WO2006044441A2 - Dispositifs de traitement de liquides equipes de multiples mecanismes d'etancheite, et procedes automatises d'exploitation des dispositifs - Google Patents

Dispositifs de traitement de liquides equipes de multiples mecanismes d'etancheite, et procedes automatises d'exploitation des dispositifs Download PDF

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Publication number
WO2006044441A2
WO2006044441A2 PCT/US2005/036633 US2005036633W WO2006044441A2 WO 2006044441 A2 WO2006044441 A2 WO 2006044441A2 US 2005036633 W US2005036633 W US 2005036633W WO 2006044441 A2 WO2006044441 A2 WO 2006044441A2
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WO
WIPO (PCT)
Prior art keywords
fluid
outlet
inlet
autosampler
stationary phase
Prior art date
Application number
PCT/US2005/036633
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English (en)
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WO2006044441A3 (fr
Inventor
Robert D. Ricker
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Agilent Technologies, Inc.
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Filing date
Publication date
Priority claimed from US10/968,296 external-priority patent/US7563410B2/en
Application filed by Agilent Technologies, Inc. filed Critical Agilent Technologies, Inc.
Publication of WO2006044441A2 publication Critical patent/WO2006044441A2/fr
Publication of WO2006044441A3 publication Critical patent/WO2006044441A3/fr

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Classifications

    • 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
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • 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
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic 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
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • 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
    • G01N1/405—Concentrating samples by adsorption or absorption

