Patent Application
20050279694
In general, the present invention is directed to disposable filter units, and in particular, to a disposable integral filter unit through which fluid flows in “parallel” through a plurality of deep gradient filter packets.
Good manufacturing practices and governmental regulations are at the core of many biopharmaceutical manufacturing process. Such manufacturing processes must often undergo mandated, often lengthy and costly validation procedures.
For example, the equipment used for the separation and purification of biopharmaceutical products must, for obvious reasons, meet stringent cleanliness requirements. The cleaning validation of new or re-commissioned equipment (such as primary and secondary filtration units) may require as much as 50 test-swabs of exposed surfaces and subsequent biological assays of such test swabs. For a single piece of filtration equipment, the associated and reoccurring cost of a single cleaning validation may readily exceed multiple thousands of dollars.
To reduce such cleaning validation costs and expenses, and/or to reduce the occasions when cleaning is needed or required, the pharmaceutical and biotech industries are increasingly exploring pre-validated modular, disposable filtration solutions.
Along these lines, there is considerable interest of late in developing a disposable solution to the primary and/or secondary clarification of industrial volumes of raw, pharmaceutically synthesized fluids (e.g., cell cultures). The high-volume, high-throughput requirements of such filtration processes generally favor the use of costly, installed stainless steel filtration apparatus, wherein replaceable filter cassette or cartridges (e.g., typically comprising stacks of lenticular filter elements) are installed within a stainless steel housing or like receptacle. At the conclusion of a filtration operation, and removal of the spent cassette or cartridge, the apparatus has to be cleaned and validated, at considerable cost and effort, prior to being used again.
Need thus exists for a disposable filtration unit that can be pre-sterilized and pre-validated and that can perform primary and secondary clarifications, comparable in respect of volume and throughput as that afforded by and expected of conventional filtration processes, but with substantially reduced need for extensive fixed plumbing, equipment, and other like filtration hardware.
Although disposable integral filter units—such as suggested in U.S. Pat. No. 5,429,742, issued to Richard G. Gutman et al. on Jul. 4, 1995—have been disclosed, these and other known technologies cannot be used soundly for, or amenable easily towards, deep bed filtration (in general) and high-throughput, high-volume primary and/or secondary clarification (in particular).
In response to the aforementioned need, the present invention provides a disposable integral filter unit 10 having an inlet 40 and an outlet 60, and comprising a plurality of filter plates 20n interposed between a pair of end plates 24,26. Each of the filter plates 20n comprises a thermoplastic framework 30 with a deep gradient filter packet 35 embedded therein. The filter plates and end plates are fused to form a substantially fixed, substantially water-tight, integral stack. Fluid entering the disposable integral filter unit 10 through said inlet 40 passes the deep gradient filter packet 35 of each filter plate 20n substantially contemporaneously prior to exiting said unit 10 through said outlet 60 (cf., “parallel” flow).
The “parallel” flow path through the embedded deep gradient filter packets 35 promotes use of the filter unit 10 for the primary and/or secondary clarification of, for example, biopharmaceutical fluids. In a preferred embodiment, the disposable integral filter unit 10 is comparatively small and compact—desirable structural characteristics that promote easier installation and handling as compared with the typical, bulkier units currently in widespread use. The filter unit is configured such that no external housing is required for its use in filtration. The filter unit 10 can be installed directly within a fluid process stream. When spent, the filter unit is removed and replaced with a fresh one.
In a particular embodiment of the present invention, the filter unit's thermoplastic framework 30: (a) is monolithic, (b) has an outer border, with interior-facing 214 and exterior-facing surfaces 216, circumscribing an internal area of said framework; and (c) provides a feed port 210, a filtrate port 212, and a filtration zone 216 within said exterior facing surface 214. A deep gradient filter packet 35 is embedded in the filtration zone 216. The packet 35 comprises strata or layers of filtration material stacked or otherwise deposited one against another to form a unitary pad-like composite. Depending on materials and manufacturing methodology, the composite is either self-supporting and/or unitized encapsulated within a porous outer envelope, sieve, or screen.
In light of the above, it is a principal object of the present invention to provide a disposable integral filter unit useful for the primary and/or secondary clarification of biopharmaceutical and like fluids.
