CN116440580A

CN116440580A - Filtering device for protein-containing feed liquid virus-removing filtration and method for carrying out protein-containing feed liquid virus-removing filtration

Info

Publication number: CN116440580A
Application number: CN202310093223.6A
Authority: CN
Inventors: 贾建东; 杨凯; 徐希晨
Original assignee: Hangzhou Cobetter Filtration Equipment Co Ltd
Current assignee: Hangzhou Cobetter Filtration Equipment Co Ltd
Priority date: 2022-01-14
Filing date: 2023-01-12
Publication date: 2023-07-18
Also published as: CN115121030A; WO2023134443A1

Abstract

The invention discloses a filtering device for removing viruses from protein-containing feed liquid and a method for removing viruses from protein-containing feed liquid, which relate to the technical field of biological filtration and comprise the following steps: the filtering unit, the packaging layer, the liquid inlet channel, the filtrate channel, the filter layer includes the virus removal membrane, remove the LRV of virus membrane to virus impurity is not lower than 4, and the protein yield is not lower than 98%, remove the virus membrane including the prefilter layer and be used for retaining virus, and aperture is less than the separating layer of prefilter layer, at least one deck prefilter layer is located and removes the surface of one side of the filtrate water conservancy diversion screen cloth of virus membrane, the invention filter equipment simple structure, convenient operation, remove the virus membrane including prefilter layer and be used for retaining virus, and aperture is less than the separating layer of prefilter layer of adoption, have good virus removal effect to the protein feed liquid.

Description

Filtering device for protein-containing feed liquid virus-removing filtration and method for carrying out protein-containing feed liquid virus-removing filtration

Technical Field

The invention relates to the technical field of biological filtration, in particular to a filtering device for removing viruses from protein-containing feed liquid and a method for removing viruses from the protein-containing feed liquid.

Background

With the development of society, recombinant proteins and antibody drugs have become important components in biological medicine due to their wide application in the treatment of various serious diseases. The recombinant protein medicine is a product expressed by utilizing a genetic engineering technology and is used for making up the deficiency of certain functional proteins in human bodies, and the antibody medicine, such as a monoclonal antibody, is an antibody secreted by single B lymphocyte clone, and because B lymphocyte only can produce an exclusive antibody aiming at an antigenic determinant, the recombinant protein medicine has the characteristics of high specificity of physicochemical property, single biological activity, strong binding specificity with antigen and the like, and has greatly progressed in the field of tumor and autoimmune disease treatment.

In the production process of recombinant proteins and antibody drugs, separation and purification of product proteins in drug solutions containing recombinant proteins or antibodies are required, wherein separation and purification are key to the preparation technology of recombinant proteins and antibody drugs, and virus removal filtration is a key step in separation and purification, however, at present, a box type filtration device is usually adopted in the prior art to remove virus filtration, such as patent CN112387119a, however, the box type filter is complex to prepare, and the filtration membrane needs to be welded with a shell, so that the damage of the filtration membrane is easily caused in the process, thereby influencing the final filtration effect.

Disclosure of Invention

The invention aims to provide a filtering device for removing viruses from protein-containing feed liquid and a method for removing viruses from protein-containing feed liquid, which have the advantages of simple structure, simplicity and convenience in operation and high virus removal rate.

In order to achieve the above purpose, the invention adopts the following technical scheme:

a filtration device for virus removal filtration of a protein-containing feed solution, comprising:

the filter unit at least comprises a filtrate diversion screen and a filter layer arranged on the side edge of the filtrate diversion screen; the plurality of filtering units are stacked, and liquid inlet channels are formed among the filtering units;

the packaging layer is used for packaging and fixing a plurality of filter units which are stacked;

the liquid inlet channel is used for conveying the protein-containing liquid to be filtered to the liquid inlet channel;

the filtrate channel is communicated with the filtrate guide screen and is used for discharging the protein-containing feed liquid after virus removal;

the filter layer comprises a virus removal membrane, the LRV of the virus removal membrane for virus impurities is not lower than 4, the protein yield is not lower than 98%, the virus removal membrane comprises a pre-filter layer and a separation layer for intercepting viruses, the pore diameter of the separation layer is smaller than that of the pre-filter layer, and at least one pre-filter layer is positioned on the surface of one side of the virus removal membrane far away from a filtrate diversion screen.

The filtering device is provided with a plurality of filtering units, a liquid inlet channel and a filtrate channel, wherein the filtering units are stacked and sealed through a peripheral packaging layer, the liquid inlet channel is only communicated with the liquid inlet channel formed between the filtering units, and the filtrate channel is only communicated with a filtrate guide screen in the filtering units; when the protein-containing feed liquid carries out virus removal filtration, can be with the protein-containing feed liquid that waits to filter in carrying the feed liquor runner through the feed liquor passageway, at this moment, the protein-containing feed liquid will be paved with the feed liquor passageway, and form the permeate entering filtrate water conservancy diversion screen cloth after removing virus filtration through the filter layer, wherein pile up and set up in inside filter unit, filtrate water conservancy diversion screen cloth both sides all are provided with the filter layer, and set up in the filter unit of the outside, filtrate water conservancy diversion screen cloth can only inwards set up the filter layer, the runner between the filter layer play liquid level struts here filtrate water conservancy diversion screen cloth's setting, prevent laminating between the filter layer play liquid level side, give filter unit good filtration space, finally the permeate is discharged with the filtrate passageway that the filter water conservancy diversion screen cloth is connected and is got the target and remove virus protein-containing feed liquid after the filtrate passageway is discharged.

Meanwhile, in order to meet the requirement that the filtering layer can have a good virus removal effect, the filtering layer adopts a virus removal membrane with the LRV of no less than 4 and the protein yield of no less than 98% for virus impurities, and the virus removal protein-containing feed liquid obtained at the moment has a good virus removal filtering effect; the virus removal membrane comprises a pre-filtering layer and a separating layer, wherein the separating layer is used for intercepting viruses, the pore diameter of the separating layer is smaller than that of the pre-filtering layer, and at least one layer of pre-filtering layer is positioned on one side surface of the virus removal membrane, which is far away from a filtrate diversion screen, so that in the use process, protein-containing liquid to be filtered firstly passes through the pre-filtering layer, wherein the pore diameter of the pre-filtering layer is larger and can be used as nano-dirt, large particle impurities in main intercepting fluid are mainly contained, the whole filtering speed of the virus removal membrane is improved, the time for filtering the protein-containing liquid is shorter, the time cost is lower, and then the protein-containing liquid passes through the separating layer, wherein the pore diameter of the separating layer is relatively smaller, the filtering precision of the virus removal membrane is improved, and the virus removal membrane is guaranteed to have higher intercepting effect on viruses. Therefore, at least one layer of pre-filtering layer is positioned on one side of the virus-removing membrane far away from the filtrate guiding screen, so that the pore diameter of the liquid inlet surface of the virus-removing membrane is relatively large, the pollutant containing amount is large, larger particle impurities can be removed in advance, blockage is not easy to occur, and a good filtering effect is achieved. Therefore, the invention has simple structure, convenient operation and good virus removal effect on protein-containing feed liquid.

Further, the method comprises the steps of,

the liquid inlet channel and the filtrate channel are both arranged on the filtering unit; or (b)

At least one of the liquid inlet channel and the filtrate channel is arranged on the packaging layer.

In the invention, the liquid inlet channel and the filtrate channel can be arranged in the filter unit, at the moment, the liquid inlet channel and the filtrate channel penetrate through the filter unit, and because the protein-containing liquid is filtered, the permeate flows to the filtrate channel, so that the permeate in the filtrate guiding screen far away from the filtrate channel needs to flow to the filtrate guiding screen near the filtrate channel, which leads to uneven filtration efficiency of virus removal membranes in all areas. Or, at least one of the liquid inlet channel and the filtrate channel may be disposed in the packaging layer, and the liquid inlet channel and/or the filtrate channel may be disposed in the packaging layer rather than being disposed in the filter unit, so that the reduction of the effective use area in the filter unit can be prevented.

