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WO2025240609A1 - Systèmes et procédés pour modules à membranes remplaçables - Google Patents

Systèmes et procédés pour modules à membranes remplaçables

Info

Publication number
WO2025240609A1
WO2025240609A1 PCT/US2025/029352 US2025029352W WO2025240609A1 WO 2025240609 A1 WO2025240609 A1 WO 2025240609A1 US 2025029352 W US2025029352 W US 2025029352W WO 2025240609 A1 WO2025240609 A1 WO 2025240609A1
Authority
WO
WIPO (PCT)
Prior art keywords
bore
membrane
module
body portion
flat
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/029352
Other languages
English (en)
Inventor
Thomas G. NEUMAN
Jr. Joseph M. SICKO
Georges Belfort
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rensselaer Polytechnic Institute
Original Assignee
Rensselaer Polytechnic Institute
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Rensselaer Polytechnic Institute filed Critical Rensselaer Polytechnic Institute
Publication of WO2025240609A1 publication Critical patent/WO2025240609A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/10—Testing of membranes or membrane apparatus; Detecting or repairing leaks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/10—Testing of membranes or membrane apparatus; Detecting or repairing leaks
    • B01D65/102—Detection of leaks in membranes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B01D2313/13—Specific connectors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B01D2313/20—Specific housing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
    • G01N15/082—Investigating permeability by forcing a fluid through a sample
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
    • G01N2015/084—Testing filters

Definitions

  • aspects of the present disclosure are directed to membrane modules allowing replacement of small scale affinity hollow fiber membrane, membrane flat sheet stack or spiral wound membrane separators that include high value ligands or molecules.
  • the membrane modules include cylindrical tubes that allow for the facile insertion and replacement of separation membranes, e.g., hollow fibers with or without various modifications tailored for specific separation or purification applications.
  • the membrane modules can then be used to perform a variety of desired analytical or separation processes. As many potential targets exist and membrane modification techniques are varied, the particular options/applications of the systems and methods of the present disclosure are broad.
  • the membrane module includes a tube body portion including a first end; a second end; a first bore extending from the first end to the second end, the first bore configured to reversibly accept a membrane, and a tube body shell extending around and defining the first bore.
  • the membrane module includes a shell flow module positioned at one of the first end and the second end, including a second bore in fluid communication with the first bore and configured to reversibly accept the membrane, and a third bore in fluid communication with the second bore and configured to facilitate fluid inflow and outflow from the first bore through the second bore.
  • the membrane module includes a tube flow module, including a fourth bore in fluid communication with the second bore and configured to facilitate fluid inflow and outflow from the first bore through the second bore.
  • the membrane module includes a tube body end fitting including a fifth bore in fluid communication with the second bore and the fourth bore, and configured to facilitate fluid flow 7 from the first bore through the fourth bore.
  • the tube flow- module is reversibly associated with the shell flow module.
  • the tube body end fitting further comprises a counter bore positioned around the fifth bore having an inner wall surface, the counter bore configured to hold an o-ring between a membrane positioned in the fifth bore and the inner wall surface.
  • the tube body portion is soldered to the shell flow module; the tube body end fitting is soldered to the shell flow module; and the tube flow module is reversibly associated with the tube body end fitting.
  • the third bore, the fourth bore, or combinations thereof are configured for integration with a high-performance liquid chromatography system.
  • the module is composed of stainless steel, polymer, glass, ceramic, or combinations thereof.
  • a membrane module including a tube body portion, including a first end; a second end; a first bore extending from the first end to the second end, the first bore configured to reversibly accept a membrane, and a tube body shell extending around and defining the first bore.
  • the membrane module includes a first shell flow module positioned at the first end and a second shell flow module positioned at the second end. wherein each of the first shell flow module and the second shell flow module include a second bore in fluid communication with the first bore and configured to reversibly accept the membrane, and a third bore in fluid communication with the second bore and configured to facilitate fluid inflow and outflow from the first bore through the second bore.
  • the membrane module includes a first tube body end fitting attached to the first flow module and a second tube body end fitting attached to the second flow module.
  • the membrane module includes a first tube flow module attached to the first tube body end fitting and a second tube flow module reversibly attached to the second tube body end fitting, wherein each of the first tube flow module and the second tube flow module include a fourth bore in fluid communication with the second bore and configured to facilitate fluid inflow and outflow from the first bore through the second inner bore.
