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WO2003008100A1 - Dispositif de traitement simultane de quantites discretes de materiau fluide - Google Patents

Dispositif de traitement simultane de quantites discretes de materiau fluide Download PDF

Info

Publication number
WO2003008100A1
WO2003008100A1 PCT/GB2002/003222 GB0203222W WO03008100A1 WO 2003008100 A1 WO2003008100 A1 WO 2003008100A1 GB 0203222 W GB0203222 W GB 0203222W WO 03008100 A1 WO03008100 A1 WO 03008100A1
Authority
WO
WIPO (PCT)
Prior art keywords
membrane
receptacles
end opening
zones
exit end
Prior art date
Application number
PCT/GB2002/003222
Other languages
English (en)
Inventor
Christopher Richard Biddell
Stefan Fischer-Fruhholz
Colin Kalman Lanyi
Original Assignee
Vivascience Ag
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 Vivascience Ag filed Critical Vivascience Ag
Publication of WO2003008100A1 publication Critical patent/WO2003008100A1/fr

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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • 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
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates

Definitions

  • the present invention relates to a device for simultaneous processing of discrete quantities of flowable material, especially for separating components of the material.
  • Separation of components of materials in liquid phase is carried out for many purposes and in many fields, including processing of very small material quantities for the purpose of purification, concentration, extraction of target substances and isolation of substances for analysis and classification.
  • Microfiltration and other such techniques frequently involve processing large numbers of individual charges of materials of the same or different composition and the time required for carrying out such processing is an important factor in economic utilisation of industrial or laboratory equipment and skilled personnel.
  • one effective method of isolating charged compounds entails loading a small-volume receptacle or column with a quantity of liquid in which the compounds are present, spinning the column to drive the material through an ion exchange membrane at an outlet end of the column by centrifugal force and subsequently eluting compounds which have been bound in the membrane by ion exchange. If processing of multiple quantities in this manner is required, it is necessary to fill single columns individually and to individually fit the columns to and subsequently remove the columns from a centrifuge, which represents a time-consuming and repetitive task.
  • units in the form of multi-well plates which have a number of receptacles or wells with open outlet ends covered by an ion exchange membrane.
  • Such a unit accelerates the processing of multiple quantities of flowable materials to be purified or concentrated, but unconstrained flow of material within the membrane and consequent communication of the individual quantities with each other imposes limitations on the scope of use of the unit.
  • the unit is unusable for processing very small amounts of material for analytical or other purposes, as losses can occur within the membrane. Communicating flow within the membrane also removes any possibility of determining the origin from the different charges of material.
  • a multi- well plate currently on the market and utilising a single microfiltration membrane sandwiched between a first moulded body defining wells and a second moulded body defining corresponding openings.
  • the two bodies have integral sharp-edged ridges which encircle the well outlets and corresponding openings and which under the action of ultrasound and pressure penetrate the membrane material and are fused together so as to secure the bodies to each other with the membrane clamped between.
  • the production cost of the plate is, however, increased by the need for a second moulded body and an associated mould and the integrally moulded ridges constitute potential points of leakage if, due to a moulding fault such as gas inclusions in mould grooves defining the ridges, the ridges are improperly formed and fail to correctly mate.
  • Location of the membrane by clamping also necessitates support, against possible displacement by fluid pressure, of the membrane zones within the fused-together ridges by support cages moulded in the openings of the second body. These cages add to production cost and increase the vulnerability of the second body to damage during mould removal and assembly.
  • the principal object of the present invention is therefore the provision of a device of simple and economic construction for processing discrete quantities of flowable material simultaneously, but without the risk of partial intermixing of the quantities during processing.
  • a device for simultaneous processing of discrete quantities of flowable material comprising a body defining a plurality of receptacles each having an entry end opening for introduction of an individual charge of the flowable material and an exit end opening for outflow of at least part of the material of the introduced charge and a single membrane permanently fixed to the body to close the exit end openings of the receptacles and to form an external face of the device and acting on the material to permit throughflow of one component thereof, but to restrain throughflow of another component thereof, the membrane being formed with individual effective zones each closing the exit end opening of a respective one of the receptacles and each separated in terms of flow from the or each other effective zone.
  • Such a device embodies the advantages of allowing simultaneous processing of multiple charges of material by way of an economic construction with a single membrane for all the charge receptacles, with secure location of the membrane and with a minimum number of components, but overcomes the disadvantages associated with communicating flow within the membrane.
  • the dispersal of substances separated from each processed charge can be confined to a small membrane zone exclusive to that charge, so that subsequent elution of the substances from the membrane may be able to be performed with a greater degree of success.