It is another object of the present invention to provide a disposable integral filter unit comprising several filter plates stacked and fused between end plates, wherein each filter plate has embedded therein a deep gradient filter packet.
It is another object of the present invention to provide a disposable integral filter unit that provides a “parallel” flow path through several deep gradient filter packets incorporated therein.
It is another object of the present invention to provide a disposable integral filter unit having incorporated therein several comparatively thick deep gradient filter packets, the packets embedded within the unit with minimized structural distortion.
It is another object of the present invention to provide a substantially water-tight filter unit useful for the primary and/or secondary clarification of, for example, biopharmaceutical fluids, without the requirement during said use of an external filter housing.
For further understanding of the nature and these and other objects of the present invention, reference should be had to the following description considered in conjunction with the accompanying drawings.
The Figures provide schematic representational illustrations. The relative locations, shapes, and sizes of objects have been exaggerated to facilitate discussion and presentation herein.
a is a cross-sectional view of a single filter plate 20, useful in the construction of a disposable integral filter unit.
b is a cross-sectional view of paired filter plates 201, 201, useful in the construction of a disposable integral filter unit.
c is a top view of an embodiment of a filter plate 20, useful in the construction of a disposable integral filter unit.
d is a top view of another embodiment of a filter plate 20, useful in the construction of a disposable integral filter unit.
a is a top view of another embodiment of a filter plate 20, the embodiment made in accordance with a two-step molding and embedding process.
b is a cross-sectional view of the filter plate 20 illustrated in
The present invention, as represented in
Among its advantages, the disposable integral filter unit 10—owing to its integral configuration—eliminates the need for a fixed outer housing, such as the comparatively expensive stainless steel housings currently in widespread use. In this regard, the flow of fluid through the filter unit is substantially contained within its integral stack of plates—a novel structural configuration that enables substantially water-tight construction. Depending though on one's particular application, a fixed outer housing may still be employed.
The disposable integral filter unit 10 can be implemented at a relatively low cost. In particular, the disposable integral filter unit 10 can be made as a “single use” item—i.e., “single use” in the sense that at the completion of the desired (or predetermined) fluid filtration operation, the filter unit 100 can either be disposed (e.g., as is sometimes required by law after filtering certain environmentally-regulated substances) or partially or completely revitalized or recycled (e.g., after filtering non-regulated substances).
The disposable integral filter unit enables comparatively high volume fluid clarification (i.e., so-called “primary clarification”) at a throughput comparable to that accomplished by large filter units, yet in a smaller, more compact footprint. This functionality is attributed in part to the device's, novel configuration and utilization of plural deep gradient filter packets, arranged within the unit 10's “parallel flow” path, such that each packet contributes to unit's overall available membrane area. Preferred embodiments of the inventive filter unit 10 are intended for high volume filtration of fluid containing particle sizes in the range of approximately 10 microns to 100 microns.
Although the embodiment shown in
Although it is expected that the filter unit 10 can be designed such that all that is needed to create a suitable water tight flow path from the inlet to the outlet are permanently-combined filter plates 20a-n and end plates 24, 26, for certain application, for example, involving comparatively high fluid pressures and temperatures, a more robust structure may be desirable. In such situations, one can can cast onto the filter unit 10 an optional overmold 80 that jackets the outer surfaces of the filter plates 20a-n. The overmold 80 can, if desired, extend at least partially into the end plates 24 and 26 to clamp or otherwise fix those components. The overmold 80 can function, for example, to make the filter unit more robust (cf., water-tight) in the face of greater fluid pressures and/or temperatures.
As stated, each of the filter plates 20n comprises a deep gradient filter packet 35 fixedly embedded within a thermoplastic framework 28. As seen in
As shown in
As shown in
Although in principal embodiments of the present invention the inlet and outlet zones are located opposite each other at far ends of the thermoplastic framework 28, with the filtration zone substantially centrally midway between the two (see e.g.,
The structural extents of the thermoplastic framework 28 are bound by an outer wall having an outer wall surface 216 and an inner wall surface 214. In certain embodiments of the present invention, when a plurality of filter plates 20n are stacked together to form a filter unit 10, the outer wall surfaces 216 of each component thermoplastic framework 28 form collectively the exterior side surfaces of the filter unit 10. In certain principal embodiments of the present invention, the resultant composite outer wall of the filter unit 10 is sufficiently water tight, durable, and robust to enable filtration without use of an external housing.
