US-12616937-B2 - Filtration units and assembly, and methods of making and using same

US12616937B2US 12616937 B2US12616937 B2US 12616937B2US-12616937-B2

Abstract

A self-contained filtration assembly with a self-contained filtration cassette therein. The cassette may be formed from one or more layers membranes and spacers (spacers, screens, or combinations thereof) all having the same general shape. The cassette may have a feed inlet path and a retentate outlet path extending through the layers of the cassette within the perimeter of the cassette, and a permeate outlet path between the cassette exterior and the interior of the cassette housing. The housing may have a generally circular or elliptical cross-section. A clamping assembly may hold together the components of the housing, and may be elongated in a direction along the flow path of the feedstream through the cassette. Various port-defining zones defined in the layers of the cassette may be sealed in a manner facilitating assembly of the cassette as well as isolation of the flow paths therein.

Inventors

Mark Perreault
Paul Lowell

Assignees

REPLIGEN CORPORATION

Dates

Publication Date: 20260505
Application Date: 20230209

Claims (17)

1 . A tangential flow filtration cassette having a first cassette end along an inlet of a feedstream into the tangential flow filtration cassette and a second cassette end along an outlet for permeate of the feedstream, said tangential flow filtration cassette comprising: at least one membrane having a feed-port-defining zone adjacent the first cassette end, a retentate-port-defining zone adjacent the second cassette end, and a permeate-port-defining zone along the sides thereof between the first cassette end and the second cassette end; at least one feed spacer defining a feed channel along an upstream side of said membrane, and having a feed-port-defining zone adjacent the first cassette end, a retentate-port-defining zone adjacent the second cassette end, and a permeate-port-defining zone along the sides thereof between the first end and the second end; and at least one permeate spacer defining a permeate channel along a downstream side of said membrane, and having a feed-port-defining zone adjacent the first cassette end and with sealant extending around the perimeter thereof, a retentate-port-defining zone adjacent the second cassette end thereof and with sealant extending around the perimeter thereof, and a permeate-port-defining zone along the sides thereof between the first end and the second end; wherein: each of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer has substantially the same shape about their respective perimeters; said feed-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer are aligned to define a feed inlet path extending along the first cassette end; said retentate-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer are aligned to define a retentate outlet path extending along the second cassette end; said permeate-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer are aligned to define a permeate outlet path extending along at least one of the sides of said tangential flow filtration cassette between the first cassette end and the second cassette end; a sealant extends around the perimeter of said at least one feed spacer to fluidly isolate feed channels from permeate channels within said tangential flow filtration cassette, whereas the permeate-port-defining zones of said at least one permeate spacer are unsealed and in fluid communication with the permeate outlet path; the tangential flow filtration cassette defines a flow path between the feed-port-defining zones and the retentate-port-defining zones; and a clamp assembly extends through a housing that houses the tangential flow filtration cassette and said tangential flow filtration cassette, the clamp assembly having a cross-sectional shape elongated in the direction of the flow path through said tangential flow filtration cassette.
2 . The tangential flow filtration cassette of claim 1 , wherein said permeate-port-defining zones of said at least one feed spacer and said at least one permeate spacer are aligned to define a permeate outlet path extending along each side of said tangential flow filtration cassette between the first cassette end and the second cassette end.
3 . The tangential flow filtration cassette of claim 1 , wherein each of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer have a curved shape along the first cassette end and the second cassette end and are flat along the sides thereof extending between the first cassette end and the second cassette end.
4 . The tangential flow filtration cassette of claim 1 , wherein at least one of said spacers includes a screen.
5 . The tangential flow filtration cassette of claim 1 , wherein all membranes and spacers of said cassette are bonded together by an encapsulating sealant formed around said membranes and spacers with a portion of said encapsulating sealant removed from the sides of said permeate spacers to place the permeate channels in fluid communication with the permeate outlet paths along the sides of the tangential flow filtration cassette.
6 . A tangential flow filtration assembly comprising: a housing; a tangential flow filtration cassette positioned within said housing and having a first end along an inlet of a feedstream into said tangential flow filtration cassette and a second end along an outlet for permeate of the feedstream from said tangential flow filtration cassette, and defining a flow path for feedstream flowing therethrough from the first end to the second end; and a clamp assembly extending through said housing and said tangential flow filtration cassette and having a cross-sectional shape elongated in the direction of the flow path through said tangential flow filtration cassette.
7 . The tangential flow filtration assembly of claim 6 , wherein said housing further comprises a housing top extending generally parallel to the flow path within said tangential flow filtration cassette, a housing bottom extending generally parallel to the flow path within said tangential flow filtration cassette, and a lock ring holding said housing top and said housing bottom together and defining a housing shell around the perimeter of said tangential flow filtration cassette, said clamp assembly holding said housing top and said housing bottom together.