  • first and second tube body end fittings each include a fifth bore
  • first and second tube body end fittings each further comprise a counter bore positioned around the fifth bore having an inner wall surface, the counter bore configured to hold an o-ring between a membrane positioned in the fifth bore and the inner wall surface.
  • the flat-sheet membrane module includes a female body portion including a sample inlet portion including a first bore having an inner wall, and a sample outlet portion including a second bore in fluid communication with the first bore.
  • the flat-sheet membrane module includes a male body portion including a system integration portion having a third bore, and a body integration portion having a fourth bore, the body integration portion configured to reversibly associate with the sample inlet portion at the inner wall.
  • the flat-sheet membrane module includes a perforated flat sheet support disk configured to support a membrane in compression between the male body portion and the female body portion.
  • the flat-sheet membrane module includes a separation stack including a plurality 7 of perforated flat sheet support disks and flat sheet membranes positioned therebetween, wherein the separation stack is configured to be reversibly held via compression between the male body portion and the female body portion.
  • the flat-sheet membrane module includes a plurality of through-holes extending between the female body portion and the male body portion, the plurality of through-holes configured to accept one or more fasteners to reversibly fasten the female body portion and the male body portion together.
  • the flat-sheet membrane module includes an o-ring positioned to direct fluid flow from the fourth bore through the second bore.
  • the female body portion further comprises an annular recess positioned in a base of the first bore and around the second bore, the annular recess configured to hold a first o-ring.
  • the male body portion further comprising a counter bore positioned around the fourth bore, the counter bore configured to hold a second o-ring.
  • the body integration portion includes a threaded outer surface portion configured to reversibly engage a threaded portion of the inner wall.
  • the body integration portion includes an annular groove configured to hold a third o-ring in contact with the inner wall when the body integration portion is associated with the sample inlet portion.
  • FIG. 1 is a schematic representation of a membrane module according to some embodiments of the present disclosure
  • FIGs. 2A-2B are schematic representations of embodiments of tube body portions included in membrane modules according to some embodiments of the present disclosure
  • FIGs. 3A-3B are schematic representations of embodiments of shell flow modules included in membrane modules according to some embodiments of the present disclosure.
  • FIGs. 4A-4B are schematic representations of embodiments of tube flow modules included in membrane modules according to some embodiments of the present disclosure.
  • FIGs. 5A-5B are schematic representations of embodiments of tube body end fittings included in membrane modules according to some embodiments of the present disclosure
  • FIGs. 6A-6B are schematic representations of a flat-sheet membrane module according to some embodiments of the present disclosure.
  • FIGs. 7A-7D are schematic representations of embodiments of female body portions included in flat-sheet membrane modules according to some embodiments of the present disclosure.
  • FIGs. 8A-8D are schematic representations of embodiments of male body portions included in flat-sheet membrane modules according to some embodiments of the present disclosure.
  • FIG. 9 is a schematic representation of embodiments of a perforated flat sheet support disk included in flat-sheet membrane modules according to some embodiments of the present disclosure;
  • FIG. 10 is a graph showing flow characteristics of membrane modules containing an unmodified regenerated cellulose fiber consistent with embodiments of the present disclosure
  • FIG. 11 is a graph show ing a general affinity purification scheme for FLuc-mRNA using membrane modules consistent with embodiments of the present disclosure
  • FIG. 12 is a graph showing flow characteristics of flat-sheet membrane modules consistent with embodiments of the present disclosure.
  • FIG. 13 is a graph showing a general affinity purification scheme for FLuc-mRNA using flat-sheet membrane modules consistent with embodiments of the present disclosure.
  • membrane module 100 some aspects of the disclosed subject matter are directed to a membrane module 100.
  • Membrane modules consistent with embodiments of the present disclosure, e.g.. membrane module 100, are configured to accept and replace separation membranes therein for a use in a variety of processes, e.g., testing of modified membrane performance, membrane quality control, product separation/purification processes, etc., or combinations thereof, as will be discussed in greater detail below.
  • separation membrane and “membrane” are used interchangeably herein.
  • membrane module 100 is composed of stainless steel, polymer, glass, ceramic, or combinations thereof.