The flow path through filter unit 10 is in large part determined by the structural configuration of the thermoplastic framework 28. In a typical arrangement, the stack of filter plate 20n comprises several pairs of filter plate 20n. As shown in
So-called “parallel flow filtration” (i.e., substantially contemporaneous flow through each component filter packet of the unit) can be accomplished by joining several of said pairs together such that all inlets and all outlets are aligned and in register. Although the use of pairs of filter plates—and thus an even number of individual plates—is preferred, those skilled in the art can appreciate that an operable fluid filtration flow path can be established using a single filter plate interposed between suitably-structured end plates. The present invention is thus not limited to whether pairs, even numbers, or odd numbers of plates are utilized. The present invention admit flexibility in such selection.
One useful embodiment of a filter plate pair is shown in
The deep gradient filter packet 35 embedded within the thermoplastic framework 28 is characterized by its thick stratified arrangement of (preferably fiber-based) filtration material. The strata or layers of filtration materials are stacked one against another forming a composite pad-like structure that—depending on selected manufacturing technique—is either “self-supporting” or is unitized encapsulated within a porous outer envelope, sieve, or screen.
Each of the layers comprising the filter packet can be made of the same or different materials. However, each layer—in respect of functionality—becomes progressively more retentive than the last, as one proceeds downstream through the packet. In an embodiment particularly useful for biopharmaceutical filtration, the upstream layer(s) provide a so-called “pre-filtration” function (i.e., approximately 25 to approximately 1 micron retention); the middle layer(s) provide a so-called “primary filtration” function (i.e., approximately 1 micron to approximately 0.3 micron retention); and the downstream layer(s) provide a so-called “fluid polishing” function (i.e., approximately 0.3 microns to approximately 0.2 micron retention).
Each layer or strata can be made of the same materials or different. Type of basic materials that can be employed for this purpose include polypropylene, polyester, glass, polyvinylchloride, polycarbonate polytetrafluoroethylene, polyvinylidene fluoride, cellulose, asbestos, nylon, polyethersulfone, and other polymeric (or non-polymeric) materials.
Aside from the basic materials, the filter materials and media disclosed in the following patents can also be considered: U.S. Pat. No. 4,645,567, issued to K. C. Hou et al. on Feb. 24, 1987; U.S. Pat. No. 4,606,824, issued to C. K. Chu et al. on Aug. 19, 1986; U.S. Pat. No. 4,511,473, issued to K. C. Hou on Apr. 16, 1985; K. C. Hou U.S. Pat. No. 4,488,969, issued to K. C. Hou on Dec. 18, 1984; U.S. Pat. No. 5,283,106, issued to K. Seller et al. on Feb. 1, 1994; U.S. Pat. No. 4,661,255, issued to G. Aumann et al. on Apr. 28, 1987; and U.S. Pat. No. 3,353,682, issued to D. B. Pall et al. on Nov. 21, 1967.
Fibrous materials are generally preferred, because of their versatility, comparative ease of deposition, its strength imparting properties, internal surface to weight ratio, cost, and because fibers can be oriented in various positions and angles. Typical fibrous materials include glass and quartz, asbestos, potassium titanate, colloidal aluminum oxide, aluminum silicate, mineral wool, regenerated cellulose, microcrystalline cellulose, polystyrene, polyvinyl chloride, polyvinylidene chloride, polyacrylonitrile, polyethylene, polypropylene, rubber, polymers of terephthalic acid and ethylene glycol, polyamides, casein fibers, zein fibers, cellulose acetate, viscose rayon, hemp jute, linen, cotton, silk, wool, mohair, paper, metallic fibers such as iron, copper, aluminum, stainless steel, brass, silver, and titanium, and clays with acicular lath-like or needle-like particles, such as montmorillonite, sepiolite, palygorskite, and attapulgite clays of this type.
The present invention is not limited to any particular morphology for the layers constituting the pre-filtration zone. For example, in one embodiment, the material is formed as a pad of non-woven synthetic needle-felt. If polypropylene is used, the polypropylene is preferably “virgin” fiber. In other words, the fibers are essentially free of binders, finishing agents, and other adjuvants which often are added to or coated on polypropylene fibers during or after its formation. “Virgin” polypropylene essentially contains no additives other than those inherent in the synthesis of the polypropylene.
