CN222641701U - Enrichment facility and aseptic concentration system - Google Patents

Abstract

The utility model discloses a concentration device and an aseptic concentration system. The concentration device is connected in parallel through a multi-channel concentrated liquid storage tank with a control valve. Concentration work is performed simultaneously in the early stage to maintain a high circulation flow rate and ensure the permeation efficiency of the membrane column. When the virus liquid droplet is high in the later stage of concentration, it can be switched to single-circuit concentration to continue to complete high-multiple concentration in a container with a smaller dead volume, thereby solving the defect that the concentration device of the prior art is difficult to meet the concentration multiple due to the large dead volume.

Description

Enrichment facility and aseptic concentration system

Technical Field

The utility model relates to the technical field of biological product concentration, in particular to a concentration device and a sterile concentration system.

Background

In the process of producing and manufacturing biological products, a membrane concentration technology is often used, wherein the concentration of virus liquid often needs high-power concentration, and the realization of high-power concentration needs to be compatible with the problems of concentration treatment efficiency and system dead volume loss.

In order to meet concentration treatment efficiency in production, larger membrane area and circulation flow rate can be used, a corresponding ultrafiltration system is required to be matched with a larger feeding and discharging pipeline, when virus liquid enters the later period of concentration, the residual volume of the system is often up to more than 10%, and for high-power concentrated liquid, larger system dead volume can cause larger economic loss when the concentrated liquid cannot be completely collected. In the actual operation process, the process staff can use the buffer to top wash the residual concentrated solution in the concentration system, so that the recovery rate of the sample is improved, the volume after the two collection needs to correspond to the final concentration volume of the process, the volume of the top wash solution cannot be smaller than the dead volume (minimum circulation volume) of the system, the first concentrated solution must use a higher concentration multiple to obtain a smaller volume, a space is reserved for the top wash solution, and excessive concentration is unfavorable for the activity of the virus solution and needs to be avoided in production. In addition, when the virus liquid needs to be concentrated in a high concentration, it is difficult for a system with a large dead volume to meet the process requirements, so how to optimally reduce the minimum circulation volume of the system to avoid excessive concentration is a problem to be considered.

Disclosure of utility model

The utility model aims to provide a concentrating device, which solves the defect that the concentrating device in the prior art is difficult to meet the concentration multiple because of large dead volume.

In order to achieve the above object, the present utility model is as follows:

The concentrating device comprises a concentrated solution storage tank, a membrane column, a collecting tank and a waste liquid tank, wherein:

the concentrated solution storage tank comprises a plurality of parallel connection parts, wherein each part is independently provided with a feeding branch pipe communicated with the feeding pipe I and a reflux branch pipe communicated with the reflux pipe I;

the feeding branch pipe and the reflux branch pipe are respectively provided with at least one control valve;

The first feeding pipe L1 is sequentially provided with a feeding pump P1 and a valve II K2 along the direction of the membrane column F1, and a collecting pipe L8 with the valve I K1 is arranged between the feeding pump P1 and the valve II K2 and is communicated with a collecting tank V3;

The discharge end of the membrane column is communicated with a waste liquid tank.

Further, the feed manifold extends to near the bottom of the concentrate tank.

Further, the concentrated solution storage tank comprises a first concentrated tank and a second concentrated tank, and the volume of the first concentrated tank is smaller than that of the second concentrated tank.

Further, the concentrate storage tank is provided with a breather.

Further, the concentration device also comprises a backwash pump, the input end of the backwash pump is communicated with the concentrated solution storage tank, and the output end of the backwash pump is communicated with the discharge end of the membrane column.

Further, the concentration device also comprises a to-be-concentrated liquid replenishing tank which is communicated with the concentrated liquid storage tank.

Another object of the present utility model is to propose a sterile concentrating system for solving the problem of the aseptic processing of the concentrate. The sterile concentration system comprises an alkali liquid tank, a cleaning liquid tank and the concentration device provided by the above, wherein the alkali liquid tank is provided with an alkali feed pipe and an alkali return pipe which are controlled by valves, the alkali feed pipe is communicated with a first feed pipe, the alkali return pipe is communicated with a first return pipe, and the cleaning liquid tank is provided with a pipeline which is controlled by valves and is communicated with a concentrated liquid storage tank.

