EP1365855A2 - Sonde de transduction ultrasonique avec capacite d'ecoulement continu du liquide et station de travail et procedes d'utilisation correspondants - Google Patents

Sonde de transduction ultrasonique avec capacite d'ecoulement continu du liquide et station de travail et procedes d'utilisation correspondants

Info

Publication number
EP1365855A2
EP1365855A2 EP01273634A EP01273634A EP1365855A2 EP 1365855 A2 EP1365855 A2 EP 1365855A2 EP 01273634 A EP01273634 A EP 01273634A EP 01273634 A EP01273634 A EP 01273634A EP 1365855 A2 EP1365855 A2 EP 1365855A2
Authority
EP
European Patent Office
Prior art keywords
probe
assembly
probe member
bore
internal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP01273634A
Other languages
German (de)
English (en)
Inventor
Vaughn A.; c/o GlaxoSmithKline AUDAIN
Charles A.; c/o GlaxoSmithKline BUCKNER
Hendrick M.; c/o University of Virginia GEYSEN
James R.; c/o GlaxoSmithKline ORMAND
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Glaxo Group Ltd
Original Assignee
Glaxo Group Ltd
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 Glaxo Group Ltd filed Critical Glaxo Group Ltd
Publication of EP1365855A2 publication Critical patent/EP1365855A2/fr
Withdrawn legal-status Critical Current

Links

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
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/23—Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
    • 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
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00534—Mixing by a special element, e.g. stirrer
    • G01N2035/00554—Mixing by a special element, e.g. stirrer using ultrasound
    • 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
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N2035/1025—Fluid level sensing
    • 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
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1058—General features of the devices using the transfer device for another function for mixing
    • 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
    • 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
    • G01N35/0099—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators

Definitions

  • the present invention generally relates to an ultrasonic probe adapted for use with an automated workstation, and methods for using the probe in liquid handling and analytical processes.
  • the present invention relates to an ultrasonic probe having liquid flow-through properties which is adapted to cooperate with a programmable robotic arm.
  • the researcher may prepare as many as fifty plates at a time. To ensure that the solids deposited in the well are completely dissolved, it is often required that the entire microtitre plate be ultrasonically excited for a period of time after the addition of solvent. Unfortunately, this process of gross or bulk sonication of the entire plate requires a large power output and tends to raise the temperature of both the plate and its contents. As a result, gross sonication bears an unacceptable risk that the compounds become damaged or chemically altered to a degree such that the compounds are rendered useless or the ensuing analytical tasks become unverifiable or inaccurate. Also, the power delivered to each individual well may differ when the bulk sonication approach is employed, resulting in non-uniform heating of the samples. Moreover, the ratio of solvent to compound must be kept high to prevent precipitation, which can lead to less accurate analytical results.
  • the present invention generally provides a hollow probe which cooperates with an ultrasonic transducing device designed with liquid flow-through capability.
  • the probe and transducing device are combined into a probe assembly which is advantageously adapted to be integrated into an automated liquid handling or sampling apparatus or workstation.
  • the probe can be connected to and manipulated by a robotic arm of the workstation, and thus programmed to move in three-dimensional space to and from various locations of the sampling apparatus.
  • the probe can be inserted into the individual wells or test tubes of a plate or rack utilized to contain sample substances.
  • the probe can be used to conduct a variety of liquid handling tasks and additionally can be used to ultrasonically excite sample substances contained in the individual wells of the plate, thereby improving dilution of such sample substances and increasing throughput of any given sample preparation procedure.
  • an apparatus for use as part of a fluid handling system and is adapted for selectively ultrasonically exciting drug, compound or chemical containing samples provided in the form of liquids, suspensions, wetted compounds, solutions or emulsions.
  • the apparatus comprises a movable robotic assembly and an ultrasonic transducer probe assembly attached to the robotic assembly.
  • the probe assembly includes an ultrasonic transducer body defining an internal fluid conduit and an elongate hollow probe member defining an internal bore.
  • the probe member is disposed in mechanical communication with the transducer body to enable vibratory energy to be transferred from the transducer body to the probe member.
  • the probe assembly includes a housing attached to the robotic assembly, and the transducer body is disposed in the housing.
  • the probe member has a sharpened tip adapted to puncture a closure provided with a substance container.
  • an apparatus has liquid flow-through capability and is adapted to sonicate a drug, compound or chemical containing substance, and is further adapted to detect the level of the substance in a container.
  • the apparatus comprises an ultrasonic transducer probe assembly and a liquid level detection device electrically connected to the probe assembly.
  • the ultrasonic transducer probe assembly includes an ultrasonic transducer body defining an internal fluid conduit and an elongate hollow probe member defining an internal bore.
  • the probe member is disposed in mechanical communication with the transducer body to enable vibratory energy to be transferred from the transducer body to the probe member.
  • the internal bore fluidiy communicates with the internal conduit and terminates at an orifice defined by the probe member.
  • a fluid handling workstation is provided, and is adapted to perform sonication tasks in individual wells of well-containing plates.
  • the workstation comprises a workstation frame including a lateral track; a robotic assembly movable along the lateral track; and an ultrasonic transducer probe assembly attached to the robotic assembly.
  • the probe assembly includes an ultrasonic transducer body defining an internal fluid conduit and an elongate hollow probe member defining an internal bore.
  • the probe member is disposed in mechanical communication with the transducer body to enable vibratory energy to be transferred from the transducer body to the probe member.
  • the internal bore of the probe member fluidiy communicates with the internal conduit of the transducer body, and terminates at an orifice defined by the probe member.
  • the robotic assembly includes a vertical arm defining a vertical track and a horizontal arm defining a horizontal track.
  • the probe assembly engages the vertical arm and is movable along the vertical track
  • the vertical arm engages the horizontal arm and is movable along the horizontal track
  • the horizontal arm is movable along the lateral track of the workstation frame.
  • the workstation comprises an injection port accessible by the probe member.
  • the injection port includes an annular sealing member adapted to receive the probe member therethrough and an injection bore adapted to receive the probe member therein.
  • the workstation comprises a rinse station accessible by the probe member.
  • the rinse station includes a main body and an adapter fitting attached to the main body.
  • the main body defines a rinsing bore adapted to receive the probe member therein.
  • the adapter fitting has an aperture fluidiy communicating with the rinsing bore and is adapted to receive the probe member therethrough. The aperture is sized to ensure that the probe member does not contact the main body when inserted into the rinsing bore.
  • the probe assembly and/or workstation provided in accordance with the present invention can operate in conjunction with a number of other devices or instruments employed in liquid handling and sample preparation tasks.
  • Such devices and instruments include, without limitation, a dilution device, a syringe pump, chromatography apparatus, and the like.