  • membrane module 100 includes a tube body portion 102.
  • Tube body portion 102 includes a bore configured to reversibly retain a membrane, and facilitate fluid flow from one end of the tube body portion, and thus one end of the membrane, to the other.
  • one or more shell flow modules 104 are positioned on tube body portion 102, e.g., at an end or ends thereof.
  • Shell flow' module 104 includes a plurality' of bores to receive fluid flow from tube body portion 102.
  • membrane module 100 includes one or more tube flow modules 106 positioned to receive fluid from one or more shell flow modules 104.
  • membrane module 100 includes one or more tube body end fittings 108 positioned between shell flow' module 104 and tube flow module 106, e.g., fluid from tube body portion 102 flows through a shell flow module 104 to a tube body end fitting 108, and then through a tube flow module 106.
  • the membrane itself extends from bore tube body portion 102 into or through shell flow module 104.
  • the membrane itself extends from bore tube body portion 102 into or through tube body end fitting 108.
  • membrane module 100 includes two shell flow modules 104, one positioned at each end of tube body portion 102. Fluid flow from tube body portion 102 enters shell flow module 104, where it can be withdrawn from membrane module 100 or further transported to a tube flow module 106, e.g., via tube body end fitting 108, as will be discussed in greater detail below. Fluid from shell flow module 104 can then be withdrawn from membrane module 100 via tube flow module 106.
  • the particular combinations of tube body portion 102, shell flow modules 104, and tube flow module 106 allow facile control over fluid through membrane module 100 and thus through any membranes positioned therein.
  • Blanked connections can be positioned in fluid inlets/outlets to enable a variety of flow orientations, e.g.. fluid inflow/outflow from membrane module 100 can be limited to shell flo ⁇ ? modules 104 by blanking tube flow modules 106, fluid inflow 7 can be allowed through both a shell flow' module 104 and a tube flow module 106 (with outflow from another tube flow module 106-only by blanking one shell flow module 104), etc.
  • tube flow module 106 allows for insertion and removal of a membrane to tube body portion 102, as will be discussed in greater detail below.
  • tube body portion 102 is reversibly attached to shell flow module 104.
  • tube body portion 102 is irreversibly attached to shell flow module 104, e.g., via soldering.
  • shell flow' module 104 is attached directly to tube flow module 106.
  • shell flow module 104 is in fluid connection with tube flow' module 106, but not directly attached, e.g., via attachment of tube body end fitting 108 therebetween.
  • shell flow module 104 is reversibly attached to tube body end fitting 108.
  • shell flow' module 104 is irreversibly attached to tube body end fitting 108, e.g., via soldering.
  • tube flow module 106 is reversibly attached to shell flow' module 104 or tube body end fitting 108, e.g., via a threaded connection. In some embodiments, a first tube flow module 106 is reversibly attached while a second tube flow module 106 is irreversibly attached.
  • tube body portion 102 includes a first end 102A and a second end 102B.
  • tube body portion 102 includes a first bore 102C extending from first end 102A to second end 102B.
  • tube body portion 102 includes a tube body shell 102D extending around and defining first bore 102C.
  • First bore 102C is configured to reversibly accept a membrane, e.g., a hollow-fiber membrane.
  • first bore 102C includes an inner diameter 102E size to accept the membrane, e.g., is slightly larger than the diameter of the membrane itself.
  • first bore 102C and/or tube body shell 102D can be any suitable shape without diverging from the embodiments of the present disclosure, however, the embodiments of the present disclosure described herein will portray first bore 102C/tube body shell 102D as being cylindrical.
  • shell flow module 104 includes a system integration portion 104A and a body integration portion 104B.
  • shell flow module 104 extends from a first end 104C in system integration portion 104A to a second end 104D in body integration portion 104B.
  • shell flow module 104 includes a second bore 104G in body integration portion 104B, having a diameter 104H.
  • second bore 104G extends completely through shell flow module 1 4.
  • shell flow module 104 includes a third bore 104E in first end 104C, having a diameter 104F.
  • third bore 104E and second bore 104G are in fluid communication with each other. In some embodiments, third bore 104E and second bore 104G are in any desired orientation with respect to each other, e.g., perpendicular as shown in FIGs. 3A-3B.