The membrane column is characterized in that a waste liquid tank is connected to the discharge end of the membrane column through a waste liquid pipe, a valve eighteen is arranged on the waste liquid pipe, the waste liquid tank is also provided with a waste liquid pipe which is connected between a backwash pump and the valve eighteen through an alkali permeation pipe, a valve sixteen and a valve seventeen are arranged on the alkali permeation pipe, and the alkali backflow pipe is connected between the valve sixteen and the valve seventeen.

Compared with the prior art, the utility model has the beneficial effects that:

The concentrating device disclosed by the utility model has the advantages that the multiple concentrated solution storage tanks with the control valves are connected in parallel, the concentration work is carried out at the early stage, the higher circulating flow is kept, the permeation efficiency of the membrane column is ensured, the concentration device is switched into single-loop concentration at the later stage of concentration when the liquid drop of the virus is higher, and the high-power concentration is continuously finished in a container with smaller dead volume, so that the defect that the concentration multiple is difficult to meet due to the large dead volume of the concentrating device in the prior art is overcome.

Drawings

Fig. 1 is a schematic diagram of a concentrating device provided by the utility model.

Fig. 2 is an overall schematic diagram of the aseptic concentrating system provided by the present utility model.

The device comprises a B1, a waste liquid tank, a B2, an alkali liquid tank, a B3, a to-be-concentrated liquid supplementing tank, a B4, a cleaning liquid tank, a V1, a first concentrating tank, a V2, a second concentrating tank, a V3, a collecting tank, a F1, a membrane column, a F2, a sterilizing filter, a L1, a first feeding pipe, a L2, a first backflow pipe, a L3, a second feeding pipe, a L4, a third feeding pipe, a L5, a second backflow pipe, a L6, a third backflow pipe, a L7, a fourth feeding pipe, a L8, a collecting pipe, a L9, a waste liquid pipe, a L10, an alkali feeding pipe, a L11 and an alkali backflow pipe, a L12 and an alkali permeation pipe, wherein K1-K18 correspond to a valve I to a valve eighteen, a P1, a feeding pump, a P2, a backwash pump, a R1, a respirator I, a R2 and a respirator II.

Detailed Description

The following description of the embodiments of the present utility model will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present utility model, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the utility model without making any inventive effort, are intended to be within the scope of the utility model.

It is to be understood that the terms "upper," "lower," "top," "bottom," "inner," "outer," and the like are used in an orientation or positional relationship based on that shown in the drawings, merely to facilitate describing the present utility model and to simplify the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus should not be construed as limiting the present utility model.

It should be further noted that unless explicitly stated or limited otherwise, terms such as "mounted," "connected," "secured," "disposed," and the like are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally formed, mechanically connected, electrically connected, directly connected, indirectly connected via an intermediate medium, or in communication between two members or in an interaction relationship between two members. It will be apparent to those skilled in the art that the terms described above have the particular meaning in the present utility model, as the case may be.

In a first embodiment, as shown in fig. 1, a concentrating device is provided, which comprises a concentrated solution storage tank, a membrane column F1, a collecting tank V3 and a waste liquid tank B1, wherein the concentrated solution storage tank is provided with a feed pipe I1 and a return pipe I2 which are communicated with a feed end of the membrane column F1, the concentrated solution storage tank comprises a plurality of parallel connection parts, each of which is respectively and independently provided with a feed branch pipe communicated with the feed pipe I1, a return branch pipe I2, at least one control valve is arranged on each of the feed branch pipe and the return branch pipe, the feed pipe I1 is sequentially provided with a feed pump P1 and a valve II K2 along the direction of the membrane column F1, a collecting pipe L8 with the valve I K1 is arranged between the feed pump P1 and the valve II K2 and is communicated with the collecting tank V3, and a discharge end of the membrane column F1 is communicated with the waste liquid tank B1 through a waste liquid pipe L9.