Further, a liquid inlet guide screen for supporting the liquid inlet flow channel is arranged between the filtering units.

The setting of feed liquor water conservancy diversion screen cloth can support the clearance between the filter unit, plays the effect that forms the feed liquor runner for the protein feed liquor carries to the feed liquor runner more smooth, filters also more evenly. Meanwhile, because the protein-containing liquid is filtered to dead end filtration, a certain pressure is required to be applied to cause the protein-containing liquid to be filtered from the filter layer, in the filtration process, the inlet liquid flow channel always has higher pressure, under the condition, the section of the edge of the virus-removing film of the filter layer is thinner and the bonding between the virus-removing film and the packaging layer is not firm, the protein-containing liquid is easy to break the bonding between the virus-removing film and the packaging layer under the pressure to form gaps, the protein-containing liquid is not filtered from the virus-removing film and penetrates from the gaps between the virus-removing film and the packaging layer, so that the integral filtration efficiency of the filtration device is influenced; therefore, the sealing performance between the packaging layer and the virus-removing membrane can be improved through the arrangement of the liquid inlet flow guiding screen, and the virus-removing membrane is far away from the surface of one side of the filtrate flow guiding screen, namely, the virus-removing surface bonded and sealed with the packaging layer permeated into the liquid inlet flow guiding screen is a pre-filtering layer with a larger aperture, and the aperture is larger in the bonding process, so that the embedding of an adhesive is facilitated, and the bonding sealing performance of the packaging layer permeated into the liquid inlet flow guiding screen and the virus-removing surface is further improved.

Further, the virus removal membrane separation layer is positioned on one side surface of the virus removal membrane close to the filtrate diversion screen.

When the virus-removing membrane separating layer is close to one side of the filtrate diversion screen, the virus-containing feed liquid firstly passes through the pre-filtering layer for filtering and then flows through the separating layer, and finally reaches the filtrate diversion screen without passing through the pre-filtering layer again for filtering, so that the structure of the virus-removing membrane is simplified while good filtering effect is ensured.

Further, the outer side of the pre-filtering layer is a first outer surface, the average pore diameter of the first outer surface is 160-440nm, and the pore area ratio of the first outer surface is 0.5-14%; the outer side of the separation layer is a second outer surface, the average pore diameter of the second outer surface is 12-40nm, and the pore area ratio of the second outer surface is 2.5-9%.

The average pore diameters of the first outer surface and the second outer surface are different, so that the whole membrane is guaranteed to have a high flow velocity and a high dirt receiving space, and the membrane has high filtering precision. Meanwhile, the average pore diameter and the pore area ratio of the first outer surface have a certain influence on the bonding firmness between the first outer surface of the virus removal membrane and the packaging layer, the average pore diameter influences the degree of the adhesive on the packaging layer capable of penetrating into the pre-filtering layer, the insufficient penetration can be caused by the too small average pore diameter of the first outer surface, and the bonding force is relatively small; the area ratio of the first outer surface hole affects the size of the area where the adhesive on the encapsulation layer can permeate, and if the area ratio of the first outer surface hole is too small, the adhesive can not effectively permeate, and the adhesive force is relatively small.

Further, the average pore diameter of the virus-removing membrane is continuously changed in a gradient manner from the surface area of one side close to the filtrate guiding screen to the surface area of one side far away from the filtrate guiding screen, and the gradient of the average pore diameter change is 2-5.5 mu m/1 mu m.

The average pore diameter of the virus-removing membrane can be changed along with the thickness change gradient, the specific value of the average pore diameter change gradient can be obtained through the difference/thickness of the average pore diameters of the surfaces at two sides, so that the unit is mu m (representing pore diameter)/1 mu m (representing thickness). In the invention, the pore diameter gradually becomes smaller from the surface area at one side far away from the filtrate diversion screen to the surface area at one side close to the filtrate diversion screen, the average pore diameter change gradient is 2-5.5 mu m/1 mu m, the change gradient value is smaller, which shows that the membrane pore diameter of the invention changes along with the thickness in a small gradient way, the membrane pore diameter does not change too fast, and too large pores are not present (when the pores of the prefilter layer are too large, the mechanical strength of the whole membrane is too low, not pressure-resistant and is easy to damage under the pressure), at the moment, the prefilter layer can play a certain supporting role on the separation layer, the whole membrane has good mechanical strength and is not easy to damage under the larger pressure; and can ensure the efficient interception of virus by the virus removal membrane, the virus removal membrane also has faster flux and larger nano-dirt amount.

Further, the average pore diameter of the pre-filtering layer is 55-190nm, and the average pore diameter of the separating layer is 16-23nm; the ratio of the average pore diameter of the pre-filter layer to the average pore diameter of the separation layer is 4-12.

The pore diameter of the prefilter layer is too small to enable the virus removal membrane to achieve good filtration flux; the separation layer is too large in pore diameter, so that the separation layer cannot play a good role in interception; the above numerical settings of the pore sizes of the pre-filter layer and the separation layer are thus advantageous for ensuring a greater flux and a higher rejection efficiency of the virus-removal membrane.

When the ratio of the average pore diameter of the pre-filtering layer to the average pore diameter of the separating layer is within a limited range, the filter membrane is ensured to have larger flux and longer service life; and the high interception efficiency of the filter membrane to viruses is ensured, and the practical requirement is met. And too large or too small a ratio can easily lead to insufficient filtration accuracy or too small a flux.

Further, the thickness of the pre-filtering layer accounts for 72-89% of the thickness of the virus-removing film, and the porosity is 77-90%; the thickness of the separation layer accounts for 11-28% of the thickness of the virus-removing film, and the porosity is 62-78%.

The thickness of the pre-filtering layer in the virus removal membrane is relatively high, the porosity is relatively high, the whole membrane is guaranteed to have higher flux and dirt receiving capacity, the filtering speed is high, and the service life is long; the thickness of the separating layer is relatively low, the porosity is relatively low, and the separating layer can play a sufficient role in intercepting viruses on the basis of further ensuring the high flux of the membrane, so that the filtering effect is ensured.

Further, the thickness of the virus removal film is 45-140 μm.

When the thickness of the virus-removing film is too small, the mechanical strength of the film is low; meanwhile, as the filtering time is too short, effective filtering cannot be performed; when the thickness of the membrane is too large, the filtering time is too long, and the time cost is too high; the thickness of the virus removing film is in the range of the invention, the virus removing film not only has higher mechanical strength, but also can effectively filter, has higher filtering efficiency, shorter filtering time and lower time cost.

Further, one or more of a polyethersulfone virus-removal membrane, a regenerated cellulose virus-removal membrane, a cellulose acetate virus-removal membrane, or a polyvinylidene fluoride virus-removal membrane.

Further, the filter layer is a plurality of virus-removing films, each layer of virus-removing film is provided with a packaging hole, the packaging holes are at least partially communicated with the liquid inlet channel, the plurality of virus-removing films at least comprise a first virus-removing film with the largest packaging hole inner diameter and a second virus-removing film with the smallest packaging hole inner diameter, and the plurality of virus-removing films are stacked to form a radial dislocation area at the packaging holes;

an annular adhesive layer is formed in the packaging hole, and covers the inner wall of the liquid inlet channel at the filtrate guiding screen, and the radial dislocation area between the inner wall of the first virus-removing film packaging hole and the adjacent packaging hole, so that sealing connection is formed between each layer of virus-removing film and between the filtrate guiding screen and the filter layer.