8 . The tangential flow filtration assembly of claim 6 , wherein: the first end of said tangential flow filtration cassette is shaped to correspond to the shape of the interior of said housing; the second end of said tangential flow filtration cassette is shaped to correspond to the shape of the interior of said housing; and at least one of the sides of said tangential flow filtration cassette between the first end and the second end is spaced apart from the interior of said housing to define a permeate outlet path along the at least one side of said tangential flow filtration cassette between the exterior of said tangential flow filtration cassette and the interior of said housing.
9 . The tangential flow filtration assembly of claim 8 , wherein: said housing has a generally circular or cross-section; the first and second ends of said tangential flow filtration cassette are curved to correspond to the circular shape of the interior of said housing; and at least one of the sides of said tangential flow filtration cassette between the first end and the second end is not curved to correspond to the circular shape of the interior of said housing and thereby defines a permeate outlet path along the at least one side and between the exterior of said tangential flow filtration cassette and the interior of said housing.
10 . The tangential flow filtration assembly of claim 8 , wherein: said tangential flow filtration cassette comprises a stack of at least one membrane, at least one feed spacer, and at least one permeate spacer layered to form said tangential flow filtration cassette; a feed-port-defining zone is defined in each of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer, along the first end of said tangential flow filtration cassette; the feed-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer together define a feed inlet path through said tangential flow filtration cassette; a retentate-port-defining zone is defined in each of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer, along the second end of said tangential flow filtration cassette; the retentate-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer together define a retentate outlet path through said tangential flow filtration cassette; a permeate-port-defining zone is defined along said at least one side of each of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer spaced apart from the interior of said housing, between the first end and the second end of said tangential flow filtration cassette; and the permeate-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer together define a permeate outlet path between the exterior of said tangential flow filtration cassette and the interior of said housing.
11 . The tangential flow filtration assembly of claim 6 , wherein: said tangential flow filtration cassette comprises a stack of at least one membrane, at least one feed spacer, and at least one permeate spacer layered to form said tangential flow filtration cassette; a feed-port-defining zone is defined in each of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer, along the first end of said tangential flow filtration cassette; the feed-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer together define a feed inlet path through said tangential flow filtration cassette; a retentate-port-defining zone is defined in each of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer, along the second end of said tangential flow filtration cassette; the retentate-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer together define a retentate outlet path through said tangential flow filtration cassette; a permeate-port-defining zone is defined along at least one side of each of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer, extending between the first end and the second end of said tangential flow filtration cassette and spaced apart from the interior of said housing; and the permeate-port-defining zones of said at least one membrane, said at least one feed spacer, and said at least one permeate spacer together define a permeate outlet path between the exterior of said tangential flow filtration cassette and the interior of said housing.
12 . The tangential flow filtration assembly of claim 6 , wherein: said housing has a generally circular cross-section; said tangential flow filtration cassette comprises a stack of at least one membrane, at least one feed spacer, and at least one permeate spacer layered to form said tangential flow filtration cassette; a feed-port-defining zone is defined in each of said at least one membrane, at least one feed spacer, and at least one permeate spacer, along the first end of said tangential flow filtration cassette; a retentate-port-defining zone is defined in each of said at least one membrane, at least one feed spacer, and at least one permeate spacer, along the second end of said tangential flow filtration cassette; and at least one side of said tangential flow filtration cassette extending between the first and second ends of said tangential flow filtration cassette is spaced apart from the interior of said housing to define a permeate outlet path along the at least one side between the exterior of said tangential flow filtration cassette and the interior of said housing.
13 . The tangential flow filtration assembly of claim 6 , wherein at least one membrane, at least one feed spacer, and at least one permeate spacer are stacked within said tangential flow filtration cassette with respective feed-port-defining zones, retentate-port-defining zones, and permeate-port-defining zones defined therein aligned to define, respectively, a feed inlet path along the first end of said tangential flow filtration cassette, a retentate outlet path along the second end of said tangential flow filtration cassette, and a permeate outlet path along one or both sides of said tangential flow filtration cassette between the first and second end thereof.