In the above embodiment, in the concentrating device, the concentrated solution storage tank and the membrane column F1 form a concentrating loop, the waste liquid formed by permeating through the membrane column F1 is collected by the waste liquid tank B1, when the concentration reaches the target multiple, the valve two K2 is closed, the valve one K1 is opened, and the concentrated solution is collected into the collecting tank V3 under the action of the feed pump P1. In the early stage, under the condition that the feeding branch pipe and the reflux branch pipe are opened, the parallel connection of multiple concentrated solution storage tanks can be realized, the higher circulating flow is kept, the permeation efficiency of a membrane column is ensured, and in the later stage of concentration, the high-power concentration is continuously finished in a small container with smaller dead volume by controlling the valves on the feeding branch pipe and the reflux branch pipe to switch into single-loop concentration.

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 being discharged from the filtering end through the filter membrane, and large virus particles cannot return to the concentrated liquid storage tank through the return pipe L2 through the filter membrane, so that the volume of the virus liquid is continuously reduced along with the continuous increase of the filtrate, and the virus content is improved, thereby realizing the concentration effect.

In a preferred embodiment, as shown in fig. 1, the concentrate tank includes a first concentrate tank V1 and a second concentrate tank V2, the first concentrate tank V1 having a smaller volume than the second concentrate tank V2. The first concentrating tank V1 is provided with a feeding pipe II L3 communicated with the feeding pump P1, and the first concentrating tank V1 is provided with a return pipe II L5 communicated with the return pipe I L2. The second concentrating tank V2 is provided with a feeding pipe three L4 communicated with a feeding pump P1, and a return pipe three L6 communicated with a return pipe one L2. Valve III K3 and valve IV K4 are correspondingly arranged on the feed pipe II L3 and the feed pipe III L4, valve five K5 and valve six K6 are correspondingly arranged on the return pipe II L5 and the return pipe III L6, and valve seven K7 is arranged on the return pipe I L2. During operation, the valves from the second K2 to the seventh K7 are kept open in the early stage to realize the simultaneous operation of the two concentrating tanks, the valve is closed for six K6 after the concentration reaches a certain concentration multiple, the concentrated solution in the second V2 of the concentrating tank is pumped out, then the valve is closed for four K4, the switching of the first V1 of the concentrating tank is realized at the moment, the volume of the concentrating system is reduced in the high-power concentrating stage, the dead volume is reduced, and the target concentration multiple is easier to realize. The double-feeding and double-return pipeline system can realize high circulation flow and improve concentration treatment efficiency, adopts single-path small-volume circulation in the later concentration stage, ensures recovery rate, can reduce excessive concentration multiple, effectively protects activity of concentrated solution, and is applicable to biological products with small concentration treatment volume and high target concentration multiple.

In a preferred embodiment, the second feeding pipe L3 and the third feeding pipe L4 extend to be close to the bottom of the storage tank, so that residues in the storage tank can be reduced. In addition, the first V1 and the second V2 of the concentration tank are correspondingly provided with a first R1 and a second R2 of the respirator respectively, and the first and second V are used for balancing pressure or applying air pressure into the tank to collect residual concentrated liquid along a pipeline. Taking the residual concentrated solution in the three L6 collecting return pipes as an example, closing the valve IV K4, stopping the feeding pump P1, and opening the valve V5 to the valve V7, wherein the second respirator R2 presses air into the second concentrating tank V2 and the residual concentrated solution enters the first concentrating tank V1 and the membrane column F1 from the first return pipe L2 and the second return pipe L5 from bottom to top through the valve V6.

