Small-scale tangential flow filtration device

Abstract

A tangential flow filtration device is provided including a first end cap, a second end cap, a feed screen intermediate the first end cap and the second end cap, and a first membrane intermediate the feed screen and the first end cap. The tangential flow filtration device has a filtration area less than about 50 cm2.

Description

SMALL-SCALE TANGENTIAL FLOW FILTRATION DEVICEBACKGROUND TECHNICAL FIELD

[0001] Embodiments of the invention relate generally to filtration systems and devices and, more particularly, to a small-area tangential flow filtration device that is linearly scalable.DISCUSSION OF ART

[0002] Filtration is a process in which membranes are used to separate components in a liquid solution or suspension based on their size differences. One existing type of filtration is tangential flow filtration (TFF), also known as cross flow filtration (CFF).

[0003] Tangential flow or cross flow filtration applications often use cassettes or other plate and frame formats. These plate and frame formats typically incorporate a plurality of flat sheet membranes arranged between external flat plates and manifolds. In tangential flow or cross flow filtration, the fluid to be filtered is passed through the inlet of the manifold, into the cassette, and tangentially to the first (or upstream) surface of the membranes. A portion of the fluid passes through each of the membranes from the first surface to the second (or downstream) surface, through the cassette and out one outlet of the manifold. Another portion of the fluid passes tangentially to the first surface of the membrane, through the cassette and out another outlet of the manifold without passing through the membranes. The fluid passing into the inlet of the manifold and into the cassette is commonly referred to as the feed. The feed contains various sized molecules and possibly debris. The fluid passing from the first surface of the membrane to the second surface of the membrane is commonly referred to as the filtrate or permeate. The filtrate or permeate contains the smaller molecules that have passed through the pores of the membrane. The fluid passing parallel to the first surface of the membrane without passing through to the second surface of the membrane is commonly referred to as retentate. The retentate contains the larger molecules that have not passed through the pores of the membrane.

[0004] Conventional cassette encapsulation is achieved by interleaving multiple layers of screen mesh and membrane in a stack to be bound together as a cohesive stack, typically with a single or two-part liquid urethane or silicone. The stack may be bound by retaining the layers between plates while impregnating and encapsulating the edges of the stacked layers with the urethane or silicone. Other methods involve the use of thermoplastics. The encapsulated stack is often termed a cassette.

[0005] Existing cassettes are manufactured in a variety of sizes having different membrane areas. For example, small-area devices may have a membrane area down to about 50 cm2, with larger area devices having a membrane area exceeding 1 m2. Existing small-scale devices, however, are not well suited for the development and testing phases, as such devices still require the use of a substantial amount of feed fluid. Moreover, existing smaller scale devices typically do not scale linearly to larger format sizes, which requires repeating development work at larger scale.

[0006] In view of the above, there is a need for a small-scale tangential flow filtration device that minimizes feed fluid usage and allows for the evaluation of processing conditions at an early stage of development, and which is linearly scalable to larger area devices used during future stages of development.BRIEF DESCRIPTION

[0007] Certain embodiments commensurate in scope with the originally claimed subject matter are summarized below. These embodiments are not intended to limit the scope of the claimed subject matter, but rather these embodiments are intended only to provide a brief summary of the possible embodiments. Indeed, the disclosure may encompass a variety of forms that may be similar to or different from the embodiments set forth below.

[0008] In one embodiment, a tangential flow filtration device is provided. The tangential flow filtration device includes a first end cap, a second end cap, a feed screen intermediate the first end cap and the second end cap, and a first membrane intermediate the feed screen and the first end cap. The tangential flow filtration device has a filtration area less than about 50 cm2.

[0009] In another embodiment, a method of manufacturing a tangential flow filtration device includes the steps of sealing a first membrane to a first end cap, the first end cap having an integrated first permeate channel, and disposing a feed screen adjacent to the first membrane opposite the first end cap. The first end cap with first membrane, the feed screen, and the second end cap form a stacked assembly.

[0010] In yet another embodiment, a tangential flow filtration device includes a first end cap having a first membrane affixed thereto, the first membrane and the first end cap defining therebetween a first permeate channel, a second end cap having a second membrane affixed thereto, the second membrane and the second end cap defining therebetween a second permeate channel, a feed screen intermediate the first membrane of the first end cap and the second membrane of the second end cap, and an enclosure encasing the first end cap and first membrane, the feed screen, and the second end cap and second membrane.

[0011] In yet another embodiment, a method for tangential flow filtration includes the steps of, in a development phase, passing a first liquid feed into a feed channel of a first tangential flow filtration device having a filtration area less than about 50 cm2, and separating permeate from the liquid feed.DRAWINGS

[0012] The present invention will be better understood from reading the following description of non-limiting embodiments, with reference to the attached drawings, wherein below:

[0013] FIG. 1 is a perspective view of a tangential flow filtration device, according to an embodiment of the invention.

[0014] FIG. 2 is an exploded, perspective view of the tangential flow filtration device of FIG. 1.

[0015] FIG. 3 A is a perspective view of a portion of the tangential flow filtration device of FIG. 1, showing the device in a partially-assembled state.

[0016] FIG. 3B is another perspective view of a portion of the tangential flow filtration device of FIG. 1, showing the device in a partially-assembled state.

[0017] FIG. 3C is another perspective view of a portion of the tangential flow filtration device of FIG. 1, showing the device in a partially-assembled state.

[0018] FIG. 4 is a perspective view of an end cap and membrane of the tangential flow filtration device of FIG. 1.

[0019] FIG. 5 is a perspective view of the end cap of the tangential flow filtration device of FIG. 1.

[0020] FIG. 6 is another perspective view of the end cap of FIG. 5, showing a reverse side thereof, illustrating a permeate channel.

[0021] FIG. 7 is an enlarged, detail view of a portion of the end cap of FIG. 6.

[0022] FIG. 8 is an enlarged, perspective view of a feed screen of the tangential flow filtration device of FIG. 1.

[0023] FIG. 9 is an enlarged, perspective view of a fitting of the tangential flow filtration device of FIG. 1.

[0024] FIG. 10A is an enlarged, top, perspective view of a gasket of the tangential flow filtration device of FIG. 1.

[0025] FIG. 10B is an enlarged, bottom, perspective view of the gasket of the tangential flow filtration device of FIG. 1.