  • third bore 104E is any suitable shape and size to facilitate fluid flow from second bore 104G and out of shell flow module 104, and vice-a-versa.
  • third bore 104E is configured for integration with a high-performance liquid chromatography (HPLC) system.
  • diameter 104F of third bore 104E is substantially constant from first end 104C to the intersection with second bore 104G.
  • diameter 104F of third bore 104E varies from first end 104C to the intersection with second bore 104G, e.g.. is conical for compatibility with HPLC male nut and/or ferrule-type connections.
  • third bore 104E includes a threaded portion.
  • second bore 104G is configured to reversibly accept a membrane.
  • second bore diameter 104H and first bore diameter 102E are substantially the same.
  • a shell flow 7 module 104 is positioned at one of first end 102A and second end 102B.
  • second bore 104G is in fluid communication with first bore 102C.
  • second bore 104G is configured to reversibly accept a membrane that is also positioned in first bore 102C.
  • shell flow module 104 is positioned to facilitate fluid flow from first bore 102C through second bore 104G to third bore 104E, and vice-a-versa.
  • second bore 104G is configured to facilitate insertion and removal of a membrane through into first bore 102C.
  • tube flow module 106 includes a system integration portion 106 A and a body integration portion 106B. Tn some embodiments, tube flow module 106 extends from a first end 106C in system integration portion 106A to a second end 106D in body integration portion 106B. In some embodiments, tube flow module 106 includes a fourth bore 106E extending from first end 106C to second end 106D, bore 106E having a diameter 106F.
  • fourth bore 106E is any suitable shape and size to facilitate fluid flow therethrough.
  • fourth bore 106E is configured for integration with an HPLC system.
  • diameter 106F is substantially constant from first end 106C to second end 106D.
  • diameter 106F varies from first end 106C to second end 106D, e.g., is conical for with HPLC male nut and/or ferrule-ty pe connections, becomes larger at second end 106D to associate with the remainder of membrane module 100, etc.
  • fourth bore 106E includes a threaded portion.
  • fourth bore 106E is in fluid communication with second bore 104G, e.g., directly, via tube body end fitting 108, etc.
  • tube flowmodule 106 is positioned to facilitate flow from first bore 102C through second bore 104G and through fourth bore 106E, and vice-a-versa.
  • fourth bore 106E is configured to facilitate insertion and removal of a membrane through into first bore 102C.
  • tube body end fitting 108 extends from a first end 108 A to a second end 108B.
  • tube body 108 includes a fifth bore 108C extending from first end 108 A to second end 108B, bore 108C having a diameter 108D.
  • fifth bore 108C is any suitable shape and size to facilitate fluid flow" therethrough.
  • diameter 108D is substantially constant from first end 108A to second end 108B. In some embodiments, diameter 108D varies from first end 108 A to second end 108B.
  • fifth bore 108C is in fluid communication with second bore 104G and fourth bore 106E.
  • tube body fitting 108 is configured to facilitate fluid flow from first bore 102C through second bore 104G and through fourth bore 106E. and vice-a-versa.
  • first end 108A is configured to associate with shell flow module 104 and second end 108B is configured to associate with tube flow module 106.
  • fifth bore 108C is configured to reversibly accept a membrane that is also positioned in first bore 102C.
  • fifth bore 108C is configured to facilitate insertion and removal of a membrane through into first bore 102C.
  • second end 108B includes a counter bore 108E having a diameter 108F.
  • counter bore 108E has an inner wall surface 108G.
  • counter bore 108E / inner wall surface 108G are positioned around fifth bore 108C.
  • counter bore 108E is configured to hold an o-ring between a membrane, e.g., positioned in fifth bore 108C, and inner wall surface 108G.
  • tube flow module 106 is reversibly associated with tube body end fitting 108.
  • fourth bore 106E is configured to fit over at least a portion of tube body end fitting 108.
  • at least a portion of an interior wall of fourth bore 106E, e.g., adjacent second end 106D, is threaded and corresponds to a threaded portion of tube body end fitting 108, e.g., portion 108H adjacent counter bore 108E.
  • At least a portion of fourth bore 106E can be threaded to enable reversible association with external systems, e.g., HPLC systems.
  • a membrane is inserted into tube body portion 102 via fifth bore 108C in tube body end fitting 108 and second bore 104G in shell flow module 104.