Definitions

  • liquid-soluble samples After liquid-soluble samples have undergone reaction, separation (SPE) and/or fractionation processing, they may be injected into the chromatographic instruments manually or by means of autosamplers, any device that can automatically provide and/or retrieve samples to multiple containers in sequence or in parallel.
  • Some autosamplers are additionally adapted to receive and/or grasp and manipulate sample containers, such as well plates, trays or individual vials containing the samples to be injected.
  • sample containers such as well plates, trays or individual vials containing the samples to be injected.
  • metered aliquots may be withdrawn and injected into chromatographic instruments.
  • Autosamplers that operate on stationary, indexed, multi-well trays or racks of sample vials, such as Series 1100 HPLC Autosamplers manufactured by Agilent Technologies of Palo Alto, California, and the Agilent 220 Micro Plate Sampler, are in wide use. Alternatively functioning autosamplers are also well known in the art, including those configured for use with rotatable trays.
  • the present invention provides integrated structures that are preferably dimensioned or otherwise adapted for receipt and movement by liquid chromatographic (LC) and mass spectrophotometric (MS) autosampling equipment such as, for example, the Agilent instruments mentioned above.
  • the structures may be integrated within individual cartridges, for example, or within devices such as modified well plates.
  • the integrated structures each have at least one inlet and at least one outlet connected by an enclosed fluid pathway.
  • Each inlet and outlet is mateable with a respective fluid transport connector to form a pressure-tight fluid communicable connection.
  • the seal formed around the connection is able to withstand the fluid pressures typically encountered during autosampler injections and extractions while preventing air bubbles to penetrate the seal into the fluid pathway created, or the fluid being transported to escape the enclosed fluid pathway formed.
  • a stationary phase is disposed downstream from the inlet and upstream from the outlet such that a fluid injected through the inlet traverses the stationary phase prior to transport to the outlet.
  • the connections formed between the autosampler fluid transport connectors and the inlet and outlet enable a fluid to be processed through the stationary phase in a single step of simultaneous injection and extraction, a process that can be very accurately controlled (e.g., rates and volumes) through use of metered pumping mechanisms of the autosampler.
  • the enclosed fluid pathway formed also prevents fluids from flowing in directions or at times not intended due to, for example, gravity.
  • Suitable stationary phases for use in the fluid processing include reversed phase, normal phase, affinity, chiral, gel filtration, ion exchange, size exclusion, HILIC, digestion, absorbent, non-polar, polar, cation exchange, anion exchange, antibody, enzymatic and reactive media and the like.
  • Modified well plates incorporating one or more of the integrated structures may be used with well plate autosamplers having the ability to simultaneously engage multiple fluid transport connectors (such as fixed or movable syringes, probes or other types of injection and/or extraction components) with indexed positions (e.g., inlets, outlets and/or reservoirs) on the well plate.
  • fluid transport connectors such as fixed or movable syringes, probes or other types of injection and/or extraction components
  • indexed positions e.g., inlets, outlets and/or reservoirs
  • Engagement may be achieved by moving the syringes and/or the well plate via one or more robotic arms into engaged positions.
  • the well plate and syringes may engage at positions along the top surface of the well plate, or alternatively on multiple surfaces (e.g., top and bottom) of the well plate.
  • the well plate may be configured with numerous such integrated structures in an indexed array or network that may additionally include sample positions, waste reservoirs, wash reservoirs, fractionation reservoirs, fraction-pooling reservoirs, reaction reservoirs, and solvent reservoirs.
  • SPE solid phase extraction
  • the inventive structure may take the form of a stand-alone cartridge.
  • a cartridge may similarly be used with well plate autosamplers ⁇ e.g., where one or more cartridges are seated in a rack that is transported by the autosampler), but are preferably designed for use with standard autosamplers, wherein robotic fingers operate to grasp the cartridge and transport it into a position of alignment with the autosampler's fluid transport connectors for simultaneous engagement of the inlet(s) and outlet(s).
  • multiple fluid transport connectors of the autosampler simultaneously engage the inlet and outlet to form the enclosed fluid pathway for processing the fluid through the stationary phase within the cartridge.
  • the present invention provides an automated fluid processing system including a standard or well plate autosampler equipped with multiple fluid transport connectors that may be sealably engaged with the inlet and outlet of fluid processing devices such as described above.
  • a wide variety of automated fluid processing methods that employ injections and extractions of fluids (e.g., samples, solvents and waste) to and from the inventive structure are possible utilizing these devices.
  • a separation material may be conditioned, then a sample loaded onto/through the separation material, after which matrix and analyte fractions may be sequentially eluted from the separation material (and optionally reconstituted in a more aqueous solvent composition.)
