Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
  • B01D63/08—Flat membrane modules
  • B01D63/082—Flat membrane modules comprising a stack of flat membranes
  • B01D63/0822—Plate-and-frame devices
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
  • B01D63/08—Flat membrane modules
  • B01D63/081—Manufacturing thereof
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
  • B01D63/08—Flat membrane modules
  • B01D63/082—Flat membrane modules comprising a stack of flat membranes
  • B01D63/084—Flat membrane modules comprising a stack of flat membranes at least one flow duct intersecting the membranes
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D2313/00—Details relating to membrane modules or apparatus
  • B01D2313/02—Specific tightening or locking mechanisms
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T29/00—Metal working
  • Y10T29/49—Method of mechanical manufacture
  • Y10T29/49826—Assembling or joining

Definitions

• the present invention relates to crossflow filtration and more particularly to a crossflow filtration cassette holder for use in bioprocess separations.
• fluid is introduced perpendicularly to the filter surface and then passes directly through the filter.
• a fluid flow is passed tangentially along the filter surface. Particles/molecules smaller than the pore size of the filter pass through the membrane as a permeate (filtrate), while everything else is retained on the feed side of the membrane as a retentate. Usually the fluid flow is recirculated across the filter surface. Since the retained products are swept along the surface by the tangential flow and do not build up at the filter surface as in direct-flow filtration, a crossflow filter can operate continuously at relatively high solids loads without being blocked by solids material.
• a crossflow filtration system typically includes a filtration module, a feed tank, a pump for feeding liquid from the feed tank to the filtration module via a feed line, a return line for circulating retentate back to the feed tank, a valve in the retentate return line for applying pressure, and a permeate line for removing permeate from the filtration module.
• crossflow filtration is classified as either a microfiltration (MF) or ultrafiltration (UF) process.
• Filter membranes are commonly configured as flat-sheet filter cassettes, which typically comprise a stacked assembly of porous membrane sheet components and permeate and retentate flow screen components, as described in e.g. US Pat. Appl. No.
• a crossflow filtration cassette holder typically includes a distributor plate, which has retentate and permeate inlet and outlet apertures in contact with the corresponding apertures on a cassette clamped towards the distributor plate.
• the retentate inlet apertures on the distributor plate are usually connected with a retentate inlet channel inside the plate, which ends in a retentate inlet connector.
• the retentate outlet, the permeate inlet and the permeate outlet apertures are connected with the corresponding channels inside the plate, each ending in a connector.
• the distributor plate is joined to an end plate with tie rods, forming a cage-like structure within which a number of cassettes are placed with their apertures in registry and the tie rods engaging in indentations on the cassette sides to lock them in place.
• the cassette stack is then clamped to the distributor plate to obtain efficient sealing, e.g. by a compressor plate between the end plate and the cassette stack.
• the assembly and disassembly of the holder can be time-consuming, involving the dismounting of the end plate from all the tie rods.
• An alternative is to include a hinged tie bar in the structure, which can be opened to allow mounting and removal of cassettes without disassembly of the holder.
• a hinged tie bar in the structure, which can be opened to allow mounting and removal of cassettes without disassembly of the holder.
• One aspect of the invention is to provide a robust crossflow filtration cassette holder allowing easy mounting and removal of the filtration cassettes. This is achieved with a cassette holder as defined in claim 1.
• One advantage is that cassettes can be mounted and dismounted without disassembly, while the construction is sturdy enough to withstand the high clamping forces needed to ensure complete sealing.
• a further aspect of the invention is to provide a robust crossflow filtration module. This is achieved with a module as defined in claim 14.
• One advantage of the module is that cassettes can be mounted and dismounted without disassembly, while the construction is sturdy enough to withstand the high clamping forces needed to ensure complete sealing.
• Another aspect of the invention is to provide a convenient method of mounting filtration cassettes in a crossflow filtration cassette holder. This is achieved with a method as described in claim 15. Further suitable embodiments of the invention are described in the depending claims.
• FIG. 1 shows a perspective view of an empty crossflow filtration cassette holder according to the invention.
• Fig. 2 shows a cross section of a cassette holder according to the invention with tie rods in a) open and b) closed position.
• Fig. 3 shows an end view of a cassette holder according to the invention with pins and tie rods in a) closed and b) open position.