[0026] FIG. 10C is a transparent, perspective view of the gasket.

[0027] FIG. 10D is an enlarged, top, perspective view of a gasket of the tangential flow filtration device of FIG. 1.

[0028] FIG. 10E is an enlarged, detail view of a portion of the tangential flow filtration device of FIG. 1.

[0029] FIG. 11 is a perspective view of a feed channel of the tangential flow filtration device of FIG 1, with all solid components removed for illustration purposes.

[0030] FIG. 12 is a perspective view of the permeate channels of the tangential flow filtration device of FIG. 1, with all solid components removed for illustration purposes.

[0031] FIG. 13 is a perspective view of the feed channel and permeate channels of the tangential flow filtration device of FIG. 1, with all solid components removed for illustration purposes.

[0032] FIG. 14 is an enlarged, detail view of a portion of the feed channel and permeate channels of the tangential flow filtration device of FIG. 1, with all solid components removed for illustration purposes.

[0033] FIG. 15 is an enlarged, top plan view of a portion of the feed channel and permeate channels of the tangential flow filtration device of FIG. 1, with all solid components removed for illustration purposes.

[0034] FIG. 16 is a cross-sectional, perspective view of a portion of the tangential flow filtration device of FIG. 1, illustrating the permeate outlet path.

[0035] FIG. 17 is a graph illustrating limiting flux across a range of TFF devices.

[0036] FIG. 18 is a chart illustrating differential pressure across a range of TFF devices.DETAILED DESCRIPTION

[0037] Reference will be made below in detail to exemplary embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference characters used throughout the drawings refer to the same or like parts.

[0038] As used herein, the “feed” refers to the solution that is delivered to a filtration device to be filtered. The feed that is delivered to a filtration device for filtration can be, for example, feed from a feed container (e.g., vessel, tank) external to the system, or retentate from a preceding filtration module in the same system.

[0039] As used herein, the term “filtration”, as used herein, generally refers to the act of separating the feed sample into two streams, a permeate and a retentate, using membranes.

[0040] As used herein, the terms “permeate” and “filtrate” refer to that portion of the feed that has permeated through the membrane.

[0041] As used herein, the term “retentate” refers to the portion of the solution that has been retained by the membrane (i.e., does not pass through the membrane).

[0042] As used herein, the term “flow path” refers to a channel supporting the flow of a liquid (e.g., feed, retentate, permeate) through all or part of a TFF system. Thus, a TFF system can have multiple flow paths, including a flow path through the entire system from the feed inlet to the retentate outlet, a flow path within a filtration device (e.g., a flow path through TFF cassettes), and a flow path between two or more adjacent filtration devices (e.g., a flow path between manifold segments in adjacent filtration modules). The flow path can have any topology which supports tangential flow (e.g., straight, coiled, arranged in zigzag fashion).

[0043] As used herein, the phrased “fluidly connected”, “fluidly coupled”, or “fluid communication” refers to two or more components of tangential flow filtration system or device that are connected by one or more conduits (e.g., a feed channel, a retentate channel, a permeate channel) such that a liquid can flow from one component to the other.

[0044] Embodiments of the invention relate to tangential flow filtration devices. A tangential flow filtration device according to an embodiment of the invention may include a first end cap, a second end cap, a feed screen intermediate the first end cap and the second end cap, and a first membrane intermediate the feed screen and the first end cap. The tangential flow filtration device may have a filtration area less than about 50 cm2.

[0045] With reference to FIGS. 1 and 2, a tangential flow filtration device 10 according to an embodiment of the invention is illustrated. As best shown in FIG. 2, the tangential flow filtration device 10 includes a first end cap 12 (also referred to herein as first membrane plate 12), a second end cap 14 (also referred to herein as second membrane plate 14), and a feed screen 16 intermediate the first end cap 12 and the second end cap 14. In an embodiment, the end caps and feed screen may be generally rectangular or I-shaped (having enlarged opposing ends). The tangential flow filtration device 10 further includes a first membrane 18 intermediate the first end cap and the feed screen 16, and a second membrane 20 intermediate the second end cap 14 and feed screen 16. As also shown in FIG 2, in one embodiment, a support layer 17, 19 is sandwiched intermediate the respective end caps and membranes. It will be appreciated, however, that the support layers 17, 19 may be omitted. In an embodiment, membranes (and support layers, where utilized) aresealed to the respective end caps 12, 14 and thus form an integral part of the respective end caps / membrane plates. In other embodiments, the membranes 18, 20 may be separate components sandwiched between the respective end caps 12, 14 and the feed screen 16. In either implementation, the first end cap 12 and the first membrane 18 define therebetween a first permeate channel, and the second end cap 14 and the second membrane 20 define therebetween a second permeate channel, the purposes of which will be described in detail hereinafter.

[0046] In one embodiment, the support layers 17, 19 lie under the respective membranes 18, 20 to support the membranes, to provide added thickness for heat sealing, and to help achieve scalability. In an embodiment, the support layers 17, 19 are formed from nonwoven sheets that are polyethylene / polypropylene core-sheath. It is contemplated, however, that other materials that are readily permeable to water, have adequate strength to support the membranes, and are thermally bondable to the membranes and membrane plates may be utilized without departing from the broader aspects of the invention. For example, polyethylene microporous membranes may also be used for the support layers 17, 19.

[0047] Referring still further to FIG. 2, a first gasket 22 is operatively connected to an upstream end of the first end cap 12, second end cap 14, and feed screen 16, and a second gasket 24 is operatively connected to a downstream end of the first end cap 12, second end cap 14 and feed screen 16, for the purpose of controlling the direction and routing of fluid flow, as described in detail hereinafter. In addition, the tangential flow filtration device 10 includes a first fitting 26 having first and second ports 28, 30, and a second fitting 32 having third and fourth ports 34, 36. In an embodiment, the first port 28, second port 30, third port 32 and fourth port 34 are configured as Luer connectors, although other connection types such as threaded, hose barb, and the like may also be utilized without departing from the broader aspects of the invention. The first fitting 26 and ports 28, 30 thereof, and the second fitting 32 and ports 34, 36 thereof, are configured to provide for fluid communication with the various flow channels of the tangential flow filtration device, as discussed in detail below.