  • liquid-soluble sample preparation processes that have been performed manually such as, for example, SPE pre-cleaning of complex chemical and biological samples, can be advantageously integrated into a standard analytical workflow with reproducible sample preparation conditions (i.e., precisely controlled flow rates, solvent volumes, and timing between sample preparation and chromatographic analysis.)
  • sample preparation conditions i.e., precisely controlled flow rates, solvent volumes, and timing between sample preparation and chromatographic analysis.
  • Driving the liquid-soluble sample flow through the integrated structures described herein with the metering piston of anautosampler, rather than by using a vacuum or gravity eliminates backpressure variations encountered in preexisting fluid processing cartridges or columns.
  • the precise timing also eliminates the possibility that the stationary phase will dry out and lead to irreversible absorption of analytes on the stationary phase.
  • FIGS. IA, IB are illustrations of a modified well plate in accordance with embodiments of the present invention.
  • Figures 2A,2B are illustrations of alternative embodiments of structures including and inlet in fluid communication with an outlet in accordance with the present invention
  • Figures 3A-3C are illustrations of alternative embodiments of inlet sealing mechanisms in accordance with the present invention
  • Figure 4A-4E are illustrations of layouts of well plates arranged in accordance with embodiments of the present invention.
  • Figure 5 is a cross-sectional view of a structure integrated within a well plate
  • Figures 6A-6E are sequential illustrations of a well plate in accordance with the present invention that exemplify an automated fluid process capable of being performed with devices in accordance with the present invention
  • Figures 7A-7F are illustrations of cartridge-type embodiments of devices for use in automated fluid processing in accordance with the invention.
  • well plate and "cartridge”, as used herein, are intended to have meanings more broad than their conventional meanings, wherein a conventional well plates might be understood to mean structures including arrays of independent wells, or wherein the meaning of the term cartridge might be limited to the conventional pipette-shaped bodies.
  • Cartridge embodiments of device 2 are preferably adapted for use with autosamplers equipped with robotic mechanisms (e.g., fingers) for grasping and transporting fluid containers such as, for example, sample vials, to positions whereby autosampler fluid connectors (e.g., needles 6', 6" and needle seats) may engage the device 2 so as to form an enclosed fluid pathway through the device 2.
  • robotic mechanisms e.g., fingers
  • autosampler fluid connectors e.g., needles 6', 6" and needle seats
  • autosamplers that operate on stationary, indexed, multi-well trays or racks of sample vials, such as Series 1100 HPLC Autosamplers manufactured by Agilent Technologies of Palo Alto, California, are in wide use.
  • Such autosamplers include a plurality of fluid transport connectors (i.e., needles 6', 6") for individually injecting fluid samples into an inlet 8 of a structure 10 integrated within the device 2.
  • fluid transport connectors i.e., needles 6', 6
  • references to "device 2" may be referred to as "plate 2" or “cartridge 2" depending upon the embodiment of device 2 being described, as many of the properties are similar.
  • the needles 6 ⁇ 6" that deliver and extract the liquid-soluble sample are transported on one or more robotic autosampler arms 4, each of which may be equipped with multiple needles for performing simultaneously multiple series of injections and extractions.
  • the autosampler preferably includes a processor for controlling the selection of sample(s) to be processed and the order of processing that is to be accomplished. The precision and reproducibility of such known automatic injection mechanisms is clearly superior to manual injection since variability of injection technique between operators is eliminated.
  • FIG. 2A illustrates a preferred embodiment of the structure 10 integrated within plate 2, which includes inlet 8 in fluid communication with an outlet 12 through a fluid pathway 14.
  • the inlet 8, outlet 12, and fluid pathway 14 are integrated in a unitary structure that may be formed as a unitary element or as multiple components securely (and preferably unalterably) connectable together.
  • At the top of the inlet 8 and outlet 12 are openings 16 through which autosampler needles 6A, 6B may respectively connect, in a relatively fluid- tight connection, to the inlet and outlet so as to form an enclosed fluid pathway through a corresponding inlet chamber 18 and outlet chamber 20 each defined in part by the inlet 8 and outlet 12.
  • the autosampler needles 6A,6B are illustrated as having different distances from plate 2, which is not a requirement of the invention (in fact, it may be preferable to arrange the needles such that they are equidistant from the plate.
  • a stationary phase 22 contained in the inlet chamber 18 serves to process the liquid-soluble sample injected via needle 6' into inlet chamber 18 as the sample traverses the stationary phase 22 as it flows along the fluid pathway 14 through the outlet chamber 20 to the outlet 12.
  • the phrase "stationary phase” includes any material that facilitates separations and/or reactions including, but not limited to, reversed phase, normal phase, affinity-based (for biological sample processing), chiral, size exclusion, HILIC, digestion media, reactive, ion-exchange, etc.
  • SPE solid phase extraction
  • Fluid pathway 14 may include a conduit 24, or a plurality of such channels, of any geometry but having sufficient cross-sectional area to permit fluid flow commensurate with the injection rate, connecting respective openings 26, 28 at or near the bottoms of inlet chamber 18 and outlet chamber 20.
