimentation, it enters the tangential flow system for final collection and impurity removal. The disc-shaped parts increase the contact area between the disc parts inside the disc centrifuge and the liquid, thereby improving centrifugation efficiency and quality.

[0011] Optionally, the suspension clarification and concentration system described herein is characterized in that: a pressure gauge, a concentration gauge and a three-way valve are sequentially arranged in the second pipeline along the discharge direction of the disc centrifuge; a third pipeline is arranged between the second pipeline and the suspension storage tank; the three-way valve is located at the connection between the second pipeline and the third pipeline; and the concentration gauge is electrically connected to the three-way valve.

[0012] By adopting the above technical solution, the concentration detector and the three-way valve are electrically connected. The concentration detector detects the concentration of the liquid output. If the concentration does not meet the standard for the next step, it is returned to the suspension liquid storage tank, which improves the utilization rate of the liquid. When the pipeline is blocked, the pressure detector can respond in time.

[0013] Furthermore, the suspension storage tank has a return end connected to a third pipeline, a raw material input end, and an output end connected to the disc centrifuge.

[0014] Preferably, a heating device is provided on the bottom wall of the suspension storage tank.

[0015] Preferably, an agitator is provided on the bottom wall of the suspension storage tank.

[0016] By adopting the above technical solutions and two preferred solutions, the suspension storage tank can ensure the cell activity in the liquid and protect the cells in the liquid, reducing cell loss during the concentration process.

[0017] Optionally, the first pipeline is equipped with a peristaltic pump and a pressure gauge.

[0018] By adopting the above technical solutions, the pressure gauge can promptly reflect whether the pipeline is blocked, and the use of a peristaltic pump ensures sufficient time for centrifugal motion.

[0019] Optionally, the clarified liquid collection bag has an inlet connected to a second pipeline, a sampling port for sampling, and a collection port connected to the tangential flow system.

[0020] By adopting the above technical solution, the liquid material processed by the disc centrifuge undergoes sedimentation treatment, which can further improve the concentration efficiency and reduce the impurity content.

[0021] Furthermore, the tangential flow system includes a circulation bottle, a diaphragm pump, a pressure gauge, and a hollow fiber column connected in sequence. The circulation bottle is provided with an inlet end connected to the clarified liquid collection bag, an outlet end connected to the diaphragm pump, and a return end connected to the hollow fiber column.

[0022] By adopting the above technical solution, the liquid that has passed through the clarified liquid collection bag is concentrated. A diaphragm pump is used to reduce shear force damage. The hollow fiber tube can provide a better physical concentration effect. At the same time, multiple pressure gauges can promptly reflect whether the corresponding connection is blocked.

[0023] In summary, this solution guarantees at least one of the following beneficial effects:

[0024] 1. The use of disc centrifuges and tangential flow ultrafiltration systems in series greatly shortens the total time for clarification and concentration processes of large-scale suspended cells;

[0025] 2. Disc centrifuges replace traditional centrifuges, greatly reducing the time spent on clarification processes and eliminating the need for open, manual operation to remove cell precipitates.

[0026] 3. The use of a diaphragm pump reduces shear force damage and avoids reduced biotiter recovery rate after concentration for products that are sensitive to membrane damage. Attached Figure Description

[0027] Figure 1 This is an overall view of Embodiment 1;

[0028] Figure 2 This is a structural diagram of the suspension storage tank in Embodiment 1;

[0029] Figure 3 This is a structural diagram of the disc centrifuge in Embodiment 1;

[0030] Figure 4 This is a schematic diagram of the tangential flow system in Embodiment 1.