14 . The tangential flow filtration assembly of claim 13 , wherein the feed inlet path is in fluid communication with a feed inlet port in said housing, the retentate outlet path is in fluid communication with a retentate outlet port in said housing, and the permeate outlet path along one or both side of said tangential flow filtration cassette is in fluid communication with a respective permeate outlet port in said housing.
15 . The tangential flow filtration assembly of claim 14 , wherein at least one of said feed inlet port, said retentate outlet port, and said permeate outlet port is configured to be connected with a sanitary connector and coupled with a fluid line for supplying feedstream to said tangential flow filtration cassette or removing retentate or permeate from said tangential flow filtration cassette.
16 . The tangential flow filtration assembly of claim 6 , wherein said housing includes a feed inlet port, a retentate outlet port, and at least one permeate outlet port, each of which is configured to be coupled directly with sanitary couplers and feed lines to feed feedstream into said tangential flow filtration cassette or remove retentate or permeate from said tangential flow filtration cassette.
17 . The tangential flow filtration assembly of claim 6 , wherein said housing has a circular cross-section.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This is a non-provisional of, and claims the benefit of the filing date of, U.S. provisional patent application No. 63/310,682, filed Feb. 16, 2022, entitled “Filtration Units and Assembly, and Methods of Making and Using Same,” the entirety of which application is incorporated by reference herein. FIELD The present disclosure relates generally to the field of filtration devices and methods of making and using same. More particularly, the present disclosure relates to tangential flow filtration units in the form of a cassette, self-contained filtration assemblies, and associated methods of making and using same. BACKGROUND Filtration is a process in which membranes are used to separate components in a fluid. Two types of filtration include tangential-flow filtration (TFF), also known as cross-flow filtration (CFF), and direct-flow filtration (DFF) also known as normal-flow filtration (NFF). Tangential-flow filtration applications use hollow fibers through which fluid to be filtered flows, or cassettes or other plate and frame formats along which fluid to be filter flows. Tangential flow filtration (TFF) cassettes are typically used in the biopharmaceutical industry to concentrate and/or diafilter process streams, such as when a drug substance is manufactured. These plate and frame formats typically incorporate a plurality of flat sheet membranes arranged between external flat plates and manifolds. More specifically, TFF cassettes are generally composed of alternating layers of membranes and spacers or screens bound together with a rigid material, such as a rigid polymer (e.g., an epoxy or engineering polymer or thermoplastic material) or a urethane or silicone. The cassette may be clamped between a flow distribution manifold and set of rigid plates (which may be known as a “plate and frame” design relying on clamping forces on membranes and spacers, generally without the use of adhesives). The manifold generally has three different flow paths: one for the feed, one for the retentate, and two for the permeate/filtrate. In TFF cassettes, the fluid to be filtered is passed through the inlet of the manifold, into the cassette, and tangentially along one or more filter membranes within the filter unit. The fluid flows tangentially along the first (or upstream) surface of the membranes. A portion of the fluid with particles smaller than the filtration capacity of the membranes passes through (normal to) each of the membranes from the first (or upstream) surface to the second (or downstream) surface, and passes out of the cassette and out one outlet (the permeate/filtrate outlet) of the manifold. Another portion of the fluid, with particles too large to pass through the membranes (e.g., particulates, macromolecules, cells, virus, etc.), passes tangentially along the first surface of the membranes, through the cassette and out another outlet of the manifold as retentate, without passing through the membranes. The retentate stream may be discarded, recycled back into the feed stream for further filtering, retained (e.g., if useful in itself), etc., as appropriate. Those of ordinary skill in the art recognize the advantages of offering a filtration cassette that is preassembled, as it affords benefits to the end user reducing set-up time and minimizing the chance of contamination. Current designs which build on an industry standard format rely on the use of a flow distribution manifold and require costly/cumbersome stainless-steel holders to clamp the cassette. Alternative self-contained technologies, such as hollow fiber or spiral wound elements, are not comparable in performance to cassettes for downstream operations. Accordingly, there is a need for a self-contained cassette, not requiring further assembly, with comparable performance to a conventional single-use cassette. SUMMARY This summary of the disclosure is given to aid understanding, and one of skill in the art will understand that each of the various aspects and features of the disclosure may advantageously be used separately in some instances, or in combination with other aspects and features of the disclosure in other instances. No limitation as to the scope of the claimed subject matter is intended by either the inclusion or non-inclusion of elements, components, or the like in this summary. In accordance with various principles of the present disclosure, a tangential flow filtration cassette has a first cassette end along an inlet of a feedstream into the tangential flow filtration cassette and a second cassette end along an outlet for permeate of the feedstream. In some embodiments, the tangential flow filtration cassette also includes at least one membrane having a feed-port-defining zone adjacent the first cassette end, a retentate-port-defining zone adjacent the second cassette end, and a permeate-port-defining zone along the sides thereof between the first cassette end and the second cassette end; at least