Feed-liquid separation system

Abstract

The utility model provides a feed liquid separation system which comprises a plurality of separation units which are sequentially connected in series, the number of the separation units is N, the multiple separation units are sequentially numbered as 1-N in the flowing direction of feed liquid, N is larger than or equal to 2, the separation unit numbered as 1 is defined as an initial separation unit and used for inputting to-be-separated feed liquid, and the separation unit numbered as 1 is defined as a separation unit numbered as 2; the separation unit numbered as N is defined as a tail separation unit and outputs the feed liquid separated by the N separation units, and the height of the initial separation unit is higher than that of the tail separation unit. A height difference is formed between an initial separation unit and a tail separation unit, a gravitational potential energy difference is formed between the initial separation unit and the tail separation unit, the gravitational potential energy difference supplements pressure drop generated in the front-end separation process of feed liquid, it is ensured that the feed liquid has enough filtering driving force in the tail separation unit, and initial pressure provided by a liquid inlet pump is not excessively increased; and the possibility of inactivation of shear force sensitive active substances in the feed liquid is obviously reduced.

Description

Technical Field

[0001] This utility model relates to the field of separation technology, and in particular to a liquid-material separation system. Background Technology

[0002] In the current medical and biopharmaceutical industries, high-concentration formulations represent the future direction. For example, high-titer viral vectors offer both high efficiency and safety in gene therapy, while high-concentration protein formulations significantly improve efficacy and reduce costs in drug development and clinical use. However, simultaneously increasing concentration while maintaining the activity of the components remains a challenge. Taking enveloped viruses and proteins with unstable three-dimensional structures as examples, increasing their concentration often requires separating components such as buffers through a concentration system. However, the concentration process is often accompanied by significant shear forces, which can lead to viral inactivation, protein depolymerization, or structural deformation, causing these shear-sensitive active substances to lose their corresponding efficacy and function.

[0003] Tangential flow filtration (TFF), as provided in US Patent No. 7520988B2, is one of the most common concentration filtration methods, offering excellent filtration capacity and product yield. However, when applied to the production of shear-sensitive high-concentration formulations, the continuous high flow rate of the feed solution, the gradual increase in viscosity, and the large shear forces resulting from repeated pressurization by the circulating pump during the TFF process can cause irreversible damage to the active ingredients.

[0004] To address the shortcomings of TFF (Tangential Flow Filtration), a Single-Pass Tangential Flow Filtration (SPTFF) method is proposed and is suitable for large-scale production. Compared to TFF, the SPTFF method connects multiple tangential flow filtration components in series, enabling high-fold concentration in a single pass. Another improvement is that the feed liquid flows at a low velocity throughout the channel, eliminating the need for repeated pressurization by a pump and reducing some shear forces. However, due to the multi-stage series connection and the superposition of resistance of the multi-stage filtration components, the overall filtration resistance of the system is relatively large. The feed liquid pressure is high but cannot be replenished. In order to ensure that the feed liquid has a certain flow rate and initial pressure so that it can pass through the downstream tangential flow filtration components to achieve the purpose of concentration, the upstream feed pump must provide the feed liquid with a very high initial pressure. Otherwise, the concentration efficiency of the entire system will be very low. Because the initial pressure and flow rate of the feed liquid are very high, the flow velocity of the feed liquid is very high during its flow through the upstream of the system, and the feed liquid is subjected to a very high shear force. In other words, the existing SPTFF method has not completely solved the problem of high shear force damaging the material and the resulting deactivation of active ingredients. In fact, the problem of difficulty in achieving both high concentration and low shear force still exists.

[0005] Therefore, it is necessary to further improve the existing single-pass tangential flow filtration system to significantly reduce the possibility of deactivation of shear-sensitive active substances in the feed solution while ensuring a certain separation rate and separation efficiency. Summary of the Invention

[0006] To address the problems in existing tangential flow filtration systems or single-pass tangential flow filtration systems, such as repeated pump pressurization, excessive feed flow rate, and excessive shear force, which damage the materials and cause deactivation of active ingredients in the feed solution, the following technical solution is proposed.

