WO2002088671A1 - Unite de separation, procede de separation et dispositif destine au montage d'une unite de separation dans un appareil de separation - Google Patents

Unite de separation, procede de separation et dispositif destine au montage d'une unite de separation dans un appareil de separation Download PDF

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Publication number
WO2002088671A1
WO2002088671A1 PCT/SE2002/000827 SE0200827W WO02088671A1 WO 2002088671 A1 WO2002088671 A1 WO 2002088671A1 SE 0200827 W SE0200827 W SE 0200827W WO 02088671 A1 WO02088671 A1 WO 02088671A1
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WO
WIPO (PCT)
Prior art keywords
fluid
separation
separation unit
receiving fluid
sample
Prior art date
Application number
PCT/SE2002/000827
Other languages
English (en)
Inventor
Jan Norberg
Eddie Thordarson
Patrik Söderlund
Fredrik HÅKANSSON
Shadi Yazarlo
Lars-Åke Larsson
Johan Berhin
Original Assignee
Esytech Ab
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 Esytech Ab filed Critical Esytech Ab
Priority to JP2002585926A priority Critical patent/JP2004529348A/ja
Priority to CA002445307A priority patent/CA2445307A1/fr
Priority to EP02728281A priority patent/EP1381840A1/fr
Publication of WO2002088671A1 publication Critical patent/WO2002088671A1/fr

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Classifications

    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/06—Preparation
    • G01N30/14—Preparation by elimination of some components
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/24—Automatic injection systems
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/06—Preparation
    • G01N2030/062—Preparation extracting sample from raw material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/06—Preparation
    • G01N30/14—Preparation by elimination of some components
    • G01N2030/146—Preparation by elimination of some components using membranes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8804—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 automated systems
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178—Special arrangements of analysers
    • G01N2035/00326—Analysers with modular structure
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N30/18—Injection using a septum or microsyringe
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6034—Construction of the column joining multiple columns
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6047—Construction of the column with supporting means; Holders

Definitions

  • the present invention relates to a modular separation system where a separation unit is separate from a mounting device that accommodates the separation unit in a separation apparatus.
  • the separation unit is used in fluid-fluid extraction of an analyte from a sample fluid into a receiving fluid.
  • the mounting device is an integral and permanent part of a separation apparatus and carries the necessary fluid fittings.
  • the invention also relates to a separation system comprising the separation unit insertable into and removable from a mounting device.
  • the invention also relates to a method for fluid-fluid extraction of an analyte from a sample fluid into a receiving fluid in a separation apparatus according to the invention.
  • Separation (extraction) units according to the prior art, e.g. as described in the reference J ⁇ nsson, J.A. et al: "Automated system for the trace analysis of organic compounds with supported liquid membranes for sample enrichment", Journal of Chromatography A, 665 (1994), pages 259-268, comprises two solid blocks usually made of polymeric materials which are identical in the way they are machined, i.e. they contain machined holes for fluid connectors, drilled holes from the end of these holes to the fluid cavity which is machined in the centre of each block.
  • One block also contains pre-drilled holes into which screws will fit and the other block contains means to receive the screws, essentially pre- machined female connections in the block itself or as steel inserts.
  • a polymer sheet often referred to as the membrane, is clamped between the blocks and the screws are tightened.
  • the described extraction system is after this ready for use.
  • a system assembled in this manner will need to be re-used because it involves so much manual work for exchanging the clamped polymer.
  • a further disadvantage with these systems is that they are susceptible to carry-over problems associated with re-use.
  • Another disadvantage is that the production of the systems is likely not to be able to deliver the best reproducibility as the blocks need to be machined and, furthermore, the operation is expensive. Since the assembly of the system is manual there is a risk that the pressure might not be uniform across the cavities and that the pressure will not be consistent from time-to-time when the system has been disassembled and reassembled again. Furthermore, the production does not guarantee that the blocks exhibit a good match when mounted and not tilted in relation to one another. Thus, if they are tilted the accessible membrane will differ and the extraction efficiency will decrease.
  • An object of the present invention is to provide a modular system with a separate separation unit and a mounting device that accommodates the separation unit in a separation system.
  • a further object of the invention is to provide a mounting device, which is an integral and permanent part of a separation apparatus and carries the necessary fluid fittings.