[0048] As further shown in FIG. 2, the components described above may be arranged in stacked relationship and positioned within a housing or enclosure having first and second housing members 38, 40. For example, first housing member 38 is generally rectangular in shape and forms a top half of the housing, while second housing member 40 is similar in shape and forms a mating bottom half of the housing. The first housing member 38 includes apertures for receiving the ports of the first and second fittings 26, 32 therethrough, as best shown in FIG. 1. The housing members 38, 40 may be manufactured from a substantially rigid material such as, for example, glass-filled polypropylene, although other materials known in the art may also be utilized without departing from the broader aspects of the invention. In an embodiment, the housing members 38, 40 are manufactured from polypropylene that incorporates about 30% weight percentage of glass fibers into the polypropylene matrix.

[0049] In an embodiment, the first and / or second housing members 38, 40 may include a plurality of ribs 42 formed in the interior of the housing members (shown, for example, in the interior of the first housing member 38). In an embodiment, the ribs 42 may extend between the plurality of bosses 56. It is contemplated, however, that other rib configurations may be employed. In any implementation, the ribs 42 are designed to strengthen the housing and inhibit deflections during use. In particular, during use, substantial pressure within the feed channel (upwards of about 60 psi) can cause deflections in the housing or enclosure, which can contribute to undesirable changes in pressure which can affect the performance of the device and inhibit the desired scalability. The ribs 42 are included to inhibit or prevent such deflections and thus minimize the possibility of undesirable pressure drop.

[0050] As further shown in FIG. 2, in an embodiment, the tangential flow filtration device may also include a first rigid plate 46 intermediate the first housing member 38 and the first end cap 12, and a second rigid plate 48 intermediate the second housing member 40 and the second end cap 14. In an embodiment, the first and second rigid plates 46, 48 are generally thin, rectangular members formed from a rigid material such as metal (e.g., 304 stainless steel), and function to ensure that the first end cap 12, second end cap 14, and feedscreen remain substantially flat and to inhibit deflections of such components. It is contemplated that other materials may be utilized such as, for example, glass filled polypropylene (the same material as the housing members 38, 40). By utilizing a non-metal material, or by having only one of the plates be metal (and the other non-metal) will facilitate the compatibility of the device with gamma irradiation (which could be blocked if metal plates were present on both sides).

[0051] In one embodiment, the tangential flow filtration device 10 may also include a pair of flat, rigid plates (not shown) on the exterior surfaces of the respective housing members 38, 40, which likewise help to inhibit or resist deflections and maintain the flatness of the components interior to the enclosure. In an embodiment, the plates may be formed from metal or other rigid material. In other embodiments, these plates may be omitted. As shown in FIGS. 2 and 3A-3C, the enclosure and internal components thereof may be secured to one another in stacked relationship via an array of bolts or screws 54. For example, the housing member 38 may have an array of bosses 56 on an underside thereof for receiving screws 54 inserted through apertures 57 in the second rigid plate 48. In an embodiment, the bosses 56 are non-threaded, and the screws 54 are self-tapping screws. It is further contemplated that other fastening means known in the art such as adhesive, clamps, heat staking, ultrasonic welding, press fit and the like may also be utilized to secure the components together in stacked relationship, without departing from the broader aspects of the invention.

[0052] Referring now to FIGS. 4-7, detailed views of the first end cap 12 are illustrated (with the second end cap being identically or substantially similarly configured). As shown in FIG. 4, the first membrane 18 is sealed to the first end cap 12 by means known in the art such as, for example, heat sealing or welding. As shown therein, the membranes 18, 20 have a pair of apertures 60 in each end thereof, allowing for the passage of fluid therethrough. Turning now to FIG. 6, the first and second end caps 12, 14 likewise include a pair of apertures 62 at the distal ends thereof, which allow for the passage of fluid therethrough. In an embodiment, the membranes 18, 20 are formed from any material, and by means, generally known in the art. In particular, as used herein, “membrane” or“filtration membrane” refers to a selectively permeable membrane for separating a feed into a permeate stream and a retentate stream using a tangential flow filtration process. The membranes 18, 20 may be, but are not limited to, ultrafiltration (UF) membranes, microfiltration (MF) membranes, reverse osmosis (RO) membranes, and nanofiltration (NF) membranes. The terms “ultrafiltration membrane” and “UF membrane” are used herein to refer to a membrane that has pore sizes in the range of between about 1 nanometer to about 100 nanometers. The term “microfiltration membranes” and “MF membranes” are used herein to refer to membranes that have pore sizes in the range between about 0.1 micrometers to about 10 micrometers.

[0053] With reference to FIG. 6, the first end cap 12 is illustrated with the first membrane 18 not present. As shown therein, the first end cap 12 includes a molded-in permeate channel 64, as disclosed above. In an embodiment, the permeate channel 64 is formed as a recessed area in the first end cap 12, extending along the length of the first end cap 12 from the first end to the second end and may include a plurality of parallel ridges 66 likewise extending end to end. Other designs of the molded-in channels are possible and are not intended to be limited to the configuration shown in FIG. 6. As will be appreciated, therefore, the use of a molded-in permeate channel obviates the need to employ a separate permeate screen and also increases manufacturing consistency. As best shown in FIG. 7, in an embodiment, the end caps 12, 14 may include a peripheral seal bead 68 that protrudes from the membrane-facing surface of the respective end caps. Accordingly, when the membrane 18 is sealed to the end cap 12, the permeate channel 64 is defined therebetween. The seal bead 68 aids in bonding of the membranes 18, 20 to the end caps 12, 14 and ensure integrity.

[0054] In an embodiment, the seal bead 68 may extend around the entire periphery of the end caps 12, 14 (encompassing the permeate channel and any holes or apertures for the flow of fluid therethrough). In one embodiment, the seal bead 68 may be the same material as end caps 12, 14, however, in other embodiments, the seal bead 68 may be a different material than the end caps 12, 14. In one example, the seal bead 68 may be the same material as the membrane 18, 20. As indicated above, the seal bead 68 may serve as agasket / seal to prevent / reduce leakage from the feed inlet and / or permeate outlet channels, inlets and outlets. Additionally, the seal bead 68 may serve to compress the components of the device 10 together to prevent air and / or fluid leakage.