  • the membrane zones are separated by cuts extending entirely through the thickness of the membrane.
  • the cuts can be applied simultaneously so that a single work step is sufficient to divide the membrane into the individual zones.
  • the separation of the zones in terms of flow is thus provided by flow barriers resulting from, for example, excision of strip portions of the membrane by way of the cuts.
  • the amount of membrane material removed by the cuts, i.e. width of the barriers can be determined in dependence on the cutting technique, porosity or permeability of the membrane and other factors. Equally, however, a flow barrier can be provided by, for example, slitting the membrane material and simultaneously heat sealing the slit edges.
  • each of the cuts follows the outline of the exit end opening of a respective one of the receptacles, so that each zone substantially corresponds in shape with the shape, which is preferably circular, of that opening.
  • Each cut is preferably disposed at a predetermined spacing outwardly of the outline of that end opening, the spacing being such that attachment to the body of the portion of membrane material defining the respective zone is not compromised, but that the overall area of the zone is no larger than desired.
  • the cuts could equally well, however, be applied in a grid arrangement.
  • cutting of the membrane represents a particularly simple method of forming the zones
  • other methods of separating the zones in terms of flow including treatment of rectilinear or curvilinear portions of the membrane to be substantially non- porous or non-permeable. This can be carried out by infusion of the membrane with a non-porous or impermeable substance, such as adhesive or other fluid-impermeable sealant, along tracks bounding the zones.
  • the zones can additionally be separated in terms of flow from portions of the membrane disposed between the zones.
  • the membrane is preferably fixed to the body by bonding, which in one advantageous embodiment can be achieved by directly moulding the body onto the membrane. This results in an intimate connection between the. materials of the body and the membrane.
  • the membrane can be bonded to the body by, for example, thermal welding or by means of an adhesive.
  • the membrane itself can be constructed for separation of components differing with respect to at least one of composition and electrical charge, in which case the membrane can be, for example, an ion exchange, a reverse phase or an affinity membrane. Additionally or alternatively, the membrane can be constructed for separation of components differing with respect to at least one of volume and mass.
  • a membrane can be a filter, including a microfilter or an ultrafilter.
  • the membrane can have, for example, a porous or non-porous, but fluid-permeable, construction as desired.
  • the cross-sectional area of the exit end opening of each receptacle can be greater than that of the entry end opening. This can be achieved by, for example, suitably shaping each receptacle such as by providing a step or inward taper at the exit end.
  • utilisation of the area available within the body can be optimised by arranging the receptacles adjacent to one another in rows, the receptacles preferably having a cylindrical form to assist flow of material therethrough.
  • the device can include a support member secured to the body and supporting the membrane at a side thereof remote from the body, such support enabling the membrane to better withstand, for example, increased throughflow pressure resulting from subjecting the device in use to higher levels of centrifugal force.
  • the support member can be, for example, a plate or grid structure provided with openings respectively coincident with the receptacle end openings of the body and thus with the effective zones of the membrane and can be fixed to the body by any suitable means, such as adhesive, ultrasonic welding, interference fit or mechanical fasteners.
  • a method of producing a device in accordance with the first aspect of the invention comprising the steps of producing a body defining a plurality of receptacles each having an entry end opening for introduction of an individual charge of the flowable material and an exit end opening for outflow of at least part of the material, permanently fixing a single membrane to the body to close the exit end openings of the receptacles and form an external face of the device and dividing the membrane into individual effective zones each closing the exit end opening of a respective one of the receptacles and each separated in terms of flow from the or each other effective zone.
  • the step of dividing preferably comprises cutting the membrane, for which purpose use of a laser cutter advantageously allows execution of precisely defined and accurately located cuts.
  • the steps of producing the body and fixing the membrane can be conveniently carried out simultaneously by injection-moulding the body on the membrane.
  • Fig. 1 is a schematic perspective view from above of a device embodying the invention
  • Fig. 2 is a cross-section, to an enlarged scale in relation to Fig. 1 and along the line ll-ll of Fig. 3, of part of the device, with components shown in exaggerated thicknesses for the sake of clarity;
  • Fig. 3 is a plan view, in the direction of arrow 111 in Fig. 2, of the part of the device shown in Fig. 2;
  • Fig. 4 is an inverted plan view, in the direction of arrow IV in Fig. 2, of a part of the device similar to that shown in Fig. 3.
  • a device in the form of a multi-well plate for simultaneous processing of discrete quantities of flowable material, in this instance for isolating charged compounds from liquid samples by an ion exchange procedure as described further below.