  • Another object of the invention is to provide a separation system which comprises a mounting device with a separation unit insertable therein and removable therefrom. It is a further object of the invention to provide a separation system which allows for automation of fluid-fluid extraction and which, furthermore, allows for connection to any final analysis device, e.g. a chromatograph, a spectroscopic device, a flow injection system etc.
  • a further object is to provide a separation apparatus comprising a separation unit, a mounting device in which a separation unit is insertable into and removable from.
  • the pressurisation of the separation unit will be uniform from unit-to-unit - Full automation possible, even when the cavities of the separation unit are used only once.
  • the present invention relates to a separation unit as defined in claim 1.
  • the separation unit may contain a separation medium, which can be of any nature, such as chromatographic materials and/or a membrane, preferably a membrane.
  • the separation medium is arranged so that one or more analytes in the sample fluid can pass from the sample fluid via the separation medium to the receiving fluid.
  • the sample fluid and the receiving fluid respectively can contact the separation medium simultaneously or sequentially.
  • the sample fluid cavity is connected to the receiving fluid cavity and the separation medium is a membrane support adapted or arranged so as to partly separate the sample fluid cavity from the receiving fluid cavity, it is meant that the sample fluid cavity, the receiving fluid cavity and the membrane support are arranged in relation to each other in a way that allows one or more analytes in the sample fluid to pass from the sample fluid through the membrane support to the receiving fluid.
  • an analyte is used, this should be understood as meaning “one or more species of analytes”. Usually, a plurality of analytes is to be extracted in the separation unit according to the present invention.
  • membrane support should be understood as any material, including synthetic and organic materials, which is capable of at least partly separating two immiscible or partly miscible fluids or of facilitating the contact between two miscible fluids.
  • the membrane support preferably has pores or perforations, which are adapted to accommodate a fluid.
  • an aqueous fluid may be accommodated in the pores or perforations
  • an organic fluid may be accommodated in the pores or perforations.
  • the membrane support having its pores or perforations filled or partly filled with a fluid constitutes a membrane.
  • a “membrane” should be understood as any device or assembly capable of at least partly separating two immiscible or partly miscible fluids while allowing certain molecules to pass through the membrane from one fluid to another.
  • the membrane support may comprise a non-porous material, such as a non- porous polymeric material, such as silicon rubber.
  • the membrane support may constitute the membrane. If the non-porous material separates an aqueous fluid from an organic fluid, the non-porous material is normally wetted by the organic fluid, in which case the wetted non-porous material constitutes the membrane. If the non-porous material separates two aqueous fluids, the non-porous material is normally not wetted by fluid, in which case the non-porous material itself constitutes the membrane.
  • fluid-fluid extraction should be interpreted broadly, as comprising any type of extraction between two fluids, such as liquids, or any kind of molecular diffusion between fluids, such as dialysis.
  • fluid-fluid extraction also comprises MMLLE (Microporous Membrane Liquid-Liquid Extraction).
  • MMLLE Membrane Liquid-Liquid Extraction
  • the sample fluid cavity preferably defines a volume of at most 50 ⁇ l, such as at most 40 ⁇ l, such as at most 20 ⁇ l, such as most 10 ⁇ l, such as at most 5 ⁇ l, such as at most 2 ⁇ l, such as at most 1 ⁇ l, such as most 0.5 ⁇ l.
  • the sample fluid cavity may be of substantially the same size as the receiving fluid cavity.
  • the volume of the receiving fluid cavity is at most 50 ⁇ l, such as at most 40 ⁇ l, such as at most 20 ⁇ l, such as at most 10 ⁇ l, such as at most 5 ⁇ l, such as at most 2 ⁇ l, such as at most 1 ⁇ l, such as most 0.5 ⁇ l.
  • the separation unit Due to the small volumes of receiving fluid and sample fluid, which may be accommodated in the separation unit, hazardous effects to an operating person and to the environment are reduced. Moreover, due to the small volumes, the separation unit enables extraction from low volumes of sample, yet preserving possibilities of high volume ratios between sample and receiving fluid, important to e.g. liquid-liquid extraction. It further enables direct connection between extraction and an analysis apparatus, such as a chromatograph. Further, the separation unit according to the invention necessitates only very few steps to be carried out by an operator, whereby automation of the extraction procedure and possibly of the subsequent analysis procedure is facilitated.
