Patent Application
20220347630
The present invention relates to an assembly of elastic end couplings, connections and a membrane filter cartridge. The invention improves operational design, reduce fabrication time, lower product price, decrease system pressure drop, and insure better performing membrane filter assembly.
Membrane technologies are conventionally used in various separation processes to conduct separations of particles contained in a fluid that may not be technically or economically viable to separate by other technologies. One advantage is that Hollow-Fiber-Filter (HFF) membrane cartridges can be manufactured at a competitive cost compared to ceramic membranes. Competitive cost is though relative and the subject of the present invention.
References is made to:
References is made to larger Hollow Fiber Filter manufactures:
Reference is made to these very informative articles:
The term “harvest” as used herein refer to the product part (such as a protein) of the broth being the expected product generated by micro-organism being cultivated in a bioreactor or fermented in a fermenter. The harvest (the filtrate, the permeate) may be separated from the broth via membrane and or CFF filtration. When permeate is removed from the CFF the broth becomes concentrated.
The term “hollow fibre module” as used herein refer to a device made from an outer rigid wall tube with end covers housing inside a bundle of thin wall tubes fabricated from porous elastic material such as polyethersulfone or other polymers. The bundle of tubes is sealed, cast into end covers separating the tube inside from the tube outside and hereby appearing as a Cross-Flow-Filter. Port for raw broth, retentate, permeate
An assembly for fluid communication with membrane separation device comprising:
1. An elastic and/or flexible end coupling assembly (100) for conveying a fluid comprising:
2. A elastic end coupling assembly (303) according to embodiment 1 for connection to a cartridge (101, 201) said elastic end coupling assemblies comprises:
said set of elastic end coupling devices (303, 402) connects to either an inlet or an outlet (204, 205) of a cartridge (101, 201, 601).
3. A simplified elastic end coupling assembly (402) according to embodiment 1 and 2 for connection to a cartridge (101, 201) said elastic end coupling comprises:
said simplified elastic end coupling devices (303, 402) connects to either an inlet or an outlet (204, 205) of a cartridge (101, 201, 601).
4. A elastic end coupling assembly according to embodiment 1, 2, 3 comprising a plurality of elastic hoses assembled into said tubular assembling body (104, 105) forming a hollow body manufactured from a variety of polymers predominantly an elastic polymer.
5. An elastic end coupling assembly according to any previous embodiments comprising a plurality of elastic hoses assembled into said tubular elastic end coupling assembly in connection points as an over-moulded assembly.
6. An elastic end coupling assembly according to any previous embodiments comprising further one or more elastic hoses, flanges or connection points with access to the inner fluid conveying volume for connection of various sensors such as pressure, temperature, dissolved oxygen, pH, biomass, mass flow, volume, velocity.
7. An elastic end coupling assembly according to any previous embodiments integrating a thermoplastic elastomeric part such as a Tri-Clamp flange, a Tri-Clamp seal, a tubular part of selectable elastomeric materials, a supporting device casted together with thermoplastic elastomeric parts in an over-moulded process.
8. An elastic end coupling assembly according to any previous embodiments integrating parts such as a Tri-Clamp flange, a Tri-Clamp seal, a tubular part of polymeric materials said supporting devices over-mould casted though bonding or through thermal welding to a thermoplastic elastomeric hollow tubular body part.
9. An assembly for separation specific suspended containments in said through passing raw fluid, according to any previous embodiments, comprising at least one cartridge (101, 201) said cartridge equipped with at least in one end one elastic end couplings (303, 402) manufactured from polymeric materials of single-use character allowing the assembly to be sterilized before use and disposed after use.
10. An assembly for separation of specific containments in raw fluids according to any previous embodiments comprising:
said assembly further comprises one or more cartridges (101, 201) mounted with in at least one end (204, 205) said elastic end coupling assembly (303, 402) said cartridge comprising:
11. A method of assembling according to any previous embodiments:
establishing a single-use membrane filter device ready for further integration in a process equipment.