  • the plate consists of an injection-moulded plate-shaped integral body 10 of a thermoplastics material, for example polypropylene or polystyrene, which is intrinsically rigid, light, low in cost, inert to organic solutions and resistant to corrosive or chemical attack by the media intended to be processed. Lightness and rigidity are provided not only by the choice of material, but also by the body design, which can combine minimum use of material in conjunction with recognised reinforcing and bracing techniques.
  • the body 10 thus comprises a hollow frame 11 of rectangular plan surrounding a plurality of thin-walled cylindrical receptacles 12 of identical volumetric capacity appropriate to the quantity of material each receptacle is to receive for processing.
  • Each receptacle 12 has an open entry end 12a at the top and open exit end 12b at the bottom.
  • the cross-sectional area of the exit end 12b is preferably less than that of the entry end 12a, so as to allow restricted outflow of the material to be processed, but relatively unrestricted inflow.
  • the reduction in cross-sectional area which is not depicted in the illustrated simplified embodiment, can be achieved by, for example, provision of a step at the exit end.
  • the receptacles 12 are arranged adjacent to one another in rows to form an array of, for example, eight-by-twelve receptacles, thus a total of ninety-six.
  • the receptacles can, however, be present in any desired number and pattern.
  • the receptacles are connected together firstly by vertical webs 13 attached to the circumferential wall of each receptacle at four equidistantly spaced points and secondly by horizontal webs 14 which together define a planar base surface 15 interrupted by the receptacle exit ends 12b.
  • the webs 13 and 14 additionally connect the receptacles 12 to the frame 11.
  • the exit ends 12b of the receptacles 12 are closed by a single rectangular membrane 16 which is permanently fixed, in particular bonded, to the body 10 at the base surface 15 so as to define an external face of the plate and which consists of, for example, a sheet of regenerated cellulose with a reinforcing weave of polyester.
  • the cellulose sheet defines a matrix in which positively or negatively charged functional groups such as sulphonic acid or quaternary ammonium have been covalently bound to provide an anion exchanger or a cation exchanger for binding, by electrostatic interaction, oppositely charged components of materials processed by the device, i.e. flowable materials introduced into the receptacles 12.
  • This form of membrane is merely one of various possibilities for component separation, but it is common to all membranes that each of the material quantities to be processed has to flow at least partially into the membrane, with at least one component of the material passing entirely through the membrane and at least one component restrained from passing through by retention within the membrane (as in ion exchange) or by being checked at the inflow or upstream surface of the membrane.
  • the difficulty arises that communicating flow of material from the different receptacles is possible within the membrane, with the result that components from the individual material charges are intermixed. This precludes accurate assessment of the origin of subsequently eluted isolated components.
  • the diffusion of isolated components within the membrane can render recovery problematic or impossible in the case of extremely small component sizes, i.e. the components remain bound in the membrane matrix.
  • This difficulty is avoided by forming the membrane 16 with individual effective zones 16a each associated with the exit end 12b of a respective one of the receptacles 12 and each separated in terms of flow from the other effective zones.
  • the zones 16a are each defined by a circular cut 17, for example of a width of about 0.25 millimetres, passing entirely through the membrane 16 and following a circular path around, but at a small spacing outwardly of, the exit end 12b of the respective receptacle.
  • the width of the cut 17, by which a narrow strip portion of the membrane material is excised, is sufficient to form a flow barrier at the perimeter of each zone 16a and thus prevent an undesired communicating flow to other zones or, as in the case of the illustrated example, the residual membrane material between the zones.
  • the spacing of the cut 17 from the boundary of the exit end 12b of the associated receptacle is kept to a minimum, but remains sufficient to ensure adhesion of the membrane material defining the zone to the base surface 15 of the body 10 at least for the expected service life of the device.
  • Production of the device can be undertaken in particularly economic manner by injection moulding the plate body 10 directly onto the membrane 16, for which purpose the latter can be placed on a support surface in a mould defining the shape of the plate and the constituent thermoplastic material for the body 10 then injected into the mould to enter into intimate connection with the membrane 16 by penetration into the pores of the membrane matrix.
  • Laser cutting of the membrane i.e. thermal destruction of the membrane material along the track of a laser beam, to define the cuts 17 and thus form the zones 16a can be carried out in an automated process with computer-controlled guidance of the beam. Cutting in this manner results in particularly accurately dimensioned zones.
  • the width of the cuts can be determined by setting the focus of the beam, which is preferably a low- power beam.
  • a device of this construction has a minimum number of components, i.e. moulded body and membrane, and thus can be produced at low cost compatible with a product intended for single use or use only a small number of times before discard.
  • the receptacles 12 are charged with the samples and sealed at their open ends 12a.
  • the plate 10 is spun in a centrifuge at appropriate speed and for a given time to drive the material of the samples through the membrane zones 16a and into a collector communicating with the membrane at its face remote from the receptacles.
  • the target compounds are retained in the membrane matrix by anion or cation exchange and can subsequently be recovered by elution with a suitable eluting solution.