  • fluid pathway is not necessarily limited to conduit connections at the bottoms of the respective chambers.
  • certain embodiments of structure 10 do not utilize conduits or distinct inlet and outlet chambers.
  • the injected fluid is required to traverse the stationary phase 22 along the fluid pathway 14 from the inlet 8 to the outlet 12.
  • FIGS 3 A-3C illustrate various non-limiting embodiments of inlet 8 of structure 10, which includes a sealing surface 30 at least partially conforming to the shape of the autosampler needle 6 A.
  • the sealing surface 30 and needle 6 A axially engage to form a pressure tight seal and an enclosed fluid pathway along which injected fluids will flow.
  • pressure tight means leak free up to about 10 bar (150 psi), and preferably pressures much higher (e.g., 100 to 200 bar.)
  • a metering pump of the autosampler provides tight control over the volume and flow rates of fluids injected through needle 6A.
  • Typical autosampler injection volumes are on the order of 0.2 to 100 ⁇ L, but may be lower or higher (e.g., up to about 3 mL.)
  • needles 6A, 6B have sufficiently wide inner diameters to transport volumes of conditioners, solvents and potentially viscous, complex chemical and biological (e.g., whole blood, urine, plasma, tissue, etc.) matrices involved in stationary phase (e.g., SPE) fluid processing. Simultaneously injecting and extracting fluids through the structure 10 provides highly precise and repeatable automated fluid processing..
  • inlet 8 comprises a rigid cap integrally-formed with the remainder of structure 10 or subsequently insertable, whose sealing surface 30 includes a tapered bore 32 substantially conforming to the shape of the tip 34 of needle 6A.
  • the cap may be a press fit component placed in the inlet chamber 18 before or after filling the chamber with the stationary phase material 22.
  • the bore 32 of the cap may be tapered to mate with the taper of needle tip 34, preferably in a conical shape having an inner diameter greater than the diameter 36 of the needle at the top of the bore but narrower than the needle diameter at the bottom of the bore.
  • inlet 8 A wide variety of alternative configurations of the inlet 8 are also possible, such as, for example: as shown in Figure 3B, wherein the bore 33 has no taper, or as shown in Figure 3 C, wherein the inlet 8 has a circular groove 37 into which the needle tip 34 may be seated.
  • the angle of the taper of the bore 32 that contacts the tip of needle 6A is preferably chosen so that self-locking will not occur and the needle will be retractable without damaging the structure 10, but which allows the fluid- tight seal to be formed with axial compression only.
  • Alternative sealing surface configurations may be utilized to mate with non-tapered needles or other autosampler connectors, such as needle seats, which are present on many autosamplers and typically are configured to receive autosampler needles transporting a volume of a liquid- soluble sample, but which, in preferred embodiments of a complete inventive system, are adapted to receive the outlet 12 of cartridge-type embodiments of the invention.
  • Outlet chamber 20 is partially defined by sealing surface 13 which preferably has a taper or conical shape arranged such that fluids (e.g., eluted fractions) can be more efficiently withdrawn by constraining the volume of processed fluid to a region where it is more easily extractable.
  • fluids e.g., eluted fractions
  • Alternative non ⁇ linear geometries that work on a similar principle(s) of picking up eluting fractions (and other fluids) with needles 6B shaped to reversibly mate with sealing surface 13.
  • Outlet chambers 20 having no taper (and no frit 42) may also be used, as the enclosed fluid pathway 14 from injector needle 6A to extractor needle 6B through structure 10 reduces the need for extraction-enhancing or backflow-preventing features.
  • Structure 10 may also include a blocking element preventing gravitational flow of fluids between the inlet chamber 18 and outlet chamber 20 that potentially could corrupt the fluid stationary phase processing.
  • Figure 7A shows a flap mechanism 40 disposed at the base of outlet chamber 20 that allows fluids to flow into the chamber 20 but blocks gravitational flow back out of the chamber. Flap mechanism 40 could also be disposed at some other position between the inlet chamber and outlet chamber. Reverse or gravitational flow may also be prevented by one or more frits 42 disposed in either or both of the inlet chamber 18 and/or outlet chamber 20 on either side of the stationary phase material 22. The frits 42 may exhibit hydrophobic properties and/or block fluid flows not driven by sufficient fluid pressure.
  • Hydrophobic properties may be inherent in the materials selected for forming the device, or may result from chemical treatment (e.g.. with silicone or TeflonTM.)
  • the stationary phase material is preferably retained by two porous discs of frits, and another frit is disposed in the outlet chamber to prevent gravitational backflow, but in simultaneous injection/extraction operation fluid flow is precisely controlled, thus reducing the need for backflow prevention.
  • FIG. 4A A top view of a well plate 2 in accordance with the present invention is illustrated in Figure 4A.
  • Well plate 2 is preferably formed of standard polymeric materials, such as polyethylene or polypropylene that are relatively rigid, resistive to wear, and having a low coefficient of friction. Plate 2 is shown configured to process 24 samples, however plate design choices could lead to a greater or fewer number of pairs 44A,44B of inlets 8 and outlets 12.