It is an object of the present invention to provide a price compatible Hollow-Fiber-Filter assembly for separation of specific containments in raw fluids comprising:
said elastic end coupling assemblies connected to a membrane filter devise.
The invented membrane assembly consists of a cartridge and a set of elastic end-couplings:
Design and fabrication of surface filtration cartridges comprising porous membranes involves different disciplines and requires a thorough understanding of the intended application. There is no such design that serves all needs. The evolution of module design and fabrication is built on a wide range of prior arts and practical experiences.
One design and fabrication of a cartridge comprises a bundle of porous wall hollow fibers inside a round tube.
One other design and fabrication of a cartridge comprising a stack of porous sheets, plates into a cartridge, frame structure.
In general, the typical round cartridge has few major parts also illustrated in
The cartridge is the functional component of the complete HFF assembly. The cartridge consists of numerous tubular membranes of diameter ranging from 0.5-10 mm packed together inside the tubular housing. The packing density is defined as the fraction or percent of the volume in the housing occupied by the Hollow-Fiber membranes. Even the cartridge is symmetrical, identical in both ends said cartridge in practical use will have one feed, broth inlet end and one exit, retentate outlet end.
The hollow fibers are an artificial, organic membranes consisting of a semi-permeable barrier in the shape of a hollow tubular fiber. The multiple pores are arranged perpendicular to the end-less fiber wall. Pores can be arranged asymmetrical, so the pores change size from inner side to outer side of the fiber wall—named asymmetrical design. Wall thickness typical from lees than few tenth of a millimetre to several millimeters.
The hollow fiber membranes divide the cartridge into two compartments or chambers. The inner side of the elongated fiber bundle refers to the space, chamber enclosed by the membrane inlet exposed to non-filtered raw fluid, broth, feed. While the fiber outside refers to the permeate within the collection area. The fiber outside form a chamber between the outer surface of the fiber bundle (separating wall for the raw fluid) and the inner side of tubular housing shell. The housing usually possesses an elongated tubular shape with one or more openings at one or both ends and a uniform circular cross section to minimize manufacturing costs.
At each end of the cartridge a cover 216 insure the open and inner volume of fibers 214 are accessible through the end faces 219, 220. This cover is an agent, a putty, a glue with good adhesion properties and some elasticity after curing such as epoxy or polyurethane or the like. The casted in cover creates a disc with a plurality of holes formed by each of the hollow fibers. The glue surrounds every hollow fiber in a fluid tight seal. The thickness of the cover ranges from a few to 50 mm, most relevant from 5 to 15 mm.
Raw non-processed fluid enters cartridge inlet end face 219 and flows through the inner side of the hollow fibers 214. Each raw fiber inner side extending from end face 219 to end face 220 is to be viewed as inlet to the membrane area. The raw fluid is flowing inside the tube, straw, lumen 214 at a desired velocity. A pressure difference across the tubular membrane wall 214 force a part of the raw non-processed fluid to pass the tubular separation wall 214. Permeate fluid having passed the membrane is collected in chamber 235 and guided to at least one end of the cartridge to exit through port 230 and further into the elastic end-coupling chamber 530, 630. Retentate flow out via cartridge exit, end face 220 for collection by one of the two the elastic end-coupling chambers shown in
Broth as the un-filtered raw fluid enters in one inlet end of the cartridge and pass through the bundle of hollow fibers along the entire length and exit as retentate in the opposite exit end. Because of a controlled Trans-Membrane-Pressure (TMP) a desired and small portion of the broth pass the porous membrane wall and become the permeate. The permeate, being the desired filtered product, is collected to exit as permeate via a side port in the cartridge housing tubular wall.
Inlet and outlet ports on the housing permit fluid introduction and exit and permeate removal from the shell side of the fiber bundle. In some designs, only one port is needed to collect the permeate from the shell side. The inlet/exit ports on the end cartridge ends permit fluid communication with the fiber lumens.