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  • 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)
  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

L'invention concerne un dispositif, sous la forme d'une plaque multipuits, destiné au traitement simultané de quantités discrètes de matériau fluide aux fins, par exemple, d'épuration, de concentration ou d'extraction de matières cibles, qui comprend un corps (10) moulé par injection doté de plusieurs réceptacles (12) chacun ayant une ouverture d'extrémité d'entrée (12a) permettant d'introduire une charge individuelle du matériau fluide et une ouverture de sortie (12b) pour évacuer au moins une partie dudit matériau. Une membrane simple (16), par exemple une membrane d'échange ionique ou de filtration, fixée au corps (10) par collage, permet de fermer les ouvertures de sortie (12b) des réceptacles et de former une face externe du dispositif. La membrane (16) est formée de zones actives individuelles (16a), chacune fermant l'ouverture de sortie (12b) du réceptacle correspondant, et chacune isolée en terme d'écoulement à partir des zones externes. Les zones (16a) peuvent être définies par des coupes traversant entièrement ladite membrane.
PCT/GB2002/003222 2001-07-17 2002-07-12 Dispositif de traitement simultane de quantites discretes de materiau fluide WO2003008100A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0117394A GB2377990B (en) 2001-07-17 2001-07-17 Device for simultaneous processing of discrete quantities of flowable material
GB0117394.7 2001-07-17

Publications (1)

Publication Number Publication Date
WO2003008100A1 true WO2003008100A1 (fr) 2003-01-30

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ID=9918653

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Application Number Title Priority Date Filing Date
PCT/GB2002/003222 WO2003008100A1 (fr) 2001-07-17 2002-07-12 Dispositif de traitement simultane de quantites discretes de materiau fluide

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GB (1) GB2377990B (fr)
WO (1) WO2003008100A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004067176A1 (fr) 2003-01-22 2004-08-12 Millipore Corporation Procede de formation de plaques de filtration multipuits
RU176819U1 (ru) * 2017-05-24 2018-01-31 федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургский государственный морской технический университет" (СПбГМТУ) Энергоустановка телеуправляемого необитаемого подводного аппарата

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0521117D0 (en) * 2005-10-18 2005-11-23 Amersham Biosciences Ab Multiwell plate

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5047215A (en) * 1985-06-18 1991-09-10 Polyfiltronics, Inc. Multiwell test plate
DE4114611A1 (de) * 1990-05-11 1991-11-14 Sartorius Gmbh Flaches mikroporoeses membranelement, insbesondere zur durchfuehrung von slot- oder dot-blottinganalysen
GB2348622A (en) * 1999-03-16 2000-10-11 Minerva Technologies Moulded filter plates
WO2001019502A2 (fr) * 1999-09-17 2001-03-22 Millipore Corporation Carte tamis de grande capacite
WO2001087484A2 (fr) * 2000-05-18 2001-11-22 Millipore Corporation Plaque a puits multiples dotee d'un filtre fixe par un adhesif

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4704255A (en) * 1983-07-15 1987-11-03 Pandex Laboratories, Inc. Assay cartridge
US5009780A (en) * 1989-07-20 1991-04-23 Millipore Corporation Multi-well filtration apparatus
JPH07502207A (ja) * 1992-10-09 1995-03-09 マイクロスキャン、インコーポレイテッド アッセイカートリッジ
US5326533A (en) * 1992-11-04 1994-07-05 Millipore Corporation Multiwell test apparatus
US6274088B1 (en) * 1998-04-06 2001-08-14 Pharmacopeia, Inc. Methods and apparatus for high throughput plate to plate or plate to membrane transfer

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5047215A (en) * 1985-06-18 1991-09-10 Polyfiltronics, Inc. Multiwell test plate
DE4114611A1 (de) * 1990-05-11 1991-11-14 Sartorius Gmbh Flaches mikroporoeses membranelement, insbesondere zur durchfuehrung von slot- oder dot-blottinganalysen
GB2348622A (en) * 1999-03-16 2000-10-11 Minerva Technologies Moulded filter plates
WO2001019502A2 (fr) * 1999-09-17 2001-03-22 Millipore Corporation Carte tamis de grande capacite
WO2001087484A2 (fr) * 2000-05-18 2001-11-22 Millipore Corporation Plaque a puits multiples dotee d'un filtre fixe par un adhesif

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004067176A1 (fr) 2003-01-22 2004-08-12 Millipore Corporation Procede de formation de plaques de filtration multipuits
US7211165B2 (en) 2003-01-22 2007-05-01 Millipore Corporation Method of forming multiwell filtration plates
US7763140B2 (en) 2003-01-22 2010-07-27 Millipore Corporation Method of forming multiwell filtration plates
RU176819U1 (ru) * 2017-05-24 2018-01-31 федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургский государственный морской технический университет" (СПбГМТУ) Энергоустановка телеуправляемого необитаемого подводного аппарата

Also Published As

Publication number Publication date
GB0117394D0 (en) 2001-09-05
GB2377990B (en) 2003-11-12
GB2377990A (en) 2003-01-29

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