  • the present invention also provides a process for preparing drug, compound or chemical containing fluid samples for subsequent analysis.
  • An automated support assembly and an ultrasonic transducer probe assembly are provided.
  • the ultrasonic transducer probe assembly is attached to the support assembly, and includes an ultrasonic transducer body defining an internal fluid conduit and an elongate hollow probe member defining an internal bore.
  • the probe member is disposed in mechanical communication with the transducer body to enable vibratory energy to be transferred from the transducer body to the probe member.
  • the internal bore fluidiy communicates with the internal conduit and terminates at an orifice defined at a tip of the probe member.
  • a plate including a plurality of wells is provided. One or more of the wells contain a drug, compound or chemical substance.
  • the support assembly transports the probe assembly to the plate and lowers the probe member into a selected one of the wells of the plate.
  • the sample substance is at least partially diluted by causing a volume of solvent to flow through the internal fluid conduit of the ultrasonic transducer body of the probe assembly, through the internal bore of the probe member, out from the orifice of the probe member, and into the selected well of the plate.
  • the sample substance is diluted by activating the probe assembly to transfer vibratory energy to the sample substance from the tip of the probe member.
  • the addition of solvent and sonication of sample substance can be repeated for each well of the plate, and well as for any other plates provided.
  • a quantity of sonicated sample substance can be withdrawn from the well into the probe member, so that this quantity can be transported to another location such as an injection port, a rinse station, or another plate.
  • the present invention also provides a sonicated sample substance prepared in accordance with the above-disclosed process.
  • the present invention further provides a sonicated organic tissue sample prepared in accordance with the above-disclosed process.
  • Figure 1 is a perspective view of an automated liquid handling apparatus in which an ultrasonic transducing probe and related components have been integrated in accordance with the present invention
  • Figure 2 is another perspective view of the liquid handling apparatus illustrated in Figure 1 wherein the plates have been removed for clarity of description;
  • Figure 3 is a perspective view of an ultrasonic transducing probe assembly mounted to a robotic arm of the liquid handling apparatus illustrated in Figure 1 ;
  • Figure 4 is a perspective, partially cutaway view of an adapter housing in which an ultrasonic transducing probe is mounted in accordance with the present invention;
  • FIG 5 is an exploded view of the ultrasonic transducing probe assembly illustrated in Figure 3;
  • Figure 6 is a cutaway view of the ultrasonic transducing probe provided in accordance with the present invention
  • Figure 6A is a cutaway view of an alternative ultrasonic transducing probe provided in accordance with the present invention.
  • Figure 7 is a partially cutaway view of the ultrasonic transducing probe inserted into an injection port in accordance with the present invention.
  • Figure 8 is an exploded view of the ultrasonic transducing probe and injection port illustrated in Figure 7;
  • Figure 9 is an exploded, cutaway view of the injection port illustrated in Figure 7;
  • Figure 10 is a cutaway view of the ultrasonic transducing probe inserted into a rinse station port in accordance with the present invention.
  • FIG 11 is a schematic view of the ultrasonic transducing probe operating in conjunction with a liquid level detection device in accordance with the present invention.
  • sampling apparatus 10 can be a modified version of a commercially available GILSONTM apparatus, of which various models are available from Gilson Medical Electronics, Inc.
  • GILSONTM Model No. 215 platform has been found to be suitable in the practice of the present invention.
  • Other apparatuses or platforms which could be adapted to operate in conjunction with the present invention include ZYMARKTM and PACKARDTM models.
  • sampling apparatus 10 provided in accordance with the present invention can be constructed from fully original components.
  • the apparatus depicted in Figures 1 and 2 is intended herein to represent either a fully original embodiment or a commercially available platform modified or adapted in accordance with the present invention.
  • Sampling apparatus 10 is generally used for sample preparation, and is capable of being programmed by means of written software to perform a wide variety of liquid handling and preparation tasks.
  • sampling apparatus 10 can be equipped with an electrical input/output interface (not shown) to enable communication with a suitable liquid or gas chromatography analysis device if desired.
  • Sampling apparatus 10 ordinarily includes a dilution module, generally designated 12, which controls the movement of liquid within various points of sampling apparatus 10.
  • a valve 14 is mounted to dilution module 12, and a syringe 16 depends therefrom.
  • a movable boundary is disposed within syringe 16 and is actuated by a stepper motor and associated drive unit (not shown) to provide both aspiration and positive pressure to the various fluid conduits associated with sampling apparatus 10.
  • the actuation may be programmed into sampling apparatus 10.
  • a length of solvent inlet tubing 18, preferably formed of PTFE, is connected to valve 14 to supply rinse solvent to sampling apparatus 10 from a solvent reservoir 20.
  • solvents commonly used include methanol, ethanol, water, acetonitrile, acetone, isopropanol, hexane, diethyl ether, and toluene.
  • Sampling apparatus 10 generally includes a main frame 22.
  • a plate holder 24 is attached to main frame 22 and includes a series of adapter plates 26.
  • a plurality of plates 28 may be mounted on plate holder 24 by means of alignment with adapter plates 26.
  • Each plate 28 includes an array of wells for containing reagents, compounds, samples of liquid substances, and the like, or includes holes for holding vials, test tubes or other vessels of differing sizes for this purpose.
  • Robotic assembly 40 includes a horizontal arm 42 and a vertical arm 44.