In a preferred embodiment, as shown in fig. 1, the concentrating device further comprises a backwash pump P2 provided on the waste liquid pipe L9. The backwashing pump P2 can work forward and backward, provides power for waste liquid output during forward rotation, and is used for backwashing and cleaning the membrane column F1 during backward rotation. Specifically, a valve nine K9 and a valve ten K10 are arranged on the waste liquid pipe L9, the valve nine K9 is close to the waste liquid tank B1, a pipeline with a valve eight K8 is arranged between the valve nine K9 and the valve ten K10 and is communicated with a return pipe three L6, and a valve eleven K11 is arranged at the position of the return pipe three L6 close to the second V2 tank opening of the concentration tank. When the concentration is carried out, the valve eight K8 is closed, the valve nine K9 to the valve eleven K11 are opened, when the back washing is carried out, the feeding pump P1 stops working, the valve nine K9 is closed, the valve eighteen K18 is opened, the back washing pump P2 works reversely, and the concentrated solution of the second V2 of the concentration tank reversely enters the membrane column F1 along the waste liquid pipe L9 to carry out the back washing.

In the above embodiment, the first concentrating tank V1 is communicated with the four L7 feeding pipes, and is provided with twelve K12 valves for replenishing the concentrated solution in the first concentrating tank V1. In particular, during concentration, in order to ensure that the first V1 and the second V2 of the concentration tank are synchronously concentrated, the control of the feeding ratio can be realized by controlling the opening and closing degree of the valve III K3 and the valve IV K4, and the control of the reflux ratio can be realized by controlling the opening and closing degree of the valve V5 and the valve V6.

In a second embodiment, as shown in fig. 2, a sterile concentration system is provided, which includes a tank B2 for the alkali solution, a tank B3 for replenishing the solution to be concentrated, a tank B4 for the cleaning solution, and the concentration device according to the first embodiment. Wherein:

The alkali liquor tank B2 is provided with an alkali feed pipe L10 with a valve fourteen K14 for controlling, a valve fifteen K15 for controlling an alkali return pipe L11, the alkali feed pipe L10 is communicated with a feed pipe I1 at the left end of the feed pump P1, and the alkali return pipe L11 is communicated with a return pipe I2 at the right end of a valve seven K7;

The to-be-concentrated liquid supplementing tank B3 and the cleaning liquid tank B4 are respectively communicated with four L7 of a concentrated liquid feeding pipe, a valve thirteenth K13 is further arranged at the lower end of the valve twelve K12, and a return pipe II L5 is communicated between the valve twelve K12 and the valve thirteenth K13. When the valves twelve K12 and thirteen K13 are opened, the to-be-concentrated liquid and the cleaning liquid can be respectively supplemented into the first concentrating tank V1 so as to enter the whole concentrating and circulating loop.

In the above embodiment, before the concentration operation, the first and second concentrating tanks V1 and V2 are not filled with the solution to be concentrated, the valve two K2 to the valve seven K7, the valve fourteen K14 and the valve fifteen K15 are opened, the valve one K1 is closed, the feed pump P1 is started, and at this time, the alkali solution enters the concentration circulation loop to perform alkaline washing sterilization on the first concentrating tank V1, the second concentrating tank V2 and the membrane column F1.

In the preferred embodiment, the outlet of the cleaning solution tank B4 is provided with a sterilizing filter F2, the cleaning solution can be pure water, and the cleaning solution can enter the circulating system through the concentration tank V1 and clean the system after alkaline cleaning and sterilization until the pH value is neutral, so that the system is qualified. In addition, the cleaning solution can also select buffer solution, and can pass through the first concentration tank V1, enter the membrane column F1 through the second feeding pipe L3 and the first feeding pipe L1 to wash the filter membrane.