[0055] In one embodiment, the seal bead may be a ridge, a protrusion, or the like. The seal bead 68 may be formed as part of the end caps 12, 14 or may be a separate component added to the end caps. The seal bead 68 may be coupled to the end caps via thermal welding, injection molding, adhesive, press-fit, or the like. The seal bead may provide a raised portion of material to be heat sealed, facilitating bonding of the membrane and the end caps. The heat is configured to displace material of the seal bead to allow bonding of the membrane and the end cap. By having the raised seal bead and material thereof displaced, the end cap and membrane may largely be insulated from excessive heat, which would cause material displacement of the end cap and / or the membrane. Said another way, the seal bead being added to the end cap builds in a level of displacement that may aid in the bonding process without displacing material of the end cap. This allows for greater consistency and reliability of the filtration system and channels therein.

[0056] It is contemplated that a cross-sectional profile of the seal bead may be one or more of arcuate, rectangular, trapezoidal, triangular, an irregular shape, or the like. The cross-sectional shape may be selected based on the shape and desired bonding characteristics of the remainder of the filtration system. The various cross-sectional shapes provide a different amount of material, as well as a different pattern of material displacement during the bonding process. Based on the filtration system and desired characteristics, a different cross-sectional shape may be selected.

[0057] The seal bead is configured and positioned to provide a bonding surface between a membrane and the end caps, as disclosed above. The seal bead allows a significant improvement in bonding depth control and uniformity. Additionally, the seal bead allows for surface imperfections on the interfacial surface of the end caps. In addition to the shape of the seal bead being able to be selected based on desired characteristics of the filtration system, the size and / or height of the seal bead may be varied, as well. In embodiments, the height of the seal bead may be between 0.001 inches and 0.03 inches. In otherexamples, the height of the seal bead may be less than or greater than this range. The height of the seal bead may be selected based on an expected deviation in a manufacturing tolerance of the end caps (and / or anticipated imperfections therein). Further, based on the height and shape of the seal bead being selectable, this allows the seal bead to have a more repeatable feed channel height. The feed channel height may be determined, in part, by the height and shape of the seal bead.

[0058] In an embodiment, the end caps 12, 14 are formed by molding, although other means known in the art may also be utilized. The end caps 12, 14 may be formed from polyethylene such as, for example, high-density polyethylene, and the first and second membrane may be sealed to the end caps to enclose the permeate channels 64 by thermally bonding, as indicated above.

[0059] Referring now to FIG. 8, a detailed view of the feed screen 16 is illustrated. As disclosed above, feed screen 16 is generally rectangular or I-shaped (having enlarged opposing ends). The feed screen 16 includes, at a first end thereof, a feed inlet port or opening 80 and a first pass-through aperture 82 adjacent to the inlet port 80, and at the opposing end, a feed outlet port or opening 84 and a second pass-through aperture 86 adjacent to the outlet port 84. A feed channel 88 extends between the inlet port 80 and the outlet port 84. When assembled, the feed channel 88 is located between the first membrane 18 of the first end cap 12, and the second membrane 20 of the second end cap 14. In an embodiment, the feed screen 16 is an over-molded feed screen which acts both as a gasket seal and as the screen to hold the membrane layers 18, 20 apart and create the necessary cleaning action to prevent buildup and fouling. In an embodiment, the feed screen 16 includes a feed screen formed from polypropylene with a thermoplastic elastomer overmold. In one embodiment, the feed screen 16 is manufactured by die-cutting a polypropylene screen and placing it into a mold (using, for example, feed and retentate holes for alignment). Thermoplastic elastomer (TPE) or silicone is then injection molded around the screen (although other material may also be utilized without departing from the broader aspects of the invention). The use of TPE or silicone for the overmold area of the feed screen provides a fluid seal when compressed between the membranes 18, 20 of theend caps 12, 14 during assembly, helping to ensure the overall integrity of the device 10. In an embodiment the feed screen 16 is an edgeless feed screen, having a flat flange surrounding the peripheral edge of the screen portion of the feed screen.

[0060] Turning now to FIG. 9, a detailed view of the first fitting 26 is illustrated (with the second fitting 32 being substantially identical). As shown therein, the fitting 26 includes a generally flat bottom 70, with first and second ports 28, 30, configured as Luer connectors, extending therefrom and defining therethrough hollow passages 72, 74 for the passage of fluid. As disclosed above, however, the ports 28, 30 can be interchanged for different geometry (Luer, threaded, barb, etc.) to meet customer specifications or the like.

[0061] FIGS. 10A, 10B and 10C are detailed views of the gasket 24, with gasket 22 being similarly configured. As shown therein, the gasket 24 is generally rectangular in shape, having a top member 87, a bottom member 89 and opposed lateral side members 91, 93 interconnecting the top member 87 and the bottom member 89, defining therebetween an opening 90 for receiving the ends of the end caps 12, 14, membranes 18, 20, and feed screen 16, therein. The gasket includes a pair of apertures 92, 94 in the top surface thereof, which are surrounded by annular sealing elements 96 on an outer surface of the top member 87. As shown in FIG. 10B, the gasket 24 also includes an annular sealing element 103 on an inner surface of the top member 87 that surrounds the aperture 92.

[0062] As further shown in FIGS. 10A-10E and 16, the interior lower surface and the interior upper surface of the gasket 24 are formed with channels 97, 98, respectively, that extend in a direction generally perpendicular to the feed screen (and feed channel) and permeate channels 64, the purpose of which will be described below. The channel 98 in the top member 87 is in fluid communication with the aperture 94, and includes a raised seal bead or sealing element 101 that surrounds the channel 98 and aperture 94. Channel 97 in the bottom member 89 also includes a raised seal bead or sealing element 103 that surrounds the channel 97. In an embodiment, the gaskets 22, 24 are formed from an elastomeric material, although other materials known in the art, including plastics, can be utilized. As discussed in detail hereinafter, the configuration of the gaskets 22, 24, when assembled with the feed screen and end caps, defines fluid pathways which enable thepermeate flows from the two permeate channels to be combined internally to the device 10 so that the combined permeate flow can exit at one side of the device 10. While the gaskets 22, 24 shown in FIGS. 10A-10C have been disclosed herein as being a single piece band that encircles the end caps and feed screen, it is further contemplated that the gaskets 22, 24 can be two separate pieces (top and bottom members) that do not interconnect with one another, as shown in FIG. 10D. FIG. 10E shows an enlarged detail view of a portion of the tangential flow filtration device, with the gasket 24', 24" of FIG. 10D. Specifically, FIG.10E shows the gasket 24', 24" coupled with the first end cap 12', the second end cap 14', and the feed screen 16'.