  • Plate 2 is additionally configured with a number of reservoirs 46, including reservoirs for waste 46-1, conditioner 46-2, wash/rinse fluid 46-3, solvent 46-4, and/or any other fluid 46-5 desired, such as, for example, for reaction processing steps.
  • a plate 2 could be configured with none, some or all of these reservoirs 46 as desired or required by the particular fluid processing being performed.
  • Well plates such as plate 2 are easily adopted into a standard, analytical workflow including analytical equipment with only minor modifications, thereby increase reproducibility of sample preparation, as all samples can be processed under precisely reproducible conditions (i.e., flow rates, defined solvent volumes, timing between sample preparation and chromatographic analysis, etc.)
  • draw volumes and draw rates should be matched to the sample to be processed and/or chamber sizes being utilized.
  • sample positions are not integrated in the embodiment of plate 2 shown in Figure 4A, samples can be drawn from a feeder plate or other sample source within the capability of the autosampler fluid transport mechanism.
  • the conditioner 46-2, wash 46-3 and elute 46-4 reservoirs each may have 16 ml volumes;up to 0.6 ml may be injected into each inlet 8 from each reservoir (injection volumes often are selected to be roughly three times (3X) the volume of stationary phase media utilized);the stationary phase (e.g., separation material) comprises 100-200 mg of C 18 , C 8 , SiOH, or similar media);the waste reservoir may hold a volume equal to the combined volumes of the three other reservoirs ( ⁇ 50ml); andthe autosampler needle wash can be accomplished in a conventional autosampler wash port.
  • the stationary phase e.g., separation material
  • Figure 5 illustrates a partial cross-sectional view of plate 2, which integrates inlet chamber 18/outlet chamber 20 and fluid pathway 14.
  • the fluid pathway 14, in this preferred embodiment, extends downward from a top surface 48 of plate 2 through the volume of the inlet chamber 18 containing the stationary phase 22.
  • Fluid pathway 14 may include a transfer channel 50 imprinted, ablated, or otherwise formed in a polypropylene base 52 of the plate 2. Both the frit 42 and inlet 8 may also be composed of polypropylene.
  • automated fluid processing such as, for example, SPE processing comprised of sequential absorption/desorption of analytes and matrix compounds on the separation medium (stationary phase 22) can be performed.
  • Figure 4B illustrates an alternative version of well plate 2.
  • This variant integrates indexed sample wells 46-6 on the plate that may be filled manually prior to initiating fluid processing, or which may be filled automatically by the autosampler, as many autosamplers have the capability to dispense fluids from cartridges or containers (not shown) separate from the well plates upon which they operate.
  • bar code 33 serves as a unique identifier of well plate 2 and each processed sample. Reading the bar code 33 with a bar code reader (not shown) would assist an operator in integrating the fluid processing into a standard analytical workflow by creating an electronic record of the processing conditions (e.g., the number of channels, etc.) utilized. Alternative identification means could be employed.
  • Certain autosamplers have the ability to uniquely identify well plates by detecting the relative positions of mechanical tabs present on the surface of well plates.
  • the unique identifier could also comprise some other form of identification (e.g., radiofrequency tag or magnetic label.)
  • the identifier facilitates compliance with governmental record-keeping requirements, such as Good Laboratory Practices (GLP's) and electronic recordkeeping requirements (e.g., "Part 11" FDA regulations.)
  • GLP's Good Laboratory Practices
  • electronic recordkeeping requirements e.g., "Part 11" FDA regulations.
  • At least one inlet 8 and one outlet 20 connected by a fluid pathway 14 are essential elements, but in certain embodiments multiple outlets 12-1, 12-2,12-3 (Figure 4C) and/or multiple inlets 8-1, 8-2, 8-3 ( Figure 4D.)
  • the layout of well plate 2 illustrated in Figure 4E is intended to demonstrate a few of the high number of possible inlet/outlet and/or reservoir arrangements, and that the geometries and volumes of the inlets, outlets, and/or reservoirs are not limited, except by the ability of the autosampler needle(s) to access positions on the plate.
  • FIG. 6A-6F an automated SPE processing method which utilizes the described apparatus in accordance with the invention will now be explained.
  • the process utilizes the well plate 2 and any conventional means for supplying a liquid-soluble sample in an autosampler environment such as, for example, a commercially-available sample plate 50 consisting of an indexed network of sample wells accessible by the autosampler needle(s).
  • samples could be dispensed automatically from a sample container other than sample plate 50, provided the autosampler has such a capability.
  • Each of the operations that follow is performed automatically by the autosampler controller that controls the movements and fluid flows in the autosampler needle.
  • Solvent and sample transfer between the different positions on plate 2A is ideally performed by an autosampler system suited for larger volume injections (e.g., the 1100 Series Autosampler with 900 ⁇ l upgrade from Agilent Technologies.)
  • an autosampler system suited for larger volume injections (e.g., the 1100 Series Autosampler with 900 ⁇ l upgrade from Agilent Technologies.)
  • a vast number of alternative steps could be envisioned by those of skill in the art depending on the sample size and required amounts of separation material and solvent needed, including, but not limited to: (a) repetitions of particular steps; (b) cleaning of the needle (or needles) used; and/or (c) extraction of waste from outlet 12 to waste reservoir 46-1 after (or contemporaneously in multi-needle autosamplers) each injection.
