Concentration device and sterile concentration system

Abstract

The utility model discloses a concentration device and a sterile concentration system, the concentration device is connected in parallel through a plurality of concentrated solution storage tanks with control valves, the concentration work is carried out at the same time in the earlier stage, the higher circulating flow is kept, and the permeation efficiency of a membrane column is guaranteed; and when the titer of the virus liquid in the later stage of concentration is relatively high, single-loop concentration can be switched, and high-power concentration can be continuously finished in a container with a smaller dead volume, so that the defect that a concentration device in the prior art is difficult to meet the concentration multiple due to large dead volume is overcome.

Description

Technical Field

[0001] The utility model relates to the technical field of biological product concentration, in particular to a concentration device and an aseptic concentration system. Background Art

[0002] Membrane concentration technology is often used in the production and manufacturing of biological products. The concentration of virus liquid often requires high-fold concentration. To achieve high-fold concentration, it is necessary to take into account both the concentration processing efficiency and the system dead volume loss.

[0003] In order to meet the concentration processing efficiency in production, a larger membrane area and circulation flow rate will be used. The corresponding ultrafiltration system needs to match a larger inlet and outlet pipeline. When the virus liquid enters the later stage of concentration, the residual volume of the system is often as high as 10% or more. For high-fold concentrated liquid, the larger system dead volume will inevitably cause greater economic losses when it cannot be collected completely. In the actual operation process, the process personnel will use buffer to top wash the residual concentrated liquid in the concentration system to improve the sample recovery rate. The volume after two collections needs to correspond to the final volume of the process concentration, and the volume of the top wash liquid cannot be less than the system dead volume (minimum circulation volume). This makes the first concentrated liquid must use a higher concentration multiple to obtain a smaller volume, leaving space for the top wash liquid, and over-concentration is not suitable for the activity of the virus liquid, which needs to be avoided in production. In addition, when the virus liquid needs to be highly concentrated, it is difficult for a system with a large dead volume to meet the process requirements. Therefore, how to optimally reduce the minimum circulation volume of the system to avoid over-concentration is a problem that needs to be considered. Utility Model Content

[0004] The utility model aims to provide a concentrating device to solve the defect that the concentrating device in the prior art is difficult to meet the concentration multiple due to the large dead volume.

[0005] To achieve the above purpose, the scheme of the utility model is as follows:

[0006] A concentration device, including a concentrated liquid storage tank, a membrane column, a collection tank and a waste liquid tank; wherein:

[0007] The concentrated liquid storage tank is provided with a feed pipe 1 and a reflux pipe 1 connected to the feed end of the membrane column; the concentrated liquid storage tank includes a plurality of parallel connected tanks, each of which is independently provided with a feed branch pipe connected to the feed pipe 1, and a reflux branch pipe connected to the reflux pipe 1;

[0008] Each of the feed branch pipe and the reflux branch pipe is provided with at least one control valve;

[0009] The feed pipe L1 is provided with a feed pump P1 and a valve K2 in sequence along the membrane column F1; a collection pipe L8 with a valve K1 is provided between the feed pump P1 and the valve K2 and is connected to the collection tank V3;

[0010] The discharge end of the membrane column is connected to the waste liquid tank.

[0011] Furthermore, the feed branch pipe extends to near the bottom of the concentrate storage tank.

[0012] Furthermore, the concentrated liquid storage tank includes a concentration tank 1 and a concentration tank 2, and the volume of the concentration tank 1 is smaller than that of the concentration tank 2.

[0013] Furthermore, the concentrated liquid storage tank is provided with a respirator.

[0014] Furthermore, the concentration device also includes a backwash pump, the input end of the backwash pump is connected to the concentrated liquid storage tank, and the output end of the backwash pump is connected to the discharge end of the membrane column.

[0015] Furthermore, the concentrating device also includes a liquid replenishing tank to be concentrated, which is connected to the concentrated liquid storage tank.