Existing Hollow-Fiber-Filter assemblies or modules are flexible membrane fibers housed inside the rigid cartridge housing. Separate rigid plastics or metal end caps connect to the cartridge for various fluid connections. Rigid plastics or metal outer tubing and end-caps is used for various fluid connections.
This traditional end-cap design requires rigid plastic fittings, external fittings, cylindrical tube spacers, conical spacers, clamps including Luer-Lok and Tri-Clamps used broadly in any such industry.
The typical cartridge consisting of a bundle of parallel and longitudinal arranged individual polymeric hollow fibers, lumens inside a polymeric round tube, housing in each end said lumens fixed to the inside of said tube by potting glue. The tube sheet housing of the cartridge forms a fluid-tight outer seal. The potting glue between fibers and inside housing separates the fluids flowing through the lumen and outside of the lumen behind the housing tube sheet wall.
Housing tube are typical transparent elongated tubular shaped allowing inspection. Diameters ranging from 5 mm up to 250 mm. Length ranging from short 100 mm to long 2.000 mm. Most often the assembly is described in membrane surface area Surface area ranging from cm2 to m2. Housing tube materials are polysulfone or polycarbonate or similar strong and transparent.
The Hollow Fibers (straw, lumen) typical manufactured from polymers like; high density polyethylene (HDPE), polyethersulfone (PES), modified polyethersulfone (mPES), Ultra-high molecular weight polyethylene (UHMWPE), Poly(tetrafluoroethylene) PTFE, Polyvinylidenefluorid (PVDF), cellulose, or ceramics typically via an extrusion process. Even in single material or sandwiched by two or more layers of different materials. Hollow fiber diameter typically ranging from less than 0.5 mm to 20 mm in diameter. Wall thickness typically range from 0.05 to 10 mm. As usual the pore size ranges from Dalton to micro meter (ym). Such as from 50 kD to 1 μm or more.
Optionally hollow fiber membranes manufactured from ceramics such as Alumina oxide, Silicon Carbide, Titanium oxide.
Conventional rigid plastic end-caps, coupling, fittings with ports typical manufactured from polysulfone able to handle autoclavation. Such fittings glued onto the cartridge tube.
Integrated end fittings, end caps, connections come with port such as;
Separate end-fittings, end-caps, connections port couplings is required for further connections. One of the important objects of the present inventions—how to avoid all these expensive extra parts as illustrated in
Further separate aseptic connectors intended for one-time use. In order to assemble parts in laboratory assembling, without parts being autoclaved, the HFF require in each end and permeate outlet one such (expansive) aseptic coupling is required, one clamp, one seal (in total 4 sets).
One clamp is required to connect two sanitary Tri-clamp flanges together around a seal. Clamps is a widely used coupling standard available in both stainless steel and glass fiber re-enforced plastics from many vendors.
Seals, gaskets are required and come in a range of material choices of Silicone, EPDM, PFTE, BUNA N, FKM Fluoroelastorner. Silicone for bio tech application in transparent platinum cured Silicone is most commonly used.
Luer-Lok—a standardized system of small-scale fluid fittings used for making leak-free connections between a male-taper fitting and its mating female part on medical and laboratory instruments. Such as syringes transferring no micro-organisms. Named after the 19th century German medical instrument maker Hermann Wülfing Luer and now defined in the ISO 594 standard. Luer-Lok male connection has an fixed inner diameter of 3.2 mm and for many biomedical applications with low volume flow not a limitation. But for medium flow application in the biotech industry a serious limitation where the high fluid velocities cause severe shear forces killing micro-organism being conveyed and processed.