  • a solvent e.g., water or an organic solvent such as methanol or acetonitrile
  • buffers salts
  • pH definition e.g., a pH definition
  • the autosampler needle not shown
  • the SPE device 2A it is advantageous for the SPE device 2A to have a high capacity for retaining target compounds of a wide range of chromatographic polarities and to be capable of maintaining target compound retention as sample interferences are washed to waste.
  • a sample (including analytes and matrix) will be loaded onto the separation material, through pickup at sample position 50-1 and injection into inlet 8.
  • sample molecules or matrix molecules or sample molecules and matrix molecules will be absorbed by the separation material in the inlet chamber.
  • the matrix and the analyte molecules absorbed by the separation material will be sequentially eluted therefrom and retrieved from outlet 12 for possible immediate injection onto, for example, an HPLC column, or for reconstitution.
  • the robotic SPE system including the well plate 2 and the autosampler
  • wash from reservoirs 46-3 and/or 46-5
  • elute from elute reservoir 46-4
  • the eluted fraction, containing analytes can be reconstituted in a weaker or stronger solvent, using the standard autosampler functions. In many cases, a higher aqueous content of solvent will improve HPLC performance with large volume injections.
  • Sample focusing can be done either on the analytical column or on the fluid-handling devices described above.
  • FIGS 7A-7F illustrates other embodiments of structure 10, configured for use with an autosampler of a type well known in the art that operates by gripping and transporting a fluid container (e.g., a sample vial) into precise alignment with the autosampler needles 6A,6B' through use of robotics (arms and fingers). No teaching of such robotic means is deemed necessary as such means are presently well known in the field.
  • structure 10, rather than being embedded in a well plate, is integrated into a free-standing module or cartridge 2B.
  • Cartridge 2B preferably has an external geometry approximating that of a conventional autosampler vial for easier adoption by standard autosamplers.
  • Any exterior surface 60 of the cartridge 2 A may be grasped by the robotic fingers or arms of the autosampler, and the handling of the cartridge 2 may be further enhanced by providing a lip 62 or other feature on the exterior surface 60 of the cartridge that forms a defined juncture at which the cartridge 2B may be grasped.
  • the inlet chamber 18 and outlet chamber 20 are integrally formed (formed together or securely connected) with, and protrude upwardly from the surface of a base of plate 62.
  • Plate 62 can be sized to be not much larger than the base of the inlet and outlet chambers, or alternatively could be the size of a well plate and integrate numerous inlet/outlet structures (in which case robotic grasping fingers would be unnecessary, as automated fluid processing to operate much like the processing utilizing a modified well plate.)
  • Figure 7B illustrates an embodiment of cartridge 2C configured to be, although not necessarily required to be, transportable by some form of tray 64.
  • Lower portions of the inlet chamber 18 and outlet chamber 20 are dimensioned to allow stable seating into one or more wells 66A,66B in order that the tray 64 may be manipulated without spillage.
  • the conduit 24 connecting inlet chamber 18 and outlet chamber 20 is illustrated as bridging a well divider 68, however well divider 68 could have a groove (not shown) to accommodate the conduit 24 (and provide further mechanical stability.)
  • the cartridge embodiment also lends itself to many applications and/or configurations, certain of which are illustrated in Figures 7C-7F, which are meant only to convey general concepts of alternative designs.
  • Figure 7C is intended to illustrate, for example, the concept that a cartridge 2D may be formed having multiple inlets 8 A, 8B in fluid communication through a fluid pathway 14' with a single outlet 12 (or, not shown, multiple outlets in connected to a single inlet) Such configurations would require additional autosampler needles to for the enclosed fluid pathway necessary for effective simultaneous injection/extraction.
  • Figure 7D shows a slight variation upon this theme, wherein multiple stationary-phase-holding chambers 70A,70B are utilized to process the liquid-soluble sample through cartridge 2E.
  • Figures 7E and 7F illustrate single-chamber cartridges 2F and 2G, respectively, which contain one or more volumes of stationary phase material 22A, 22B separated and constrained by one or more frits 46.
  • cartridges 2G for example, shown in Figure 7F
  • certain embodiments of the well plates made in accordance with the present invention can be "stacked" to create a customized flow path and separation/processing arrangement.
  • two cartridges 2G containing distinct types of stationary phase materials 22 can be stacked together.
  • the permutations and possibilities are thus almost infinite. In such embodiments, however, there is a small void volume between each body.
  • Some embodiments constructed in accordance with the present invention may provide the ability to perform extremely accurate high or low volume separations, fractionations and/or reactions, and is amenable to analyses where the sample is limited and may include samples for genomic or proteomic assays.
  • the invention has been described with respect to various SPE embodiments, it should be realized this invention is also capable of a wide variety of further and other embodiments within the spirit and scope of the appended claims.

