Abstract:
A hollow probe cooperates with an ultrasonic transducing device designed with liquid flow-through capability. The probe and transducing device are combined into a probe assembly, which can be integrated into an automated liquid handling workstation. As a functional component of the 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. In particular, 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. A liquid level detection device can be connected to the probe assembly.

Description:
TECHNICAL FIELD  
         [0001]    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. In particular, the present invention relates to an ultrasonic probe having liquid flow-through properties which is adapted to cooperate with a programmable robotic arm.  
         BACKGROUND ART  
         [0002]    As part of many compound generation and screening processes, small quantities of compound, in the form of powder or particles, are often deposited onto the well surfaces of plates such as microtitre and deep-well plates. Modern processes usually require the use of 96-well plates and are carried out in an automated manner at a workstation having robotic liquid-handling capabilities. The deposited solids often must be dissolved in preparation of a further task such as liquid chromatography analysis. In a time-consuming process, exact portions of solvent are added to each well of a microtitre plate. Each plate is then sealed to prevent evaporation, although it has been observed by those skilled in the art that evaporation is still a problem which can reduce the accuracy of analytical results. In order to successfully implement a high-throughput screening process, 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.  
           [0003]    Another approach toward ensuring complete dissolution has been to manually agitate the plate. The disadvantages of this approach, including the time, imprecision and human effort required, are readily acknowledged by those skilled in the art.  
           [0004]    Accordingly, those skilled in the art will appreciate the need for an apparatus which reduces the amount of time required to dissolve solid-phase compound samples in wells, reduces the amount of solvent evaporation, permits a higher concentration of compound within wells, enables sonic excitation to be effected in the individual wells of a plate, enables sonication to be performed at a lower power level, and enables individual analyte samples to be aspirated immediately after dissolution. Such an apparatus would advantageously result in relatively little sample temperature rise, increased automation of the screening or liquid handling process, elimination of compound damage, and would therefore yield a more accurate and repeatable analysis. The present invention, as described hereinafter in the context of exemplary embodiments and processes, is provided to meet these needs.  
         DISCLOSURE OF THE INVENTION  
         [0005]    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. As a functional component of the 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. In particular, the probe can be inserted into the individual wells or test tubes of a plate or rack utilized to contain sample substances. By the design of the present invention, 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.  
           [0006]    According to one aspect of the present invention, an apparatus is provided 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 internal bore of the probe member fluidly communicates with the internal conduit of the transducer body, and terminates at an orifice defined by the probe member.  
           [0007]    According to another aspect of the present invention, the probe assembly includes a housing attached to the robotic assembly, and the transducer body is disposed in the housing.  
           [0008]    According to an additional aspect of the present invention, the probe member has a sharpened tip adapted to puncture a closure provided with a substance container.  
           [0009]    According to a further aspect of the present invention, 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 fluidly communicates with the internal conduit and terminates at an orifice defined by the probe member.  
           [0010]    According to yet another aspect of the present invention, 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 fluidly communicates with the internal conduit of the transducer body, and terminates at an orifice defined by the probe member.  
           [0011]    According to still another aspect of the present invention, 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, and the horizontal arm is movable along the lateral track of the workstation frame.  
           [0012]    According to a further aspect of the present invention, 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 sealing member is disposed in an internal sealing region defined by the injection port.  
           [0013]    According to a still further aspect of the present invention, 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 fluidly 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.  
           [0014]    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.  
           [0015]    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 fluidly 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. Moreover, 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.  
           [0016]    The present invention also provides a sonicated sample substance prepared in accordance with the above-disclosed process.  
           [0017]    The present invention further provides a sonicated organic tissue sample prepared in accordance with the above-disclosed process.  
           [0018]    It is therefore an object of the present invention to provide an ultrasonic transducer device in which a probe can transmit vibratory energy to a substance to improve dissolution thereof, as well as aspirate and dispense the substance.  
           [0019]    It is also an object of the present invention to provide an ultrasonic transducer device adapted to transport solvent to a sample substance, especially a substance contained in a well of a plate, sonicate the substance, and then immediately aspirate the substance from the well if desired.  
