||Einweghalter für Querstromfiltrationsapparate
||Millipore Corp., Billerica, Mass., US
||Hunt, Stephen G., North Billerica Massachusetts 01862, US;
Pesakovich, Boris, Brookline Massachusetts 02445, US
||derzeit kein Vertreter bestellt
||AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MT, NL, PL, PT, RO, SE, SI, SK, TR
|Sprache des Dokument
|Veröffentlichungstag im Patentblatt
B01D 61/18(2006.01)A, F, I, 20070918, B, H, EP
B01D 61/20(2006.01)A, L, I, 20070918, B, H, EP
B01D 65/00(2006.01)A, L, I, 20070918, B, H, EP
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. In order
to provide sufficient strength and rigidity under operating conditions, the liners
have a grid pattern of ribs that abut the holder plates to help prevent the liners
from torquing under clamping force.
BRIEF DESCRIPTION OF THE DRAWINGS
DETAILED DESCRIPTION OF THE INVENTION
- Figure 1 is an exploded view of the filtration device in accordance with the
- Figure 2 is a top perspective view of a liner in accordance with the present
- Figure 3 is bottom perspective view of a liner in accordance with the present
Turning first to Figure 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. Polysulfone is particularly preferred in view of
its strength and rigidity. 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 Figure 2, the liner 16 includes a first
port 17A, five sub-ports 17C a second port 17B and four sub-ports 17D. Port 17A
is for introduction of feed or removal of retentate depending on its orientation
within the assembly, with port 17B for removal of permeate, while preventing admixture
of the filtrate with the retentate or feed, as is conventional. Port 17A is connected
to the five sub-ports 17C in a manifold arrangement. Port 17B is connected to the
four sub-ports 17D in a similar manner. The ports 17A and 17B may be located on
opposite sides of the liner in order to provide adequate spacing and avoid interferences
with other components. However, in the application shown, where spacing is sufficient
or no interference occurs, they may be located on the same side. Each port 17A,
17B 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.
The passageways are preferably tapered, narrowing as they
proceed away from their respective port, to normalize pressure at each of the sub-ports
17C and 17D.
Turning back to Figure 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 17A 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 17B of the liner communicates
with the permeate ports in both orientations.
Preferably one side of the liners 16, 20 includes a plurality
of inter-engaging ribs, as best seen in Figure 3. The ribs provide added rigidity
to the liners, and can be formed in the molding process. The ribs are positioned
on the side of the liner that contacts the holder plate. The ribs extend from one
side of the liner to the other, except where interrupted by a port. In the rib configuration
shown, a grid is formed by a plurality of longitudinal and latitudinal ribs, with
nine latitudinal ribs 25A-25I and nine longitudinal ribs 25A-26I. The latitudinal
ribs are preferably parallel with one another, and the longitudinal ribs are preferably
parallel with one another and perpendicular to the latitudinal ribs. The latitudinal
ribs 25B-25H are preferably equally spaced, whereas the respective spaces between
latitudinal rib 25A and 25B and 25A and the sidewall 225 of the liner are smaller,
as are the spaces between ribs 25H and 25I and rib 25I and the opposite sidewall
226 of the liner. Clustering the ribs more closely together at the sidewalls provides
additional strength to the liner. Longitudinal ribs 25A-26I are all equally spaced,
with the spacing preferably the same or substantially the same as that of latitudinal
ribs 25B-25H, so that the grid defined between ribs 25B-25H and ribs 26A-26I includes
a plurality of squares, the grid formed between ribs 25H, sidewall 226, and ribs
26A-26I includes a plurality of rectangles, and the grid formed between ribs 25B
and sidewall 225 and ribs 26A-26I includes a plurality of rectangles. A U-shaped
rib 27A is formed around the permeate port 17B, as is U-shaped rib 27B around retentate
The intricate rib configuration shown provides strength
and rigidity to the liner. When assembled, there is significant clamping force applied
to the filter element 20 and the liner, with sealing taking place between the smooth
side of the liner and the filter element 20. Without the rib configuration, the
liner would not remain flat, and therefore would not seal properly to the filter
element 20. The ribs make it possible to effectively assemble the liners in the
filtration device of the invention, in sealing engagement upon the application of
pressure, without the necessity of having corresponding grooves in the holder plates
to mate with the ribs. Accordingly, the respective surfaces of the holder plates
that abut the grids of the liners are preferably flat, and need not be specially
designed to fit the liners.
Filtration apparatus, comprising:
a top plate;
a bottom plate spaced from said top plate;
a filtration member positioned between said top plate and said bottom
a first disposable liner positioned between said top plate and said
filtration member, said first liner having a fluid inlet, a fluid outlet, a plurality
of fluid inlet apertures, and a pattern of ribs on one side thereof facing said
a second disposable liner positioned between said bottom plate and said
filtration member, said second liner having a fluid inlet, a fluid outlet, a plurality
of fluid outlet apertures and a plurality of ribs on one side thereof facing said
wherein said top and bottom plates are devoid of fluid flow paths and each has a
substantially flat surface that mates with said plurality of ribs on a respective
The filtration apparatus of claim 1, wherein said respective patterns
of ribs on said first and second liners define a grid pattern.
The filtration apparatus of claim 2, wherein said grid pattern retains
said liner in a flat configuration when mated with the respective top and bottom
plates and subjected to pressure.
The filtration apparatus of claim 1, wherein said plurality of ribs
on each respective liner are inter-engaging.
The filtration apparatus of claim 1, wherein said top and bottom plates
comprise stainless steel.
The filtration apparatus of claim 1, wherein each said liner comprises
A liner for a filtration apparatus and adapted to seal between a holder
plate and a filter element, said liner comprising a flat face adapted to abut said
filter element and an opposite face having a plurality of inter-engaging ribs adapted
to abut said holder plate, said inter-engaging ribs providing sufficient strength
to said liner so as to enable said liner to be effectively sealed under pressure
in said apparatus.
The liner of claim 7, wherein said ribs define a grid pattern.
The liner of claim 7, wherein the liner comprises polysulfone.
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