In the invention, in order to make the virus removal efficiency higher, a multi-layer virus removal membrane design can be adopted, when the multi-layer virus removal membranes are fixedly packaged, particularly when a liquid inlet channel is arranged in a filtering unit, an annular gel layer is formed between the multi-layer virus removal membranes through forming in a packaging hole, the annular gel layer fills a radial dislocation area between adjacent virus removal membranes and the inner wall of the liquid inlet channel at a filtrate diversion screen, and a first virus removal membrane is positioned on the inner wall of the packaging hole, specifically, part of adhesive permeates into the filtrate diversion screen, meshes of the filtrate diversion screen are filled, the virus removal membrane close to the filtrate diversion screen is directly bonded with the filtrate diversion screen, and meanwhile, the inner wall of the liquid inlet channel at the filtrate diversion screen is coated with the annular gel layer; the virus-removing films cannot permeate the adhesive, so that the rest of the virus-removing films form encapsulation through the adhesive filled in the radial dislocation areas among the encapsulation holes, the adjacent virus-removing films are firmly adhered, and meanwhile, the annular adhesive layers are adhered to the inner side walls of the encapsulation holes of the first virus-removing films, which also indicate that the annular adhesive layers are required to be encapsulated on the side walls of the first virus-removing films with the largest inner diameters of the encapsulation holes, and the multi-layer virus-removing films can be adhered by the radial dislocation area adhesion mode, so that the annular adhesive layers form a firm adhesion effect between all the virus-removing films and the filtrate diversion screen, the unfiltered virus-containing feed liquid is prevented from permeating from gaps, and the good filtration effect of the virus-removing films is ensured; the side edges of the annular adhesive layer and the virus-removing films are sealed, and the upper and lower sides of the annular adhesive layer can firmly adhere the adjacent virus-removing films, so that the sealing holes are sealed, and the protein-containing liquid to be filtered is ensured to enter from the liquid inlet channel during filtration.

Further, the second virus removal membrane is positioned at one side of the filter layer far away from the filtrate diversion screen; or the second virus removal membrane is positioned at one side of the filter layer close to the filtrate diversion screen.

The second virus-removing film with the largest inner diameter of the packaging hole is positioned at the outer side, so that the adhesive can flow to the packaging hole with the smaller inner diameter along the packaging hole with the larger inner diameter, the manufacture of the annular adhesive layer is simpler, and the adhesive structure is more stable; the second virus-removing film with the largest inner diameter of the packaging hole is positioned at the inner side, so that the second virus-removing film with the smallest inner diameter of the packaging hole is prevented from being positioned at the inner side, the glue layer of the second virus-removing film positioned at the inner side wall of the packaging hole is scraped when the glue scraping treatment is carried out in the packaging hole, the annular glue sealing layer cannot achieve good sealing effect, and meanwhile the function of enabling the adhesive to achieve better sealing effect along the step flow can be achieved.

Further, the inner diameter of the packaging hole is in a step change, and the inner diameter of the packaging hole is gradually reduced outwards from one side close to the filtrate diversion screen, or is gradually increased outwards from one side close to the filtrate diversion screen.

The annular adhesive layer can cover all radial dislocation areas, and the structural design ensures that the bonding firmness between all virus-removing films of the filtering layer is higher; the inner diameter of the packaging hole is in step change, so that the annular adhesive sealing layers are arranged on the side walls of all adjacent virus removing films, and the annular adhesive sealing layers are also arranged on the steps of the radial dislocation areas, so that the bonding between the virus removing films is more stable, and the stable bonding is realized in two directions, so that the protein-containing liquid is not easy to break through the annular adhesive sealing layers, thereby leading the flow passage to permeate into the packaging hole, and permeate is discharged from the filtrate channel communicated with the filtrate guide screen.

Further, the filter unit further comprises an isolation layer arranged between the filter layer and the filtrate diversion screen.

In the filtering process of the filtering device, under the condition of larger pressure of liquid to be filtered, the filtrate diversion screen is easily embedded into the filtering layer, the membrane aperture of the filtering layer is damaged, the virus removal rate of the filtering layer is easily reduced, and the whole service life of the virus removal filtering device is also influenced. According to the invention, the isolation layer is arranged between the filter layer and the filtrate diversion screen, the isolation layer plays a role in isolating the filter layer and the filtrate diversion screen, so that the damage to membrane holes of the filtrate diversion screen caused by embedding the filtrate diversion screen into the filter layer in the filtering process is avoided, and a good protection effect is formed on the filter layer; when filtering, the isolation layer both sides can laminate with filter layer and filtrate water conservancy diversion screen cloth respectively, also can be to have the clearance between isolation layer and the filter layer, also have the clearance between isolation layer and the filtrate water conservancy diversion screen cloth, the isolation layer not only plays the isolation effect, still plays the effect of water conservancy diversion, the flowing back space of isolation layer cooperation filtrate water conservancy diversion screen cloth formation two-layer promptly reduces the backpressure, has increased the filtration flux for the filtration is more smooth and easy, and filtration efficiency improves.

Further, the roughness of the surface of the side of the isolation layer close to the filter layer is 2-25 mu m, and the softness is 100-250mN.

The surface roughness of one side of the isolation layer close to the filtering layer is overlarge to form a plurality of protrusions, and the protrusions are embedded into the virus-removing membrane holes on the premise of being pressed in the filtering process to damage the pore structure of the virus-removing membrane; or the filter layer is embedded between the adjacent protrusions, so that the filtering efficiency is reduced; the above surface roughness value can reduce the influence on the filter layer on the premise of ensuring the flatness of the surface of the isolation layer. Meanwhile, the softness of the isolation layer can also affect the filtering layer, the softness of the isolation layer is smaller, hard protrusions are caused to damage the filtering layer, deformation is easy to occur when the softness is larger, folds between the filtering layer and the isolation layer are easy to cause, and the filtering efficiency is affected.

Further, the thickness of the isolation layer is h1, the thickness of the filtrate diversion screen is h2, and the ratio of h1 to h2 is 1:1-5.

The larger the thickness of the isolation layer is, the larger the liquid discharge space is, the higher the contribution to the filtration flux is, but the thickness is too large to easily cause the thickness increase of the filtration device, and the too small thickness cannot play a good isolation role, and the filtration diversion screen mesh is easily deformed to be embedded into the virus removal membrane; the selection of the thickness ratio can ensure the filtering efficiency and avoid the overlarge thickness of the whole filtering device.

Further, the thickness of the isolation layer is 80-150 μm, and the air permeability is 60-160cc/cm ² Sec; the thickness of the filtrate diversion screen is 400-650 mu m, and the porosity is 25-35%.

The thickness of the isolation layer is in the range of the values, so that the isolation layer has good isolation effect, the embedding of virus removal membranes is avoided, more liquid discharge spaces are provided, and the filtration flux is increased; too large ventilation volume can cause too many pores to easily embed the filtrate diversion screen, and too small ventilation volume can reduce the filtration flux; in addition, in the numerical range of the ventilation quantity, the adhesive can well permeate when the virus-removing filter device is packaged, so that the virus-removing filter device can be packaged conveniently. Meanwhile, the thickness and the porosity of the filtrate diversion screen can ensure that the filtration flux of the virus-removing filtration device is in a proper range, and simultaneously, the good filtration efficiency is ensured.

Further, the fiber diameter of the isolating layer is 10-25 μm, and the gram weight is 15-40g/m ² 。

The combination of thicker diameter and lower fiber density is adopted to achieve the air permeability of the isolation layer, thereby ensuring the filtration flux of the virus-removing filter device and facilitating the bonding and encapsulation of the virus-removing filter device; compared with the scheme of adopting a smaller diameter but a larger fiber density, the isolating layer has better supporting performance and smaller specific surface area, so that the non-specific adsorption of the isolating layer to the protein is reduced, the probability of inactivation caused by repeated collision of the protein and the fiber of the isolating layer can be reduced, and in the flowing process of the penetrating fluid, less vortex is formed in the isolating layer, the shearing force of the protein is reduced, and the protein yield and the effective protein rate are higher.