The formation of a filter pad or mat can be effected by various conventional techniques, of which mechanical, aerodynamic, or hydrodynamic web formation is used for natural and synthetic staple fibers and filaments and electrostatic formation for very fine denier fibers.
Spunbonded materials can be formed from melt-spun filaments of thermoplastics, e.g., polyethylene, polypropylene, polyamide, or polyester, which are substantially consolidated by needling, a shrinkage treatment, or by the addition of a binder. Advantage may be realized by the spunbonded process in which the filament-forming polymers are in one operation melt-spun and cooled in air streams, drawn and then directly laid in pad or mat form. Spunbonded non-wovens are often desirable for use as filter material on account of their commercial and qualitative advantages over other non-wovens.
For cellulose-based materials, one method of manufacture commences by first preparing a slurry comprising cellulose fibers, filter additives, and a polymeric thermoset binder. The slurry is vacuum felted and then cured at elevated temperature. The cationic resin, when cured, forms a permanent, interconnected rigid structure. The result is a composite structure having a tortuous structure of flow channels and comprising the filter additives embedded in a cellulose matrix.
The non-wovens used for manufacturing the filter are desirably used in the consolidated state. The materials can be consolidated in any conventional manner, for example by thermal bonding under pressure, in which the material is subjected to a calendering treatment, or by needling, or by thermal bonding using binders, such as hot-melt adhesives, for example in fiber or powder form, in which case the hot-melt adhesive must have a melting point which is lower than that of the fiber material of the web, or the pre-consolidation can be effected using a combination of the aforementioned measures.
The filter material under certain circumstances can benefit by the incorporation of non-fiber additives, i.e., so-called “filter aids”. These can be incorporated by use of suitable anionic, cationic, or nonionic binding resins. Examples of additives include, but are not limited to, acid-washed diatomaceous earth, perlite, fumed precipitated silica (for hydrophobic absorption); and activated carbon (for absorption certain homones and pyrogens).
The incorporation of the deep gradient filter packet 35 into a thermoplastic framework 28 is preferably accomplished by injection molding. While conventional injection molding methodologies can be used for certain applications, the well-documented post-formation, pre-curing structural instabilities of many thermoplastic materials (e.g., shrinkage) can have an unintended influence on the structural integrity of the incorporated filtration material. For example, if the density gradient filter packet 35 sought to be incorporated is of a type engineered to enable high resolution separations (such as common in biopharmaceutical fluid separations), even a slight structural permutation of the surrounding thermoplastic framework 28, even if short lived and temporary, can compromise unacceptably the structural integrity of said filter packet 35. Certain thermoplastic raw material, as the case also with large bulky frame formats, can produce such severe structural contortions during curing that the structural and functional integrity of even robust density gradient filter packets would not be immune from such influences.
In the present invention, the thermoplastic framework 28 affords greater functionality, if designed sufficiently thick to withstand the force of internal pressure during operation of the completed device. However, the more thickly molded the frame, the greater the inclination for it to shrink. Concerns over distortion and shrinkage can also limit material selection.
To counter such manufacturing issues, when relevant, one can use a two-step molding process wherein a substantial first portion of the frame is made and allowed to shrink to its natural state, with the remaining lesser portion molded during or contemporaneously with the embedding of the deep gradient filter packet. More particularly, a two-step molding process can comprise the steps of: (a) forming a first portion of said thermoplastic framework from a thermoplastic polymer, said outer first portion providing at least said filtration zone; (b) placing said deep gradient filter packet in said filtration zone; and (c) forming a second portion of said thermoplastic framework from said thermoplastic polymer, said second portion completing said thermoplastic framework and embedding said deep gradient filter packet in place.
The advantages of the two-step molding process flows principally from the stabilizing, bracing effect provided by the first formed portion. As the thermoplastic material of the second formed portion cures (or otherwise hardens), shrinkage or warping will likely occur, but will be much more limited in view of the spatial constraints imposed by the dimensionally-stabilized first portion and its comparatively smaller mass. The density gradient filter packet 35 thus becomes embedded robustly within the thermoplastic framework, under conditions that are comparatively gentle and thus less likely to compromise its structural and functional integrity.