[0007] A liquid-material separation system includes multiple separation units connected in series, the number of which is N. Following the flow direction of the liquid, the multiple separation units are sequentially numbered 1-N, where N≥2. The separation unit numbered 1 is defined as the starting separation unit and is used to input the liquid to be separated. The separation unit numbered N is defined as the ending separation unit and is used to output the liquid processed by the N separation units. The height of the starting separation unit is higher than the height of the ending separation unit.

[0008] As the feed liquid flows from the initial separation unit to the inlet port of the final separation unit, the concentration of the feed liquid increases, and correspondingly, the viscosity of the feed liquid also increases, resulting in an increase in the flow resistance that the feed liquid needs to overcome when passing through the final separation unit.

[0009] In the feed-liquid separation system provided in this application, the height of the initial separation unit is higher than that of the final separation unit, i.e., there is a height difference between the initial and final separation units. As the feed liquid flows from the initial separation unit to the final separation unit, the height decreases, and the gravitational potential energy decreases. This decrease in gravitational potential energy is converted into a transmembrane driving force at the inlet port of the final separation unit, thus increasing the pressure of the feed liquid at the inlet port of the final separation unit. This increases the pressure difference between the upstream and downstream sides of the final separation unit, which can at least partially offset the increase in flow resistance caused by the increase in viscosity, allowing the feed liquid to smoothly pass through the final separation unit to complete the separation. Therefore, by setting a height difference between the initial and final separation units, the initial transmembrane driving force of the feed liquid provided by the feed pump can be reduced accordingly. Consequently, this greatly reduces the shear force experienced by the feed liquid when pressurized in the pump, without affecting the sequential passage of the feed liquid through multiple separation units. Furthermore, by adjusting the height difference between the initial separation unit and the final separation unit according to the characteristics of the actual liquid system, this system can be adapted to the separation process of liquids with different characteristics. This significantly reduces the initial pressure provided by the feed pump, and the shear force experienced by the liquid as it passes through the separation unit at the front end of the separation system is greatly reduced, thereby better solving the problem of deactivation of the target components in the liquid due to excessive shear force.

[0010] In simple terms, this involves creating a height difference between the initial and final separation units, thereby generating a gravitational potential energy difference. This difference increases the pressure of the feed solution at the inlet of the final separation unit. Since feed pressure is the primary driving force for transmembrane flow, it offsets some of the flow resistance the feed solution needs to overcome to pass through the final separation unit. This ensures that the feed solution can still pass through the final separation unit at a relatively high rate without excessively increasing the initial pressure provided by the feed pump, and reduces the risk of deactivation of target components in the feed solution. Consequently, the feed solution achieves both high concentration and low shear force, significantly solving the current problem of the difficulty in simultaneously achieving high concentration and low shear force.

[0011] It is particularly important to note that even shear-sensitive active materials are not entirely intolerant of shear force. However, as the shear force gradually increases, the probability of damage and inactivation increases significantly. Especially after reaching a certain threshold, noticeable damage and inactivation will occur. Furthermore, the shear force experienced by the feed liquid in the pump is the greatest in the entire system, making it a critical control node. The separation system in this application reduces the shear force experienced by the feed liquid during pump pressurization at the critical control node by controlling the elevation difference between the separation units at non-critical nodes, thus significantly reducing the shear force experienced by the feed liquid throughout the entire separation system. Moreover, compared to pump pressurization, gravity pressurization is significantly gentler, resulting in lower shear force even at the end of the separation unit where the feed liquid viscosity is higher.

[0012] Furthermore, the number of separation units N≥3, the separation unit located between the starting separation unit and the ending separation unit is the intermediate separation unit, and the height of the intermediate separation unit is not higher than the height of the starting separation unit and not lower than the height of the ending separation unit.