Further, the isolating layer is one or more of non-woven fabrics, woven fabrics or porous films.

Further, an isolation layer liquid inlet which is at least partially opposite to and communicated with the liquid inlet channel is formed in the isolation layer, and the isolation layer is bonded with the filter layer and the filtrate diversion screen through an adhesive layer on the isolation layer.

Furthermore, the adhesive layer is permeated in the isolation layer and is arranged around the isolation layer liquid inlet, and the adhesive layer covers the inner wall of the isolation layer liquid inlet so as to avoid a through liquid flow passage entering from the inner wall of the isolation layer liquid inlet from being formed between the isolation layer liquid inlet and the isolation layer.

The adhesive layer can penetrate into the isolation layer so as to achieve the purpose of bonding with the filter layer and the filtrate diversion screen, and in order to prevent liquid from entering from the inner wall of the isolation layer liquid inlet, the adhesive layer is arranged around the isolation layer liquid inlet and covers the inner wall of the isolation layer liquid inlet, so that a through liquid flow channel entering from the inner wall of the isolation layer liquid inlet is prevented from being formed between the isolation layer liquid inlet and the isolation layer, and liquid is prevented from entering from the isolation layer liquid inlet.

Furthermore, a step dislocation area is formed at the liquid inlet of the isolation layer and the inner wall of the liquid inlet channel of the filtering layer.

The step dislocation area is adopted, so that the adhesive can be filled in the step dislocation area, packaging of the isolation layer and the filter layer can be realized under the condition that the adhesive does not permeate into the isolation layer, the material liquid is prevented from flowing out from gaps between the isolation layer and the filter layer, and good filtering effect of the virus removal film is ensured.

A method for carrying out virus removal and filtration on protein-containing feed liquid by adopting a filtering device comprises the following steps:

s1: buffer replacement: continuously conveying the buffer solution into the liquid inlet flow channel from the liquid inlet channel until the buffer solution flows out of the filtrate channel of the filtering device to form permeation buffer solution, so that the filtering device is filled with the buffer solution;

s2: feeding liquid: continuously conveying the protein-containing feed liquid into the feed liquid flow channel from the feed liquid channel;

s3: and (3) filtering: the protein-containing feed liquid permeates along the tangential direction through a feed liquid guide screen and passes through a filter layer in the filter unit to form virus-removing permeate;

s4: liquid discharge: and the virus-removing permeate flows along the filtrate diversion screen and is discharged from the filtrate channel, so that the protein-containing feed liquid after virus removal is obtained.

When the filtering device is used for removing viruses from protein-containing feed liquid, firstly, the original protective liquid or air in the filtering device needs to be replaced by buffer liquid, namely, the buffer liquid is continuously conveyed into a liquid inlet channel from the liquid inlet channel until the buffer liquid flows out of a filtrate channel of the filtering device, so that the buffer liquid can be fully filled in the filtering device, then the operation of feeding liquid is ensured, before the liquid is fed, if the filtering device is provided with a plurality of liquid inlet channels, the liquid can be fed into the liquid inlet channels at the same time, preferably, when the filtering device is provided with a plurality of liquid inlet channels, the protein-containing feed liquid is conveyed into one liquid inlet channel, and the other liquid inlet channels are blocked, because when the liquid inlet channels are fed simultaneously, the whole flux of the filtering device is not easy to adjust, and meanwhile, the liquid inlet pressure of the liquid inlet channels at certain positions is required to be matched, and the phenomenon that the protein-containing feed liquid flows back occurs even occurs. And then, after the protein-containing feed liquid passes through a filter layer in the filter unit, virus-removing penetrating liquid is formed, flows along a filtrate diversion screen, and is discharged from a filtrate channel to obtain the virus-removed protein-containing feed liquid. The filtering device of the invention has simple and convenient virus removal and filtration operation and higher efficiency.

Further, the pressure of the feed liquid in the step S2 is 20-40psi.

Further, the filtration flux is greater than 180L/(m) ² *h)。

The filtering device has simple structure and convenient operation, has good virus removing effect on protein-containing feed liquid, adopts the virus removing membrane which comprises a pre-filtering layer and a separating layer for intercepting viruses, wherein the pore diameter of the separating layer is smaller than that of the pre-filtering layer, and at least one layer of pre-filtering layer is positioned on the surface of one side of the virus removing membrane far away from a filtrate flow guiding screen, so that the high-efficiency interception of viruses by the filtering device can be ensured, and the filtering device has larger flux and sewage containing capacity.

Drawings

The invention is further described below with reference to the accompanying drawings:

fig. 1 is an exploded view of the filter device of the present invention.

Fig. 2 is a cross-sectional view of the filter device of the present invention.

Fig. 3 is a partial cross-sectional view of a filter unit of the present invention (excluding the annular seal layer) where the separator layer is a nonwoven fabric.

FIG. 4 is a partial cross-sectional view of a filter unit of the present invention wherein the separator is a nonwoven fabric.

Fig. 5 is a partial cross-sectional view of a filter unit of the present invention (excluding the annular gel coat layer) where the separator layer is a porous membrane.

FIG. 6 is a partial cross-sectional view of a filter unit of the present invention wherein the separator is a porous membrane.

FIG. 7 is an electron microscope image of the invention wherein the isolation layer is a nonwoven fabric.

FIG. 8 is a partial cross-sectional view of a filtration unit of the present invention (excluding the annular seal layer) with three virus-free membranes.

FIG. 9 is a partial cross-sectional view of a filtration unit of the present invention, wherein the number of virus-free membranes is three.

FIG. 10 is a cross-sectional view of the virus-elimination filter apparatus of the invention, in which the virus-elimination membrane includes a pre-filter layer and a separation layer.

FIG. 11 is an electron micrograph of a virus removal membrane of the present invention including a pre-filter layer and a separation layer.

FIG. 12 is a cross-sectional view of a virus-elimination filter apparatus of the invention, in which the virus-elimination membrane includes two pre-filter layers and a separation layer.

FIG. 13 is a schematic view of a filtration device according to example 2 of the present invention.

FIG. 14 is a cross-sectional view of a liquid inlet passage of a filtration device according to example 2 of the present invention.

FIG. 15 is a cross-sectional view of a filtrate channel of a filtration device according to example 2 of the present invention.

FIG. 16 is a schematic view of a filtration device according to example 3 of the present invention.

Fig. 17 is an exploded view of the filter device according to embodiment 5 of the present invention.

The device comprises a 101-liquid inlet channel, a 102-filtrate channel, a 103-packaging layer, a 1-liquid inlet guide screen, a 11-first liquid inlet, a 12-first filtrate inlet, a 121-second groove structure, a 2-filtering unit, a 21-isolation layer, a 211-isolation layer liquid inlet, a 212-isolation layer filtrate inlet, a 22-second liquid inlet, a 23-second filtrate inlet, a 3-filtrate guide screen, a 311-first groove structure, a 4-filtering layer, a 41-virus removal film, a 411-packaging hole, a 412-conducting port, a 413-first virus removal film, a 414-second virus removal film, a 415-third virus removal film, a 416-prefilter layer, a 417-separating layer, a 5-radial dislocation area, a 51-step dislocation area, a 6-annular adhesive layer and a 61-adhesive layer.

Detailed Description

In order that the above-recited objects, features and advantages of the present invention will be more clearly understood, a more particular description of the invention will be rendered by reference to the appended drawings and appended detailed description. It should be noted that, in the case of no conflict, the embodiments of the present application and the features in the embodiments may be combined with each other.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, however, the present invention may be practiced in other ways than those described herein, and therefore the scope of the present invention is not limited to the specific embodiments disclosed below.