[0016] Another purpose of the utility model is to propose an aseptic concentration system for solving the problem of concentrated aseptic treatment. Specifically, the aseptic concentration system includes an alkali liquid tank, a cleaning liquid tank and the above-mentioned concentration device; the alkali liquid tank is provided with an alkali feed pipe and an alkali reflux pipe controlled by a valve, the alkali feed pipe is connected to a feed pipe 1, and the alkali reflux pipe is connected to a reflux pipe 1; the cleaning liquid tank is provided with a pipeline controlled by a valve connected to a concentrated liquid storage tank.

[0017] Furthermore, a waste liquid pipe is provided at the discharge end of the membrane column to connect to the waste liquid tank, and a valve 18 is provided on the waste liquid pipe; the alkali liquid tank is also provided with an alkali permeation pipe to connect to the waste liquid pipe between the backwash pump and the valve 18, and valves 16 and 17 are provided on the alkali permeation pipe; the alkali reflux pipe is connected between valves 16 and 17.

[0018] Compared with the prior art, the beneficial effects of the utility model are:

[0019] The concentrating device of the utility model is connected in parallel by multiple concentrated liquid storage tanks with control valves. In the early stage, the concentration work is carried out simultaneously to maintain a high circulation flow rate and ensure the permeation efficiency of the membrane column. In the later stage of concentration, when the virus liquid titer is high, it is switched to single-loop concentration to continue to complete high-multiple concentration in a container with a smaller dead volume, thereby solving the defect that the concentrating device of the prior art is difficult to meet the concentration multiple due to the large dead volume. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a schematic diagram of a concentration device provided by the utility model.

[0021] Figure 2 This is an overall schematic diagram of the aseptic concentration system provided by the utility model.

[0022] Among them: B1, waste liquid tank; B2, alkali liquid tank; B3, replenishment tank for concentrated liquid; B4, cleaning liquid tank; V1, concentration tank one; V2, concentration tank two; V3, collecting tank; F1, membrane column; F2, sterilizing filter; L1, feed pipe one; L2, reflux pipe one; L3, feed pipe two; L4, feed pipe three; L5, reflux pipe two; L6, reflux pipe three, L7, feed pipe four; L8, collecting pipe; L9, waste liquid pipe; L10, alkali feed pipe; L11, alkali reflux pipe; L12, alkali permeation pipe; K1~K18 correspond to valve one to valve eighteen respectively; P1, feed pump; P2, backwash pump; R1, respirator one; R2, respirator two. DETAILED DESCRIPTION

[0023] The following will be combined with the drawings in the embodiments of the utility model to clearly and completely describe the technical solutions in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0024] It should be understood that the terms "upper", "lower", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship are based on the orientation or position relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0025] It should also be noted that, unless otherwise clearly specified and limited, the terms such as "install", "connect", "connect", "fix", "set" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral one; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two components or the interaction relationship between two components. For ordinary technicians in this field, the specific meanings of the above terms in this utility model can be determined according to specific circumstances.

[0026] In the first embodiment, if Figure 1As shown, a concentrating device is provided, including a concentrated liquid storage tank, a membrane column F1, a collecting tank V3 and a waste liquid tank B1; wherein: the concentrated liquid storage tank is provided with a feed pipe L1 and a reflux pipe L2 connected to the feed end of the membrane column F1; the concentrated liquid storage tank includes a plurality of parallel-connected ones, each of which is independently provided with a feed branch pipe connected to the feed pipe L1, and a reflux branch pipe connected to the reflux pipe L2; the feed branch pipe and the reflux branch pipe are each provided with at least one control valve; the feed pipe L1 is provided with a feed pump P1 and a valve K2 in sequence along the direction of the membrane column F1; a collecting pipe L8 with a valve K1 is provided between the feed pump P1 and the valve K2 and is connected to the collecting tank V3; the discharge end of the membrane column F1 is connected to the waste liquid tank B1 through a waste liquid pipe L9.