[0063] Referring back to FIGS. 3A-3C, the tangential flow filtration device 10 is constructed and assembled by first stacking the first end cap or membrane plate 12, support 17 and membrane 18 and heat sealing these elements together to form a first end cap assembly. The second end cap or membrane plate 14, support 19 and membrane 20 are stacked and heat sealed in the same manner to form a second end cap assembly. In an embodiment, these components may be then trimmed to shape, if necessary, after heat sealing. The first end cap assembly, feed screen, and second end cap assembly are then stacked together (such that the feed screen is positioned intermediate the first end cap assembly and second end cap assembly), and the respective gaskets 22, 24 are installed over the opposing ends to hold the stack together.

[0064] With reference to FIG. 3 A, the first housing member 38 is then turned upside-down to expose the interior of the housing 38. The fittings 26, 32 are installed in the housing member 38 in a manner such that the respective ports extend through the housing member 38. Rigid plate 46 is then positioned within the housing member 38. As shown in FIG.3B, the stack including the first end cap assembly, feed screen, and second end cap assembly (held together by the gaskets 22, 24) is positioned in the housing member 38. Turning to FIG. 3C, the second rigid plate 48 is then placed atop the stacked components. Screws 54 are inserted through the apertures 57 in the second rigid plate 48 and screwed into the bosses 56 in the underside of the first housing member 38. In one embodiment, the end-most screws may be inserted first to align the plate 48. In other embodiments, thehousing member 38 may instead, or additionally, include alignment pins 49 in the housing member 38 that facilitate proper positioning and alignment of the plate 48. Once properly aligned, the remaining screws 54 can be inserted to secure the plate 48 to the housing member 38. Once the screws 54 are inserted, the stacked assembly is held securely within the first housing member 38. The second housing member 40 can then be secured to the first housing member 38 (to secure all components within) via a press fit or snap fit connection, although other fastening means known in the art such as adhesives and the like may also be utilized.

[0065] Referring back to FIGS. 1 and 2, in an embodiment, port 30 of fitting 26 is configured as a feed inlet port configured for connection to a feed source for receiving a flow of fluid therefrom. The feed inlet port 30 is fluidly connected to the inlet opening 80 of feed screen 16, and is thus in fluid communication with the feed channel 88. Similarly, the feed outlet opening 84 in the feed screen 16 is in fluid communication with the feed outlet port 34 of the fitting 32 and provides a means of egress for the feed / retentate after passing through the feed channel 88. In this respect, feed inlet port 30 of the fitting 26, inlet opening 80 of the feed screen 16, feed channel 88, outlet opening 84 in the feed screen, and outlet port 34 of fitting 32 define therebetween a pathway for the flow of feed / retentate.

[0066] In addition, ports 28 and 36 of fittings 26 and 32 are configured as permeate outlet ports and are in fluid communication with the permeate channels 64 in both the first end cap 12 and second end cap 14. The permeate outlet ports 28, 36 thus provide a means of egress for the permeate that passes from the feed channel, through membranes 18, 20, into the permeate channels 64 of the first and second end caps 12, 14.

[0067] In use, as is known in the art, a feed flow is passed into the device 10 through feed inlet port 30 of the first fitting 30 as described above, and flows through feed channel 88. A portion of the fluid (including molecules small enough to pass through the pores of the membranes) passes from the feed channel 88 through the first and second membranes 18, 20 into the permeate channel 64 of the respective end caps 12, 14. FIGS. 11-15 illustrate the feed channel 88 defined by the feed screen 16, and the permeate channels 64 defined by the respective end caps. In particular, FIG. 11 illustrates the feed channel 88 (with thefeed screen removed). FIG. 12 illustrates the permeate channels 64 formed by the respective end cap assemblies (with the respective end cap assemblies, including end caps 12, 14, support layers 17, 19 and membranes 18, 20 removed). FIG. 13 illustrates the feed channel 88, with permeate channels 64 on opposite sides thereof (again, with components removed and illustrating just the flow of fluid).

[0068] With reference to FIG. 16, at either end of the permeate channel 64, the flow jumps through the endcaps 12, 14 to the backside, as indicated by arrows A and B in FIG. 16. Here, it is encapsulated between the gaskets 22, 24 and the end caps 12, 14. The flow passes through the channels 97, 98 in the gaskets 22, 24 which connects the permeate channels 64 to the permeate ports 28, 36 while sealing it from the feed inlet and outlet ports 30, 34. As shown in FIG. 16, the flow from the non-port side passes back through the end cap 14 via aperture 62, through the aperture 86 in the feed screen 16, through the end cap 12 via aperture 62, and joins the other permeate channel. The permeate then exits the tangential flow filtration device 10 via the port 36 of fitting 32. Accordingly, the tangential flow filtration device 10 combines the permeate channel flows internally, which is then passed through the permeate outlet ports 28, 36 on a single side of the housing / enclosure. Similarly, both the feed inlet port 30 and retentate port 34 are located on the same side of the device as the permeate outlet ports 28, 36.

[0069] The present invention thus separates the outlet ports 28, 36 from the membrane plates / end caps and uses the port gaskets 22, 24 as both the sealing mechanisms between the membrane plate and the ports and the permeate passthrough connector. It is envisioned, however, that the functionality of bringing the permeate flows to one side using a passthrough, passing fluid through a channel in the gasket and then combining with other flows, or simply passing back through a separate passthrough, has utility outside of its use in the device 10 and / or in the field of tangential flow filtration.

[0070] In an embodiment the feed channel 88 has a flow path length (defined by the distance between the center of the inlet port 84 to the center of the outlet port 84, measured horizontally) between about 6.7 inches to about 6.8 inches. In an embodiment, the feed channel 88 has a flowpath length of about 6.75 inches. In an embodiment, the activefiltration area of the tangential flow filtration device 10 is less than about 50 cm2. In an embodiment, the active filtration area of the tangential flow filtration device 10 is less than about 20 cm2. In an embodiment, the active filtration area of the tangential flow filtration device 10 is about 18 cm2. In any of these embodiments, the flow path length of the tangential flow filtration device 10 is substantially equivalent to the flow path length of larger scale devices (having active filtration areas greater than about 88cm2). Moreover, the pressure drop (also referred to as differential pressure) across the device 10 is substantially similar to the pressure drop seen in larger scale devices, including those in excess of about 1 m2), at similar concentrations. Moreover, the feed screen 16, as disclosed above, may be substantially similar in configuration and construction to those utilized in large scale devices (albeit with a smaller area). In addition, the device 10 of the invention and enclosure (including housing members 38, 40 thereof) experience a deflection of less than about 0.0005 inches at a feed channel pressure of 60 pounds per square inch.