Example 1:

as shown in fig. 1, a filtration device for virus removal filtration of a protein-containing feed solution, comprising:

a liquid inlet guide screen 1, which is provided with a first liquid inlet 11 and a first filtrate inlet 12 and is used for guiding the fluid to be filtered to permeate along the tangential direction;

in the embodiment, two ends of the liquid inlet guide screen 1 are respectively provided with a first liquid inlet 11 and a first filtrate inlet 12, and the inner wall of the first filtrate inlet 12 is sealed by an adhesive permeated into the liquid inlet guide screen 1;

the filtering unit 2 is arranged at the downstream of the liquid inlet guide screen 1, is provided with a second liquid inlet 22 and a second filtrate inlet 23 which are at least partially and directly communicated with the first liquid inlet 11 and the first filtrate inlet 12, and two ends of the filtering unit are respectively provided with a liquid inlet; the filter unit 2 at least comprises a filtrate guiding screen 3 and filter layers 4 arranged at two sides of the filtrate guiding screen 3, and the filter layer 4 is arranged at one inward side of the outermost filter unit 2;

In this embodiment, the liquid inlet channel 101 and the filtrate channel 102 are both disposed in the filtration unit, where the first liquid inlet 11 and the second liquid inlet 22 together form the liquid inlet channel 101, the first filtrate inlet 12 and the second filtrate inlet 23 form the filtrate channel 102, the diameters of the first liquid inlet and the second liquid inlet are 11mm, and the diameters of the first filtrate inlet and the second filtrate inlet are 6mm; the plurality of filtering units and the liquid inlet guide screen cloth 1 are stacked and fixed in a packaging mode through the packaging layer 103; and the encapsulation layer 103 permeates into the inlet guide screen 1, and the encapsulation layer 103 permeated into the inlet guide screen 1 is bonded and fixed with the first outer surface of the virus-removing film 41.

Of course, in other embodiments, the liquid inlet guide screen 1 is not required, and the liquid inlet channel can be opened by pressure after the liquid containing viruses is conveyed into the liquid inlet channel during filtration, so that filtration is completed.

In this embodiment, the filter layer 4 includes a virus removal film 41 having an LRV of not less than 4 for virus impurities and a protein yield of not less than 98%; the virus-removal membrane 41 further comprises a pre-filter layer 416 and a separation layer 417, wherein the pore size of the separation layer 417 is smaller than that of the pre-filter layer 416, and the pre-filter layer 416 is used for interception, and at least one pre-filter layer 416 is positioned on one side of the virus-removal membrane 41 away from the filtrate guiding screen.

As shown in fig. 10, the virus removal membrane 41 includes a pre-filtering layer 416 and a separating layer 417, the separating layer 417 is located at a side close to the filtrate guiding screen 3, the outer side of the pre-filtering layer is a first outer surface, the average pore diameter of the first outer surface is 160-440nm, and the pore area ratio of the first outer surface is 0.5-14%; the outer side of the separation layer is a second outer surface, the average pore diameter of the second outer surface is 12-40nm, and the pore area ratio of the second outer surface is 2.5-9%; wherein the average pore diameter of the pre-filtering layer is 55-190nm, the thickness of the pre-filtering layer accounts for 72-89% of the thickness of the virus-removing film, the porosity of the pre-filtering layer is 77-90%, the average pore diameter of the separating layer is 16-23nm, the thickness of the pre-filtering layer accounts for 11-28% of the thickness of the virus-removing film, and the porosity of the pre-filtering layer is 62-78%; the ratio of the average pore diameter of the pre-filtering layer to the average pore diameter of the separating layer is 4-12, the average pore diameter of the virus-removing membrane continuously changes in a gradient manner from the surface area of one side close to the filtrate guiding screen to the surface area of one side far away from the filtrate guiding screen, the gradient of the average pore diameter change is 2-5.5 mu m/1 mu m, and the whole thickness of the virus-removing membrane is 45-140 mu m.

Referring again to FIG. 11, in this example, the upper side was a pre-filter layer, the lower side was a separation layer, the overall thickness of the virus-free membrane was 60. Mu.m, the average pore diameter of the first outer surface was 230nm, the pore area ratio was 10.6%, the average pore diameter of the second outer surface was 20.6nm, the pore area ratio was 8.4%, and the gradient of the average pore diameter change was 3.49 μm/1. Mu.m; the average pore diameter of the pre-filter layer was 80nm, the thickness was 52 μm, the porosity was 81.1%, the average pore diameter of the separation layer was 19nm, the thickness was 8 μm, and the porosity was 74%.

In other embodiments, as shown in FIG. 12, where the virus removal membrane 41 includes two pre-filter layers 416 and a separation layer 417, the separation layer 417 is located between the two pre-filter layers 416; where one of the pre-filter layers 416 is located on a side away from the barrier layer 21 and one of the pre-filter layers 416 is located on a side proximate to the barrier layer 21.

In the filtration unit of this embodiment, the porosity of the filtrate guiding screen 3 is 25-35% and the thickness thereof is 400-650 μm.

The filter layer 4 is a single-layer virus-removing film 41 or a multi-layer virus-removing film 41, two ends of the virus-removing film 41 are respectively provided with a packaging hole 411 and a conducting port 412, and the packaging hole 411 is at least partially and directly communicated with the second liquid inlet 22.

In this embodiment, as shown in fig. 1 to 4, the virus removal membrane 41 is a PES virus removal membrane, and the filtration unit 2 includes an isolation layer 21 provided between the filtration layer 4 and the filtrate guiding screen 3. The thickness of the isolation layer 21 is defined as h1, and the thickness of the filtrate guiding screen 3 is defined as h2, and the ratio of h1 to h2 is 1:1-5. More specifically, in the present embodiment, the thickness of the separation layer 21 is 80-150 μm, and the air permeability is 60-160cc/cm ² /sec。

The pore diameter of the surface of the isolation layer 21 adjacent to the filter layer 4 is defined as d1, and the average pore diameter of the second outer surface of the isolation layer 21, which is the virus-removal membrane in this embodiment, is defined as d2, the ratio d1:d2 is 1000-5000. More specifically, the pore diameter of the separation layer 21 closer to the side surface of the filter layer 4 in this embodiment is 20 to 120 μm.

The softness of the barrier layer 21 is 100-250mN; the roughness of the surface of the side of the isolation layer 21 close to the filter layer 4 is 2-25 mu m; the isolation layer 21 may be a nonwoven fabric with a fiber diameter of 10-25 μm and a gram weight of 15-40g/m ² . The isolation layer 21 may be one of a woven fabric and a porous film, and the material may be a polymer material, for example PP, PE, PES.

The isolating layer 21 is provided with an isolating layer liquid inlet 211 and an isolating layer filtrate inlet 212 which are at least partially and directly communicated with the second liquid inlet 22 and the second filtrate inlet 23 respectively, and the isolating layer is bonded with the filtering layer and the filtrate diversion screen mesh through an adhesive layer 61 on the isolating layer; the adhesive layer 61 is permeated into the isolation layer and surrounds the isolation layer liquid inlet, and the adhesive layer covers the inner wall of the isolation layer liquid inlet to avoid forming a through liquid flow channel between the isolation layer liquid inlet and the isolation layer entering from the inner wall of the isolation layer liquid inlet, meanwhile, the surrounding width of the adhesive layer is l, the diameter of the isolation layer liquid inlet is d and is the same as the diameter of the first liquid inlet, the d is 1-10:10, and a step dislocation area can be formed at the positions of the isolation layer liquid inlet and the second liquid inlet of the filter layer, so that the adhesive is filled in the step dislocation area to form the adhesive layer 61. In this embodiment, when the isolation layer 21 is a nonwoven fabric, as shown in fig. 7, the adhesive may penetrate into the nonwoven fabric at this time, and the adhesive layer penetrating into the isolation layer or the step dislocation region 51 may be used to achieve stable adhesion with the virus removal film 41. In the other embodiments, when the separator 21 is a porous film, since the adhesive cannot penetrate, it is necessary to provide the above-mentioned stepped dislocation region 51, as shown in fig. 5 and 6.