In the preferred embodiment, valve eighteen K18 is arranged on waste liquid pipe L9, alkali liquor tank B2 is also provided with waste liquid pipe L9 which is communicated between backwash pump P2 and valve eighteen K18 through alkali permeation pipe L12, valve sixteen K16 and valve seventeen K17 are arranged on alkali permeation pipe L12, and alkali return pipe L11 is communicated between the two valves. When the concentration work is finished and the membrane column F1 needs to be reversely cleaned to recover flux, the valve eighteen K18 is closed, the valve sixteen K16 and the valve seventeen K17 are opened, the backwash pump P2 is reversed, and alkali liquor reversely enters the membrane column F1 from the alkali permeation tube L12 to backwash, so that the flux of the filter membrane is recovered, and the concentration efficiency is improved. Preferably, in the backwashing process, the feed pump P1, the valve II K2, the valve fourteen K14 and the valve fifteen K15 are all opened, alkali liquor is fed forward through the alkali feed pipe L10 and flows back simultaneously, and the membrane column F1 is backwashed through the alkali permeation pipe L12, so that damage to a filter membrane caused by overlarge backwashing pressure is avoided. In the concentration working process, when the flux of the membrane column F1 needs to be recovered, the concentrated solution can be transferred to the second concentration tank V2, and the cleaning solution tank B4 is started to supplement the buffer solution to the concentration tank V1. Closing the feeding and return pipelines of the second concentrating tank V2, opening the feeding and return pipelines of the concentrating tank V1 and the feeding pump P1 to circulate buffer solution to the membrane column F1, closing the valve sixteen K16 and the valve eighteen K18, opening the valve fifteen K15 and the valve seventeen K17, reversing the backwashing pump P2, and shunting the buffer solution to the alkali permeation tube L12 to reversely enter the membrane column F1 for backwashing.

Although embodiments of the present utility model have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the utility model, the scope of which is defined in the appended claims and their equivalents.

Claims (8)

1. The concentrating device is characterized by comprising a concentrated solution storage tank, a membrane column (F1), a collecting tank (V3) and a waste liquid tank (B1), wherein:

The concentrated solution storage tank is provided with a feed pipe I (L1) and a return pipe I (L2) which are communicated with the feed end of the membrane column (F1), and comprises a plurality of parallel connection parts, wherein the feed pipe I (L1) and the return pipe I (L2) are respectively and independently provided with a feed branch pipe and a return branch pipe;

the feeding branch pipe and the reflux branch pipe are respectively provided with at least one control valve;

The first feeding pipe (L1) is sequentially provided with a feeding pump (P1) and a valve II (K2) along the direction of the membrane column (F1), and a collecting pipe (L8) with the valve I (K1) is arranged between the feeding pump (P1) and the valve II (K2) and is communicated with the collecting tank (V3);

the discharge end of the membrane column (F1) is communicated with a waste liquid tank (B1).

2. The concentrating apparatus of claim 1 wherein said feed manifold extends to near the bottom of the concentrate reservoir.

3. The concentrating device of claim 1 wherein the concentrate reservoir comprises a first concentrate tank (V1) and a second concentrate tank (V2), the first concentrate tank (V1) having a smaller volume than the second concentrate tank (V2).

4. The concentrating apparatus of claim 1 wherein said concentrate reservoir is provided with a breather.

5. The concentrating device according to claim 1, further comprising a backwash pump (P2), wherein an input of the backwash pump (P2) is connected to the concentrate reservoir and an output is connected to a discharge of the membrane column (F1).

6. The concentrating device according to claim 1, further comprising a tank (B3) for replenishing the concentrate to be concentrated in communication with the concentrate tank.

7. The sterile concentration system is characterized by comprising an alkali liquid tank (B2), a cleaning liquid tank (B4) and a concentration device according to any one of claims 1-6, wherein the alkali liquid tank (B2) is provided with an alkali feed pipe (L10) with valve control and an alkali return pipe (L11), the alkali feed pipe (L10) is communicated with a first feed pipe (L1), the alkali return pipe (L11) is communicated with a first return pipe (L2), and the cleaning liquid tank (B4) is provided with a pipeline with valve control and communicated with a concentrate storage tank.

8. The sterile concentration system according to claim 7, wherein a waste liquid pipe (L9) is arranged at the discharge end of the membrane column (F1) and is communicated with a waste liquid tank (B1), a valve eighteen (K18) is arranged on the waste liquid pipe (L9), the alkali liquid tank (B2) is further provided with an alkali permeation pipe (L12) which is communicated with the waste liquid pipe (L9) between a backwashing pump (P2) and the valve eighteen (K18), a valve sixteen (K16) and a valve seventeen (K17) are arranged on the alkali permeation pipe (L12), and the alkali backflow pipe (L11) is communicated between the valve sixteen (K16) and the valve seventeen (K17).