Further details regarding the two-step molding process used for embedding the deep gradient filter packet 35 is described in U.S. Pat. App. Att'y Dkt. No. MCA-688, filed on even date herewith, entitled “Method for the Manufacture of a Composite Filter Plate”.
A representative example of a deep gradient filter packet 35 is shown in
In the preferred assembly of the disposable integral filter unit 10, each of the aforementioned pre-bonded filter plate pairs are sequentially brought together, positioned into appropriate register, then permanently bonded together, forming water-tight seals. After the stack is completed, the end caps 24 and 26 are positioned on the downstream and upstream sides of the stack, respectively, and permanently bonded in a manner that forms water-tight seals. The permanent bonds can be accomplished by use of, for example, mechanical couplers, adhesives, thermal sealing, and the like.
In respect of thermal sealing procedures—particularly for the assembly of embodiments of the type illustrated in
Vibration welding and the several variants thereof are well known technologies. During vibration welding, the components to be fused are at certain pre-designated points of contact made to vibrate at frequencies, for example, in excess of 20,000 cycles per second (i.e., 20 Hz). Intense heat is generated in a matter of microseconds to melt the thermoplastic material and weld the layers at said points of contact. Vibration welding is preferred over other thermal welding process as the generated heat is comparatively narrowly localized and is quickly dissipated, thus eliminating the necessity of elaborate and/or costly heat removal systems.
Vibration welding is the preferred method for thermally bonding rectangular, “un-jacketed” configurations of the inventive filter unit. This configuration consists essentially of several rectangular filter plates (e.g., of the type shown in
The resultant “un-jacketed” filter unit can be used for filtration of industrial volumes of fluids in either a vertical or horizontal position with comparatively minimal housing and installation requirements. The use of common compression plates, inlets, outlets, and associated flow controls would likely be all that is structurally needed in respect of installation.
Three variants of vibration welding useful for fusing all or some of the components envisioned herein (particular in the construction of rectangular “un-jacketed” vertical or horizontal filter units) are: Angular welding (using frequencies up to 100 Hz, and angles up to 15 degrees); linear welding (using frequencies of 100 to 300 Hz and amplitudes of 0.5 to 2.5 mm); and biaxial oscillating motions (using frequencies of 80 to 250 Hz, and amplitudes up to 0.7 mm).
As indicated, the end caps 24 and 26 seal off the upstream and downstream ends of the stack of filter plates. They are generally made of the same thermoplastic polymeric materials as the thermoplastic framework of the filter plates, and can be molded or cast as a singly unitary monolithic piece or can be a conglomerate of assembled pieces. Preferably, the end caps 24 and 26 will have integrally formed thereon the filter unit's inlet 40 and outlet 60, respectively.
Port plugs can also be used, as appropriate, to plug or otherwise block the upstream and downstream ends of the feed and filtrate lines running orthogonally through the stack of the filter plates 20n. See e.g.,
The materials and structural assemblage of the port plugs, end caps, and the thermoplastic framework should be selected with an eye towards promoting the disposability and the integral character sought by the invention. Toward these objectives, the structural and/or rigid filter unit components—essentially all components, excepting the filter materials—should generally be formed monolithically (i.e., as a single, homogenous, unitary, unassembled piece) from polymeric material, for example, by well-known injection molding processes.
Examples of generally suitable polymeric material include, but are not limited to, polycarbonates, polyesters, nylons, PTFE resins and other fluoropolymers, acrylic and methacrylic resins and copolymers, polysulphones, polyethersulphones, polyaryl-sulphones, polystryenes, polyvinyl chlorides, chlorinated polyvinyl chlorides, ABS and its alloys and blends, polyurethanes, thermoset polymers, polyolefins (e.g., low density polyethylene, high density polyethylene, and ultrahigh molecular weight polyethylene and copolymers thereof), polypropylene and copolymers thereof, and metallocene generated polyolefins.
While the present invention has been described with reference to certain particular embodiments thereof, those skilled in the art, having the benefit of the teachings of the present invention set forth herein, can effect numerous modifications thereto. The modifications are to be considered as encompassed within the scope of the present invention as set forth in the appended claims.