  • the volume of the sample fluid cavity suitably is less than 50 ⁇ l
  • the amount of sample fluid used for extraction is usually higher, as, during extraction, a flow of sample fluid is preferably continuously led through the sample fluid cavity.
  • the amount of sample fluid flowing through the separation unit may preferably be between 0.3 and 5 ml.
  • the receiving fluid may be stagnant, i.e. not flowing, during extraction, in which case the volume of receiving fluid used for extraction is approximately equal to the volume of the receiving fluid cavity.
  • the sample fluid may be an aqueous liquid or an organic liquid or a gas.
  • aqueous liquids are any physiological liquid, e.g. chosen from the group consisting of whole blood, urine, sweat, plasma, serum, nasal secrete, cerebrospinal fluid and other liquids from living organisms. It can also be a non-physiological liquid, e.g. a liquid chosen from the group consisting of river water, sea water, lake water, effluent water, influent water, drinking water, ground water or a fine dispersion of solid matter in aqueous solution, e.g. soil samples, food samples, plant samples, tissue samples or aqueous samples of dissolved airborne compounds, or liquid foodstuff e.g. juice, milk, wine and coffee.
  • the sample volume is small and is between about 20 ⁇ l, more often 100 ⁇ l, and about 20 ml, preferably between 0.3 and 5 ml. Volumes outside the above-defined range may also be applicable, however in rare cases.
  • the analytes of interest in the sample are preferably compatible with the final analysis equipment and may for example be chosen from any group of volatile or semi-volatile or non-volatile organic or inorganic or organometallic compounds.
  • the receiving fluid may be a hydrophobic liquid, such as an organic liquid, or an aqueous liquid or a gas.
  • the receiving fluid is preferably chromatography compatible and may for example be a hydrophobic organic liquid or a hydrophilic liquid, such as a buffer.
  • a hydrophobic organic liquid or a hydrophilic liquid such as a buffer.
  • the membrane support may be hydrophobic or hydrophilic, normally hydrophobic.
  • membrane supports are polytetrafluoroethylene (PTFE), polyvinylidenedi- fluoride (PVDF), polypropylene (PP), polyethylene (PE), polystyrene (PS), polysulfone, cellulose, polyethersulfone (PES) and silicone rubber.
  • PTFE polytetrafluoroethylene
  • PVDF polyvinylidenedi- fluoride
  • PP polypropylene
  • PE polyethylene
  • PS polystyrene
  • polysulfone polysulfone
  • cellulose polyethersulfone
  • silicone rubber silicone rubber
  • the membrane support may be provided with a stabilizing backing.
  • the sample fluid containing the analytes is separated from the receiving fluid by the membrane support, serving as a phase separator, thereby facilitating the interaction, i.e. the analyte transfer, between the two fluids in question (interfacial support).
  • the separation unit of the invention may be used in dialysis, wherein molecules diffuse from a first aqueous solution, e.g. blood or urine, through a hydrophilic or hydrophobic membrane, normally a hydrophilic membrane, to a second aqueous solution.
  • a suitable membrane support for many applications is a Celgard ® 2400 or 2500, which is a polypropylene polymer with elongated pores manufactured by Celanese/Hoechst.
  • the membrane support is usually provided in the form of strips or sheets, which are cut into an appropriate form prior or subsequent to assembling of the separation unit.
  • the receiving fluid preferably a hydrophobic liquid, fills the pores of the polymer as well as the receiving fluid cavity. Alternatively, the sample fluid fills the pores.
  • the pores may be filled with a hydrophobic fluid separating two aqueous fluids, or the pores may be filled with an aqueous liquid separating two hydrophobic fluids.
  • the receiving fluid or the sample fluid in the pores constitutes the membrane.
  • Membrane support material made of PTFE are also suitable, e.g. Fluoropore FG from Millipore and TE 35 from Schleicher & Schuell.
  • membrane supports are, among others, applicable to the separation unit according to the invention:
  • Fluoropore FGLP Fluoropore FGLP, PTFE with polyethene backing, Millipore Corporation, USA
  • the porosity of the membrane support may vary between 0 and 90%, preferably between 40 and 85%.
  • the average pore size is 0-10 ⁇ m, preferably about 0.01-0.5 ⁇ m.