In general, all the Tri-Clamp fittings, tube parts, clamps, etc. design originate from the dairy industry almost 100 years ago. Tri-Clamp became the brand since 1919 best known from Tri-Clover-Machine Co. in USA. Metal Tri-Clamps are now owned by AlfaLaval. Tri-Clamps are defined in standard ISO-1127 from 1996 and DIN-32676 among others. Sizes range from ¾″ to more than 4″. Flow properties, laminar flow was not of concern and parts design originate from what sheet metal, metal banks, metal rods were available for easy machining and welding. Exactly the same dairy stainless-steel dairy design has continued into the biotech industry with now injection moulded plastic parts. But for the pharma industry flow properties, laminar flow, dead volumes are of outmost importance to avoid.
The total assembly is often designed to be all single-use and as the HFF cartridge is integrated with the Single-Use-Bioreactor also the HFF is of single-use design. The custom designed elastic rubber body is mounted on each of the housing shell ends said rubber body facilitate two sealing area on the housing shell circumference. The first seal area is behind the permeate housing shell wall outlet the second seal area is in front of the permeate housing shell wall outlet. Hereby supplying a tight permeate outlet. The second seal area is in front of the permeate housing shell wall outlet further insure a fluid tight broth inlet and retentate outlet. Said broth inlet and retentate outlet is via the integrated hoses in connection with external means and as to such operating under sterile conditions inside elastic rubber body and inside the Hollow-Fiber-Filter module housing shell.
Permeate exit is a suitable in size cut hole in the rigid plastic housing wall close to at least one end of the rigid plastic wall before the putting glue secure fiber ends fluid tight end faces inside each of the cartridge ends.
Further assembling requires the invented silicone elastic end-couplings is pressed in over the end of the cartridge housing shell. As to the elastic end-couplings elasticity fluid tightness is obtained and tightness around the permeate exit hole in the tubular cartridge wall as well as the cartridge tube ends accessing the fiber bundle. Further fluid tightness may be obtained by adding plastics or metal clamps outside the elastic end-couplings.
In small scale bioreactor application, the rigid plastic HFF housing tube is equipped with rigid plastics end fittings, end caps, connections with port. These HFF ports are most often of type Luer-Lok or the larger sanitary flange type. Further connection required yet sets of Luer-Lok or sanitary flanges equipped with barbs for connection to elastic tubing. A costly construction which add unwanted extra internal dead volume, fluid length, very different broth velocities, complexity to keep liquid tight, and in specific add to system pricing. For various cultivation in the pharma industry the product is separated from the micro-organisms containing broth. Its very important to keep internal dead volume, fluid length to a minimum. Its here that the micro-organisms find low velocity media areas to accumulate and die.
Reality is that the rigid plastic Hollow-Fiber-Filter round cartridge, housing only need the invented elastic hose connections for the transport of fluids to and from. One hose for broth inlet, one for retentate outlet and one or two for permeate recovery. The many end caps, ports, connections are not needed for operation and only increase weight, complexity, possible leaks, physical size and product cost significantly.
The present invention eliminates all the expensive coupling parts and reduce significantly unwanted extra internal dead volume by adding the elastic hoses directly to the rigid plastic cartridge housing. The elastic T-design of the elastic end-coupling assembly insure simultaneously tight connection for: 1. broth inlet and: 2. retentate outlet and: 3. permeate exit—all by the invented elastic assembly connected to the cartridge.
Materials such as rigid polymers to form one or more parts of the invention are, but not limited to materials such as; polycarbonates, polyesters, nylons, polyimide, PTFE resins and other fluoropolymers, acrylic and methacrylic resins and copolymers, polysulphones, polyethersulphones, polyarylsulphones, polystyrenes, polyetherimides, polyethylene terephthalates, polyvinyl chloridcs, chlorinatcd polyvinyl chloridcs, ABS and its alloys and blends, polyolefins, preferably polyethylenes such as linear low density polyethylene, low density polyethylene, high density polyethylene, and ultrahigh molecular weight polyethylene and copolymers thereof, polypropylene and copolymers thereof and metallocene generated polyolefins.
