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WO2025171243A1 - Microplaque de dialyse à puits multiples - Google Patents

Microplaque de dialyse à puits multiples

Info

Publication number
WO2025171243A1
WO2025171243A1 PCT/US2025/014980 US2025014980W WO2025171243A1 WO 2025171243 A1 WO2025171243 A1 WO 2025171243A1 US 2025014980 W US2025014980 W US 2025014980W WO 2025171243 A1 WO2025171243 A1 WO 2025171243A1
Authority
WO
WIPO (PCT)
Prior art keywords
plate surface
dialysis
microplate
well section
segment
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/US2025/014980
Other languages
English (en)
Inventor
Ashley M. RIBERA
Hui Zhou
Hubert W. VESPER
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.)
US Department of Health and Human Services
Original Assignee
US Department of Health and Human Services
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 US Department of Health and Human Services filed Critical US Department of Health and Human Services
Publication of WO2025171243A1 publication Critical patent/WO2025171243A1/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
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B01L3/50255—Multi-well filtration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0609—Holders integrated in container to position an object
    • B01L2300/0618—Holders integrated in container to position an object for removable separation walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0858—Side walls
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4005—Concentrating samples by transferring a selected component through a membrane
    • G01N2001/4016—Concentrating samples by transferring a selected component through a membrane being a selective membrane, e.g. dialysis or osmosis