In other embodiments, the virus-removal membrane 41 may be one or a combination of several of a regenerated cellulose virus-removal membrane, a cellulose acetate virus-removal membrane, or a polyvinylidene fluoride virus-removal membrane.

In this embodiment, the filter layer 4 is a plurality of virus-removing films 41, each layer of virus-removing film 41 is provided with a packaging hole 411 and a through hole 412, the packaging holes 411 are at least partially opposite to and communicated with the second liquid inlet 22, the plurality of virus-removing films 41 at least comprise a first virus-removing film 413 with the largest inner diameter of the packaging hole and a second virus-removing film 414 with the smallest inner diameter of the packaging hole, and the plurality of virus-removing films 41 are stacked to form a radial dislocation region 5 at the packaging hole.

An annular sealing layer 6 is formed in the packaging hole, and the annular sealing layer 6 covers the inner wall of the second liquid inlet 22, the inner wall of the isolating layer liquid inlet 211 and the inner wall of the first virus-removing film 413 and the radial dislocation area 5 between the adjacent packaging holes, so that sealing connection is formed between each layer of virus-removing film 41 and between the filtrate guiding screen 3 and the filtering layer 4.

Specifically, as shown in fig. 3 and 4, in the present embodiment, the filter layer 4 includes two virus-removing membranes 41, specifically a first virus-removing membrane 413 having a larger inner diameter of the package hole and a second virus-removing membrane 414 having a smaller inner diameter of the package hole, wherein the first virus-removing membrane 413 is located near the inner side of the filtrate guiding screen 3, and the second virus-removing membrane 414 is located far from the outer side of the filtrate guiding screen 3.

As shown in fig. 4, an annular sealing layer 6 is formed in the packaging hole, and the annular sealing layer 6 covers the inner wall of the second liquid inlet 22, the inner wall of the isolation layer liquid inlet 211, the inner wall of the first virus-removing film 413, and the radial dislocation area 5 of the first virus-removing film 413 and the second virus-removing film 414, so that sealing connection is formed between the first virus-removing film 413 and the second virus-removing film 414 and between the filtrate guiding screen 3 and the first virus-removing film 413.

During packaging, the conducting port 412 and the second filtrate port 23 are at least partially and directly communicated, vacuum is pumped to the second filtrate port 23 and the conducting port 412, and the adhesive injected into the second filtrate port 22 and the packaging hole 411 flows along the circumferential direction under the action of negative pressure to form the annular adhesive layer 6.

Of course, in other embodiments, as shown in fig. 8 and 9, the number of the virus-removing membranes 41 may be three, the first virus-removing membrane 413 having the largest inner diameter of the encapsulation hole is located at the outermost side far from the filtrate guiding screen 3, the second virus-removing membrane 414 having the smallest inner diameter of the encapsulation hole is located near the filtrate guiding screen 3, and the third virus-removing membrane 415 is located between the first virus-removing membrane 413 and the second virus-removing membrane 414, and the inner diameter of the encapsulation hole is also smaller than the inner diameter of the encapsulation hole of the first virus-removing membrane 413 and larger than the inner diameter of the encapsulation hole of the second virus-removing membrane 414.

In other words, the inner diameter of the packing hole is stepwise changed, which gradually increases from the side close to the filtrate guiding screen 3 to the outside. The above structural design makes the adhesion between all virus-removing membranes 41 of the filter layer 4 higher.

As shown in fig. 9, an annular seal layer 6 is formed in the package hole, and the annular seal layer 6 covers the inner wall of the third virus-removing film 415, the inner wall of the first virus-removing film 413, the inner wall of the isolation layer liquid inlet 211, and the radial offset regions of the third virus-removing film 415 and the first virus-removing film 413, and the radial offset regions of the third virus-removing film 415 and the second virus-removing film 414. So that a sealing connection is formed between the second virus-removing membrane 414 and the third virus-removing membrane 415, between the third virus-removing membrane 415 and the first virus-removing membrane 413, between the isolating layer 21 and the first virus-removing membrane 413, and between the filtrate guiding screen 3 and the isolating layer 21.

Wherein: the measurement mode of the average pore diameter of the membrane surface can be used for carrying out morphology characterization on the membrane structure by using a scanning electron microscopeMeasuring by computer software (such as Matlab, NIS-Elements, etc.) or manually, and performing corresponding calculation; in the preparation of the membrane, the characteristics such as pore size distribution are substantially uniform in the direction perpendicular to the membrane thickness (the direction is a planar direction if the membrane is in the form of a flat plate membrane; the direction is perpendicular to the radial direction if the membrane is in the form of a hollow fiber membrane); the average pore size of the whole on the corresponding plane can be reflected by the average pore size of the partial region on the plane. In practice, the surface of the film can be characterized by electron microscopy to obtain a corresponding SEM image, and a certain area, such as 1 μm, can be selected because the pores on the surface of the film are substantially uniform ² (1 μm by 1 μm) or 25 μm ² (5 μm by 5 μm), measuring the aperture of all holes on the specific area according to the actual situation, and calculating to obtain the average aperture of the surface; of course, the person skilled in the art can also obtain the above parameters by other measuring means, which are only used as reference. The parameters of average pore diameter, porosity, thickness and the like of the pre-filtering layer and the separating layer can be divided into the separating layer and the pre-filtering layer by tearing the virus removing film, and then the pre-filtering layer is subjected to corresponding parameter test, wherein the average pore diameter is tested by adopting a PMI pore diameter tester; or the film section structure is calculated and measured by using computer software (such as Matlab, NIS-Elements and the like) or manually after the appearance of the film section structure is represented by using a scanning electron microscope; of course, the person skilled in the art can also obtain the above parameters by other measuring means, which are only used as reference.

Roughness test: three surface areas of approximately 0.65X 0.45 mm in size (area size defined by constant 5X magnification and auto focus using a scanning microscope) were scanned over a 6X 6 mm surface area using a ContourGT-X three-dimensional optical profilometer (Bruker, geman), taking n=6 linear tracks (200 μm each), profile filter: the cut-off wavelength λs=0.8 μm, λc=0.08 mm, roughness was measured, and an average value was calculated.

Softness test: speed of test with reference to standard ASTM D6828-2002 (2011): 1.2mm/s.

A method for carrying out virus removal filtration on protein-containing feed liquid by adopting the filtering device comprises the following steps:

s1: buffer replacement: the buffer solution is continuously conveyed into the liquid inlet flow channel from the liquid inlet channel 101 at one side of the filtering device, namely the first liquid inlet 11 until the buffer solution flows out from the filtrate channel of the filtering device, namely the second filtrate inlet 23 to form permeation buffer solution, so that the filtering device is filled with the buffer solution;

s2: feeding liquid: sealing the liquid inlet channel at one side, and continuously conveying the protein-containing liquid into the liquid inlet channel from the liquid inlet channel at the other side, wherein the liquid inlet pressure is 20-40psi;

In the specific application of the filtering device with the structure of the embodiment in virus removal and filtration, 7 samples are taken, and the samples are respectively:

sample 1, sample-provided separator 21; the separator 21 is a nonwoven fabric, the surface roughness of the side close to the filter layer 4 is 3 μm, and the softness is 100mN, d1: d2 is 1000; d is 3:10, thickness h1 of the isolation layer 21: h2 is 1:5, wherein h1 is 85 μm, the thicknesses h2 of the inlet flow guiding screen and the filtrate flow guiding screen are 425 μm, the porosity of the filtrate flow guiding screen is 25%, and the ventilation amount of the isolation layer 21 is 60cc/cm ² Sec; the fiber diameter of the separator 21 was 12. Mu.m, and the grammage was 16g/m ² 。