[0071] Accordingly, the tangential flow filtration device 10 provides linear scalability to larger scale devices, including those having a filtration area in excess of about 88 cm2, in excess of about Im2, and / or up to about 1.3 m2, and / or in excess of about 2.5 m2. This is in contrast to existing devices which do not provide true linear scalability, and which require the use of a substantial amount of feed fluid and / or require repeating development work when moving to larger scale.

[0072] As used herein, linear scalability means that a range of tangential flow filtration devices (having different filtration areas) perform similarly to one another at similar setpoints. Accordingly, with respect to the invention described herein, linear scalability of the device 10 (in embodiments where the active filtration area is less than about 88 cm2, less than about 50 cm2, less than about 20 cm2, and / or about 18 cm2) means that such device 10 performs similarly to TFF devices having a greater active filtration area (including devices having an active filtration area in excess of about 90 cm2, in excess of about .1 m2, in excess of about .5 m2, in excess of about 1.3 m2, and in excess of about 2.5 m2), at similar setpoints. The typical controlled parameters in TFF are all flowrates normalized to filter area (flux), and / or are pressures which are independent of filtration area. Accordingly, ifsubstantially the same pressures and substantially the same feed or crossflow flux is maintained across all such devices, then the output permeate flux should be substantially the same.

[0073] In connection with the above, linear scalability of a given TFF device, or range of devices, can be assessed by running a variety of tests. One test used to evaluate scalability is a “flux excursion” test. In such test, a particular molecule and concentration is fed into the TFF device where the feed flux is held constant, typically around 300 LMH (Liters / Meter2 / hour), and the transmembrane pressure (TMP) is slowly increased in steps. The permeate flowrate is recorded and converted to a flux. The Flux vs TMP graph is then reviewed across all sizes and the graphs should (within tolerance) line up with each other. The important vitals from this test are the limiting flux (the flux at which increasing TMP no longer increases permeate flowrate) and the critical TMP the pressure at which that limiting flux is reached - these parameters should be within a tolerance for all device sizes. FIG. 17 is a graph that illustrates the results of such tests for the device 10 of the invention, a Centramate™ cassette (CM01) having an effective filtration area of 93 cm2, a Centramate™ cassette (CM12) having an effective filtration area of .1 m2, a Centrasette™ cassette (CS12) having an effective filtration area of 0.57 m2, and two stacked Centrasette™ cassettes (CS27) each having an effective filtration area of 2.5 m2, all of which are available from Cytiva®. As can be seen from this graph, the results of the test on device 10 largely mirror the results of the tests on the larger filtration area devices (within less than about 10% deviation), indicating that the device 10 is linearly scalable to all such devices indicated on the graph.

[0074] Another test to assess scalability is to run a concentration where a particular molecule and concentration is fed from a reservoir through the TFF device at a fixed feed flux and a fixed TMP. The volume of solution in the reservoir is proportional to the area of the filter to provide a particular loading in grams / meter2. The permeate flow is discarded which means that the solution is constantly concentrating. The permeate flowrate is recorded as a function of concentration and then graphed both in standard and log scales. For two devices within the same product family that scale to each other, theshape and slope of these graphs should be similar. One metric that is compared in this test is the mass transfer coefficient which is the slope of the line of best fit on the permeate flux / In(concentration) graph. Two devices that scale to each other should have a similar mass transfer coefficient. If the slopes and shapes of the graphs are similar, then that means that the permeate flux decreases with increasing concentration in a predictable fashion and that across a range of concentrations and pressures, the smaller and larger devices perform similarly to each other. Through such testing, it has been verified that the device 10 of the invention is linearly scalable to each of the larger filtration area devices listed in the graph of FIG. 17.

[0075] Finally, FIG. 18 is a chart showing the results of differential pressure testing for the device 10 of the invention, as well as for a Centramate™ cassette (CM01) having an effective filtration area of 93 cm2, a Centramate™ cassette (CM 12) having an effective filtration area of .1 m2, a Centrasette™ cassette (CS12) having an effective filtration area of 0.57 m2, a Centrasette™ cassette (CS27) having an effective filtration area of 1.25 m2, and two stacked Centrasette™ cassettes (CS27 x 2) each having an effective filtration area of 2.5 m2, all of which are available from Cytiva®. As shown therein, the differential pressures across this range of devices only varies about 15%, indicating linear scalability across the range of devices.

[0076] Accordingly, the tangential flow filtration device 10 of the invention provides a small membrane area, flat-sheet tangential flow device that is linearly scalable to larger area devices to minimize drug product volumes consumed during development. This reduces both time and costs for the customer. In addition, the device 10 disclosed herein allows more tests to be run from a smaller batch size. Moreover, the Luer-lock ports and the fact that no holder is required for the device 10 result in an ease of use heretofore not seen in the art.

[0077] While the embodiments disclosed above illustrate the use of an enclosure in the form of housing members 38, 40 sandwiching the end caps 12, 14, the invention is not intended to be so limited in this regard. In particular, it is contemplated that the end caps themselves may be rigid and / or be placed inside a clamping mechanism or enclosure bythe end user. Moreover, it is contemplated that the membranes, rather than being bonded to the end caps via the seal bead that protrudes from the end caps, may be placed within a recess formed within the end caps that generally corresponds to the size and shape of the membranes. In addition, depending on the rigidity of parts and the particular clamping / mounting mechanism utilized, housing members 38, 40, plates 46, 48 and / or plates 50, 52 may be omitted.

[0078] In some embodiments, the gaskets 22, 24 may also be omitted, in which case the permeate from each permeate channel 64 of the respective end caps 12, 14 can exit each side of the housing / enclosure (as opposed to the same side of the housing / enclosure). In such an embodiment, the permeate exiting each side of the housing can be combined via tubing external to the tangential flow filtration device.