  • the thickness of the membrane support may vary between 10 and 500 ⁇ m, preferably between 10 and 200 ⁇ m.
  • the sample preferably an aqueous liquid passes the membrane. Hydrophobic, uncharged molecules then distribute between the sample and the membrane, most often with a much higher affinity for the membrane.
  • the analytes diffuse into the receiving fluid in the receiving fluid cavity.
  • the receiving fluid is preferably kept stagnant during extraction. Hence, extraction over time will lead to an increase in analyte concentration in the receiving fluid compared to the original sample.
  • the body portion comprises a first and a second wall member and means for fixing the wall members in relation to each other.
  • the wall members are preferably made from a plastic material, such as a polypropylene.
  • the wall members may be coated in case the separation unit is to be used with an aggressive solvent. Thus, they may for example be chromium, gold or platinum plated or they may be coated with a fluorinated polymer such as PTFE.
  • the two wall members may be assembled by fitting of complementary parts provided on the two wall members, such as projections and fitting holes or bores.
  • the body portion is flattened and defines an upper and a lower surface and at least one rim or edge portion.
  • the ratio between a maximal height of the rim or edge portion and a maximal diagonal dimension of the upper and lower surface is at most 1 to 4, such as at most 1 to 5, 1 to 6, 1 to 8, 1 to 10, 1 to 12, 1 to 15, 1 to 18, 1 to 20, 1 to 25, 1 to 40, 1 to 60, or 1 to 80.
  • Grooves or cut-outs may be provided in one or both of the wall members so as to provide the sample fluid and/or the receiving fluid cavities.
  • the sample fluid cavity may be limited by a groove or cut-out formed in the first wall member and, when a membrane is used as a separation medium, a first surface of the membrane support.
  • the receiving fluid cavity may be limited by a groove or cut-out formed in the second wall member and, when a membrane is used as a separation medium, a second surface of the membrane support.
  • the first and second wall members are identical which facilitates mass production of the separation unit.
  • each wall member is provided with holes and bores arranged with a distance to a number of projections, which preferably equals the number of bores or holes.
  • the projections of one wall member will fit into the bores or holes of the other wall member when pressing the two members against one another.
  • the first and the second wall members may further comprise means for indicating a correct mutual position of the wall members in relation to each other. Such indications may, e.g., comprise an optical indication such as notch in the wall material or a coloured dot.
  • a protrusion may be provided on one of the surfaces of one of the wall members, whereby the protrusion prevents wrong assembling of the two wall members.
  • the notch for indicating a correct mutual positioning of the two wall members may also be used for fixing the separation unit in relation to the device.
  • the membrane support comprises a sheet or strip, which is arranged between the first and the second wall member.
  • the separation unit may be a disposable separation unit for one-time use only, or it may be re-used several times.
  • the separation unit can be moulded by e.g. injection moulding which makes it possible to produce identical first and second wall members. Moulding the two parts of the separation unit in the same mould assures high part-to-part precision in cavity geometry and dimension as well as perfect matching of opposing cavities (cf. Figure 2c).
  • One or more of the sample fluid inlets or outlets may comprise a pipe in the body portion, see for example Figure 14. All inlets and outlets may comprise a pipe.
  • the inlets or outlets may extend at a substantially right angle or at an acute angle to one of the upper and lower surfaces of the body portion. Alternatively, at least one of the inlets and outlets may extend substantially parallel to one of the upper and lower surfaces of the body portion.
  • turbulence may be generated in the respective cavities. Turbulence may also be generated when the inlet and/or outlets, in particular the sample fluid inlet, is bent so that the sample fluid takes a sharp turn before entering the sample fluid cavity.
  • a turbulent flow may be desirable in the sample fluid cavity in order to increase diffusion of analytes from the sample fluid to the receiving fluid.
  • the pipe or pipes are preferably integral with the body portion of the separation unit.
  • the inner diameter of the inlets and outlets are substantially equal to a diameter or a maximal width of the grooves or cut-outs.
  • the inlets and outlets may also have an inner diameter which is smaller or larger than a diameter or maximal width of the grooves or cut-outs, which might increase mass transfer within the sample fluid or decrease dispersion of receiving fluid.
  • At least the sample fluid cavity may comprise means, such as spoilers, for obstructing the flow of sample fluid through the cavity.