[0027] In the above embodiment, in the concentration device, the concentrated liquid storage tank and the membrane column F1 constitute a concentration loop, and the waste liquid formed by the membrane column F1 is collected by the waste liquid tank B1. When the concentration reaches the target multiple, the valve 2 K2 is closed and the valve 1 K1 is opened, and the concentrated liquid is collected in the collection tank V3 under the action of the feed pump P1. In the early stage, when the feed branch pipe and the reflux branch pipe are both opened, multiple concentrated liquid storage tanks can be connected in parallel to maintain a high circulation flow rate and ensure the permeation efficiency of the membrane column; and in the later stage of concentration, when the virus liquid titer is high, the valves on the feed branch pipe and the reflux branch pipe are controlled to switch to single-loop concentration, and high-multiple concentration is continued in a small container with a smaller dead volume.

[0028] In the above embodiment, taking virus concentration as an example, the virus liquid enters the membrane column from the feed pipe L1, wherein small molecular impurities such as salts, serum and other cell metabolites can be removed by passing through the filter membrane and discharged from the filtration end, while large virus particles cannot pass through the filter membrane and return to the concentrated liquid storage tank through the reflux pipe L2. As the filtrate continues to increase, the volume of the virus liquid continues to decrease, the virus content is improved, and the concentration effect is achieved.

[0029] In a preferred embodiment, Figure 1As shown, the concentrated liquid storage tank includes a concentration tank 1 V1 and a concentration tank 2 V2, and the volume of the concentration tank 1 V1 is smaller than that of the concentration tank 2 V2. The concentration tank 1 V1 is provided with a feed pipe 2 L3 connected to the feed pump P1, and the concentration tank 1 V1 is provided with a return pipe 2 L5 connected to the return pipe 1 L2. The concentration tank 2 V2 is provided with a feed pipe 3 L4 connected to the feed pump P1, and a return pipe 3 L6 connected to the return pipe 1 L2. The feed pipe 2 L3 and the feed pipe 3 L4 are provided with valve 3 K3 and valve 4 K4 respectively; the return pipe 2 L5 and the return pipe 3 L6 are provided with valve 5 K5 and valve 6 K6 respectively; the return pipe 1 L2 is provided with valve 7 K7. During operation, valves 2 K2 to 7 K7 are kept open in the early stage to realize the simultaneous operation of two concentration tanks. After the concentration reaches a certain concentration multiple, valve 6 K6 is closed first to evacuate the concentrated liquid in concentration tank 2 V2, and then valve 4 K4 is closed. At this time, the switch of reduction tank 1 V1 is realized, which reduces the volume of the concentration system in the high concentration stage, reduces the dead volume, and makes it easier to achieve the target concentration multiple. The double feed and double reflux pipeline system can achieve a high circulation flow rate and improve the concentration treatment efficiency; in the later stage of concentration, a single-channel small volume circulation is used to ensure the recovery rate and reduce the over-concentration multiple, effectively protecting the activity of the concentrated liquid, which is also applicable to biological products with small concentration treatment volume and high target concentration multiple.

[0030] In a preferred embodiment, the feed pipe 2 L3 and the feed pipe 3 L4 extend to near the bottom of the storage tank, which can reduce the residue in the tank. In addition, the concentration tank 1 V1 and the concentration tank 2 V2 are respectively provided with a respirator 1 R1 and a respirator 2 R2, which are used to balance the pressure or apply air pressure to the tank to collect the residual concentrated liquid along the pipeline. Taking the collection of the residual concentrated liquid in the reflux pipe 3 L6 as an example, close the valve 4 K4, stop the feed pump P1, and open the valves 5 K5 to 7 K7. At this time, the respirator 2 R2 presses air into the concentration tank 2 V2 and the residual concentrated liquid enters the concentration tank 1 V1 and the membrane column F1 from the bottom to the top through the valve 6 K6 through the reflux pipe 1 L2 and the reflux pipe 2 L5.