  • Horizontal arm 42 is slidably carried on a track 46 mounted within main frame 22.
  • An additional track 48 is formed on horizontal arm 42, in which vertical arm 44 is slidably carried.
  • One or more stepper motors and associated drives (not shown) disposed within main frame 22, or on vertical arm 44 as in the case of motor 50, provide actuation for robotic assembly 40 along a three-axis coordinate system. As in the case of dilution module 12, this actuation may be controlled by software interfacing with sampling apparatus 10.
  • a sampling needle (not shown) would be movably mounted to a vertically disposed track 49 of vertical arm 44 and employed to load and extract liquid substances to and from different positions over and proximate to plates 28 shown in Figure 1.
  • a length of transfer tubing 54 (see Figure 1), preferably formed of PTFE, would provide fluid communication between this sampling needle and valve 14 of dilution module 12.
  • an ultrasonic transducing probe assembly generally designated 80, equipped with a probe 82 having liquid flow-through capability has been substituted in the place of a conventional sampling needle.
  • probe 82 may be programmed to accomplish not only sonication tasks, but also chromatography injection, and a variety of liquid handling and sample preparation tasks such as transferring solvent to vials and/or wells disposed in plates 28 and transferring liquid substances from one vial or well to another vial or well.
  • a remote keypad or computer 60 may be connected to sampling apparatus 10 via a ribbon cable 62 and used for entering instructions into memory, recalling previously written programs, and otherwise controlling the operation of sampling apparatus 10, including robotic assembly 40 and ultrasonic probe assembly 80.
  • Sampling apparatus 10 also includes an injection port, generally designated 120, which is accessible by probe 82. Injection port 120 fluidiy communicates with an injection valve 122, and is used to deliver samples to a high-pressure liquid chromatography (HPLC) device or gas chromatography device (not shown) if desired.
  • Sampling apparatus 10 further includes a rinsing station, generally designated 140, which may be used for eliminating waste products and purging the fluid paths of sampling apparatus 10 between the operative steps of an intended procedure.
  • Rinsing station 140 includes a trough or a cup 142, which is also accessible by probe 82, and a drain tube 144 (see Figure 2).
  • Probe assembly 80 includes a ultrasonic converter body or handpiece 84, such as a MISONIXTM handpiece commercially available from Misonix Inc. of Farmingdale, New York, as Part No. 2325.
  • Converter body 84 has a flow-through design, and accordingly includes an internal passage (not shown) to enable fluid to flow from transfer tubing 54, through a tubing adapter 86 and a top fitting 88, through converter body 84, and finally to probe 82.
  • a suitable probe 82 is also available from Misonix Inc. as Part No. 1825.
  • the body of probe includes a neck section 82A to which top fitting 88 is secured such as by threading.
  • the outside diameter of probe 82 is reduced over one or more tapered sections.
  • the outside diameter of a distal section 82B is small enough to permit probe 82 to be inserted into the wells of a standard-sized plate 28.
  • Probe 82 has a hollow interior bore 92 terminating at a distal orifice 94 defined at a tip 82C of probe 82.
  • Hollow interior bore 92 includes a reduced-diameter section within distal section 82B of probe 82.
  • orifice 94 has a 0.6 mm diameter.
  • Probe 82 serves as an elongate horn member which transfers sonic energy to probe tip 82C.
  • a fluid such as a solvent
  • probe assembly 80 has been designed so as not to leak under operating back pressures of up to approximately 120 psi, which makes probe assembly 80 suitable for use in conjunction with liquid chromatographic injection.
  • Probe tip 82C in Figure 6A has been cut, either arcuately or at an angle such as 30E, so as to present a sharpened edge.
  • the sharpened edge is useful in the case where a substance container such as a vial or test tube includes a closure such as a septum. The sharpened edge facilitates the penetration or puncturing of the septum by probe 82.
  • converter body 84 fits into a probe assembly adapter or housing 102 and is protected by a removable front cover 104.
  • Probe assembly adapter or housing 102 is preferably constructed from machined aluminum, and is shaped to accommodate converter body 84 as well as tubing adapter 86 and fitting 88.
  • an elongate chamber 102A can be formed to accommodate converter body 84, and an upper chamber 102B formed to accommodate tubing adapter 86 and fitting 88.
  • a slot 102C is formed on probe assembly adapter 102 to accommodate fluid transfer tubing 54 (see Figure 1) and an electrical control cable 104 to pass therethrough.
  • Control cable 104 is attached between converter body 84 and a remote generator device or base station 106 so that base station 106 (see Figure 1) can provide electrical power to converter body 84 and thus drive the vibratory action.
  • Another cable (not shown) can be run between base station 106 and computer 60 or other electronic device (see Figure 1 ) to turn probe assembly 80 ON and OFF.
  • Converter body 84 can be secured within probe assembly adapter 102 such as by threading a screw (not shown) into an aperture 102D of probe assembly adapter 102.
  • probe assembly adapter 102 is adapted to fit onto vertical arm 44 of robotic assembly 40 in the place of a standard sampling needle, using the same mounting boss and screws 108.
  • injection port 120 is illustrated in more detail.
  • Injection port 120 is designed to receive probe 82 and enable probe 82 to inject sample media without leakage.
  • Injection port 120 includes an upper body 124, a lower body 126, a collar 128, and a TEFLON 7 seal 130.
  • Upper and lower bodies 124 and 126 may be secured together by providing mating threads on upper and lower bodies 124 and 126 and on collar 128.
  • Upper body 124 has a tapering inside surface 124A (see Figure 9) to accommodate probe 82.
  • Lower body 126 includes an internal flow-through bore 126A with which tip 82C of probe 82 makes contact. As shown in Figure 7, tip 82C and internal bore 126A preferably have complementary tapered or chamfered surfaces to improve their contact.