[0013] The number of intermediate separation units can be selected as needed, for example, one, two, or more, which can easily increase the effective separation area of ​​the entire feed-liquid separation system and improve separation efficiency. The height of each intermediate separation unit is no higher than the height of the initial separation unit and no lower than the height of the final separation unit, which can avoid reverse gravitational potential energy caused by reverse height difference. Of course, if the separation and concentration requirements of the feed liquid are high, making it difficult for the system to reach the required concentration in a single run, it is acceptable to transport the feed liquid output from the final separation unit to the initial separation unit for further separation and concentration through pipelines, etc. Compared with ordinary TFF systems, this system still significantly reduces the shear force caused by repeated pump pressurization.

[0014] It should be noted that when there are two or more intermediate separation units, there can be a height difference between any two adjacent intermediate separation units, or only some of the intermediate separation units can have a height difference. For example, two adjacent intermediate separation units can be of equal height, or the height of the later separation unit can be lower than the height of the earlier separation unit. However, regardless of the number of intermediate separation units or their relative heights, the height of all intermediate separation units should not be higher than the height of the starting separation unit and should not be lower than the height of the last separation unit.

[0015] Depending on the actual properties and requirements of different feed liquids, the setting of the intermediate separation unit can be adaptively adjusted without affecting the overall feed liquid separation system. By creating a height difference between the initial separation unit and the final separation unit, and increasing the pressure at the inlet port of the final separation unit, the separation efficiency can be improved while protecting the activity of the target components in the feed liquid.

[0016] Furthermore, the height difference ΔH between two adjacent separation units satisfies ΔH N-2 ≤ΔH N-1 , where ΔH N-2 Let ΔH be the height difference between separation unit N-2 and separation unit N-1. N-1 This represents the height difference between the separation unit numbered N-1 and the separation unit numbered N.

[0017] In the entire feed-liquid separation system, the concentration of the feed gradually increases along the flow direction. According to the modified Mooney equation, the viscosity of the feed increases exponentially with concentration, and the flow resistance also increases with viscosity. Therefore, the flow resistance increases more rapidly in the later part of the feed flow direction. This means that the feed faces the greatest flow resistance when passing through separation unit N, or the flow resistance to pass through separation unit N is at least as great as that to pass through separation unit N-1. Therefore, it is necessary to increase the height difference between separation units N-1 and N, i.e., ΔH in the entire feed-liquid separation system. N-1 It should be the maximum, or at least not less than ΔH. N-2 This ensures that the gravitational potential energy difference is large enough when the liquid flows from the N-1 separation unit to the N separation unit, thus offsetting the greater flow resistance that the liquid needs to overcome to pass through the N separation unit and ensuring that the liquid can pass through the final separation unit at a relatively fast rate.

[0018] Furthermore, the number of separation units N ≥ 4, ΔH N-2 <ΔH N-1 And ΔH N-1 -ΔHN-2 ≥ΔH2-ΔH1.

[0019] Further optimization of the height difference between adjacent separation units can further reduce the initial pressure of the feed pump, providing better protection for the active ingredients in the feed solution. Specifically, as mentioned earlier, the viscosity of the feed solution increases exponentially with concentration, and the concentration of the feed solution increases after each separation unit. This means that the viscosity of the feed solution increases closer to the last separation unit, requiring a larger transmembrane pressure difference for separation, i.e., a greater transmembrane driving force. Therefore, when there are many separation units, the height difference between the first, second, and third separation units should be smaller than that between the last two separation units, and the height difference between adjacent units should also be smaller than the height difference between the last three separation units. Of course, ΔH1 and ΔH2 can be 0, in which case the difference between ΔH1 and ΔH2 is 0.

[0020] Furthermore, all N separation units are tangential flow filtration components, each having an inlet port, a permeate port, and a residual permeate port.

[0021] Any two adjacent separation units are connected in series through the residual liquid port of the preceding separation unit and the liquid inlet port of the following separation unit.

[0022] Preferably, all separation units are hollow fiber tangential flow filter components.

[0023] Furthermore, the ratio of the feed volume to the residual liquid volume of the initial separation unit is denoted as V1, and the ratio of the feed volume to the residual liquid volume of the final separation unit is denoted as V. N Satisfying: V1≥V N .