           [0020]    It is another object of the present invention to provide an automated liquid handling workstation which includes the novel ultrasonic transducer device instead of a more conventional sampling needle.  
           [0021]    It is yet another object of the present invention to provide a rinse station for a liquid handling apparatus which is adapted to receive the novel ultrasonic transducer device.  
           [0022]    It is still another object of the present invention to provide an injection port, especially of the type employed in conjunction with chromatography equipment, which is adapted to receive the novel ultrasonic transducer device.  
           [0023]    It is a further object of the present invention to provide a process for preparing sample substances using the novel ultrasonic transducer device.  
           [0024]    Some of the objects of the invention having been stated hereinabove, other objects will become evident as the description proceeds, when taken in connection with the accompanying drawings as best described hereinbelow.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0025]    [0025]FIG. 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;  
         [0026]    [0026]FIG. 2 is another perspective view of the liquid handling apparatus illustrated in FIG. 1 wherein the plates have been removed for clarity of description;  
         [0027]    [0027]FIG. 3 is a perspective view of an ultrasonic transducing probe assembly mounted to a robotic arm of the liquid handling apparatus illustrated in FIG. 1;  
         [0028]    [0028]FIG. 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;  
         [0029]    [0029]FIG. 5 is an exploded view of the ultrasonic transducing probe assembly illustrated in FIG. 3;  
         [0030]    [0030]FIG. 6 is a cutaway view of the ultrasonic transducing probe provided in accordance with the present invention;  
         [0031]    [0031]FIG. 6A is a cutaway view of an alternative ultrasonic transducing probe provided in accordance with the present invention;  
         [0032]    [0032]FIG. 7 is a partially cutaway view of the ultrasonic transducing probe inserted into an injection port in accordance with the present invention;  
         [0033]    [0033]FIG. 8 is an exploded view of the ultrasonic transducing probe and injection port illustrated in FIG. 7;  
         [0034]    [0034]FIG. 9 is an exploded, cutaway view of the injection port illustrated in FIG. 7;  
         [0035]    [0035]FIG. 10 is a cutaway view of the ultrasonic transducing probe inserted into a rinse station port in accordance with the present invention; and  
         [0036]    [0036]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.  
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0037]    Referring now to FIGS. 1 and 2, an automated liquid handling or sampling apparatus, generally designated  10 , is illustrated in accordance with the present invention. In the exemplary, inventive embodiment illustrated herein, sampling apparatus  10  can be a modified version of a commercially available GILSON™ apparatus, of which various models are available from Gilson Medical Electronics, Inc. For example, a GILSON™ 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 ZYMARK™ and PACKARD™ models. It will be understood, however, that automated sampling apparatus  10  provided in accordance with the present invention can be constructed from fully original components. Thus, the apparatus depicted in FIGS. 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. For example, 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.  
         [0038]    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. As is well known in the art, 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 . Examples of solvents commonly used include methanol, ethanol, water, acetonitrile, acetone, isopropanol, hexane, diethyl ether, and toluene.  
         [0039]    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 . As shown in FIG. 1, a plurality of plates  28  may be mounted on plate holder  24  by means of alignment with adapter plates  26 . A wide variety of plates  28 , such as microtitre plates, deep-well plates and test tube racks, are available depending on the desired application. 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.  
         [0040]    As best shown in FIG. 2, also attached to main frame  22  is a movable robotic assembly, generally designated  40 . 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 . In the conventional form of 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 FIG. 1. A length of transfer tubing  54  (see FIG. 1), preferably formed of PTFE, would provide fluid communication between this sampling needle and valve  14  of dilution module  12 . In the present invention, however, as shown in FIGS. 1 and 2, 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.  
         [0041]    Through the movement of horizontal arm  42 , vertical arm  44  and ultrasonic probe assembly  80 , probe  82  according to the present invention 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  (see FIG. 1) 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 .  
         [0042]    Sampling apparatus  10  also includes an injection port, generally designated  120 , which is accessible by probe  82 . Injection port  120  fluidly 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 FIG. 2).  