[0079] Lastly, while the device 10 has been described herein as including two end caps 12, 14 and two permeate channels 64 on opposing sides of the feed screen 16, it is not intended that the invention be so limited in this regard. In particular, it is contemplated that the second end cap 14 and membrane 20 may be omitted so that filtration only occurs using the first end cap 12 and membrane 18 thereof. For example, in an embodiment where only a single membrane is used on one side of the feed screen, a dummy membrane plate / end cap, which has no permeate channels, no feed or permeate holes, etc. may be installed on the opposite side of the feed screen. In such a case, instead of a piece of membrane affixed to the end cap, a membrane-simulating layer is utilized. Such membrane-simulating layer is formed from a material of a similar thickness to the membrane (around 0.01”) such as, for example, a silicone sheet since, although materials known in the art may also be utilized. This dummy plate and membrane-simulating layer seal off the other side of the feed screen to make the liquid seal and press into the feed screen similarly to the membrane so that the fluid flows through the feed screen similarly to how it would with membrane on both sides.

[0080] According to an embodiment of the invention, a tangential flow filtration device includes a first end cap, a second end cap, a feed screen intermediate the first end cap and the second end cap, and a first membrane intermediate the feed screen and the first end cap. The tangential flow filtration device has a filtration area less than about 50 cm2. In anembodiment, the tangential flow filtration device has a filtration of about 18 cm2. In an embodiment, the tangential flow filtration device is linearly scalable to tangential flow filtration devices having a filtration area greater than about 88 cm2. In an embodiment, the first end cap includes a first permeate channel and a first permeate outlet in fluid communication with the first permeate channel. The first membrane may be sealed with the first end cap and defines therebetween the first permeate channel. In an embodiment, the second end cap includes a second permeate channel and a second permeate outlet in fluid communication with the second permeate channel. The tangential flow filtration device may further include a second membrane intermediate the feed screen and the second end cap, the second membrane being sealed with the second end cap and defining therebetween the second permeate channel. In an embodiment, the device may include one or more gaskets operatively connected to the first end cap and the second end cap, at least one gasket of the one or more gaskets including a first inlet for receiving a flow of permeate from the first permeate channel, a second inlet for receiving a flow of permeate from the second permeate channel, and an outlet fluidly connected to the first inlet and the second inlet. In an embodiment, the second inlet and the outlet define therebetween a flowpath for the flow of the permeate. The feed screen may include an aperture positioned along the flowpath so that the permeate from the second permeate channel is permitted to flow into the second inlet of the gasket, through the aperture in the feed screen, and to the outlet of the gasket. In an embodiment, the device may include an outlet port in fluid communication with the outlet of the gasket, the outlet port having one of a Luer, a threaded, or a barb connection mechanism. In an embodiment, the outlet port is a separate component from the gasket. In an embodiment, the tangential flow filtration device includes an enclosure enclosing the first end cap, the first membrane, the feed screen, the second membrane, and the second end cap. In an embodiment, the enclosure includes a first housing member and a second housing member, wherein the tangential flow filtration device further includes a first rigid plate intermediate the first end cap and the first housing member, and a second rigid plate intermediate the second end cap and the second housing member. In an embodiment, the tangential flow filtration device has a flow path length ofabout 6.75 inches. In an embodiment, the feed screen is an edgeless feed screen, and the first end cap includes a peripheral seal bead projecting from a membrane-facing surface of the first end cap, the peripheral seal bead being configured to bond with the first membrane to create a seal between the first membrane and the first end cap.

[0081] According to another embodiment of the invention, a method of manufacturing a tangential flow filtration device includes the steps of sealing a first membrane to a first end cap, the first end cap having an integrated first permeate channel, and disposing a feed screen adjacent to the first membrane opposite the first end cap. The first end cap with first membrane, the feed screen, and the second end cap with second membrane form a stacked assembly. In an embodiment, the method may also include the step of sealing a second membrane to a second end cap, the second end cap having an integrated second permeate channel, wherein the feed screen is located intermediate the first end cap and the second end cap. In an embodiment, the method may further include the step of operatively connecting at least one gasket to the stacked assembly to place a permeate outlet of the first end cap and a permeate outlet of the second end cap in fluid communication with a single outlet in the gasket. In one embodiment, the at least one gasket may include two separate portions that make up the at least one gasket. In an embodiment, the method may further include the steps of disposing the stacked assembly intermediate a first housing member and a second housing member, and connecting the first housing member to the second housing member. In an embodiment, the tangential flow filtration device has a filtration area less than about 20 cm2, and the tangential flow filtration device is linearly scalable to tangential flow filtration devices having a filtration area greater than about 88 cm2.

[0082] According to yet another embodiment of the invention, a tangential flow filtration device includes a first end cap having a first membrane affixed thereto, the first membrane and the first end cap defining therebetween a first permeate channel, a second end cap having a second membrane affixed thereto, the second membrane and the second end cap defining therebetween a second permeate channel, a feed screen intermediate the first membrane of the first end cap and the second membrane of the second end cap, and an enclosure encasing the first end cap and first membrane, the feed screen, and the secondend cap and second membrane. In an embodiment, the tangential flow filtration device is configured such that a flow of permeate from the first permeate channel and a flow of permeate from the second permeate the channel exit the housing on a common side of the housing. In an embodiment, the tangential flow filtration device has a filtration area less than about 20 cm2, and the tangential flow filtration device is linearly scalable to tangential flow filtration devices having a filtration area greater than about 88 cm2.

[0083] According to yet another embodiment of the invention, a method for tangential flow filtration includes the steps of, in a first phase (e.g., a development phase or when a customer has a small volume of fluid), passing a first liquid feed into a feed channel of a first tangential flow filtration device having a filtration area less than about 50 cm2, and separating permeate from the liquid feed. In an embodiment, the method further includes the steps of, in a second phase (e.g., a production phase) subsequent to the first phase, passing a second liquid feed into a feed channel of a second tangential flow filtration device having a filtration area greater than about 88 cm2, and separating permeate from the second liquid feed. The first tangential flow filtration device is linearly scalable to the second tangential flow filtration device. In an embodiment, the method may further include the steps of flowing the permeate through a first permeate channel and a second permeate channel on opposite sides of the feed channel, combining the permeate from the first permeate channel and the second permeate channel into a combined permeate flow, and outputting the combined permeate flow from the first tangential flow filtration device.