[0024] Following the flow direction of the feed liquid, the volume of the feed liquid gradually decreases before and after passing through a certain separation unit, while the concentration gradually increases. The closer to the next separation unit, the slower the increase in concentration. Correspondingly, the volume decrease before and after passing through the next separation unit also slows down. Therefore, the ratio of feed volume to residual liquid volume gradually decreases, meaning the concentration rate gradually declines. It should be noted that although various types of tangential flow filter modules can be used in this system, hollow fiber tangential flow filter modules are a better choice than membrane-encapsulated tangential flow filter modules because they do not require supporting screens and other components, thus reducing the likelihood of additional shear forces.

[0025] Furthermore, at least one of the separation units has a flow control component installed at its permeate port.

[0026] The flow control component is used to adjust the flow rate of the residual liquid discharged from the separation unit, and can also be used to adjust the flow resistance of the residual liquid port of the corresponding separation unit. Thus, under the premise that the feed liquid pressure upstream of the filter membrane remains unchanged, the pressure of the residual liquid downstream of the filter membrane is adjusted, thereby controlling the transmembrane pressure difference of the separation unit, so as to regulate the transmembrane driving force and flow rate of the separation unit, which facilitates the improvement of the overall flow rate stability and uniformity of the separation system.

[0027] Furthermore, the effective separation area of ​​the initial separation unit is denoted as S1, and the effective separation area of ​​the final separation unit is denoted as S... N Satisfying: S1≥S N .

[0028] In a feed-liquid separation system, the closer to the initial separation unit, the lower the viscosity of the feed liquid, and the easier the transmembrane separation. Therefore, the flow rate of the feed liquid through the initial separation unit is greater than that through the final separation unit. Based on the different flow rates, in order to make the flow rates of the initial and final separation units more similar, so that the entire system has a relatively stable flow rate and avoids the generation of shear force due to flow rate changes, the initial separation unit can be further controlled to have a larger effective separation area, while the final separation unit has a smaller effective separation area.

[0029] Furthermore, the number of separation units N ≥ 3, and the effective separation area of ​​the separation unit numbered N-2 is denoted as S. N-2 The effective separation area of ​​the separation unit numbered N-1 is denoted as S. N-1 Satisfying: S N-2 ≥S N-1 ≥S N And S N-2 -S N-1 ≥S N-1 -S N .

[0030] In the entire liquid-feed separation system, the flow rate of the liquid gradually decreases along the flow direction. Therefore, the effective separation area required by the separation unit gradually decreases. Furthermore, the rate of decrease in flow rate slows down towards the later stage, and correspondingly, the rate of decrease in the effective separation area of ​​the separation unit also slows down. This can improve the uniformity of the flow rate and avoid the generation of shear force caused by uneven flow rate.

[0031] Furthermore, at least one of the separation units consists of a plurality of tangential flow filter components connected in parallel and of equal height.

[0032] To control the effective separation area of ​​the separation unit, tangential flow filter components of different specifications can be selected. For example, a larger tangential flow component can be used for the initial separation unit. Alternatively, multiple tangential flow filter components of the same or different specifications can be connected in parallel to control the effective separation area of ​​that stage of the separation unit. Of course, to ensure that each tangential flow filter component in the same stage of the separation unit has a basically the same separation process, it is preferable to control multiple parallel tangential flow filter components to have the same height and consistent specifications.

[0033] The beneficial effects of this invention are as follows: By creating a height difference between the initial separation unit and the final separation unit connected in series in the liquid-feed separation system, a gravitational potential energy difference is formed between them. This gravitational potential energy difference increases the inlet pressure of the liquid at the final separation unit, offsetting part of the flow resistance that the liquid needs to overcome to pass through the final separation unit. Thus, without excessively increasing the initial pressure provided by the inlet pump, it is possible to ensure that the liquid can pass through the final separation unit at a higher rate, significantly reducing the problem of deactivation of the target components in the liquid. Attached Figure Description

[0034] Figure 1 This is the liquid-material separation system provided in Embodiment 1 of the present invention;

[0035] Figure 2 This is the liquid-material separation system provided in Embodiment 2 of this utility model.

