Patent Application
20140224748
The present disclosure generally relates to the field of fluid filter elements or cells and fluid filter assemblies or capsules for purifying fluids from bioprocess applications and processes for using the same.
Products of bioprocesses, specifically biopharmaceuticals, are valuable. During research and development of such products, careful consideration and attention during all aspects of preparation are given to minimize waste and maximize yield of these products. As such, with specific reference to a filtering step, filtration assemblies used for such processes should strive to minimize waste.
It is well-recognized that the pressure drop of a filter increases through collection of residue on the filter. Because of this, filters typically have pressure ratings to accommodate a caked-up or plugged filter and a subsequent blow-down of the filter to recover filtrate or filtered material. By their geometries, a spherical or an elliptical dome-shaped design for a filter provides high pressure ratings. Such designs, however, result in higher than desirable upstream and residual volumes of valuable products of bioprocesses.
In reducing internal volume of filtration devices to help reduce upstream and residual volumes, there is a trade-off on pressure rating. To accommodate this, sometimes external equipment is associated with filtration devices to improve pressure rating. During research and development of bioprocesses, often laboratory and/or pilot scale operations are undertaken under conditions of limited space and storage. As a result, additional external equipment is not desired.
There is a continuing need to provide filtration devices that reduce and/or minimize upstream and residual volumes while providing an adequate pressure rating without requiring too much space.
Provided are fluid filter elements or cells and fluid filter assemblies or capsules for purifying fluids from bioprocess applications and processes for using the same. More particularly, the fluid filter elements or cells and fluid filter assemblies or capsules minimize upstream and residual volumes and also ensure a pressure rating to permit the assemblies or capsules without the use of external equipment.
In a first aspect, a filtration capsule comprises: a first and second shells that are sealably attached to each other, wherein one or both shells comprises a curved exterior surface and a substantially flat interior wall that is integral to the shell; an inlet and an outlet; and one or more filter elements contained in the filtration capsule, each filter element comprising an outer surface in fluid communication with the inlet and an inner surface in fluid communication with the outlet.
In a first embodiment, the filtration capsule further comprises a ribbing structure on one or both of the curved exterior surfaces of the shells. The ribbing structure can be integral to the one or both shells. Moreover, the ribbing structure can be effective to impart a pressure rating such that the filtration capsule is stand alone. Detailed embodiments provide that the ribbing structure comprises one or a plurality of peripheral support rings, one or a plurality of axial lengths on one or both of the shells.
The substantially flat interior walls of the first shell, the second shell, or both can independently comprise one or more protrusions.
One embodiment provides that the filtration capsule is a single use device.
Another embodiment provides that one or both of the shells are formed from a translucent or transparent material. Both of the shells can be formed from a material that comprises a tensile strength at yield of 10,000 psi or greater and exhibits chemical resistance, weldability, and sterilizability. In a specific embodiment, the material comprises polysulfone.
In one embodiment, the inlet and the outlet are both integral to the second shell. A detailed embodiment provides that the inlet and the outlet are substantially horizontal.
The filtration capsule can comprise at least two legs. One embodiment provides that there are three legs spaced approximately 120° apart on the curved exterior surface of the second shell.
With respect to size, the first shell can have substantially the same capacity as the second shell. On the other hand, the first shell can have a capacity that is 1.1 to 10 or more times the capacity of the second shell.
As to the filter element, it can comprise one or more media layers. Another embodiment provides that the filter element further comprises a flow inhibitor.
In an embodiment, the filtration capsule further comprises an o-ring seal between the capsule and the filter element, specifically between a protrusion of the second shell of the capsule and an inner overmold of the filter element.
Another aspect provides a filtration assembly that comprises a plurality of filtration capsules according embodiments provided herein. The plurality of filtration capsules can be assembled in parallel. On the other hand, the plurality of filtration capsules can be assembled in series. In one or more embodiments, a footprint of the assembly is independent of the number of filtration capsules.
In a further aspect, provided are methods of filtering comprising: introducing an incoming fluid into the filtration capsule according to embodiments provided herein and collecting a filtered fluid from the outlet.
Other aspects include methods of making a filter assembly comprising: providing the filtration capsule according to embodiments provided herein such that an upstream volume is minimized as compared to a comparative filtration capsule of constant capacity that does not have a substantially flat interior wall that is integral to the first or second shell. In one embodiment, the method further comprises providing a ribbing structure on or integral to the filtration capsule such that the filtration capsule is stand alone. Another embodiment includes the method further comprising providing the inlet and the outlet in a substantially horizontal configuration. Yet another embodiment provides that the method further comprises forming one or both of the shells from a translucent or transparent material such that a fluid in the filtration capsule can be monitored. In a further embodiment, the method further comprises stacking a plurality of filtration capsules to form an assembly wherein a footprint of the assembly is independent of the number of filtration capsules. An additional embodiment is the method further comprising an o-ring seal between a protrusion of the second shell and an inner overmold of the filter element. The method can further comprise installing a flow inhibitor on the filter element. The method can also include where the second shell is configured to receive the first shell independent of the capacity of the first shell.
