Abstract:
Tangential flow filtration device is provided wherein liners are provided between the filtration element and the top and bottom holders or manifolds. The liners incorporate the flow channels and inlet and outlet ports that were previously present in the manifolds. The liners are made of an inexpensive material and therefore are disposable after a single use, making it more cost effective to dispose of them than to clean the conventional manifolds. In addition, the liners can be pre-sterilized.

Description:
BACKGROUND OF THE INVENTION 
   Tangential Flow Filtration (TFF) is a separation process that uses membranes to separate components in a liquid solution or suspension on the basis of size or molecule weight differences. Applications include concentration, clarification, and desalting of proteins and other biomolecules such as nucleotides, antigens, and monoclonal antibodies; buffer exchange; process development; membrane selection studies; pre-chromatographic clarification to remove colloidal particles; depyrogenation of small molecules such as dextrose and antibiotics; harvesting, washing or clarification of cell cultures, lysates, colloidal suspensions and viral cultures; and sample preparation. 
   In TFF, the solution or suspension to be filtered is passed across the surface of the membrane in a cross-flow mode. The driving force for filtration is the transmembrane pressure, usually created with a peristaltic pump. The velocity at which the filtrate is passed across the membrane surface also controls the filtration rate and helps prevent clogging of the membrane. Because TFF recirculates retentate across the membrane surface, membrane fouling is minimized, a high filtration rate is maintained, and product recovery is enhanced. 
   Conventional TFF devices are formed of a plurality of elements, including a pump, a feed solution reservoir, a filtration module and conduits for connecting these elements. In use, the feed solution is directed from the feed solution reservoir to the filtration module while the retentate from the filtration module is recirculated from the filtration module to the feed solution reservoir until the desired volume of retentate is obtained. The membrane is sandwiched between top and bottom manifolds or holders, which serve to provide accurate mechanical constraint against the internal hydraulic pressure of the device, and also serve to distribute the filtration stream across the multiple flow paths within the device. These manifolds or holders are typically made of stainless steel and must be cleaned and validated prior to each use, particularly in biopharmaceutical and other sanitary applications. This is an expensive and time-consuming process. 
   It would be desirable to provide a filtration device that eliminates the need for the aforementioned cleaning and validation steps when replacing the filtration medium. 
   SUMMARY OF THE INVENTION 
   In accordance with the present teachings, a tangential flow filtration device is provided wherein liners are provided between the filtration element and the top and bottom holders or manifolds. The liners incorporate the flow channels and inlet and outlet ports that were previously present in the manifolds. The liners are made of an inexpensive material and therefore are disposable after a single use, making it more cost effective to dispose of them than to clean the conventional manifolds. In addition, the liners can be pre-sterilized. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1  is an exploded view of the filtration device in accordance with the present invention; 
       FIG. 2  is a perspective view of a liner in accordance with the present invention; 
       FIG. 3  is a top view of a liner in accordance with the present invention; 
       FIG. 4  is bottom view of a liner in accordance with the present invention; and 
       FIG. 5  a cross-sectional view of a liner in accordance with the present invention. 
   

   DETAILED DESCRIPTION OF THE INVENTION 
   Turning first to  FIG. 1 , there is shown an exploded view of a filtration device  10  in accordance with the instant teachings. The device  10  includes a top holder plate  12  and a spaced bottom holder plate  13 . The holder plates  12 ,  13  are preferably made of stainless steel and are sufficiently rigid and durable to provide accurate and effective mechanical constraint of the assembly against internal hydraulic operating pressures, such as 50-60 psi. Apertures  28  are provided in the holder plates  12 ,  13  and in each layer of the assembly to accommodate tie rods or threaded pins or bolts  14  or other clamping device to secure the assembly together. Spacers  15  are provided, and can be spring-loaded. No filtration stream passageways are present in the holder plates  12 ,  13 . 
   Positioned beneath holder plate  12  in the assembled state is disposable liner  16 . The liner  16  is preferably made of inexpensive material, suitable for the application, that is acceptable for pharmaceutical assays (and preferably is government approved). Suitable materials of construction include plastics, such as polystyrene, preferably polyolefins, such as polypropylene, polyethylene, copolymers and mixtures thereof. The liner  16  is preferably molded with passageways and openings. Alternatively, and less preferred, it may be formed by milling, drilling and other such methods. 
   As best seen in  FIG. 2-5 , the liner  16  includes a first port  17 A, five sub-ports  17 C a second port  17 B and four sub-ports  17 D. Port  17 A is for introduction of feed or removal of retentate depending on its orientation within the assembly, with port  17 B for removal of permeate, while preventing admixture of the filtrate with the retentate or feed, as is conventional. Port  17 A is connected to the five sub-ports  17 C in a manifold arrangement. Port  17 B is connected to the four sub-ports  17 D in a similar manner. Preferably the ports  17 A and  17 B are located on opposite sides of the liner as shown, in order to provide adequate spacing and avoid interferences with other components. However, in other applications, especially where spacing is sufficient or nor interference occurs, they may be located on the same side. Each port  17 A,  17 B is in fluid communication with flow paths or passageways that communicate with respective apertures to accommodate flow of feed, retentate or permeate as is conventional, thereby defining multiple flow paths for the filtration stream within the device. 
   As seen in  FIG. 3 , the passageways are preferably tapered, narrowing as they proceed away from their respective port, to normalize pressure at each of the sub-ports  17 C and  17 D. 
   Turning back to  FIG. 1 , there is shown positioned below liner  16  a filtration element  20 . The filtration element  20  can be a single membrane, and is preferably a plurality of stacked membranes, such as stacked ultrafiltration or microfiltration membranes, most preferably provided in the form of a cassette. Although a single cassette of membranes is shown, those skilled in the art will appreciate that multiple cassettes can be used. Suitable cassettes are sold under the name PELLICON® and are commercially available from Millipore Corporation. 
   Positioned below the filter element  20  is a second liner  22 . Preferably the second liner  22  is identical in construction to the first liner  16 , but is when the device is in the assembled state, the liner  22  is inverted relative to the position of the first liner  16 , as shown. This allows Port  17 A to communicate with the feed ports of the device in its normal orientation, while communicating with the retentate ports while in the inverted position. Port  17 B of the liner communicates with the permeate ports in both orientations. 
   Preferably one side of the liners  16 ,  20  includes a plurality of ribs, as best seen in  FIGS. 2 and 3 . The ribs provide added rigidity to the liners, and are formed in the molding process. The ribs are positioned on the side of the liner that contacts the holder plate. In the rib configuration shown, a transverse rib  25 A extends through the center of the liner the width of the liner. A rib  25 B also extends through the center of the liner, perpendicular to rib  25 A. The center of the liner is circumscribed by circular rib  25 C, and two opposite and symmetrical sets of four spaced ribs  25 D,  25 E,  25 F and  25 G extend from circular rib  25 C to the perimeter of the liner as shown. Those skilled in the art will appreciate that the embodiment shown is for illustrative purposes only; other rib configurations are within the scope of the present invention. 
   In order to properly and effectively assembly the liners in the filtration device of the invention, the holder plates  12 ,  13  preferably include a configuration of grooves  26  that correspond to the pattern of the configuration of ribs in the liner which is adjacent to it. When properly aligned, the ribs in each liner mate with the grooves in each respective holder plate to form an integral unitary assembly that can be sealed under pressure.