[0036] Among them, 10-liquid separation system, 11-initial separation unit, 12-final separation unit, 13-intermediate separation unit, 14-intermediate separation unit, 20-flow control component, 30-feed pump, 40-raw material liquid container, 50-permeate container, 60-residual liquid container. Detailed Implementation

[0037] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort should fall within the scope of protection of the present invention.

[0038] Example 1

[0039] like Figure 1The liquid separation system 10 shown includes multiple separation units connected in series. In this embodiment 1, the number of separation units is 2. Following the flow direction of the liquid, the two separation units are numbered 1 and 2 in sequence. The separation unit numbered 1 is defined as the starting separation unit 11 and is used to input the liquid to be separated. The separation unit numbered 2 is defined as the ending separation unit 12 and is used to output the liquid separated by the two separation units. The height of the starting separation unit 11 is higher than the height of the ending separation unit 12.

[0040] Specifically, both the initial separation unit 11 and the final separation unit 12 are tangential flow filtration components. For example, they can be hollow fiber components disclosed in the prior art, such as those with patent numbers US6544424B1 and CN219922602U, or conventionally commercially available hollow fiber components, depending on the characteristics of the feed liquid; or stacked tangential flow filtration membrane packs disclosed in the prior art, such as those with patent numbers CN219376699U, CN220779353U, US20050269255A1, and US20080264852A1, or conventionally commercially available membrane pack components, depending on the characteristics of the feed liquid.

[0041] Among them, the tangential flow filtration component is used for the separation of components in the feed solution, specifically for the concentration, buffer replacement, and purification of the feed solution.

[0042] Tangential flow filtration components all have an inlet port, a permeate port, and a residual liquid port. The permeate port is used to discharge small molecule materials such as solvents that have passed through the hollow fiber membrane or ultrafiltration membrane, while the residual liquid port is used to discharge large molecule materials that have not passed through the hollow fiber membrane or ultrafiltration membrane.

[0043] The initial separation unit 11 and the final separation unit 12 are connected in series to form a liquid-material separation system 10. The actual usage of this liquid-material separation system 10 is as follows:

[0044] The raw material liquid container 40 is connected to the inlet port of the initial separation unit 11 via a pipeline to input the liquid to be separated into the initial separation unit 11. A feed pump 30 is also installed on this pipeline to adjust the feed pressure and flow rate. The permeate port of the initial separation unit 11 and the inlet port of the final separation unit 12 are connected in series via a pipeline. A flow control component 20 is installed on this pipeline or at the permeate port of the initial separation unit 11. Both the permeate port of the initial separation unit 11 and the permeate port of the final separation unit 12 discharge their respective permeates to the permeate container 50 via pipelines. The permeate port of the final separation unit 12 discharges the liquid, i.e., the permeate, after separation by the two separation units, to the permeate container 60 via another pipeline. Specifically, the flow control component 20 can be a valve.

[0045] by Figure 1Taking the direction shown as an example, the starting separation unit 11 is located above the ending separation unit 12, and there is a height difference between the two. Alternatively, at least the axial center line of the starting separation unit 11 is higher than the axial center line of the ending separation unit 12.

[0046] Preferably, when both the starting separation unit 11 and the ending separation unit 12 are hollow fiber assemblies, the hollow fiber assemblies are placed horizontally.

[0047] As the liquid flows from the initial separation unit 11 to the inlet port of the final separation unit 12, the concentration of the liquid increases, and correspondingly, the viscosity of the liquid also increases, resulting in an increase in the flow resistance that the liquid needs to overcome when passing through the final separation unit 12.