[0031] In a preferred embodiment, Figure 1As shown, the concentration device also includes a backwash pump P2, which is arranged on the waste liquid pipe L9. The backwash pump P2 can work in forward and reverse directions. When rotating forward, it provides power for the waste liquid output, and when rotating reversely, it is used to backwash and clean the membrane column F1. Specifically, valve nine K9 and valve ten K10 are arranged on the waste liquid pipe L9, and valve nine K9 is close to the waste liquid tank B1; a pipeline with valve eight K8 is arranged between valve nine K9 and valve ten K10 to communicate with the reflux pipe three L6, and valve eleven K11 is arranged at the position of the reflux pipe three L6 near the mouth of the concentration tank two V2. When concentrating, valve eight K8 is closed, and valve nine K9 to valve eleven K11 are opened; when backwashing, the feed pump P1 stops working, valve nine K9 is closed, valve eighteen K18 is opened, and the backwash pump P2 works in reverse, and the concentrated liquid from the concentration tank two V2 enters the membrane column F1 along the waste liquid pipe L9 in the reverse direction for backwashing.

[0032] In the above embodiment, the concentration tank V1 is connected to the feed pipe L7 and is provided with a valve K12 for adding concentrated liquid to the concentration tank V1. During the concentration, in order to ensure that the concentration tank V1 and the concentration tank V2 are concentrated synchronously, the feed ratio can be controlled by controlling the opening and closing degree of the valve K3 and the valve K4, and the reflux ratio can be controlled by controlling the opening and closing degree of the valve K5 and the valve K6.

[0033] In the second embodiment, if Figure 2 As shown, a sterile concentration system is provided, comprising an alkali liquid tank B2, a liquid replenishing tank B3, a cleaning liquid tank B4 and the concentration device described in the first embodiment.

[0034] The alkali liquid tank B2 is provided with an alkali feed pipe L10 controlled by a valve 14 K14 and an alkali reflux pipe L11 controlled by a valve 15 K15. The alkali feed pipe L10 is connected to the feed pipe 1 L1 at the left end of the feed pump P1, and the alkali reflux pipe L11 is connected to the reflux pipe 1 L2 at the right end of the valve 7 K7.

[0035] The liquid to be concentrated replenishment tank B3 and the cleaning liquid tank B4 are connected to the concentrated liquid feed pipe 4 L7 respectively; a valve 13 K13 is also provided at the lower end of the valve 12 K12, and the return pipe 2 L5 is connected to the valve 12 K12 and the valve 13 K13. When the valve 12 K12 and the valve 13 K13 are opened, the liquid to be concentrated and the cleaning liquid can be added to the concentration tank 1 V1 respectively and then enter the entire concentration circulation loop.

[0036] In the above embodiment, before the concentration work, the concentration tank 1 V1 and the concentration tank 2 V2 are not injected with the liquid to be concentrated, the valve 2 K2 to the valve 7 K7, the valve 14 K14, and the valve 15 K15 are opened, the valve 1 K1 is closed, and the feed pump P1 is started. At this time, the alkaline solution enters the concentration circulation loop, and the concentration tank 1 V1, the concentration tank 2 V2, and the membrane column F1 are alkaline washed and sterilized.

[0037] In a preferred embodiment, a sterilizing filter F2 is provided at the outlet of the cleaning liquid tank B4, and the cleaning liquid can be pure water, which can enter the circulation system through the concentration tank V1 and clean the system after alkali washing and sterilization until the pH is neutral, which is qualified. In addition, the cleaning liquid can also be a buffer solution, which can enter the membrane column F1 through the concentration tank V1, the feed pipe L3 and the feed pipe L1 to wash the filter membrane.