         [0043]    Referring now to FIGS.  3 - 6 , ultrasonic transducing probe assembly  80  is illustrated in more detail. Probe assembly  80  includes a ultrasonic converter body or handpiece  84 , such as a MISONIX™ handpiece commercially available from Misonix Inc. of Farmingdale, N.Y., 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. As best shown in FIG. 6, the body of probe includes a neck section  82 A 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  82 B 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  82 C of probe  82 . Hollow interior bore  92  includes a reduced-diameter section within distal section  82 B of probe  82 . In the exemplary embodiment, orifice  94  has a 0.6 mm diameter. Probe  82  serves as an elongate horn member which transfers sonic energy to probe tip  82 C. In use, when a fluid such as a solvent is pumped through converter body  84  and probe  82  with probe assembly  80  activated, a fine mist can be produced at orifice  82 C. In the present embodiment, 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.  
         [0044]    An alternative version of probe  82  is illustrated in FIG. 6A. Probe tip  82 C in FIG. 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 .  
         [0045]    Referring back to FIGS.  3 - 5 , 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 . For example, an elongate chamber  102 A can be formed to accommodate converter body  84 , and an upper chamber  102 B formed to accommodate tubing adapter  86  and fitting  88 . In addition, a slot  102 C is formed on probe assembly adapter  102  to accommodate fluid transfer tubing  54  (see FIG. 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 FIG. 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 FIG. 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  102 D of probe assembly adapter  102 . As shown in FIG. 3, 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 . Preferably, the respective lengths of probe assembly adapter  102  and probe  82  are such that probe tip  82 C matches the position originally assumed by the sampling needle, and hence eliminates the need for major z-axis compensation.  
         [0046]    Referring to FIGS.  7 - 9 , 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 TEFLON7 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  124 A (see FIG. 9) to accommodate probe  82 . Lower body  126  includes an internal flow-through bore  126 A with which tip  82 C of probe  82  makes contact. As shown in FIG. 7, tip  82 C and internal bore  126 A preferably have complementary tapered or chamfered surfaces to improve their contact. An internal volume  126 B 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  82 B of probe  82 , thereby filling the space of the sealing region and establishing a good seal between probe  82  and injection port  120 .  
         [0047]    Referring now to FIG. 10, rinsing station  140  is illustrated in more detail. 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  152 A communicating with an aperture  148 A of fitting  148  and a closed end  152 B terminating at a point within main body  146 . Rinsing bore  152  may be tapered to accommodate probe  82 . The diameter of aperture  148 A is sized relative to rinsing bore  152  such that when probe  82  is inserted through aperture  148 A 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.  
         [0048]    An exemplary operation of probe  82  as integrated into sampling apparatus  10  will now be described, with general reference being made to all Figures disclosed herein. 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 . Depending on the particular application, 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 . Also, it 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 . Upon activation of sampling apparatus  10 , 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. If desired, 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.  
         [0049]    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. At each well, 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. However, in the appropriate situation, vibrating probe  82  could be operated long enough to deliberately cause a rise in sample temperature.  
         [0050]    After sonication, 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. In addition, probe assembly  80  can move to injection port  120  and probe  82  inserted therein as shown in FIG. 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. It is also possible to provide a port or other probe receiving means which fluidly connects probe to a gas chromatograph. Finally, probe assembly  80  can be moved to rinse station  140  and probe  82  installed therein as shown in FIG. 10, so that probe  82  can be cleaned to prevent cross-contamination.  
         [0051]    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.  
         [0052]    As an additional application of the present invention, 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.  
         [0053]    In another, more specific application of the present invention, tissue samples can be homogenized in preparation for RNA extraction. In this application, tissue samples are added to the wells of plate  28  or to individual containers such as EPPENDORFJ tubes held in a suitable plate  28 . In the latter case, plate  28  is provided in the form of a rack adapted to hold such tubes. After the addition of a suitable solvent to a given tissue sample, 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 .  
         [0054]    Referring now to FIG. 11, 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 FIGS. 1 and 2. When probe  82  is inserted into a well or other container, represented in FIG. 11 as  206 , and contacts the solution or suspension contained therein, device  200  can measure the level of liquid in container  206 . 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.  
         [0055]    It will be understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation—the invention being defined by the claims.