[0048] In the liquid-feed separation system 10 provided in this application, the height of the initial separation unit 11 is higher than the height of the final separation unit 12, i.e., there is a height difference between the initial separation unit 11 and the final separation unit 12. As the liquid flows from the initial separation unit 11 to the final separation unit 12, the height decreases, and the gravitational potential energy decreases. This decreased gravitational potential energy is converted into pressure potential energy at the inlet port of the final separation unit 12, thus increasing the pressure of the liquid at the inlet port of the final separation unit 12. This can increase the pressure difference between the upstream and downstream sides of the final separation unit 12, and can at least partially offset the flow caused by the increase in viscosity. The increased resistance allows the liquid to pass through the final separation unit 12 at a faster rate. Consequently, the initial pressure provided by the feed pump 30 can be reduced accordingly. As a result, the flow rate of the liquid through the separation unit at the front of the liquid separation system 10 decreases, and the shear force it experiences is reduced. Furthermore, the height difference between the initial separation unit 11 and the final separation unit 12 can be adjusted as needed to significantly reduce the initial pressure provided by the feed pump 30. The shear force experienced by the liquid during its passage through the separation unit at the front of the liquid separation system 10 is greatly reduced, thereby completely solving the problem of deactivation of the target components in the liquid due to excessive shear force.

[0049] In short, by creating a height difference between the initial separation unit 11 and the final separation unit 12, a gravitational potential energy difference is formed between them. This gravitational potential energy difference increases the pressure of the liquid at the inlet port of the final separation unit 12, offsetting some of the flow resistance that the liquid needs to overcome to pass through the final separation unit 12. Thus, without excessively increasing the initial pressure provided by the inlet pump 30, it is ensured that the liquid can still pass through the final separation unit 12 at a relatively high rate, and the problem of deactivation of the target component in the liquid is completely solved.

[0050] In a single tangential flow filtration operation, the ratio of the feed volume to the residual liquid volume in the initial separation unit 11 is denoted as V1, and the ratio of the feed volume to the residual liquid volume in the final separation unit 12 is denoted as V2, satisfying the condition: V1 ≥ V2. Specifically, this can be understood as follows: For example, in the initial stage of a tangential flow filtration operation, the feed volume into the initial separation unit 11 is 10L, the volume of residual liquid output from the initial separation unit 11 is 6L, this 6L of residual liquid is fed into the final separation unit 12, and the final volume of residual liquid output from the final separation unit 12 is 4L. Calculations show V1 = 1.67 and V2 = 1.5, i.e., V1 > V2.

[0051] The reasons for the above phenomenon are as follows: along the flow direction of the liquid, the volume of the liquid before and after passing through a certain separation unit will gradually decrease, and the concentration of the liquid will gradually increase. The closer to the later separation unit, the slower the increase in the concentration of the liquid. Correspondingly, the volume of the liquid before and after passing through the later separation unit will decrease more slowly. Therefore, the ratio of feed volume to residual liquid volume will gradually decrease, that is, the concentration rate will gradually decrease.

[0052] Because the flow rate or volume of the liquid passing through the initial separation unit 11 in the liquid-feed separation system 10 is greater than that passing through the final separation unit 12, the initial separation unit 11 needs a larger effective separation area. The effective separation area of ​​the initial separation unit 11 is denoted as S1, and the effective separation area of ​​the final separation unit 12 is denoted as S2, satisfying: S1 ≥ S2. This ensures that the flow velocity of the liquid passing through the initial separation unit 11 and the flow velocity passing through the final separation unit 12 are closer to or equal to the flow velocity of the liquid, preventing turbulence and fluid impact caused by velocity changes from damaging target components such as proteins and viruses in the liquid.

[0053] Preferably, the starting separation unit 11 and / or the ending separation unit 12 are composed of multiple tangential flow filter components connected in parallel and of equal height, thereby allowing for convenient adjustment of the effective separation area of ​​the starting separation unit 11 and the ending separation unit 12. For example, the starting separation unit 11 may include two, three or more tangential flow filter components connected in parallel and of equal height, and the ending separation unit 12 may include two, three or more tangential flow filter components connected in parallel and of equal height.