  • the grooves or cut-outs forming the receiving fluid and sample fluid cavities preferably extend longitudinally in the wall members.
  • the inlets and outlets are preferably arranged at opposing ends of the two grooves.
  • a surface of at least one of the wall members may have a projecting portion.
  • the grooves or cut-outs are preferably formed in the projecting portion.
  • the grooves or cut-outs may be formed in the projection portion solely, or they may also extend into the material of the wall member material.
  • the projection is preferably made from the same material as the wall members. It may be made from a flexible material in order to facilitate assembling of the two wall members.
  • the two wall members may be releasably secured in relation to each other solely by means of friction between portions of the respective wall members which facilitates assembly and disassembly of the separation unit so as to thereby facilitate mounting or exchange of the membrane support.
  • the invention further relates to the use of the separation unit for molecular diffusion, such as in dialysis, and to the use of the separation unit for molecular extraction.
  • the present invention relates to a method for fluid-fluid extraction of an analyte from a sample fluid into a receiving fluid in a separation unit as defined in claim 13.
  • the receiving fluid may be led directly from the receiving fluid outlet to an analysing apparatus, such as a chromatograph.
  • an analysing apparatus such as a chromatograph
  • the separation unit By allowing the separation unit to be discarded and replaced with a new separation unit, frees an operator of the separation unit from disassembling the unit, replacing the membrane support and assembling the unit again. Further, the separation unit may be delivered to the user or operator in a ready-to-use form, whereby the user only needs to unpack the unit and mount it in an appropriate set-up.
  • the present invention relates to a device for mounting a separation unit in a separation apparatus as defined in any of claims 8-10.
  • the mounting device may have an upper and a lower part between which parts the separation unit may be placed, the two parts being movable towards each other so as to create a pressure on the separation unit.
  • Both the upper and lower part may be movable, or alternatively only one of them may be movable.
  • the upper and lower parts may comprise injectors and extractors for receiving fluid and sample fluid, whereby one single relative movement between the upper and lower part of the device not only confers an appropriate pressure on the separation unit but also properly connects injectors and extractors to the inlets and outlets of the separation unit.
  • the device may comprise or be operatively connected to a control system for controlling positioning of at least the receiving fluid extractor in relation to the receiving fluid outlet and/or of the sample fluid injector in relation to the sample fluid inlet.
  • the control system may further be adapted to control positioning of the receiving fluid injector in relation to the receiving fluid inlet and/or of the sample fluid extractor in relation to the sample fluid outlet.
  • the invention relates to a separation system as defined in claim 11.
  • the invention relates to a separation apparatus as defined in claim 12.
  • the separation unit is either automatically replaceable (utilising a cassette or equivalent means for replacing the used unit with a new unit) or in case many cavities are present in the separation unit the used cavities are automatically replaced by new cavities, see for example Figures 2a and 2b.
  • the separation system according to the invention works in the following manner
  • the mounting device opens up -
  • the new separation unit is introduced automatically or new cavities in the separation unit are automatically put into position
  • the mounting device closes - rendering the system ready for operation.
  • the receiving fluid cavity is provided with the receiving fluid volume desired, whereby the receiving fluid extractor will be filled with the receiving fluid.
  • analytes of interest partition between the sample and the membrane, diffuse into the receiving fluid cavity and are accumulated therein.
  • the receiving fluid containing the analytes is displaced via a fluid delivery system into the analysis apparatus by introducing additional receiving fluid into the receiving fluid cavity.
  • the separation unit and the receiving fluid extractor contain pure receiving fluid, i.e. they have been regenerated and are ready for a new sample flow.
  • an intermediate washing step is included.
  • the separation unit when the separation unit utilises e.g. chromatographic material as a separation medium the sample fluid and the receiving fluid might be introduced sequentially.
  • the separation medium can in these cases be confined in the sample fluid cavity or in the receiving fluid cavity or in both cavities.
  • the whole analysis operation or parts thereof including the steps of feeding the separation unit with receiving fluid and sample, the sample flow interruption, the regeneration of the stagnant phase with fresh receiving fluid, the separation, the detection and the data accumulation can be performed automatically, e.g. controlled by a computer system.
  • the total analysis time is 5-120 min, mostly 10-40 min.