Sample 2, sample set up isolation layer 21, isolation layer 21 selects the non-woven fabrics, and its side surface roughness that is close to filter layer 4 is 18 mu m, and the compliance is 118mN, d1: d2 is 1300; d is 1:2, thickness h1 of the isolation layer 21: h2 is 1:4, wherein h1 is 140 μm, the thicknesses h2 of the inlet flow guide screen and the filtrate flow guide screen are 560 μm, the porosity of the filtrate flow guide screen is 28%, and the ventilation volume of the isolation layer 21 is 115cc/cm ² Sec; isolation layer21 has a fiber diameter of 10 μm and a grammage of 15g/m ² 。

Sample 3, sample provided with a spacer layer 21; the separator 21 is a nonwoven fabric, the surface roughness of the side close to the filter layer 4 is 19 μm, and the softness is 165mN, d1: d2 is 2100; d is 2:5, thickness h1 of the isolation layer 21: h2 is 1:4.5, wherein h1 is 142 μm, the thicknesses h2 of the inlet flow guide screen and the filtrate flow guide screen are 639 μm, the porosity of the filtrate flow guide screen is 30%, and the ventilation volume of the isolation layer 21 is 92cc/cm ² Sec; the fiber diameter of the separator 21 was 14. Mu.m, and the grammage was 40g/m ² 。

Sample 4, sample set up the isolation layer 21, the isolation layer 21 selects the non-woven fabrics, and its side surface roughness that is close to filter layer 4 is 12 mu m, and the compliance is 195mN, d1: d2 is 2200; d is 3:5, thickness h1 of the isolation layer 21: h2 is 1:3.5, wherein h1 is 121 μm, the thicknesses h2 of the inlet flow guide screen and the filtrate flow guide screen are 423.5 μm, the porosity of the filtrate flow guide screen is 32%, and the ventilation volume of the isolation layer 21 is 124cc/cm ² Sec; the fiber diameter of the separator 21 was 17. Mu.m, and the grammage was 18g/m ² 。

Sample 5, sample set up isolation layer 21, isolation layer 21 selects the non-woven fabrics, and its side surface roughness that is close to filter layer 4 is 20 mu m, and the compliance is 220mN, d1: d2 is 3200; d is 3:10, thickness h1 of the isolation layer 21: h2 is 1:3.8, wherein h1 is 150 μm, the thicknesses h2 of the inlet flow guiding screen and the filtrate flow guiding screen are 426 μm, the porosity of the filtrate flow guiding screen is 35%, and the ventilation amount of the isolation layer 21 is 152cc/cm ² Sec; the fiber diameter of the separator 21 was 18. Mu.m, and the grammage was 36g/m ² 。

Sample 6, sample set up isolation layer 21, isolation layer 21 selected from the non-woven fabrics, and its side surface roughness that is close to filter layer 4 is 25 μm, and the compliance is 248mN, d1: d2 is 4300; d is 2:5, thickness h1 of the isolation layer 21: h2 is 1:3.5, wherein h1 is 138 μm, the thicknesses h2 of the inlet flow guiding screen and the filtrate flow guiding screen are 570 μm, the porosity of the filtrate flow guiding screen is 27%, and the ventilation amount of the isolation layer 21 is 148cc/cm ² Sec; the fiber diameter of the separator 21 was 20. Mu.m, and the grammage was 32g/m ² 。

Example 2: the difference from example 1 is that:

as shown in fig. 13-15: according to the invention, a liquid inlet channel 101 is arranged on a packaging layer 103, a filtrate channel 102 is arranged at the center of a stacked structure of a filtering unit 2 and a liquid inlet guide screen, wherein the liquid inlet channel 101 is communicated with the liquid inlet guide screen 1, the filtering unit 2 on the inner side wall of the liquid inlet channel 101 is sealed by an annular sealing layer 6, and the liquid inlet guide screen 1 on the inner side wall of the filtrate channel 102 is sealed by an adhesive permeated into the liquid inlet guide screen 1.

The method for carrying out virus removal filtration on the protein-containing feed liquid by adopting the filtering device comprises the following steps:

s1: buffer replacement: the buffer solution is continuously conveyed into the liquid inlet flow channel from the liquid inlet channel 10 at one side of the filtering device until the buffer solution flows out from the filtrate channel of the filtering device to form permeation buffer solution, so that the filtering device is filled with the buffer solution;

s2: feeding liquid: continuously conveying the protein-containing feed liquid from the feed liquid channel into the feed liquid channel, wherein the feed liquid pressure is 20-40psi;

In this example, the virus removal membrane was PES virus removal membrane having an overall thickness of 50. Mu.m, an average pore diameter of the first outer surface of 200nm, a pore area ratio of 8.7%, an average pore diameter of the second outer surface of 18.2nm, a pore area ratio of 6.9%, and an average pore diameter variation gradient of 3.64 μm/1. Mu.m; the average pore diameter of the prefilter layer was 70nm, the thickness was 44 μm, the porosity was 78.2%, the average pore diameter of the separator layer was 17nm, the thickness was 6 μm, and the porosity was 72.1%.

In this example, a separator 21 was provided, and the separator 21 was a nonwoven fabric, the surface roughness of which was 8 μm at the side close to the filter layer 4, the softness was 135mN, d1: d2 is 3800; d is 3:10, thickness h1 of the isolation layer 21: h2 is 1:4.8, wherein h1 is 98 μm, the thickness h2 of the filtrate guiding screen is 470.4 μm, the porosity of the filtrate guiding screen is 26%, and the isolation layer 21 is breathableIn an amount of 155cc/cm ² Sec; the fiber diameter of the separator 21 was 22. Mu.m, and the grammage was 21g/m ² 。

Example 3: the difference from example 2 is that:

as shown in fig. 16: according to the invention, a liquid inlet channel 101 and a filtrate channel 102 are both arranged on a packaging layer 103, wherein the liquid inlet channel 101 is communicated with a liquid inlet guide screen 1, a filter unit 2 on the inner side wall of the liquid inlet channel 101 is sealed by an annular glue sealing layer 6, and the liquid inlet guide screen 1 on the inner side wall of the filtrate channel 102 is also sealed by an adhesive permeated into the liquid inlet guide screen 1.

In this example, the virus removal membrane was PES virus removal membrane having an overall thickness of 70. Mu.m, an average pore diameter of the first outer surface of 260nm, a pore area ratio of 12.4%, an average pore diameter of the second outer surface of 22.1nm, a pore area ratio of 8.9%, and an average pore diameter variation gradient of 3.4 μm/1. Mu.m; the average pore diameter of the pre-filter layer was 90nm, the thickness was 60 μm, the porosity was 83.4%, the average pore diameter of the separation layer was 20nm, the thickness was 10 μm, and the porosity was 75.7%.

In this example, a separator 21 was provided, and the separator 21 was a nonwoven fabric, the surface roughness of which on the side close to the filter layer 4 was 10. Mu.m, the softness was 210mN, d1: d2 is 5000; d is 3:10, thickness h1 of the isolation layer 21: h2 is 1:2.8, wherein h1 is 150 μm, the thickness h2 of the filtrate guiding screen is 420 μm, the porosity of the filtrate guiding screen is 33%, and the ventilation amount of the isolation layer 21 is 160cc/cm ² Sec; the fiber diameter of the separator 21 was 24. Mu.m, and the grammage was 25g/m ² 。

Example 4: the difference from example 1 is that:

the isolation layer 21 is not provided with an isolation layer liquid inlet 211 and an isolation layer filtrate inlet 212, as shown in fig. 17, and the periphery of the isolation layer can be bonded with the filtrate guiding screen and the filter layer through an adhesive.