[0038] In a preferred embodiment, a valve 18 K18 is provided on the waste liquid pipe L9, and an alkali liquid tank B2 is also provided with an alkali permeable pipe L12 connected to the waste liquid pipe L9 between the backwash pump P2 and the valve 18 K18. The alkali permeable pipe L12 is provided with valves 16 K16 and 17 K17, and the alkali reflux pipe L11 is connected between the two valves. At the end of the concentration work, when the membrane column F1 needs to be reversely cleaned to restore the flux, the valve 18 K18 is closed, the valve 16 K16 and the valve 17 K17 are opened, the backwash pump P2 is reversed, and the alkali liquid enters the membrane column F1 from the alkali permeable pipe L12 in the reverse direction for backwashing, so that the filter membrane recovers the flux and improves the concentration efficiency. As a preferred embodiment, during the backwashing process, the feed pump P1, the valve 2 K2, the valve 14 K14 and the valve 15 K15 are all opened, the alkali liquid is forwardly fed through the alkali feed pipe L10 and refluxed at the same time, and the membrane column F1 is backwashed through the alkali permeable pipe L12 to avoid damage to the filter membrane caused by excessive backwashing pressure. During the concentration process, when the flux of the membrane column F1 needs to be restored, the concentrate can be transferred to the second concentration tank V2, and the cleaning liquid tank B4 is activated to supplement the buffer solution to the concentration tank V1. Close the feed and reflux pipelines of the second concentration tank V2, open the feed, reflux pipelines and feed pump P1 of the concentration tank V1 to circulate the buffer solution to the membrane column F1; at the same time, valve 16 K16 and valve 18 K18 are closed, valve 15 K15 and valve 17 K17 are opened, the backwash pump P2 is reversed, and the buffer solution is diverted to the alkali permeation tube L12 and reversely enters the membrane column F1 for backwashing.

[0039] Although the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A concentration device, characterized in that: It includes a concentrate storage tank, a membrane column (F1), a collection tank (V3) and a waste liquid tank (B1); wherein: The concentrated liquid storage tank is provided with a feed pipe 1 (L1) and a reflux pipe 1 (L2) connected to the feed end of the membrane column (F1); the concentrated liquid storage tank includes a plurality of parallel connected tanks, each of which is independently provided with a feed branch pipe connected to the feed pipe 1 (L1), and a reflux branch pipe connected to the reflux pipe 1 (L2); Each of the feed branch pipe and the reflux branch pipe is provided with at least one control valve; A feed pump (P1) and a valve 2 (K2) are sequentially arranged on the feed pipe 1 (L1) along the direction of the membrane column (F1); a collection pipe (L8) with a valve 1 (K1) is arranged between the feed pump (P1) and the valve 2 (K2) and is connected to a collection tank (V3); The discharge end of the membrane column (F1) is connected to the waste liquid tank (B1).

2. The concentrating device according to claim 1, characterized in that: The feed branch pipe extends to near the bottom of the concentrate storage tank.

3. The concentrating device according to claim 1, characterized in that: The concentrated liquid storage tank comprises a concentration tank 1 (V1) and a concentration tank 2 (V2), and the volume of the concentration tank 1 (V1) is smaller than that of the concentration tank 2 (V2).

4. The concentrating device according to claim 1, characterized in that: The concentrated liquid storage tank is provided with a respirator.

5. The concentrating device according to claim 1, characterized in that: It also includes a backwash pump (P2), the input end of the backwash pump (P2) is connected to the concentrated liquid storage tank, and the output end is connected to the discharge end of the membrane column (F1).

6. The concentrating device according to claim 1, characterized in that: It also includes a concentrated liquid replenishment tank (B3) which is connected to the concentrated liquid storage tank.

7. Aseptic concentration system, characterized in that: It comprises an alkali liquid tank (B2), a cleaning liquid tank (B4) and a concentrating device as described in any one of claims 1 to 6; the alkali liquid tank (B2) is provided with an alkali feed pipe (L10) and an alkali reflux pipe (L11) with valve control, the alkali feed pipe (L10) is connected to a feed pipe 1 (L1), and the alkali reflux pipe (L11) is connected to a reflux pipe 1 (L2); the cleaning liquid tank (B4) is provided with a pipeline with valve control connected to a concentrated liquid storage tank.

8. The aseptic concentration system according to claim 7, characterized in that: A waste liquid pipe (L9) is provided at the discharge end of the membrane column (F1) to connect with the waste liquid tank (B1), and a valve 18 (K18) is provided on the waste liquid pipe (L9); the alkali liquid tank (B2) is also provided with an alkali permeation pipe (L12) to connect with the waste liquid pipe (L9) between the backwash pump (P2) and the valve 18 (K18), and a valve 16 (K16) and a valve 17 (K17) are provided on the alkali permeation pipe (L12); the alkali reflux pipe (L11) is connected between the valve 16 (K16) and the valve 17 (K17).

Images