Definitions

  • Dialysis is an analytical technique used in scientific and clinical research that involves the separation of particles and compounds having different characteristics and sizes by the selective diffusion of those particles through a semipermeable membrane.
  • a liquid solution of particles and compounds can be placed in a liquid-containing volume where it is separated from a buffer solution by the semipermeable membrane.
  • the semipermeable membrane is a porous material such as cellulous or synthetic resins that includes pores or openings of defined sizes. The pore size of the membrane allows particles and compounds of appropriate sizes to travel between the sample solution and the buffer by diffusion through the pores, while preventing the passage of larger particles and compounds which are retained in the sample.
  • Dialysis can be used, for example, to separate larger particles such as proteins and nucleic acids from smaller molecules within solution for further research and study.
  • dialysis systems have been developed for simultaneously processing a plurality of samples in a structure that includes a corresponding number of liquid-containing volumes or receiving wells for the liquid buffer.
  • the structure with the receiving wells may be referred to as a dialysis microplate or tray due to its planar, tray-like shape.
  • the dialysis samples can be introduced into a separate sample receiving vessel, which may be referred to as a sample vessel segment or sample vessel cartridge, which defines an internal vessel volume bounded by the semipermeable membrane.
  • the sample vessel segments are placed into the buffer-containing receiving wells and the dialysis process proceeds.
  • the plurality of receiving wells allows for the simultaneous dialysis of a plurality of sample vessels.
  • the dialysis process is affected by several considerations concerning the design of the dialysis system, including the interface between the liquid sample and the buffer across the semipermeable membrane.
  • the surface area over which the solutions contact the semipermeable membrane and the duration of contact are examples of such design considerations.
  • the present disclosure is directed to a dialysis system incorporating novel design enhancements for improving the dialysis process.
  • each of the plurality of receiving wells can include an upper well section, an intermediate well section, and a lower well section that are vertically arranged within the sample microplate.
  • the upper well section can have a shape and dimensional configuration to accommodate the upper segment header of the sample vessel segment so that the lower segment body is supportively suspended in the remainder of the receiving well.
  • the intermediate well section can include opposing first and second major sidewalls that are arranged to face the respective first and second planar segment faces when the sample vessel segment is received in the receiving well.
  • the receiving wells can be geometrically and spatially configured to promote efficient dialysis with the fluid samples received in the sample vessel segments.
  • the receiving wells can be sized to establish a volumetric ratio of approximately one-to-one with the volume of fluid sample introduced to the sample vessel segment.
  • the major and/or minor sidewalls of the receiving wells can taper with respect to each other to establish space or gaps between the sample vessel segment to allow for the circulation and flow of the fluid buffer over the planar segment surfaces of the sample vessel segment.
  • Figure 2 is a rear perspective view of the multi-well dialysis microplate disclosed in Figure 1, illustrating the exterior of the bottom well sections of the receiving wells.
  • Figure 3 is a front elevation view of an embodiment of a sample vessel segment that can be placed in one of the plurality of receiving wells of the multi-well dialysis microplate.
  • Figure 4 is a side elevation view of the sample vessel segment.
  • Figure 5 is a schematic diagram showing the profde of a receiving well for accommodating a sample vessel segment in accordance with an embodiment of the disclosure.
  • Figure 7 is a schematic diagram illustrating the shape of the intermediate well section of the receiving well defined by a pair of opposing major sidewalls and a pair of opposing minor sidewalls.
  • the dimension of the longer peripheral side 116 can be approximately 128 mm and the dimension of the shorter peripheral side 118 can be approximately 85.5 mm.
  • the peripheral plate skirt 108 of the dialysis microplate 100 may have a vertical height in the vertical direction 114 of approximately [0021] Attached to and protruding outwardly from the peripheral plate skirt 108 at the intersection with the lower plate surface 106 can be a lip or peripheral outside flange 120.
  • the peripheral outside flange 120 can conform to the overall rectangular shape of the microplate 100 and can circumscribe the lower plate surface 106.
  • the lower plate surface 106 may be configured as a rectangular opening 124 peripherally boarded by the peripheral outside flange 120.
  • the lower extensions of the plurality of receiving wells 102 may be visibly exposed through the rectangular opening 124 in the lower plate surface 106.
  • the dialysis microplate 100 is therefore a substantially hollow structure for reduced weight and material use.
  • the microplate 100 can be produced from thermoplastic such as polystyrene or polypropylene by an injection molding operation.
  • the thermoplastics or polymers suitable for the molded microplate 100 are preferably biochemically inert for the dialysis application.
  • the rectangular opening 124 can facilitate stacking of the microplates 100.
  • the plurality of sample receiving wells 102 can be arranged in 6 x 8 configuration for a total of 48 wells in the dialysis microplate 100.
  • a 48 well grid design may conform to a format for commercial sample microplates and facilitates use of the disclosed microplate 100 with automated fluid dispensing machines.
  • the microplate 100 can have a 96 well grid with the plurality of receiving wells 102 arranged in an 8 x 12 configuration.
  • Other contemplated embodiments of the sample microplate 100 may have different numbers and arrangements of the plurality of sample receiving wells 102.
  • each of the sample receiving wells 102 is geometrically configured to receive and accommodate a sample vessel segment that contains a liquid sample for dialysis.
  • the sample vessel segment 130 can be formed as a structural framework that may be fabricated from plastic and that may define an internal vessel volume 132 for receiving the fluid sample.
  • the upper segment header 136 can include one or more pipette ports that can interface with the tip of a pipette and direct the liquid sample to the internal vessel volume.
  • the upper segment header 136 can be a block-like cubic rectangle and can be dimensionally sized larger to overhang the rectangular cross-section of the lower segment body 134.
  • the upper segment header 136 can be configured with releasable snap connections so that a plurality of sample vessel segments 130 can be interconnected into rows that correspond with rows defined by the grid pattern of the receiving wells 102 located in the dialysis microplate 100.
  • the sample vessel 130 can be a commercially available component such as the MD1000 Xpress Mini Dialyzer from Scienova GmbH of Germany.
  • the sample vessel 130 can have an overall height in the vertical direction 114 of approximately 46 mm.
  • the rectangular block of the upper segment header 136 can have longitudinal dimension in the longitudinal direction 110 of about 20 mm and a lateral dimension in the lateral direction 112 of about 6-7 mm, while the corresponding longitudinal and lateral dimensions of the lower segment body 134 may be smaller.