In this embodiment, the separator 21 is a nonwoven fabric, and the surface roughness of the side of the separator adjacent to the filter layer 4 is 15 μm, and the softness is 145mN, d1: d2 is 1800; d is 7:10, thickness h1 of the isolation layer 21: h2 is 1:3, wherein h1 is 148 μm, the thickness h2 of the filtrate guiding screen is 444 μm, the porosity of the filtrate guiding screen is 29%, and the ventilation of the isolation layer 21 is 85cccm ² Sec; the fiber diameter of the separator 21 was 25. Mu.m, and the grammage was 30g/m ² 。

Example 5: the difference from sample 6 is that this example employs a double-layer CA virus removal membrane, the average pore size of the prefilter layer is 95nm, and the average pore size of the separation layer is 20nm.

Example 6: the difference from sample 6 is the thickness h1: h2 is 1:6, where h1 is 70 μm.

Example 7: the difference from sample 6 is that the barrier gas permeability was 40cc/cm ² /sec。

Example 8: the difference from sample 6 is that the fiber diameter of the separator 21 was 7. Mu.m, and the gram weight was 32g/m ² 。

Comparative example 1: the difference from sample 6 is that no isolation layer is provided.

Comparative example 2: the difference from sample 6 is that the roughness is 35 μm.

Comparative example 3: the difference from sample 6 is that the softness is 350mN.

The filtration apparatus of the above examples and comparative examples was subjected to a virus removal filtration test under conditions of 7.5log pfu/ml MVM virus (particle size 20 nm) of 10g/L monoclonal antibody protein solution at 30psi pressure. Wherein the virus-removing filter device adopts 8 filter units 2, namely 16 filter layers 4 and 32 virus-removing membranes 41, and the filter area reaches 0.08m ² . The results are shown in the following table.

The table shows that the embodiment of the invention has better virus removal and filtration effects on protein-containing feed liquid.

As is clear from example 6, when the thickness of the separator 21 and the value of h1:h2 are too small, the filtration flux of the filtration device is relatively small.

As can be seen from example 7, when the air permeability of the barrier layer is too small, the filtration flux of the filtration device is relatively small.

From example 8, it is clear that at the same gram weight, the smaller the fiber is, the more vortex is formed in the isolating layer, the higher the specific surface area is, the larger the protein collision probability is, and the effective protein rate and the final protein yield are relatively lower.

As is clear from comparative example 1, no isolation layer was provided, and the LRV was relatively low when PES was used for removing virus, indicating that the provision of the isolation layer can provide good protection for the membrane pores of the separation layer of the virus removal membrane.

As is clear from comparative example 2, the virus removal rate LRV of the protein-containing liquid medicine after filtration was relatively low, indicating that when the surface roughness of the separation layer 21 was too large, the separation layer membrane pores of the virus removal membrane 41 were easily damaged during the test.

As is clear from comparative example 3, the virus removal rate LRV of the protein-containing liquid medicine after filtration was relatively low, indicating that when the softness of the separation layer 21 was too small, the separation layer membrane pores of the virus removal membrane 41 were easily damaged during the test.

While the preferred embodiments of the present invention have been described in detail, it will be appreciated that those skilled in the art, upon reading the above teachings, may make various changes and modifications to the invention. Such equivalents are also intended to fall within the scope of the claims appended hereto.

Claims

1. A filter device for virus removal and filtration of protein-containing feed liquid, which is characterized in that: comprising the following steps:

2. A filter device as claimed in claim 1, wherein,

3. The filter device according to claim 1, wherein a liquid inlet guide screen for supporting a liquid inlet channel is arranged between the filter units.

4. The filter device of claim 1, wherein the virus removal membrane separation layer is positioned on a side surface of the virus removal membrane proximate to the filtrate deflection screen.

5. The filter device of any one of claims 1-4, wherein the outer side of the pre-filter layer is a first outer surface, the first outer surface has an average pore size of 160-440nm, and the first outer surface has a pore area ratio of 0.5-14%; the outer side of the separation layer is a second outer surface, the average pore diameter of the second outer surface is 12-40nm, and the pore area ratio of the second outer surface is 2.5-9%.

6. The filtration device of any one of claims 1 to 4, wherein the average pore size of the virus-removing membrane is continuously changed in a gradient from a surface area on a side close to the filtrate guiding screen to a surface area on a side far from the filtrate guiding screen, and the average pore size is changed in a gradient of 2 to 5.5 μm/1 μm.

7. The filter device according to claim 1, wherein the pre-filter layer has an average pore size of 55-190nm and the separation layer has an average pore size of 16-23nm; the ratio of the average pore diameter of the pre-filter layer to the average pore diameter of the separation layer is 4-12.

8. The filter device of claim 1, wherein the prefilter layer has a thickness of 72-89% of the thickness of the virus-free membrane and a porosity of 77-90%; the thickness of the separation layer accounts for 11-28% of the thickness of the virus-removing film, and the porosity is 62-78%.

9. The filtration device of claim 1, wherein the virus-removal membrane has a thickness of 45-140 μm.

10. The filtration device of claim 1, wherein the virus-removal membrane comprises one or more of a polyethersulfone virus-removal membrane, a regenerated cellulose virus-removal membrane, a cellulose acetate virus-removal membrane, or a polyvinylidene fluoride virus-removal membrane.

11. The filter device of claim 2, wherein the filter layer is a plurality of virus-removing membranes, each of the virus-removing membranes having a packaging hole in communication with at least a portion of the feed-in channel, the plurality of virus-removing membranes including at least a first virus-removing membrane having a largest packaging hole inner diameter and a second virus-removing membrane having a smallest packaging hole inner diameter, the plurality of virus-removing membranes being stacked to form a radial dislocation region at the packaging hole;

12. The filter device of claim 11, wherein the second virus removal membrane is located on a side of the filter layer remote from the filtrate deflection screen; or the second virus removal membrane is positioned at one side of the filter layer close to the filtrate diversion screen.

13. The filter device of claim 12, wherein the inner diameter of the packing hole is stepped, and is gradually decreased from a side near the filtrate guiding screen to the outside, or is gradually increased from a side near the filtrate guiding screen to the outside.

14. The filtration device of claim 1 or 2, wherein the filtration unit further comprises an isolation layer disposed between the filtration layer and the filtrate guiding screen.

15. The filter device according to claim 14, wherein the surface roughness of the side of the separation layer adjacent to the filter layer is 2-25 μm and the softness is 100-250mN.

16. The filter device of claim 14, wherein the spacer layer has a thickness h1, the filtrate deflection screen has a thickness h2, and h1: h2 is 1:1-5.

17. The filter device according to claim 14, wherein the spacer layer has a thickness of 80-150 μm and a ventilation of 60-160cc/cm ² Sec; the thickness of the filtrate diversion screen is 400-650 mu m, and the porosity is 25-35%.

18. The filter device of claim 14, wherein the barrier layer is one or more of a nonwoven fabric, a woven fabric, or a porous membrane.

19. The filter device of claim 14, wherein the separator is provided with a separator inlet at least partially in direct communication with the inlet channel, and wherein the separator is bonded to the filter layer and the filtrate guiding screen by an adhesive layer on the separator.

20. The filter device of claim 19, wherein the adhesive layer is impregnated into the spacer layer and surrounds the spacer layer inlet and the adhesive layer covers the inner wall of the spacer layer inlet to prevent a through fluid passage from being formed between the spacer layer inlet and the spacer layer from entering the inner wall of the spacer layer inlet.

21. The filter device of claim 19, wherein the spacer layer inlet forms a stepped offset region with the inner wall of the filter layer inlet channel.

22. A method of performing a protein-containing feed solution virus removal filtration using the filtration device of any one of claims 1-21, comprising the steps of:

23. The method of claim 22, wherein the pressure of the feed solution in step S2 is 20-40psi.

24. The method for removing virus from protein containing feed liquid according to claim 22, wherein the filtration flux is greater than 180L/(m) ² *h)。