[0054] Example 2

[0055] In this embodiment, as Figure 2As shown, the number of separation units is 4, i.e., N=4. Following the flow direction of the liquid, the four separation units are numbered 1, 2, 3, and 4 sequentially. That is, based on Example 1, two intermediate separation units 13 and 14 are connected in series between the initial separation unit 11 and the final separation unit 12. The height of the initial separation unit 11 is higher than the height of the final separation unit 12, and the height of the intermediate separation units 13 and 14 is lower than the height of the initial separation unit 11 but higher than the final separation unit 14. Figure 2 Taking the direction shown as an example, the starting separation unit 11, the intermediate separation unit 13, the intermediate separation unit 14, and the ending separation unit 12 are connected in series, with the installation height gradually decreasing, and there is a height difference between any two adjacent separation units.

[0056] The intermediate separation units 13 and 14 can increase the overall effective separation area of ​​the liquid separation system 10, thereby improving the separation efficiency. They do not affect the overall protection of the activity of the target components in the liquid. The pressure of the liquid at the inlet port of the end separation unit 12 is increased by the height difference between the starting separation unit 11 and the end separation unit 12, without affecting the protection of the activity of the target components in the liquid.

[0057] In the entire liquid-feed separation system 10, the concentration of the liquid gradually increases along the flow direction, while the viscosity of the liquid increases exponentially with concentration, and the flow resistance also increases exponentially with viscosity. Therefore, the flow resistance increases more rapidly in the latter part of the liquid's flow direction.

[0058] In other words, the flow resistance that the liquid needs to overcome to pass through separation unit number 4 is the greatest, or the flow resistance that the liquid needs to overcome to pass through separation unit number 4 is at least no less than the flow resistance that the liquid needs to overcome to pass through separation unit number 3. Therefore, it is necessary to increase the height difference between separation unit number 3 and separation unit number 4. That is, in the entire liquid separation system, ΔH3 should be the greatest, or at least no less than ΔH2, so that the gravitational potential energy difference generated by the liquid flowing from the residual liquid port of separation unit number 3 to the liquid inlet port of separation unit number 4 is large enough to offset the greater flow resistance that the liquid needs to overcome to pass through separation unit number 4, so as to ensure that the liquid can pass through the final separation unit at a relatively fast rate.

[0059] Wherein, ΔH2 is the height difference between separation unit numbered 2 and separation unit numbered 3, and ΔH3 is the height difference between separation unit numbered 3 and separation unit numbered 4. That is, the height difference ΔH2 between intermediate separation unit 13 and intermediate separation unit 14 is not greater than the height difference ΔH3 between intermediate separation unit 14 and end separation unit 12. For example, ΔH2 is 0.5m, and ΔH3 is 0.5m, or 0.8m or more.

[0060] Better yet, the height difference ΔH2 between intermediate separation unit 13 and intermediate separation unit 14 is less than the height difference ΔH3 between intermediate separation unit 14 and end separation unit 12. For example, ΔH2 is 0.5m, and ΔH3 is 0.55m, 0.6m, or 0.8m or more.

[0061] Furthermore, based on the condition that ΔH2 < ΔH3, the control ΔH is further optimized. N-1 -ΔH N-2 ≥ΔH2-ΔH1, that is, the difference ΔH3 between the intermediate separation unit 14 and the end separation unit 12 and the difference ΔH2 between the intermediate separation unit 13 and the intermediate separation unit 14. N-1 -ΔH N-2 The height difference between adjacent separation units is not less than the difference between the height difference ΔH2 between intermediate separation unit 13 and intermediate separation unit 14 and the height difference ΔH1 between the initial separation unit 11 and intermediate separation unit 13, ΔH2-ΔH1. Further optimization and control of the height difference between adjacent separation units can further reduce the initial pressure of the feed pump 30, better protect the active ingredients in the feed liquid, and ensure a high separation rate and efficiency.

[0062] Similarly, in a single tangential flow filtration operation, the ratio of the feed volume to the residual liquid volume of the initial separation unit 11 is denoted as V1, and the ratio of the feed volume to the residual liquid volume of the final separation unit 12 is denoted as V4, satisfying: V1 ≥ V4. Accordingly, the effective separation area of ​​the initial separation unit 11 is denoted as S1, and the effective separation area of ​​the final separation unit 12 is denoted as S4, satisfying: S1 ≥ S4.