  • an o-ring can then be placed in counter bore 108E, and fourth bore 106E can be screwed onto portion 108H.
  • the o-ring in counter bore 108E can be compressed in fourth bore 106E, e.g., against an interior surface 106G, to facilitate fluid flow between fifth bore 108C and the fourth bore.
  • the o-rings are made of a material including elastomers, silicone, fluoroelastomers, thermoplastic elastomers, or combinations thereof.
  • membrane modules 100 when in use, can be incorporated into methods for separation and purification of a sample, testing of a modified membrane, etc.
  • a hollow 7 fiber membrane can be inserted into first bore 102C.
  • Module 100 can then be connected to a fluidic delivery system and/or analytical device.
  • a sample to be separated/purified can then be introduced to the membrane, and flow 7 through module 100 can be controlled using fluidic delivery.
  • a target analyte can be collected, e.g., through a shell flow module 104 via third bore 104E.
  • regeneration steps can be performed.
  • the hollow 7 fiber can be removed from membrane module 100, e.g., for discarding or later re-use, and another membrane can be inserted for performance of additional separation/purification processes.
  • flat-sheet membrane module 600 includes a female body portion 602.
  • flat-sheet membrane module 600 includes a male body portion 604.
  • each of female body portion 602 and male portion 604 include one or more bores to facilitate fluid flow therethrough.
  • female body portion 602 and male body portion 604 are configured to reversibly associate with each other, e.g., by a portion of the male body portion being reversibly positioned within a bore of the female body portion.
  • fluid flow entering one of female body portion 602 and male body portion 604 is directed through and out of the corresponding other body portion.
  • flat-sheet membrane module 600 includes a flat-sheet support disk 606 configured to be compressed between female body portion 602 and male body portion 604 when they are associated with each other.
  • flat-sheet support disk 606 is configured to be a platform upon which a flat-sheet separator, e.g., a membrane, can be positioned to facilitate separation of components in a fluid as that fluid flows, e g., from male body portion 604 through flat-sheet support disk 606 and subsequently through female body portion 602, as will be discussed in greater detail below.
  • a flat-sheet separator e.g., a membrane
  • female body portion 602 and male body portion 604 are reversibly associated via a threaded connection, one or more fasteners, or combinations thereof, as will be discussed in greater detail below.
  • flat-sheet membrane module 600 is composed of stainless steel, polymer, glass, ceramic, or combinations thereof.
  • flat-sheet membrane module 600 includes one or more o- rings 608, e.g., o-rings 608 A, 608B, 608C. positioned to control fluid flow through module 600, as will be discussed in greater detail below.
  • o-rings 608 are made of a material including elastomers, silicone, fluoroelastomers, thermoplastic elastomers, or combinations thereof.
  • female body portion 602 includes a sample inlet portion 602A and a sample outlet portion 602B.
  • female body portion 602 extends from a first end 602C in sample inlet portion 602A to a second end 602D in sample outlet portion 602B.
  • female body portion 602 includes a first bore 602E in first end 602C having a first diameter 602F.
  • female body portion 602 includes a second bore 602G in second end 602D having a second diameter 602H.
  • first bore 602E and second bore 602G are in fluid communication with each other.
  • first diameter 602F and second diameter 602H are substantially the same diameter. In some embodiments, first diameter 602F and second diameter 602H are different diameters.
  • first bore 602E is shaped and sized to reversibly associate with male body portion 604.
  • first diameter 602F is substantially constant
  • first bore 602E is configured for integration with male body portion 602.
  • sample inlet portion 602A of female body portion 602 includes an inner wall 602J configured to reversibly associate with male body portion 604, as will be discussed in greater detail below.
  • second bore 602G is any suitable shape and size to facilitate fluid flow therethrough.
  • second diameter 602H is substantially constant.
  • second diameter 602H varies, e.g.. second bore 602G is conical for associated with HPLC male nut and/or ferrule-type connections, etc.
  • male body portion 604 includes a system integration portion 604A and a body integration portion 604B.
  • male body portion 604 extends from a first end 604C in system integration portion 604A to a second end 604D in body integration portion 604B.
  • male body portion 604 includes a third bore 604E in first end 604C having a third diameter 604F.