These and various other features and advantages will be apparent from a reading of the following detailed description.
The disclosure may be more completely understood in consideration of the following detailed description of various embodiments of the disclosure in connection with the accompanying drawings, in which:
The figures are not necessarily to scale. Like numbers used in the figures refer to like components. It will be understood, however, that the use of a number to refer to a component in a given figure is not intended to limit the component in another figure labeled with the same number.
Provided are fluid filter elements or cells and fluid filter assemblies or capsules for purifying fluids from bioprocess applications and processes for using the same. More particularly, the fluid filter elements or cells and fluid filter assemblies or capsules minimize upstream and residual volumes and also ensure a pressure rating to permit the assemblies or capsules without the use of external equipment. Such capsules and assemblies can be disposable. The cells and capsules are in particular suitable for intermediate filtration volumes (150-2500 cm2 effective filtration area (EFA)) of biopharmaceutical processes. One or more of the following features are also provided by these cells and capsules: ergonomic connections, stand alone device with desired pressure rating, offer a small footprint when running in series or parallel, ability to monitor fluid level during operation, provide various EFA sizes to allow for use with minimal fluid volumes, and offer an integral seal between clean and dirty process fluid streams.
In particular, fluids/products of bioprocesses tend to be expensive and to be generated in limited quantities. Such fluids almost always require filtration. There is a particular need to minimize volumes of fluids of bioprocesses that become unusable due to hold up in filtration devices. One or more embodiments minimize the amount of fluid needed to fill the filtration capsules or device (upstream volume) and reduce amount of unfiltered material left after filtration (residual volume). One or more embodiments have eliminated a spherical design and, while keeping a curved exterior surface introduced a substantially flat interior surface. Reference to “curved” means that the exterior walls are shaped to extend in an arc. Reference to “substantially flat” means that the walls are shaped to minimize upstream volume while providing acceptable shape and structure to accommodate external features (such as ribbing) and internal features (such as filtration elements).
One or more embodiments ensure that a desired pressure rating is achieved in a stand alone structure that meets minimizing upstream and residual volumes and accounts for a need to affix the shells together by, for example, vibration welding. Reference to “stand alone” means the ability of the filtration capsule to withstand pressures greater than atmospheric that are needed to accommodate a plugged filter and/or blowing down the filter without the need for an external device to anchor and/or surround and/or hold the vessel. One or more embodiments have provided a ribbing structure external to the vessel to provide structural support.
One or more embodiments of the filtration assemblies maintain a small footprint no matter whether individual capsules are connected in series or in parallel with no restriction on fluid level in capsule. Capsules can be stacked as needed. Configuration (number and spacing) of legs on the capsule facilitates placement of any capsule in virtually any orientation with respect to the other capsules.
One or more embodiments of the capsules provide ergonomic connections, meaning the inlets and outlets are easy to assemble with gauges, pipes, tubing, and the like that provide incoming fluid and that route filtered fluid to another capsule or to a holding tank or to a packaging location or to other destinations. One way ergonomic connections are achieved is by providing an inlet and an outlet that are both “substantially horizontal,” in that the inlet and the outlet are generally parallel to the interior substantially flat walls.
Suitable materials for the shell include materials having desired properties of one or more of the following mechanical strength, chemical resistance, weldability, material safety, and sterilization. Reference to “mechanical strength” means that the filter provides adequate structure to withstand at least a desired pressure rating and assembly of multiple capsules stacked on top of each other. Reference to “chemical resistance” means that the material does not degrade in the presence of chemicals in the incoming fluid including, but not limited to, one or more of the following: bases, alcohols, alkali. By “weldability,” it is meant that the material will sealably adhere to itself and minimizes off-gassing and fuming upon welding by methods including, but not limited to, hot plate welding and ultrasonic bonding. With respect to “material safety,” it is expected that suitable materials will have extraction profiles suitable for pharmaceutical contact. In terms of “sterilization,” a suitable material should be able to be sterilized without negative impact on the material by methods including, but not limited to, autoclave sterilization.
In the following description, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration several specific embodiments. It is to be understood that other embodiments are contemplated and may be made without departing from the scope or spirit of the present invention. The following detailed description, therefore, is not to be taken in a limiting sense.
All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.
Unless otherwise indicated, the numerical parameters set forth in the foregoing specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings disclosed herein.
As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” encompass embodiments having plural referents, unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.