[0031] Figure reference numerals: 1. Suspension storage tank; 11. Input end; 12. Output end; 13. Return end; 14. Stirring paddle; 15. Heating device; 2. Disc centrifuge; 21. Inlet end; 22. Outlet end; 23. Rotary drum; 24. Disc-shaped part; 25. Discharge channel; 3. Clarified liquid collection bag; 31. Liquid inlet; 32. Sampling port; 33. Collection port; 4. Tangential flow system; 41. Circulation bottle; 411. Inlet end; 412. Air filter; 42. Diaphragm pump; 43. Hollow fiber column; 5. First pipeline; 51. Peristaltic pump; 6. Second pipeline; 61. Concentration meter; 62. Three-way valve; 7. Third pipeline; Detailed Implementation

[0032] To make the technical solution of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0033] Example 1

[0034] Combination Figure 1 As shown, the suspension storage tank is connected to the inlet of the disc centrifuge via a first pipeline, and the outlet of the disc centrifuge is connected to the clarified liquid collection bag via a second pipeline. The second pipeline is equipped with a concentration detector and a three-way valve electrically connected to it. The three-way valve is connected to the suspension storage tank via a third pipeline. The collection port of the clarified liquid is connected to the inlet of the circulation bottle, and the circulation bottle is sequentially connected to the diaphragm pump, pressure gauge, and hollow fiber column.

[0035] The suspension storage tank contains the liquid to be concentrated that has been transferred from the outside into the system. The liquid is sent to a disc centrifuge by a peristaltic pump on the first pipeline for centrifugation. After centrifugation, the liquid enters the clarified liquid collection bag through the outlet at the top of the disc centrifuge for sedimentation. After sedimentation, the supernatant is taken and sent to the tangential flow system for concentration.

[0036] Combination Figure 2As shown, the inner side of the suspension storage tank is equipped with a heating device and a stirring paddle controlled by an interactive panel. Both are installed at the bottom of the inner cavity. During the concentration process, the stirring paddle rotates according to the set speed to ensure that the concentration of the liquid in the tank is uniform, and the heating device ensures that the temperature inside the tank is constant according to the set temperature.

[0037] Further integration Figure 1 As shown, the suspension storage tank and the disc centrifuge are connected by a first pipeline. The first pipeline is equipped with a peristaltic pump and a pressure gauge. During operation, the suspension is drawn out from the inside of the suspension storage tank by the peristaltic pump and then slowly and uniformly enters the inlet of the disc centrifuge.

[0038] Combination Figure 3 As shown, the disc centrifuge has a rotating drum containing several sets of disc-shaped parts. The centrifuge also includes an adapter with a hollow shaft connecting to the inlet and an outlet. When the feed liquid enters the rotating drum through the feed pipe and then into the disc assembly, it accelerates in the distribution chamber until it synchronizes with the drum speed. As the suspension (or emulsion) flows through the gaps between the discs, solid particles settle onto the discs under centrifugal force, forming sediment. The sediment slides along the disc surface, detaches from the discs, and accumulates in the solids collection chamber at the largest diameter part of the drum. The solid phase is discharged by controlling the sealing water and discharge water, while the separated liquid exits the drum from the outlet.

[0039] Further integration Figure 1 As shown, the disc centrifuge is connected to the suspension collection bag via a second pipeline. A pressure gauge and a concentration gauge are installed on the second pipeline. One end of the third pipeline is located between the concentration gauge and the clarified liquid collection bag. A three-way valve electrically connected to the concentration gauge is installed at the connection point. The other end of the third pipeline is connected to the reflux end of the suspension storage tank.

[0040] After passing through the disc centrifuge, the concentration of the liquid is determined by the concentration detector on the second pipeline. Only when the concentration meets the standard can it enter the clarified liquid collection bag. Otherwise, it enters the suspended liquid collection tank through the return end for centrifugation again.

[0041] Further integration Figure 1 As shown, the inlet of the clarified liquid collection bag is connected to the second pipeline, and the outlet is connected to the tangential flow system through a conduit. The conduit opening is located at the top of the clarified liquid collection bag.

[0042] After the liquid enters the collection bag through the second pipeline and undergoes physical sedimentation, the liquid level reaches the lowest point of contact with the conduit, and the conduit continuously removes a certain amount of the upper clear liquid.