  • An internal volume 126B of lower body 126 defines a sealing region into which seal 130 is installed. Seal 130 is generally interposed between upper and lower bodies 124 and 126 in coaxial relation to distal section 82B of probe 82, thereby filling the space of the sealing region and establishing a good seal between probe 82 and injection port 120.
  • Rinsing station 140 includes a main body 146 and an annular adapter fitting 148 attached to main body 146 generally above cup 142.
  • Main body 146 includes a rinsing bore 152 having an open end 152A communicating with an aperture 148A of fitting 148 and a closed end 152B terminating at a point within main body 146.
  • Rinsing bore 152 may be tapered to accommodate probe 82.
  • the diameter of aperture 148A is sized relative to rinsing bore 152 such that when probe 82 is inserted through aperture 148A into rinsing bore 152, the outer surfaces of probe 82 are close to but not touching rinsing bore 152.
  • Rinsing station 140 is thus designed to receive probe 82 therein so that cleaning solvent can be aspirated through probe 82 and its orifice 94, and conducted through rinsing bore 152 so that both the inner and outer surfaces of probe 82 are contacted by the cleaning solvent and cleaned thereby.
  • Plates 28 such as microtitre plates containing samples of dry compound in one or more wells (or, alternately, racks supporting a plurality of test tubes, vials or other substance containers) are placed into plate holder 24.
  • the respective labels or identifications of the compounds, their coordinate positions in 96-well plate 28, their respective masses, and the positions of plates 28 in plate holder 24 can be inputted into computer 60 as part of the programming of tasks to be performed by robotic assembly 40 and dilution module 12.
  • robotic assembly 40 may be desired to initially cause robotic assembly 40 to transport probe assembly 80 to rinse station 140 and insert probe 82 therein, and to cause dilution module 12 to draw a volume of rinse solvent from reservoir 20 and pump the solvent through probe 82 in order to flush the fluid lines and pre-clean probe 82.
  • robotic assembly 40 transports probe assembly 80 to the wells of one or more plates 28, lowers probe 82 into individual wells, and dispenses a controlled amount of solvent or other fluid through probe 82 into each well.
  • sampling apparatus 10 may be programmed to mix two or more different types of solvents in a given well in order to create binary, tertiary, quaternary, etc. solvent systems. If a closure such as a septum exists, probe 82 is capable of puncturing such a barrier.
  • probe 82 Prior to sonication, residual solvent can be removed from probe 82 by drawing air in order to prevent excessive or unwanted dilution of a sample.
  • probe 82 is then caused to make contact with the wetted substance contained therein, and probe assembly 80 is activated to transfer vibrational energy to tip 94 of probe 82 and thereby sonicate the substance for a predetermined period of time (e.g., a few seconds).
  • the primary function of the sonication process in the exemplary embodiment is to effect complete dissolution of the dry compound contained in a given well.
  • vibrating probe 82 could be operated long enough to deliberately cause a rise in sample temperature.
  • probe 82 is further employed to aspirate a predetermined quantity of sample of the dissolved compound.
  • Robotic assembly 40 can then transport probe assembly 80 to a variety of locations of sampling apparatus 10, depending on the particular procedure being undertaken. For instance, probe assembly 80 can move to another plate 28 containing wells or holding test tubes, and the aspirated sample can be dispensed through probe tip 94 into the wells or test tubes as part of some analytical or combinatorial process.
  • probe assembly 80 can move to injection port 120 and probe 82 inserted therein as shown in Figure 7, and the aspirated sample can then be provided for analysis in a liquid chromatograph, for example. It is possible to provide more than one chromatograph, such that multiple analyses can occur simultaneously to thereby increase throughput.
  • probe assembly 80 can be moved to rinse station 140 and probe 82 installed therein as shown in Figure 10, so that probe 82 can be cleaned to prevent cross- contamination.
  • Sampling apparatus 10 can be programmed to execute one or more of the above-described process steps for each well of one or more plates 28 in a repeatable, cyclical process.
  • plates 28 could be constructed from a translucent or transparent material such as quartz, to enable the examination of optical and spectral properties of the substances residing in each well.
  • Sample substances could be initially provided in a quartz microtitre plate, or probe assembly 80 could be employed to transport samples to the quartz plate from another type of plate.
  • tissue samples can be homogenized in preparation for RNA extraction.
  • tissue samples are added to the wells of plate 28 or to individual containers such as EPPENDORFJ tubes held in a suitable plate 28.
  • plate 28 is provided in the form of a rack adapted to hold such tubes.
  • the sonication carried out by probe 82 generally occurs over a period longer than a few seconds, for example approximately 30 to 60 seconds, in order to adequately break up and dissolve the tissue sample.
  • Probe 82 is then used to aspirate and deliver a predetermined quantity of the dissolved tissue sample to another container for further processing. This other container may be mounted at sampling apparatus 10.
  • a liquid level detection task can be made a part of the various processes involving the use of probe 82.
  • a liquid level detection device 200 such as a conventional capacitive-type transducer, is electrically coupled to probe assembly 80 such as at converter body 84.
  • Liquid level detection device 200 is also connected to some type of readout or display 204, which may be part of an electronic device separate from or integrated into sampling apparatus 10 of Figures 1 and 2.
  • An ON/OFF switch 208 can be provided on control cable 104 to isolate the operation of liquid level detection device 200 and thereby ensure its accuracy.
  • Liquid level detection device 200 correlates the level of solution or suspension in container 206 to a sensed measurement of capacitance, and readout 204 displays an indication of that level.