  • male body portion 604 includes a fourth bore 604G in second end 604D having a fourth diameter 604H.
  • third bore 604E and fourth bore 604G are in fluid communication with each other.
  • third diameter 604F and fourth diameter 604H are substantially the same diameter. In some embodiments, third diameter 604F and fourth diameter 604H are different diameters.
  • third bore 604E is any suitable shape and size to facilitate fluid flow therethrough.
  • third bore 604E is configured for integration with an HPLC system.
  • third diameter 604F is substantially constant.
  • third diameter 604F varies, e.g., third bore 604E is conical for association with HPLC male nut and/or ferrule-type comments, etc. At least a portion of third bore 604E can be threaded to enable reversible association with external systems, e.g., HPLC systems.
  • fourth bore 604G is any suitable shape and size to facilitate fluid flow therethrough.
  • fourth diameter 604H is substantially constant.
  • fourth diameter 604H varies, e.g., includes a conical section.
  • body integration portion 604B of male body portion 604 is shaped and sized to reversibly associate with female body portion 602.
  • body integration portion 604B includes an outer wall 604J configured to associate with female body portion 602, e.g., at inner wall 602J of sample inlet portion 602A.
  • the diameter of outer wall 604J is slightly smaller than inner wall 602J, and contact between outer portions of body integration portion 604B and inner portions of sample inlet portion 602A prevent fluid flow from flat-sheet membrane module 600 other than through the desired flow path, e.g., third bore 604E to fourth bore 604G to first bore 602E to second bore 602G, when male body portion 604 is engaged with female body portion 602.
  • flat sheet support disk 606 includes a perforated region 606A.
  • flat sheet support disk 606 includes a perforated region 606A and a non-perforated region 606B.
  • flat sheet support disk 606 has a diameter 606C.
  • flat sheet support disk 606 is any suitable shape and size to support a membrane in compression between female body portion 602 and male body portion 604, e.g., diameter 606C is slightly smaller than first diameter 602F.
  • flat-sheet membrane module 600 includes a separation stack including a plurality of perforated flat sheet support disks 606 and flat sheet membranes positioned therebetween. In this embodiment, the separation stack is also configured to be reversibly held via compression between female body portion 602 and male body portion 604.
  • female body portion 602 includes an annular recess 602K positioned in a base of first bore 602E and around second bore 602G.
  • annular recess 602K is configured to hold an o-ring, e.g., o-ring 608A from FIG. 6A.
  • male body portion 604 includes a counter bore 604K positioned around fourth bore 604G.
  • counter bore 604K is configured to hold a second o-ring, e.g., 608B from FIG. 6A.
  • outer wall 604J is configured to associate with female body portion 602, e.g., at inner wall 602J of sample inlet portion 602A.
  • body integration portion 604B includes a threaded portion, e.g., on outer wall 604J, configured to reversibly engage a corresponding threaded portion on sample inlet portion 602A, e.g., on inner wall 602J.
  • O-ring 608A can be positioned within annular recess 602K. and then flat-sheet support disk 606 can be positioned on that o-ring. A suitable flat-sheet membrane can then be positioned on flat-sheet support disk 606.
  • Second o-ring 608B can then be positioned within counter bore 604K. and the threaded portions of outer wall 604J and inner wall 602J can be engaged with each other. As female body portion 602 and male body portion 604 are screwed together via the threaded portions of outer wall 604J and inner wall 602J, flat-sheet support disk 606 and the associated membrane are compressed. In this compressed state, the o- rings, e.g., 608A and 608B, can direct fluid flow from fourth bore 604G through flat-sheet support disk 606 and the associated membrane to second bore 602G while preventing leaks at the interface of the engaged female body portion 602 / male body portion 604.
  • the o- rings e.g., 608A and 608B
  • body integration portion 604B includes an annular groove 604L in outer wall 604J.
  • annular groove 604L is configured to hold an o-ring. e.g., o-ring 608C from FIG. 6B.
  • outer wall 604J of body integration portion 604B is configured to associate with female body portion 602, e.g., at inner wall 602J of sample inlet portion 602A.
  • outer wall 604J is shaped and sized such that when an o-ring is positioned in annular groove 604L, the o-ring contacts inner wall 602J when body integration portion 604B is associated with sample inlet portion 602A.