  • Fig. 1a illustrates a device for mounting a separation unit according to the invention in a separation apparatus
  • Fig. 1b is a front view of the device of Fig. 1a),
  • Fig. 1c) is a side view of the device of Figs. 1a) and 1b),
  • Fig. 2a illustrates a separation system wherein A is the mounting device, B are hole(s) to access the cavities of the separation unit, C is the separation unit and D is connecting tube,
  • Fig. 2b illustrates an example of a separation unit containing multiple cavities.
  • Fig. 2c illustrates an example of a cross-section of the two wall members of the body portion wherein F is the first wall member and G the second wall member,
  • Fig. 3 is an exploded view illustration of a third embodiment of a separation unit according to the invention
  • Fig. 4 is an illustration of the separation unit of Fig. 3 when assembled
  • Fig. 5 illustrates a wall member of the separation unit of Figs. 3 and 4,
  • Fig. 6 is a bottom view of the wall member Fig. 5,
  • Fig. 7 is a cross-sectional illustration along line A-A of Fig. 6,
  • Fig. 8 is a cross-sectional illustration along line B-B of Fig. 6,
  • Fig. 9 is an illustration of detail C of Fig. 8,
  • Fig. 10 is an illustration of detail F of Fig. 8,
  • Fig. 11 is an illustration of a wall member for a fourth embodiment of the separation unit according to the invention.
  • Fig. 12 is a side view of the wall member of Fig. 11 .
  • Fig. 13 is a bottom view of the wall member of Figs. 11 and 12,
  • Fig. 14 is a cross-sectional view along line A-A of Fig. 13,
  • Fig. 15 illustrates a detail of a separation unit according to the invention mounted in a mounting device according to the invention
  • Figs. 1 a), 1b) and 1c) illustrate a device 300 for mounting a separation unit 100 in a separation apparatus.
  • the device comprises a lower part 302 through which receiving fluid is led to and from the separation unit via a receiving fluid injector 306 and a receiving fluid extractor 308, and an upper part 304 through which sample fluid is led to and from the separation unit via a sample fluid injector 310 and a sample fluid extractor 312.
  • the receiving fluid extractor 308 may be directly connected to an analysis device.
  • the separation unit 100 is inserted into the device 300 in a way that prevents wrong positioning of the separation unit in relation to the device.
  • the lower part 302 of the device and the upper part 304 are clamped together, thus creating a pressure that seals the grooves of the separation unit against the membrane support.
  • Either one of the upper and lower parts 302 and 304 may be movable, or they may both be movable. They can be manually moved by mechanical means, which may be electrically, pneumatically or hydraulically supported.
  • the separation unit can be inserted from the long end (Fig. 1b) or from the short end (Fig. 1c).
  • an indication such as a light diode, that is lit when the separation unit is correctly positioned, thus either triggering the upper and lower parts 302 and 304 to clamp the separation unit or telling the operator that he or she may close the device.
  • Fig. 2a illustrates a separation system according to the invention wherein the separation unit has a circular shape with multiple .cavities.
  • Fig. 2b illustrates the inside of the separation unit, which is used in the separation system in Fig. 2a),
  • Fig. 2c illustrates a cross-sectional view of the body portion with the two wall members of a separation unit provided with guiding protrusions for accurate positioning of the two parts.
  • Fig. 3 is an exploded view illustration of a separation unit 100.
  • the unit comprises two identical wall members 102, each of which has an upper surface 104 and a lower surface 106.
  • the two wall members 102 and means for fixing the wall members in relation to each other together define a body portion of the separation unit.
  • a groove 108 is provided in a protrusion 110.
  • the groove 108 of one of the wall members constitutes a sample fluid cavity
  • the groove 108 of the other one of the wall members constitutes a receiving fluid cavity.
  • Inlets 112 and outlets 114 are provided in one of the wall members for inlet and outlet of sample fluid, whereas identical inlets and outlets are provided in the other one of the wall members for receiving fluid inlet and receiving fluid outlet.
  • a membrane support 116 is provided between the two wall members.
  • Projections 118 are provided on each one of the wall members.
  • the projections 118 fit into corresponding holes 120, which are further, provided in each one of the wall members.
  • Notches 121 are provided in each one of the wall members so as to indicate to 5 the person assembling the wall members that they are positioned correctly in relation to each other when he or she assembles the separation unit.