[0043] Combination Figure 1 , Figure 4The tangential flow system comprises a circulation bottle, a diaphragm pump, a pressure gauge, and a hollow fiber column, connected in sequence. In operation, connect the clarified feed collection bag to the tangential flow inlet piping, close the air filter of the circulation bottle to ensure airtightness, then start the diaphragm pump to fill the entire ultrafiltration system piping with feed liquid, maintaining the liquid level in the circulation bottle at a medium-high level. Open the permeate valve, set the pressure, and use the computer control system of the tangential flow system to maintain dynamic balance of the circulation bottle weight throughout the concentration process until the clarified feed volume reaches the target concentration factor.

[0044] Example 2

[0045] The bottom center of the suspension storage tank is equipped with a heating tube and a magnetic induction propeller controlled by an interactive panel. During the concentration process, the uniformity of turbidity of the sample in the tank can be ensured to avoid local precipitation. The rest of the implementation method is the same as in Example 1.

[0046] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A suspended liquor clarification concentration system characterized by: The application relates to a disc centrifuge, a suspension liquid storage tank, a clarified liquid collecting bag and a tangential flow system, wherein the disc centrifuge comprises an inlet end, an outlet end and a waste collecting end, the disc centrifuge is internally provided with a drum, a plurality of disc-shaped parts are arranged in the drum, the disc centrifuge is provided with an adapter, the shaft of the adapter is hollow and connected with the inlet end, the top of the adapter is connected with the outlet end, the inlet end of the disc centrifuge is connected with the suspension liquid storage tank through a first pipeline, the outlet end of the disc centrifuge is connected with the clarified liquid collecting bag through a second pipeline, and the clarified liquid collecting bag is connected with the tangential flow system in series.

2. A system for clarification and concentration of a suspension liquid according to claim 1, characterized in that The disc centrifuge is internally provided with a drum, the bottom of the drum is provided with a driving device, a plurality of disc-shaped parts are arranged in the drum in a sleeved mode, the disc-shaped parts are uniformly arranged in the drum, and the bottom of the drum is provided with a filter residue discharging channel.

3. A system for clarifying and concentrating a suspension liquid as claimed in claim 1, characterized in that: The second pipeline is sequentially provided with a pressure detection meter, a concentration detection meter and a three-way valve along the discharging direction of the disc centrifuge, a third pipeline is arranged between the second pipeline and the suspension liquid storage tank, the three-way valve is arranged at the connection position of the second pipeline and the third pipeline, and the concentration detection meter is electrically connected with the three-way valve.

4. A system for clarification and concentration of a suspension liquid according to claim 3, characterized in that The suspension liquid storage tank is provided with a backflow end connected with the third pipeline, a material input end and an output end connected with the disc centrifuge.

5. A suspended liquor clarification concentration system as claimed in claim 4, wherein: The suspension liquid storage tank is internally provided with a heating device on the bottom wall.

6. A suspended liquor clarification concentration system as claimed in claim 4, wherein: The suspension liquid storage tank is internally provided with a stirring paddle on the bottom wall.

7. A system for clarification and concentration of a suspension liquid as claimed in claim 1, wherein: The first pipeline is provided with a peristaltic pump and a pressure detection meter.

8. A suspended liquor clarification concentration system as claimed in claim 1, wherein: The clarified liquid collecting bag is provided with a liquid inlet connected with the second pipeline, a sampling port for sampling and a collecting port connected with the tangential flow system.

9. A suspended liquor clarification concentration system as claimed in claim 8, wherein: The tangential flow system comprises a circulating bottle, a diaphragm pump, a pressure detection meter and a hollow fiber column which are connected in series, the circulating bottle is provided with an inlet end connected with the clarified liquid collecting bag, an outlet end connected with the diaphragm pump and a backflow end connected with the hollow fiber column.

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