  • flat-sheet support disk 606 and the associated membrane can be compressed therebetween.
  • contact between the o-ring in annular groove 604L with inner wall 602J forms a seal, directing fluid flow from fourth bore 604G through flat-sheet support disk 606 and the associated membrane to second bore 602G while preventing leaks at the interface of engaged female body portion 602 / male body portion 604.
  • flat-sheet membrane module 600 includes a plurality of through-holes 610 extending between female body portion 602 and male body portion 604.
  • through-holes 610 are configured to accept one or more fasteners to reversibly fasten female body portion 602 and male body portion 604 together.
  • the one or more fasteners include screws, which can be inserted into through- holes 610 while female body portion 602 and male body portion 604 are engaged, and tightened to compress flat-sheet support disk 606 and the associated membrane therebetween.
  • flat-sheet membrane module 600 when in use, can be incorporated into methods for separation and purification of a sample.
  • an o-ring can be inserted into counter bore 604K of male body portion 604, and one or more flatsheet membranes can be positioned on the o-ring.
  • Another o-ring can be positioned within annular recess 602K of female body portion 602, and flat sheet support disk 606 can be positioned on that o-ring.
  • Male body portion 604 can then be attached to female body portion 602, compressing the O-rings with flat sheet support disk 606 and the membrane.
  • Flatsheet membrane module 600 can then be connected to a fluidic del i ⁇ ery system and/or analytical device, .e.g., at third bore 604E.
  • a sample to be separated/purified can then be introduced to the membrane, and flow through the module using fluidic delivery' can be controlled.
  • a target analyte can be collected, e.g., from second bore 602G.
  • regeneration steps can be performed.
  • flat sheet support disk 606 and the membrane can then be removed from flat-sheet membrane module 600, e.g., for discarding or later re-use, and another membrane can be inserted with flat sheet support disk 606 for performance of additional separation/purification processes.
  • the membranes for use in modules according to embodiments of the present disclosure can be any suitable membrane composition and sized to perform the desired separation given the dimensions of the module itself.
  • the membranes include regenerated cellulose, polysulfone. poly vinylidene fluoride, embedded hydrogels in a porous membrane matrix, etc., or combinations thereof.
  • the membranes include one or more surface modifications, e.g., polymer layers applied via techniques such as Single Electron Transfer - Living Radical Polymerization (SET-LRP), Activators ReGenerated by Electron Transfer - Atom Transfer Radical Polymerization (ARGET-ARP). etc., or combinations thereof.
  • FIG. 10 the flow characteristics of membrane modules consistent with embodiments of the present disclosure, containing an unmodified RC fiber, are illustrated, showcasing the integration of the module into an HPLC system.
  • the chromatograms measured at 260 nm, represent the response obtained from the injection of a pure sample including either 50 pL of 0.003 mg/mL Uracil. 10 ng/pL Oligo-dAeo (OdAeo) and 10 ng/pL of Firefly Luciferase (FLuc) mRNA at a flow rate of 0.50 mL/min.
  • the system tracers exhibited symmetrical and continuous profiles indicating favorable flow characteristics within the module and hollow fiber.
  • FIG. 11 the performance of membrane modules consistent with embodiments of the present disclosure is illustrated in a general affinity 7 purification scheme for FLuc-mRNA.
  • This embodiment included the insertion of an 01igo-dT2o modified hollow fiber into modules, and further integrated into an HPLC system.
  • 5 pg of mRNA was injected into the system using a binding buffer.
  • the resulting chromatogram was recorded by measuring the wavelength at 260 nm.
  • the flow through, or unbound faction can be seen in the first peak between 0 - 3 min.
  • the elution peak corresponds to the release of the target molecule from the affinity ligand on the surface of the modified hollow fiber.
  • the flow characteristics of a flat-sheet membrane module was investigated, showcasing integration of the module into an HPUC system.
  • the flat-sheet membrane module contained a stack of 8 unmodified RC flat sheet membranes.
  • the chromatograms measured at 260 nm, represent the response obtained from the injection of a pure sample of either 50 pL of 0.003 mg/mL Uracil, 10 ng/pL Oligo-dAeo (OdAeo) and 10 ng/pL of Firefly Luciferase (FLuc) mRNA at a flow rate of 0.50 mL/min.