Materials elastic suitable for manufacturing the invented elastic end-couplings are medical grade polymeric materials and elastic polymeric materials. In general Silicones are excellent for the purpose. Relevant groups of Silicone materials are among many Elastosil Silicone from Wacker. Hoses made from PVC is also relevant. Combinations of different materials by various gluing or welding methods. Such as a rigid plastic Tri-clamp and the elastic hose part.
Methods for shaping, casting, moulding with polymers are via the pressure cast/curing of one component RTV silicone. Extrusion moulding of Silicones benefit from dual compound Silicones.
Pressure casting or injections moulding give advantage to a free design of the internal shape with focus on laminar flow properties, controlled fluid velocities and elimination of dead volumes. As to such broth velocities are kept identical all over the fluid cross section and hereby advantageous for the micro-organisms living in the media.
Injection moulding or press moulding of the elastic end coupling allow a choice of integration of multiple elastic and/or elastic or rigid plastic connections or barbs or fittings for different purposes.
An elastic end coupling may integrate a rigid injection moulded thermoplastic part such as a Tri-Clamp flange or a tube part. Alternatively, elastomeric Tri-Clamps flanges, Tri-Clamp seal, a tubular part of selectable elastomeric materials, a supporting device may be cast together with thermoplastic elastomeric part in an over-moulded process.
Such as add on, connections with Single Use Pressure Sensors as offered by American company PendoTech or ScriLog from Parker. Standard available with barb, Luer-Lok and Tri-Clamp connections.
The choice of elastic hoses for inlet and exit allow use of clamp-on flow sensors. Such as LeviFlow offered by Swiss company Levitronics. Or the German Em-Tec clamp-on-sensor or similar from SonoTec. This type of sensors benefits from the elastic tube to measure flow, velocity inside and its flexibility for installation, clamp-on procedure.
Further benefit of the invented elastic end coupling assembly is the free choice of integrated multiple elastic and selectable length hoses connecting by welding. Very often used in the biopharma industry to connect two silicon hoses of the same diameter via welding. Such tube welding can be done sterile with equipment from Terumo, Saint-Gobain, AdvantaPure, etc.
With a hose fully integrated Tri-Clamps, Y or X connections is named over-moulded. Such single-use moulded manifolds and connections provide a seamless internal transition between tubing and connections for a continuous, leak-proof flow. Moulded connections include Y, T, cross, reducer, Tri-Clamp®, and mini Tri-Clamp styles. Over-moulded Tri-Clamp ends greatly reduce bioburden entrapment situations associated with conventional barb-type fittings. They integrated parts of the present invention cost significant less than rigid plastics counterparts or manual mount, making the invented design an attractive option for pharmaceutical, medical, surgical, food, beverage, etc.
The invented elastic end coupling assembly and membrane filter assembly is suitable for applications involving aseptic transfer, sterile processing, and other critical applications in the pharmaceutical, biopharmaceutical, and high purity industries in general. The assemblies reduce manufacturing cost, installation time, improve cleanliness, and retain the many benefits of silicone.
The invented elastic end coupling assembly facilitates optionally more than one integrated cartridge connection. Cartridge elastic end coupling with multiple connections allow multiple cartridges obtaining specific advantages. Such as filter area alteration, length modification keeping filter surface area constant. Or multiple cartridges of different housing dimensions and specifications.
Inlet chamber 534 surrounded by funnel 513 (613) between inlet hose 507 and tubular part 504 guides the feed, broth from inlet at Tri-clamp flange 520 to cartridge body 501 inlet face 519.
For a fluid tight connection between cartridge 501 and tubular part 504 a circular area of specific awareness is created. These areas 535, 536 is part of the tubular part 504 and intended for compression by external means to secure tightness. Optional on the external surface of tubular part 504 extra re-enforcement may be added. Such a strips, bands, clamps made from Nylon or metals.