[0063] The effective separation area of ​​separation unit numbered 2 is denoted as S2, and the effective separation area of ​​separation unit numbered 3 is denoted as S3. The following conditions must be met: S2≥S3≥S4 and S2-S3≥S3-S4. That is, the effective separation area S2 of intermediate separation unit 13 is not less than the effective separation area S3 of intermediate separation unit 14, and the effective separation area S3 of intermediate separation unit 14 is not less than the effective separation area S4 of end separation unit 12. At the same time, the difference between the effective separation area S2 of intermediate separation unit 13 and the effective separation area S3 of intermediate separation unit 14, S2-S3, is not less than the difference between the effective separation area S3 of intermediate separation unit 14 and the effective separation area S4 of end separation unit 12, S3-S4. The effective separation area of ​​each separation unit is set to decrease in the above manner in order to make the liquid flow through each separation unit at a relatively uniform rate.

[0064] Similar to Embodiment 1, at least one separation unit includes a plurality of tangential flow filter components connected in parallel and of equal height. For example, the initial separation unit 11 consists of two, three or more tangential flow filter components connected in parallel and of equal height.

Claims

1. A feed liquid separation system, characterized by, The separation unit includes a plurality of separation units connected in series, the number of the separation units is N, the plurality of the separation units are numbered in sequence as 1-N along the flow direction of the feed liquid, wherein N≥2, the separation unit numbered as 1 is defined as a starting separation unit and is used for inputting the feed liquid to be separated, the separation unit numbered as N is defined as an ending separation unit and is used for outputting the feed liquid processed by the N separation units, and the height of the starting separation unit is higher than the height of the ending separation unit.

2. The feed and liquor separation system of claim 1, wherein, The number of the separation units is N≥3, the separation units between the starting separation unit and the ending separation unit are intermediate separation units, and the heights of the intermediate separation units are all not higher than the height of the starting separation unit and not lower than the height of the ending separation unit.

3. The feed liquid separation system of claim 2, wherein, The height difference ΔH between two adjacent separation units satisfies ΔH N-2 ≤ ΔH N-1 , wherein ΔH N-2 is the height difference between the separation unit numbered N-2 and the separation unit numbered N-1, and ΔH N-1 is the height difference between the separation unit numbered N-1 and the separation unit numbered N.

4. The feed liquid separation system of claim 3, wherein, N > 4, ΔH N-2 < ΔH N-1 and ΔH N-1 - ΔH N-2 ≥ ΔH2- ΔH1.

5. The feed liquid separation system according to any one of claims 1-4, wherein, The N separation units are all tangential flow filtration assemblies, the tangential flow filtration assembly has a liquid inlet port, a permeate liquid port and a retentate liquid port. Any two adjacent separation units are connected in series through the retentate liquid port of the former separation unit and the liquid inlet port of the latter separation unit.

6. The feed liquid separation system of claim 5, wherein, The ratio of the feed volume to the retentate volume of the initial separation unit is denoted by V1, and the ratio of the feed volume to the retentate volume of the final separation unit is denoted by V N , with the following condition being met: V1≥ V N .

7. The feed liquid separation system of claim 5, wherein, The retentate liquid port of at least one of the separation units is provided with a flow control assembly.

8. The feed solution separation system of claim 1, wherein, The effective separation area of the initial separation unit is denoted as S1, and the effective separation area of the final separation unit is denoted as S N , which satisfies: S1≥S N .

9. The feed liquid separation system of claim 8, wherein, The number of separation units N ≥ 3, the effective separation area of the separation unit numbered N-2 is denoted as S N-2 , the effective separation area of the separation unit numbered N-1 is denoted as S N-1 , and the following conditions are met: S N-2 ≥ S N-1 ≥ S N , S N-2 -S N-1 ≥ S N-1 -S N .

10. The feed liquid separation system of claim 8 or 9, wherein, At least one of the separation units is composed of a plurality of tangential flow filtration assemblies connected in parallel and having equal heights.

Images