  • the lower segment body 134 may have a longitudinal dimension in the longitudinal direction 110 of about 15.2 mm and may have a thickness in the lateral direction of about 3.7 mm.
  • a plurality of six sample vessel segments 130 can be attached in a row via the releasable interconnections of the upper segment header 136 to form a cartridge that enables simultaneous dialysis of multiple fluid samples.
  • Each of the plurality of receiving wells 102 can have an advantageous geometric shape to facilitate dialysis with a liquid sample introduced to the sample vessel segments 130 that are received therein.
  • the receiving wells 102 can each include an upper well section 150, a middle or intermediate well section 152, and a lower well section 154 that are aligned with respect to the vertical direction 114.
  • the upper well section 150 is accommodated proximate to the upper plate surface 104 and the lower well section 154 is directed towards the lower plate surface 106.
  • the upper well section 150 can be shaped as a cubic rectangle and is complementary to the upper segment header 136.
  • the upper well section 150 may have a longitudinal length 160 in the longitudinal coordinate 110 of approximately 17 mm, a lateral width 162 in the lateral coordinate 112 of approximately 7.8 mm, and a vertical height 164 in the vertical coordinate 114 of approximately 3.1 mm.
  • the upper well section 150 can spatially accommodate the upper segment header 136 when the sample vessel segment 130 is installed into the receiving well 102 of the dialysis microplate 100.
  • the cross section of the upper well section 150 defined by the longitudinal length 160 and the lateral width 162 can be dimensionally larger than the corresponding rectangular crosssection of the remainder of the receiving well 102 so that the lowermost surface of the upper well section 150 forms a shelf or shoulder on which the upper segment header 136 contacts and rests when the sample vessel segment 130 is inserted in the receiving well 102.
  • the shelf formed by the upper well section 150 therefore vertically supports the remaining lower segment body 134 of the sample vessel segment 130 within the plurality of receiving wells 102.
  • the intermediate well section 152 may be an elongated rectilinear shape that is generally tapered with a cross-section that reduces in dimension from the upper extension thereof to the lower extension thereof.
  • the rectangular shape of the intermediate well section 152 can be defined by a pair of opposing first and second major sidewalls 170, 172 that are orthogonally arranged with respect to a pair of opposing first and second minor sidewalls 174, 176.
  • the first and second major sidewalls 170, 172 may be angled or inclined toward each other, rather than being strictly parallel, such that the intermediate well section 152 defines an upper lateral width 180 of approximately 6.6 mm and a lower lateral width 182 of approximately 5.0 mm.
  • the first and second minor sidewalls 174, 176 may be angled or inclined toward each other such that the intermediate well section 152 defines an upper longitudinal length 184 of approximately 16.5 mm and a lower longitudinal length 186 of approximately 16.2 mm.
  • the angular orientation of the first and second major sidewalls 170, 172 and the first and second minor sidewalls 174, 176 with respect to the upper plate surface 104 and lower plate surface 106 differs from exact 90° right angles.
  • the distance between the upper lateral width 180 and upper longitudinal length 184 and the lower lateral width 182 and the lower longitudinal length 186 may define the vertical dimension or depth 188 of the intermediate well section 152.
  • the lower well section 154 can be shaped as a semicircular structure to geometrically conform to the lower segment cup 138 of the lower segment body 134.
  • the lower well section 154 can include a first and a second semicircular sidewalls 190, 192 that are co-planar with the respective first and second major sidewalls 170, 172 of the intermediate well section 152.
  • the first and second semicircular sidewalls 190, 192 accordingly are inclined and laterally taper towards each other with respect to the plane defined by the longitudinal coordinate 110 and the vertical coordinate 114.
  • the first and second semicircular sidewalls 190, 192 orthogonally intersect with and are spaced apart by a semi- circumferential bottom wall 194 that may be arranged or directed toward the lower plate surface 106 of the microplate 100.
  • the geometric size difference between the receiving wells 102 and the sample vessel segment 130 further promotes circulation of the liquid buffer around and about the lower segment body 134 that is vertically suspended in the receiving well 102.
  • the first and second major sidewalls 170, 172 of the intermediate well section 152 are spaced apart from the corresponding first and second planar segment faces 140, 142 of the lower segment body 134 by approximately 1-1.5 mm.
  • the spacing between the first and second major sidewalls 170, 172 and the first and second planar segment faces 140, 142 provides for sufficient volumetric flow of the liquid buffer across the semipermeable membranes 144, and the substantial surface area provided by the first and second planar segment faces 140, 142 enables the liquid buffer to sufficiently interface with the liquid sample contained in the internal vessel volume 132 of the sample vessel segment 130.
  • the dialysis process and the particular or molecular exchange between the liquid buffer and liquid sample therefore proceeds expediently.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne une microplaque ou un plateau d'échantillonnage permettant de réaliser une dialyse d'un échantillon de liquide comprenant une pluralité de puits de réception destinés chacun à recevoir un segment de récipient d'échantillon définissant un volume de récipient interne rempli d'un échantillon de dialyse de liquide. Chaque puits de la pluralité de puits de réception peut présenter un segment de puits supérieur, une section de puits intermédiaire, et une section de puits inférieure. Le segment de puits supérieur peut être un rectangle cubique conçu pour recevoir un collecteur de récipient supérieur de forme correspondante du segment de récipient d'échantillon. La section de puits intermédiaire comprend des première et seconde parois latérales principales opposées qui se rétrécissent l'une vers l'autre et qui, en partie, définissent un volume de puits initial. Le volume de puits initial peut être conçu pour établir un rapport volumique approximatif de 1:1 avec le volume de récipient interne du segment de récipient d'échantillon.
PCT/US2025/014980 2024-02-09 2025-02-07 Microplaque de dialyse à puits multiples Pending WO2025171243A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202463551965P 2024-02-09 2024-02-09
US63/551,965 2024-02-09

Publications (1)

Publication Number Publication Date
WO2025171243A1 true WO2025171243A1 (fr) 2025-08-14

Family

ID=94925059

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2025/014980 Pending WO2025171243A1 (fr) 2024-02-09 2025-02-07 Microplaque de dialyse à puits multiples

Country Status (1)

Country Link
WO (1) WO2025171243A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7128878B2 (en) * 2002-10-04 2006-10-31 Becton, Dickinson And Company Multiwell plate
US20180280918A1 (en) * 2017-03-21 2018-10-04 Hexanomics, Inc. Sealed microwell assay
US10272433B2 (en) * 2014-03-31 2019-04-30 Scienova Gmbh Vertical functional reaction vessel

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7128878B2 (en) * 2002-10-04 2006-10-31 Becton, Dickinson And Company Multiwell plate
US10272433B2 (en) * 2014-03-31 2019-04-30 Scienova Gmbh Vertical functional reaction vessel
US20180280918A1 (en) * 2017-03-21 2018-10-04 Hexanomics, Inc. Sealed microwell assay

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