  • Fig. 4 illustrates the assembled separation unit having an upper and a lower surface 122 and an edge portion 124.
  • Figs. 5-10 illustrate a wall member 102 of the separation unit of Figs. 3 and 4.
  • Fig. 7, 10 which is a cross-sectional illustration along line A-A in Fig. 6, the inlet 112 and outlet 114 are funnel-shaped so as to be complementary with a conical end of a conical end portion of an injector and extractor for sample fluid and receiving fluid, respectively.
  • Fig. 8 is a cross-sectional illustration along line B-B of Fig. 6.
  • the groove 108 has a triangular shape. Any other geometry of the groove is possible such as 15 rectangular, rounded, etc.
  • Figs. 11-14 illustrate a wall member 202 for a second embodiment of the separation unit according to the invention.
  • the wall member comprises a groove 208 constituting a cavity for either the sample fluid or the receiving fluid.
  • the groove is provided in a protrusion
  • FIG. 14 The cross-sectional view of Fig. 14 illustrates that an inlet 212 and an outlet 214 are arranged at acute angles to an upper surface 204 of the wall member.
  • the inlet and outlet are partly funnel-shaped.
  • Projections 218 and holes 220 are provided for fitting two identical wall parts together, so as to form a separation unit, wherein the inlets and outlets for sample fluid and receiving fluid are arranged at an acute angle to the upper and lower
  • Fig. 15 illustrates a detail of a separation unit 100 according to the invention mounted in the device of Figs. 15-17, more particularly the fitting of the receiving fluid extractor 308 into the receiving fluid outlet of the separation unit.
  • the receiving fluid extractor 308
  • a tube 314 provided with an opening 316 in a wall of the tube, the opening 316 being aligned with the groove 108 of the separation unit.
  • a piston 318 is provided which is moveable in an upward and a downward direction as indicated by arrow 319.
  • the piston comprises a plunger 320.
  • the receiving fluid 109 is dislocated from the groove 108, through opening 316, into the tube 314.
  • the plunger 320 is thereafter moved downwards, pressing receiving fluid into e.g. a chromatograph, as indicated by arrows 322.
  • the plunger 320 may be moved back to its initial position in which it blocks the opening 316 in the tube wall. Moving receiving fluid in the groove 108 will now regenerate new receiving fluid in the membrane support. Thereafter the plunger is moved to a position above the opening 316, and the groove 108 is filled with receiving fluid.
  • the plunger 320 may also be moved to a position above the opening 316 prior to leading receiving fluid into the groove 108 in order to regenerate the membrane support.
  • the piston and the plunger may be spring biased towards the position in which the plunger block the opening in the tube wall.
  • the piston and the plunger may also be movable by means of e.g. hydraulic, electric or pneumatic driving means.
  • the tube 314 is formed as a tube made from stainless steel with the opening 316 being formed as a bore or drilled hole.
  • the plunger 320 is moved so fast when displacing receiving fluid into an analysis apparatus that a so-called split-splitless injector on a gas chromatograph may be used optimally.
  • the tube 314 may have a conical outer shape, which facilitates insertion of the tube into the receiving fluid outlet of the separation unit.
  • the other injectors and extractors of the device of Figs. 1a), 1b) and 1c) may be designed in a similar way.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

L'invention concerne un système de séparation modulaire dans lequel une unité de séparation (100) est séparée d'un dispositif de montage (300) qui reçoit l'unité de séparation, dans un appareil de séparation. Le dispositif de montage fait partie intégrante de l'appareil de séparation. L'invention concerne également un procédé d'extraction liquide-liquide permettant de faire passer un analyte d'un échantillon liquide dans le liquide d'extraction, dans un appareil de séparation.