• Fig. 4 shows top and side views of a cassette holder according to the invention with rotatable tie rods in a) closed and b) open orientation.
• Fig. 5 shows a rotatable tie rod with truncated circle cross section in perspective and projection drawings.
• Fig. 6 shows a cross section of a cassette holder according to the invention with rotatable tie rods in a) open and b) closed orientation.
• the present invention discloses a crossflow filtration cassette holder 1;31, which comprises a distributor plate 2;32, an end-plate 3;33, a plurality of essentially parallel tie rods 4,6;34,36 which connect the distributor plate with the end-plate, and a compression plate 5;35 which is slidably mounted on the tie rods between the distributor plate and the end plate.
• At least one 6;36 of the tie rods 4,6;34,36 can be moved in its entirety between a) an open position 7 or orientation 37, where it is possible to mount or remove one or more filtration cassettes 9;39, and b) a closed position 8 or orientation 38, where the movable tie rod is in engaged connection with the cassette and locks it in the holder by a locking means 10;40.
• the locking means can e.g. be one or more indentations 10;40 on the cassette 9;39, which are adapted to engage a movable tie rod 6;36.
• a cassette or a stack of cassettes can be placed between the tie rods in the cage structure formed by the tie rods and oriented so that the locking means are facing the movable tie rod or tie rods.
• the cassette or stack of cassettes is locked in place and prevented from movement in the plane perpendicular to the tie bars, which would cause leakage during use.
• An advantage of the invention is that the cassette holder is easy to open without disassembling the tie bars and that the tie bars are robust enough to withstand the clamping force needed to ensure sealing.
• Typical clamping forces used with crossflow filtration cassettes can be in the range of 4 -15 kN, depending on the liquid pressure (e.g. 0 - 4 bar) and the cross section area of the cassettes (e.g. 100 - 350 cm 2 ). When larger cassettes are used, the clamping force may be up to 30 kN. The clamping force is easily applied to the compression plate without
• the movable tie bar or tie bars 6;36 can be formed as single piece constructions.
• An advantage of avoiding joints, hinges or similar weak elements in the tie bars is that their strength is increased and also that the risk of jamming due to e.g. corrosion or encrustation is diminished.
• the plates 2,3,5;32,33,35 and/or the tie bars 4,6;34,36, including the movable tie bar or tie bars 6;36 can comprise a ferrous metal such as stainless steel.
• Stainless steels, e.g. 316L and similar qualities are routinely used in bioprocess equipment and it is desirable to be able to use them also for the movable tie bars. If a hinged tie bar according to the prior art is used, the weakness of the hinge must be compensated by using high strength corrosion-resistant materials like titanium, which is highly expensive and also poses difficulties in machining.
• the movable tie rod or tie rods 6;36 have a diameter less than about 20 mm, such as about 10 - 15 mm.
• the indentations 10;40 on most commercially available filtration cassettes are accommodated to engage with tie rods of 10 - 15 mm, which sets a practical limitation on the rod diameters.
• tie rods of diameters less than about 20 mm An advantage of the tie rods of the invention is that even with limited rod diameters they still give sufficient strength to withstand the clamping force.
• At least two 6;36 of the tie rods 4,6;34,36 are movable in their entirety between an open position or orientation and a closed position or orientation.
• at least two tie rods should be movable to allow mounting and removal of the cassettes.
• one movable tie rod can be sufficient, although it is also possible to have two movable tie rods; one on each side of the cassette. In the latter case, an advantage of having tow movable tie rods is that the difference between closed and open position/orientation can be lower for each tie bar. This can allow for more convenient constructions.
• the distributor plate 2;32 comprises retentate 14;44 and permeate 15;45 inlet and outlet connectors, which are fluidically connected with retentate 16 and permeate 17 apertures corresponding to apertures 10;40 on a filtration cassette 9;39.
• a cassette or a stack of cassettes When a cassette or a stack of cassettes is mounted in the holder, it can be placed so that the apertures on the cassette(s) fit the apertures on the distributor plate and any further cassettes are stacked with their apertures in registry. Fluidically connected retentate and permeate loops are then formed to allow for crossflow filtration.
• a distributor plate with retentate and permeate apertures on both sides of the plate. In this case, two end plates will be used, with one cassette or stack of cassettes between each end plate and the distributor plate.
• the retentate inlet may alternatively be called a feed inlet.
• the cassette holder 1;31 also comprises compression means 49, which is arranged to act on the compression plate 5;35.
• the compression means can e.g. comprise a hydraulic cylinder or one or more screws, bolts, threaded rods, cantilevers, excenter clamps etc.