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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)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Extraction Or Liquid Replacement (AREA)

Abstract

L'invention concerne des procédés et un appareil réalisé par assemblage d'éléments destinés au traitement automatisé de liquides par l'utilisation de structures intégrées dans des plaques ou des cartouches pouvant être reçues dans des échantillonneurs automatiques. L'appareil comprend au moins une entrée et au moins une sortie, entre lesquelles un matériau de phase stationnaire est disposé. Un circuit de traitement des liquides fermé est formé par raccordement automatique d'un connecteur de transport des liquides d'un échantillonneur automatique, tel qu'une aiguille d'échantillonneur automatique, à chaque entrée et chaque sortie, et par injection simultanée d'un liquide à traiter dans la ou les entrées et extraction d'un liquide traité de la (des) sortie(s).
PCT/US2005/036633 2004-10-19 2005-10-12 Dispositifs de traitement de liquides equipes de multiples mecanismes d'etancheite, et procedes automatises d'exploitation des dispositifs WO2006044441A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10/968,296 2004-10-19
US10/968,296 US7563410B2 (en) 2004-10-19 2004-10-19 Solid phase extraction apparatus and method
US11/184,170 2005-07-19
US11/184,170 US20060083663A1 (en) 2004-10-19 2005-07-19 Fluid processing devices with multiple sealing mechanisms and automated methods of use thereof

Publications (2)

Publication Number Publication Date
WO2006044441A2 true WO2006044441A2 (fr) 2006-04-27
WO2006044441A3 WO2006044441A3 (fr) 2007-02-01

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016097429A1 (fr) * 2014-12-18 2016-06-23 Ikerlan, S. Coop. Dispositif jetable approprié pour la réalisation simultanée d'une pluralité d'expériences biologiques dans des échantillons fluidiques
CN109187088A (zh) * 2018-11-07 2019-01-11 青海盐湖工业股份有限公司 一种在线液体取样器
US11608484B2 (en) 2016-01-29 2023-03-21 Eppendorf Ag Single-use connection device

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5702672A (en) * 1992-10-08 1997-12-30 Warner-Lambert Company Apparatus and method for multiple simultaneous synthesis

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5702672A (en) * 1992-10-08 1997-12-30 Warner-Lambert Company Apparatus and method for multiple simultaneous synthesis

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016097429A1 (fr) * 2014-12-18 2016-06-23 Ikerlan, S. Coop. Dispositif jetable approprié pour la réalisation simultanée d'une pluralité d'expériences biologiques dans des échantillons fluidiques
US11608484B2 (en) 2016-01-29 2023-03-21 Eppendorf Ag Single-use connection device
CN109187088A (zh) * 2018-11-07 2019-01-11 青海盐湖工业股份有限公司 一种在线液体取样器

Also Published As

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