Abstract

L'invention porte sur une sonde creuse qui coopère avec un transducteur ultrasonique à capacité d'écoulement continu du liquide. La sonde et le transducteur sont combinés de façon à former un ensemble qui peut être intégré dans une station de travail automatisée de traitement du liquide. En tant que composant fonctionnel de la station de travail, la sonde peut être raccordée à un bras robotique et manipulée par celui-ci, et être ainsi programmée pour se déplacer dans un espace tridimensionnel vers et à partir de différents points de l'échantillonneur. La sonde peut être notamment insérée dans les puits ou tubes de test individuels d'une plaque ou panier utilisé pour y placer les substances d'échantillons. La sonde peut être utilisée pour acheminer une variété de tâches de traitement du liquide et également pour exciter par ultrasons des substances d'échantillons et augmenter le rendement de toute procédure donnée d'opération d'échantillons. Le dispositif de détection du niveau du liquide peut être raccordé à l'ensemble sonde.
EP01273634A 2000-11-09 2001-11-05 Sonde de transduction ultrasonique avec capacite d'ecoulement continu du liquide et station de travail et procedes d'utilisation correspondants Withdrawn EP1365855A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US24757200P 2000-11-09 2000-11-09
US247572P 2000-11-09
PCT/US2001/044451 WO2002079751A2 (fr) 2000-11-09 2001-11-05 Sonde de transduction ultrasonique avec capacite d'ecoulement continu du liquide et station de travail et procedes d'utilisation correspondants

Publications (1)

Publication Number Publication Date
EP1365855A2 true EP1365855A2 (fr) 2003-12-03

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EP01273634A Withdrawn EP1365855A2 (fr) 2000-11-09 2001-11-05 Sonde de transduction ultrasonique avec capacite d'ecoulement continu du liquide et station de travail et procedes d'utilisation correspondants

Country Status (3)

Country Link
EP (1) EP1365855A2 (fr)
AU (1) AU2001297745A1 (fr)
WO (1) WO2002079751A2 (fr)

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GB201000527D0 (en) 2010-01-13 2010-03-03 Pera Innovation Ltd Sonication apparatus and method
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