• the compression means may act on the compression plate 5;35 through an opening 18;48 in the end plate 3;33.
• the compression means can provide the clamping force needed to allow for leak-free connection between the cassettes and between the cassettes and the distribution plate.
• the movable tie rod or tie rods 6 are laterally movable, i.e. in a plane essentially parallel to the distribution 2 and end 3 plates and/or essentially perpendicular to the length axes of the tie rods 4,6. They can be movable in a direction essentially towards and away from a cassette 9 placed in the holder 1. Such movement can e.g. be accomplished by having the ends of each movable tie rod 6 slidably connected to the end-plate 2 and the distributor plate 3, e.g. by mounting them through elongated openings 13 in the plates.
• the openings 13 can be elongated in a direction essentially towards and away from a cassette 9 placed in the holder, which allows the tie rod to slide in this direction.
• the movable tie rods can be spring loaded so that they can be moved by an external force and then return e.g. to the locked position through the action of a spring.
• the shape of the openings may e.g. be generally rectangular with two opposite ends capped by circle arcs such as hemicircles.
• the movable tie rods may be freely slidable when no clamping force is applied and locked in place when a compression means acts upon the compression plate.
• the cassette holder 1 comprises pins 11 mounted in the distributor plate 2 and the end plate 3. These pins are arranged to move the laterally movable tie rod or tie rods 6 between an open 7 and a closed 8 position.
• the pins can comprise indentations 12 which engage with the laterally movable tie rod or tie rods 6. When the pins are pushed towards the plates 2,3, the movable tie rods move inwards to a closed position 8, although it is also possible to arrange the pins with the indentations and e.g. spring loaded tie bars so that the tie bars move outwards upon pushing the pins. It is also possible to arrange the pins 11 and the indentations 12 so that the tie bars 6 are laterally moved upon rotation of the pins 11.
• the movable tie rod or tie rods 36 are mounted to be rotatable around their length axes. They can suitably have a circular cross section in the regions 42 contacting the distributor plate and the end plate and a truncated circle cross section in at least part of the region 41 between the distributor plate 32 and the end plate 33. They are then supported by the distributor and end plates and when they are rotated around the length axes, they move from an open orientation 37 where the truncated part of the circle faces the cassette to a closed orientation 38 where the circular arc faces the cassette and engages in a cassette indentation 40.
• the transition from circular to truncated circle cross section can be gradual, such as with a radius of curvature, to avoid local stress concentration when a clamping force is applied.
• the invention discloses a crossflow filtration module comprising a crossflow filtration cassette holder 1;31 and at least one filtration cassette 9;39 mounted in the holder.
• the holder can be constructed according to any of the embodiments described above and the module may comprise one cassette or a stacked plurality of cassettes.
• the module may be used for e.g. ultrafiltration or microfiltration of fluids in bioprocessing of e.g. biopharmaceuticals or other biomacromolecules. Examples of applications for such a module include buffer exchange by ultrafiltration in a diafiltration mode, concentration of protein solutions, removal of small molecule contaminants from proteins, vaccines etc and removal of particulates from protein solutions.
• the invention discloses a method of mounting a filtration cassette 9;39 in a crossflow filtration cassette holder 1;31.
• the method comprises placing the cassette in the holder and moving at least one tie rod 6;36 in its entirety from an open position 7 or orientation 37 to a closed position 8 or orientation 38 where the tie rod is in a locking engagement with the cassette.
• the holder can be constructed according to any of the embodiments described above.
• the method may also comprise a step of moving at least one tie rod in its entirety from a closed position or orientation to an open position or orientation, to be performed before placing the cassette in the holder.

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• Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Manufacturing & Machinery (AREA)
• Separation Using Semi-Permeable Membranes (AREA)

Priority Applications (4)

Applications Claiming Priority (2)

Publications (1)

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Family Applications (1)

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Cited By (1)

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Citations (4)

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• 2012
  • 2012-04-25 JP JP2014508317A patent/JP6027605B2/ja active Active
  • 2012-04-25 WO PCT/SE2012/050433 patent/WO2012148348A1/en not_active Ceased
  • 2012-04-25 EP EP12777409.9A patent/EP2701828B1/en active Active
  • 2012-04-25 US US14/113,460 patent/US9707519B2/en active Active
  • 2012-04-25 CN CN201280020290.5A patent/CN103492053B/zh active Active

Patent Citations (4)

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