[0084] As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” should be understood as not excluding plural of said elements or steps, unless such exclusion is explicitly stated. Furthermore, references to “one embodiment” of the present invention are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the recited features. Moreover, unless explicitly stated to the contrary, embodiments “comprising,” “including,” or “having” an element or a plurality of elements having a particular property may include additional such elements not having that property.

[0085] This written description uses examples to disclose several embodiments of the invention, including the best mode, and also to enable one of ordinary skill in the art to practice the embodiments of invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to one of ordinary skill in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims.

Claims

WHAT IS CLAIMED IS:

1. A tangential flow filtration device, comprising:a first end cap;a second end cap;a feed screen intermediate the first end cap and the second end cap; and a first membrane intermediate the feed screen and the first end cap;wherein the tangential flow filtration device has a filtration area less than about 50 2cm .

2. The tangential flow filtration device of claim 1, wherein:wherein the tangential flow filtration device has a filtration of about 18 cm2.

3. The tangential flow filtration device of claim 1, wherein:the tangential flow filtration device is linearly scalable to tangential flow filtration devices having a filtration area greater than about 88 cm2.

4. The tangential flow filtration device of claim 1, wherein:the first end cap includes a first permeate channel and a first permeate outlet in fluid communication with the first permeate channel.

5. The tangential flow filtration device of claim 4, wherein:the first membrane is sealed with the first end cap and defines therebetween the first permeate channel.

6. The tangential flow filtration device of claim 5, wherein:the second end cap includes a second permeate channel and a second permeate outlet in fluid communication with the second permeate channel; andwherein the tangential flow filtration device further includes a second membrane intermediate the feed screen and the second end cap, the second membranebeing sealed with the second end cap and defining therebetween the second permeate channel.

7. The tangential flow filtration device of claim 6, further comprising:one or more gaskets operatively connected to the first end cap and the second end cap, at least one gasket of the one or more gaskets including a first inlet for receiving a flow of permeate from the first permeate channel, a second inlet for receiving a flow of permeate from the second permeate channel, and an outlet fluidly connected to the first inlet and the second inlet.

8. The tangential flow filtration device of claim 7, wherein:the second inlet and the outlet define therebetween a flowpath for the flow of the permeate; andwherein the feed screen includes an aperture positioned along the flowpath so that the permeate from the second permeate channel is permitted to flow into the second inlet of the gasket, through the aperture in the feed screen, and to the outlet of the gasket.

9. The tangential flow filtration device of claim 7, further comprising:an outlet port in fluid communication with the outlet of the gasket, the outlet port having one of a Luer, a threaded or a barb connection mechanism.

10. The tangential flow filtration device of claim 9, wherein:the outlet port is a separate component from the gasket.

11. The tangential flow filtration device of claim 6, further comprising:an enclosure enclosing the first end cap, the first membrane, the feed screen, the second membrane and the second end cap.

12. The tangential flow filtration device of claim 11, wherein:the enclosure includes a first housing member and a second housing member; andwherein the tangential flow filtration device further includes a first rigid plate intermediate the first end cap and the first housing member, and a second rigid plate intermediate the second end cap and the second housing member.

13. The tangential flow filtration device of claim 1, wherein:the tangential flow filtration device has a flow path length of about 6.75 inches.

14. The tangential flow filtration device of claim 1, wherein:the feed screen is an edgeless feed screen, andthe first end cap includes a peripheral seal bead projecting from a membranefacing surface of the first end cap, the peripheral seal bead being configured to bond with the first membrane to create a seal between the first membrane and the first end cap.

15. A method of manufacturing a tangential flow filtration device, comprising the steps of:sealing a first membrane to a first end cap, the first end cap having an integrated first permeate channel; anddisposing a feed screen adjacent to the first membrane opposite the first end cap;wherein the first end cap with first membrane, the feed screen, and the second end cap form a stacked assembly.

16. The method according to claim 15, further comprising the step of:sealing a second membrane to a second end cap, the second end cap having an integrated second permeate channel;wherein the feed screen is located intermediate the first end cap and the second end cap;17. The method according to claim 16, further comprising the step of: operatively connecting at least one gasket to the stacked assembly to place a permeate outlet of the first end cap and a permeate outlet of the second end cap in fluid communication with a single outlet in the gasket.

18. The method according to claim 15, further comprising the steps of:disposing the stacked assembly intermediate a first housing member and a second housing member; andconnecting the first housing member to the second housing member.

19. The method according to claim 15, wherein:the tangential flow filtration device has a filtration area less than about 50 cm2; andwherein the tangential flow filtration device is linearly scalable to tangential flow filtration devices having a filtration area greater than about 88 cm2.

20. A tangential flow filtration device, comprising:a first end cap having a first membrane affixed thereto, the first membrane and the first end cap defining therebetween a first permeate channel;a second end cap having a second membrane affixed thereto, the second membrane and the second end cap defining therebetween a second permeate channel;a feed screen intermediate the first membrane of the first end cap and the second membrane of the second end cap; andan enclosure encasing the first end cap and first membrane, the feed screen, and the second end cap and second membrane.2821. The tangential flow filtration device of claim 20, wherein:the tangential flow filtration device is configured such that a flow of permeate from the first permeate channel and a flow of permeate from the second permeate the channel exit the housing on a common side of the housing.

22. The tangential flow filtration device of claim 20, wherein:the tangential flow filtration device has a filtration area less than about 50 cm2; andwherein the tangential flow filtration device is linearly scalable to tangential flow filtration devices having a filtration area greater than about 88 cm2.

23. A method for tangential flow filtration, comprising the steps of:in a first phase, passing a first liquid feed into a feed channel of a first tangential flow filtration device having a filtration area less than about 50 cm2; andseparating permeate from the liquid feed.

24. The method according to claim 23, further comprising the steps of:in a second phase subsequent to the first phase, passing a second liquid feed into a feed channel of a second tangential flow filtration device having a filtration area greater than about 88 cm2; andseparating permeate from the second liquid feed;wherein the first tangential flow filtration device is linearly scalable to the second tangential flow filtration device.

25. The method according to claim 23, further comprising the steps of:flowing the permeate through a first permeate channel and a second permeate channel on opposite sides of the feed channel;combining the permeate from the first permeate channel and the second permeate channel into a combined permeate flow; and29outputting the combined permeate flow from the first tangential flow filtration device.30

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