Turning to the figures,
The second or bottom shell 14 also comprises an inlet 26 which can have a flange 28, and an outlet 30 that can also have a flange 32. For ease of construction, it is preferred that the inlet 26 and the outlet 30 are integral to the second or bottom shell 14. It is recognized, however, that the location of the inlet or the outlet or both can be moved to the first or top shell should such a need arise. The inlet 26 and outlet 30 are defined by respective passages through the shell structure and are substantially horizontal. In use, attached to the flange 28 is a gauge, pipe, tubing, or the like that supplies an incoming fluid that contains particles or other contaminants to be removed by the filtration capsule 10. The fluid then enters the upstream volume 34 and contacts an outer surface 38 of a filter element 36. In one or more embodiments, the filter element 36 is lenticular. The outer surface 38 provides entry to the filter element, passing through a media pack 39 whose filtration media removes the particles and other contaminants from the incoming fluid. Filtration media can be a single layer or multiple layers. Examples of suitable filtration media may include cellulosic media, synthetic media, or a combination thereof. Media may be a non-woven material, and in some embodiments, may be charge modified, e.g., electrostatically treated. Media may have fine fibers or nanofibers present dispersed throughout media or present as a layer thereon. One exemplary material for media is cellulosic depth media, optionally containing filter aid such as diatomaceous earth or perlite. Examples of such media include Zeta Plus™ filtration media made by CUNO 3M.
After flowing through the media pack, the fluid is then considered to be a filtered fluid which exits the media pack from an inner surface 40 that is in fluid communication with the outlet 30. A separator 37 can be used to direct flow. In a specific embodiment, the separator 37 has passages that direct the flow from the inner surface 40 to the outlet 30. The filtration element 36 has an inner overmold 35 that separates the filtered fluid from the incoming fluid. The inner overmold 35 in conjunction with an endcap 33 to prevent bypass of the incoming fluid to the outlet 30. As desired, surface area available for filtration can be varied by the use of a flow inhibitor 42, which covers and/or sealably affixes to the separator 37 or to all or some portion of the media pack 39 to prevent fluid from entering the media pack 39.
The substantially horizontal configuration of the inlet 26 and outlet 30 allows users to make easy, ergonomic connections of tubing and equipment without the need to use peripheral equipment. A user can position the filtration capsule on a work surface such as a table or laboratory bench and have easy accessibility to the connections. Integration of the inlet 26 and outlet 30 into the shell components 12 and/or 14 results in a clean, finished appearance while not requiring additional manufacturing steps in making the shells. Shells can be manufactured in ways understood by those skilled in the art, including plastic injection molding or steel or plastic machining Suitable materials for the shell include materials having desired properties of one or more of the following mechanical strength, chemical resistance, weldability, material safety, and sterilization. In addition, one or both of the shells can be formed from a translucent or transparent material. One suitable material is polysulfone (PS). The second or bottom shell 14 has at least two legs 44a and 44b. In an embodiment having 2 legs, they can be spaced about 180° apart. Another detailed embodiment provides that there are 3 legs, which are spaced about 120° apart. Yet another embodiment provides that there are 4 legs, which are spaced about 90° apart.
As shown in
Polysulfone is desirable for the construction of the shell because it has desired structural properties and it is translucent. TPR and polysulfone do not bond, however, due to the difference in material properties. It was unexpectedly found that the use of an o-ring provides a superior seal as compared to the use of an adhesive between the two components or a mechanical joining method. Traditionally, the use of an o-ring to seal against TPR, an elastomeric material, has been discouraged due to the inherent nature of the TPR to act elastically. A high durometer TPR can be used in a specific embodiment to overcome this challenge. Moreover, the TPR is circumferential and thus gains support via hoop strength. The o-ring as chosen provides decreased risk of bypass, low upstream volume, low risk of breaching seal integrity during shipping and shell flex during pressurization, and low design molding complexity. The choice of an o-ring seal results in simplicity in the mold design due to elimination of need for secondary manufacturing steps or highly complex tooling due to undercuts.
Various materials for the shell were tested with respect to mechanical strength, chemical resistance, material safety, weldability, and sterilization. Visual observation of opacity was also done. Table 1 provides a summary of a suitable material and a comparative material.
A ASTM Spec. D-638
B Cytotoxicity Test
C Bovine Spongiform Encephalopathy/Transmissible Spongiform Encephalopathy, which is an indicator that the material does not contain products from animal products.
As shown in Table 1, the polysulfone provides many properties, in particular chemical resistance as compared to polycarbonate, making it suitable for the filtration capsules provided herein.
Configuration of various ribbing structures as formed from polysulfone were tested and analyzed. Predictive analysis using FEA (Finite Element Analysis) was done to show expected maximum stress and maximum deflection. Table 2 provides a summary.
It can be concluded from Table 2 that various configurations of ribbing structures can be utilized to meet pressure ratings as desired.
Reference throughout this specification to “one embodiment,” “certain embodiments,” “one or more embodiments” or “an embodiment” means that a particular feature, structure, material, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. Thus, the appearances of the phrases such as “in one or more embodiments,” “in certain embodiments,” “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily referring to the same embodiment of the invention. Furthermore, the particular features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments. The order of description of the above method should not be considered limiting, and methods may use the described operations out of order or with omissions or additions.
It is to be understood that the above description is intended to be illustrative, and not restrictive. Many other embodiments will be apparent to those of ordinary skill in the art upon reviewing the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US2012/053639 | 9/4/2012 | WO | 00 | 3/7/2014 |
| Number | Date | Country | |
|---|---|---|---|
| 61536363 | Sep 2011 | US |