PCT/SE2002/000827 2001-04-26 2002-04-26 Unite de separation, procede de separation et dispositif destine au montage d'une unite de separation dans un appareil de separation WO2002088671A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2002585926A JP2004529348A (ja) 2001-04-26 2002-04-26 分離ユニット、分離方法、及び分離ユニットを分離装置に取り付けるためのデバイス
CA002445307A CA2445307A1 (fr) 2001-04-26 2002-04-26 Unite de separation, procede de separation et dispositif destine au montage d'une unite de separation dans un appareil de separation
EP02728281A EP1381840A1 (fr) 2001-04-26 2002-04-26 Unite de separation, procede de separation et dispositif destine au montage d'une unite de separation dans un appareil de separation

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DK200100667 2001-04-26
DKPA200100667 2001-04-26
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Cited By (8)

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FR2911403A1 (fr) * 2007-01-16 2008-07-18 Commissariat Energie Atomique Realisation de cavites remplies par un materiau fluidique dans un compose microtechnologique optique
DE102007011866A1 (de) * 2007-03-08 2008-09-11 Friedrich-Schiller-Universität Jena Vorrichtung zur Aufnahme, Behandlung und Aufbewahrung kleinvolumiger Proben
US8246184B2 (en) 2006-02-09 2012-08-21 Commissariat A L'energie Atomique Production of cavities that can be filled with a fluid material in an optical microtechnological component
US8477406B2 (en) 2008-06-27 2013-07-02 Commissariat A L'energie Atomique Et Aux Energies Alternatives Method for making enclosures filled with liquid and closed by a membrane
US9063410B2 (en) 2008-04-04 2015-06-23 Commissariat à l'énergie atomique et aux énergies alternatives Method for making micron or submicron cavities
US9116269B2 (en) 2010-07-21 2015-08-25 Commissariat A L'energie Atomique Et Aux Energies Alternatives Microstructure with walls of determined optical property and method for making microstructures
WO2019034596A1 (fr) * 2017-08-14 2019-02-21 Trasis S.A. Dispositif de préparation d'un échantillon liquide pour chromatographe à phase gazeuse
EP1715348B2 (fr) † 2005-07-15 2019-05-08 Agilent Technologies, Inc. Unité de manipulation des dispositifs microfluidiques avec moyens de serrage

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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1715348B2 (fr) † 2005-07-15 2019-05-08 Agilent Technologies, Inc. Unité de manipulation des dispositifs microfluidiques avec moyens de serrage
US8246184B2 (en) 2006-02-09 2012-08-21 Commissariat A L'energie Atomique Production of cavities that can be filled with a fluid material in an optical microtechnological component
US7729033B2 (en) 2007-01-16 2010-06-01 Commissariat A L'energie Atomique Production of cavities filled with a fluid material in an optical microtechnological compound
FR2911403A1 (fr) * 2007-01-16 2008-07-18 Commissariat Energie Atomique Realisation de cavites remplies par un materiau fluidique dans un compose microtechnologique optique
EP1947482A1 (fr) * 2007-01-16 2008-07-23 Commissariat A L'energie Atomique Realisation de cavités remplies par un matériau fluidique dans un composé microtechnologique optique
DE102007011866A1 (de) * 2007-03-08 2008-09-11 Friedrich-Schiller-Universität Jena Vorrichtung zur Aufnahme, Behandlung und Aufbewahrung kleinvolumiger Proben
US9063410B2 (en) 2008-04-04 2015-06-23 Commissariat à l'énergie atomique et aux énergies alternatives Method for making micron or submicron cavities
US8477406B2 (en) 2008-06-27 2013-07-02 Commissariat A L'energie Atomique Et Aux Energies Alternatives Method for making enclosures filled with liquid and closed by a membrane
US9116269B2 (en) 2010-07-21 2015-08-25 Commissariat A L'energie Atomique Et Aux Energies Alternatives Microstructure with walls of determined optical property and method for making microstructures
WO2019034596A1 (fr) * 2017-08-14 2019-02-21 Trasis S.A. Dispositif de préparation d'un échantillon liquide pour chromatographe à phase gazeuse
CN111386459A (zh) * 2017-08-14 2020-07-07 特拉西斯股份有限公司 用于制备用于气相色谱仪的液体样品的设备
JP2020530573A (ja) * 2017-08-14 2020-10-22 トラシス・エス・アー ガスクロマトグラフ用の液体試料を調製するための装置
US11275060B2 (en) 2017-08-14 2022-03-15 Trasis S.A. Device for preparing a liquid sample for a gas chromatograph
CN111386459B (zh) * 2017-08-14 2022-08-23 特拉西斯股份有限公司 用于制备用于气相色谱仪的液体样品的设备
JP7191091B2 (ja) 2017-08-14 2022-12-16 トラシス・エス・アー ガスクロマトグラフ用の液体試料を調製するための装置

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EP1381840A1 (fr) 2004-01-21
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