  • the system tracers exhibited relatively symmetrical and continuous profiles indicating favorable flow characteristics within the module.
  • the membrane module included four Oligo- dT2o modified flat sheet RC membranes placed between two unmodified membranes on either side of the stack, which was then integrated into an HPLC system.
  • the purification scheme 5 pg of mRNA was injected into the system using a binding buffer. The resulting chromatogram was recorded by measuring the wavelength at 260 nm. The flow through, or unbound faction, can be seen in the first peak between 0 - 3 min.
  • the modules allow for multiple use and reuse of different types of modified fibers or stacks as they provide a mechanism for removal, modification and further re-installment of different membranes, expanding the range of separation capabilities and accommodating complex membrane purification needs.
  • the module is designed to facilitate ultra-small-scale (pl-ml) separations in a variety of membrane flow orientations. This feature is attractive when working with expensive, low-quantity, raw materials, as it reduces waste and increases utilization efficiency.
  • the embodiments of the present disclosure enable accurate, high-throughput testing and capture of target ligand species with minimum mixing and dispersion. Specifically, the use of modified single hollow fiber membranes and flat sheet membrane stacks is enabled for both analytical and preparatory laboratory scales, filling a market gap as a technology supporting this type of platform/usage is unavailable.
  • the invention's design allows for facile integration into established analytical techniques such as HPLC or other chromatographic or non-chromatographic devices. This compatibility enhances the versatility and applicability of the embodiments of the present disclosure by allowing for integration into already existing laboratory 7 setups and workflows.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
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  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

Les modules à membranes de la présente divulgation permettent une utilisation aisée de fibres creuses et d'empilements de feuilles planes modifiés après commercialisation à l'échelle analytique et préparative au laboratoire. Les modules permettent une utilisation et une réutilisation multiples de différents types de fibres ou d'empilements modifiés étant donné qu'ils fournissent un mécanisme de retrait, de modification et de réinstallation supplémentaire de différentes membranes, d'extension de la plage de capacités de séparation et permettent de répondre à des besoins complexes de purification sur membrane. Le module est conçu pour faciliter des séparations à très petite échelle (du µl au ml) dans diverses orientations d'écoulement sur membrane. Cette caractéristique est intéressante lorsque l'on travaille sur des matières premières coûteuses, en faible quantité, car elle réduit les pertes et augmente l'efficacité d'utilisation.
PCT/US2025/029352 2024-05-14 2025-05-14 Systèmes et procédés pour modules à membranes remplaçables Pending WO2025240609A1 (fr)

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US202463647414P 2024-05-14 2024-05-14
US63/647,414 2024-05-14
US202463663778P 2024-06-25 2024-06-25
US63/663,778 2024-06-25
US202563805458P 2025-05-14 2025-05-14
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060273003A1 (en) * 2003-08-08 2006-12-07 Kazunori Sudo Simplified filter device
US20130043177A1 (en) * 2008-06-05 2013-02-21 Celgard Llc Wafer-shaped hollow fiber module for in-line use in a piping system
US20150182916A1 (en) * 2012-07-05 2015-07-02 Toray Industries, Inc. Hollow fiber membrane module
CN112387122A (zh) * 2020-11-11 2021-02-23 四川大学 微通道膜蒸馏组件和装置及用微通道强化膜蒸馏传递过程的方法
US20230149855A1 (en) * 2017-04-21 2023-05-18 New Jersey Institute Of Technology Hollow Fiber Membrane Module for Direct Contact Membrane Distillation-Based Desalination

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060273003A1 (en) * 2003-08-08 2006-12-07 Kazunori Sudo Simplified filter device
US20130043177A1 (en) * 2008-06-05 2013-02-21 Celgard Llc Wafer-shaped hollow fiber module for in-line use in a piping system
US20150182916A1 (en) * 2012-07-05 2015-07-02 Toray Industries, Inc. Hollow fiber membrane module
US20230149855A1 (en) * 2017-04-21 2023-05-18 New Jersey Institute Of Technology Hollow Fiber Membrane Module for Direct Contact Membrane Distillation-Based Desalination
CN112387122A (zh) * 2020-11-11 2021-02-23 四川大学 微通道膜蒸馏组件和装置及用微通道强化膜蒸馏传递过程的方法

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