At figure part 5B the cartridge 501 (601, 701) facilitate through the plastic tube housing wall 515 permeate outlet hole 530 (not shown second hole (730, 731)) of the tubular body to which the inlet elastic end coupling 502 tubular part 504 and permeate inlet 518 matches avoiding to restricting permeate fluid exiting hole 530.
Shown with a dashed cross of two lines 540 the cartridge end surface area and with arrow 541 the approximate length from cartridge 501 end face 519 equivalent to internal length 542 of tubular part 504. Almost identical for both cartridge 501 ends.
The inlet elastic end coupling 502 inlet opening 532 for the cartridge 501 (701) enclosed fluid tight around the cartridge 501 end surface 504.
Expanded sectional part 6B of complete assembly 6A part show details of the invention. The assembly is cut half through lengthwise for explanatory purposes. Of the inlet elastic end coupling 602 the tubular part 604 is press mounted over cartridge 601 cylindrical end part 606. The cartridge 601 consist of the bundle of hollow fibers 614 (four shown) inside the plastic tube housing wall 615 assembled in inlet end (outlet end as well) with putty 616 insuring ail fibers 614 are mechanical hold in place and insure a fluid tight separation of inner and outer fiber 614 surfaces.
Inlet elastic end coupling, 602 extent from its cylindrical tube part 604 to a funnel 612 with conical funnel walls 613 to insure identical velocity (laminar flow) calculated of inlet tube 607 inner cross section to the bundled fibers 614 total cross section (fiber 614 number×fiber inner cross section area).
The permeate outlet hole 630 on cartridge 601 rigid plastic tubular housing wall 61 to be aligned with the permeate receiving inlet funnel 618 in front of permeate hose 609 (or hole 731 aligned up with hose barb 711 at exit).
The illustrated invented membrane filter assembly consist of only 3 individual parts!
The membrane filter assembly 700 (Hollow-Fiber-Filter (HFF)) is only available as the assembly 700 consisting of the raw cartridge 701 integrated with, glued on traditional rigid plastics end-caps 702, 703 in both ends of cartridge 701 creating inlet port 706 and outlet end port 707 as well as permeate exit ports 708 and 709.
Each rigid plastic end-cap 702, 703 equipped with two tri-clamp flanged ports 706, 708 and 707, 709, For end-cap 702 axial broth inlet 706 and radial exit 708. For end-cap 703 axial retentate exit 707 and radial permeate exit 709. Of the dual radial exit ports 708, 709 for the filtered product, the permeate typically only one port is used 709 and the radial port 708 closed or vice versa. The clamp 714 holds blocking-plate 710 tight via the seal 712 to tri-clamp flange on port 708. Its worth to notice that all 4 ports on the two rigid plastics end-caps 702, 703 facilitate Tri-clamp flanges.
At membrane filter assembly 700 rigid plastics inlet end-cap 702 axial port 706 is equipped with various and necessary fittings: silicone ring seal 716, Tri-clamp flange aseptic connector 720, clamp 718 and possible further one tri-clamp aseptic connector (not shown) and hose 724 connection.
At membrane filter assembly 700 axial end-cap 703 the retentate exit port 707 following parts is needed; silicone ring seal 726, sanitary flange barb connector 728, clamp 727, hose 729 mounted on barb 728.
Permeate outlet radial port 709 is open exit via ring seal 713, sanitary flange 1 barb connector 711 secured with clamp 715 to be mounted with hose 725,
Cartridge 701 have two housing permeate outlets 730 one in each end of the cartridge with access to the fibers outside surface and permeate collection volume.
Standard available membrane filter assemblies consist of >18 individual parts. Significantly adding to assembling time and cost of the membrane filter assembly.
While the present invention has been described in connection with the particular embodiments thereof, it will be understood by those skilled in the art that many changes and modifications may be made without departing from the scope of the invention as defined by the appending claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| PA 2019 01194 | Oct 2019 | DK | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/078275 | 10/8/2020 | WO |
