Abstract:
An HPLC injection valve is mounted to a probe drive system close to the probe axis to minimize probe movements required for sample injections into a mobile phase column. The probe is directly connected by a short conduit to the injection valve, eliminating the need to dispense aspirated samples from the probe into a remote injection port.

Description:
FIELD OF THE INVENTION  
     The present invention relates to sample handling and more particularly to a high throughput sample injection system for liquid sample analysis systems such as liquid chromatography. 
     DESCRIPTION OF THE PRIOR ART 
     In performing high pressure liquid chromatography, samples are injected into a mobile phase that is supplied to a sample analysis assembly such as a chromatography column and detector. In order to automate the process and to achieve high sample throughput, an automated liquid handler may be used for supplying the samples in a predetermined sequence. In a known sample injection system, each sample is aspirated with a probe from one of an array of sample containers and the aspirated sample is then dispensed from the probe into a remote injection port associated with an injection valve. 
     Although this type of known sample injection system has been quite successful, it is limited in throughput capabilities because of the use of a remote injection port that receives samples dispensed from the liquid handler probe. One difficulty is that sample cross contamination or carryover can occur as sequential samples are dispensed by the probe into the injector port. Such carryover decreases the accuracy of the sample analysis and results in loss of injection reproducibility. Although carryover can be reduced by sufficient intra sample rinsing, this adds to the time required to perform a series of sample injections and increases sample handling times and reduces sample throughput. 
     In a typical known system, the injection port into which samples are dispensed by the probe may be located as much as about two feet from certain ones of the liquid sample containers. Another difficulty is the time and the number of discrete operating steps needed for the liquid handler to move the probe into registration with each sample and then move the probe from the sample to the remote injection port. This also increases sample handling times and reduces sample throughput. 
     SUMMARY OF THE INVENTION 
     A primary object of the present invention is to provide a sample injection system having high sample throughput capability and increased injection repeatability but with minimal sample cross contamination carryover. Other objects are to provide a sample injection system in which the time and distance required for sample transfer are minimized and to provide a sample injection system that overcomes problems with known injection systems. 
     In brief, in accordance with the invention there is provided a sample injection system including a work surface for supporting a plurality of liquid sample containers and including a probe having a vertical axis. A probe drive system includes an X arm extending horizontally in an X direction, a Y arm slideably mounted on the X arm and extending horizontally in a Y direction, and a Z arm slideably mounted on the Y arm and extending vertically in Z direction. A probe holder holds the probe and is slideably mounted on the Z arm. A probe pump provides positive and negative pressure for the probe for sample dispensing and aspiration. The system includes a sample analyzer and a source of pressurized liquid phase. An injector valve is connected to the probe, to the probe pump, to the source of pressurized liquid phase and to the sample analyzer. A conduit connects the probe to the injector valve and the injector valve is mounted on the probe drive system. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWING 
       The present invention together with the above and other objects and advantages may best be understood from the following detailed description of the preferred embodiment of the invention illustrated in the drawings, wherein: 
         FIG. 1  is an isometric view of an automated liquid handler having a sample injection system constructed in accordance with the present invention; 
         FIG. 2  is an exploded isometric view of the injection valve assembly of the sample injection system; 
         FIG. 3  is a schematic illustration of the sample injection system with the injection valve in the sample load position; and 
         FIG. 4  is a schematic illustration of the sample injection system with the injection valve in the sample injection position. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Having reference now to  FIG. 1  of the drawings, there is illustrated an automated liquid handler  10 . The liquid handler  10  is provided with a sample injection system generally designated as  12  and constructed in accordance with the principles of the present invention. 
     The liquid handler  10  includes a base  14  providing a work surface  16  for locating and supporting an array of many sample containers or receptacles  18  in which liquid samples are held. The containers can take many forms, including microplates, test tubes and bottles. A control housing  20  is located at one end of the base  14 . Liquid samples are aspirated from the containers  18  by a hollow probe  22  moved relative to the work surface  14  by a probe drive system  24 . 
     The probe drive system is a three axis X-Y-Z drive system. An X arm  26  extends horizontally in an X direction and is supported along the rear of the work surface  16  between the upstanding control housing  20  and a support pedestal  28 . A Y arm  30  extends horizontally in a Y direction from the X arm  26 . The base of the Y arm  30  is slideably supported on the X arm for movement across the work surface  16  in the X direction. An X motor  32  is coupled to the Y arm and drives it in the X direction. 
     A Z arm  34  extends vertically in a Z direction from the Y arm  30 . The base of the Z arm is slideably supported on the Y arm for movement in the Y direction across the work surface  16 . A Y motor  36  is coupled to the Z arm and drives it in the Y direction. The X and Y motors  32  and  36  are operated by a controller  38  ( FIGS. 3 and 4 ) within the control housing  20  in order to precisely position the probe  22  above any selected sample container  18 . 
     The probe  22  is carried by a probe holder  40 . The probe holder  40  is mounted on the Z arm  34  for vertical sliding movement. A Z motor  42  is coupled to the probe holder  40  and drives it in the vertical Z direction. When the probe  22  is aligned with a selected sample container  18 , the Z motor  42  is operated by the controller  38  to lower the probe  22  into or raise the probe  22  upwardly from a liquid sample held in the sample container  18 . 
     The automated liquid handler  10  may be of the construction disclosed in Gilson U.S. Pat. No. 4,422,151, incorporated herein by reference. The disclosure of that patent may be referred to for a description of the liquid handler  10  beyond that needed for an understanding of the present invention. 
     A syringe probe pump  44  applies positive or negative pressure to the probe  22  for dispensing or aspirating liquid from or into the probe  22 . The pump  44  includes a pump piston  46  moved within a cylinder  48  by a syringe pump motor  49  ( FIGS. 3 and 4 ) located within the control housing  20  and operated by the controller  38 . A three way syringe pump valve  50  is connected to the syringe pump  44  and is movable between one position in which the syringe pump  44  is able to communicate through a conduit  52  with the probe  22  and another position in which the syringe pump  44  communicates through a conduit  54  with a container  56  of dilutant or solvent ( FIGS. 3 and 4 ). A syringe pump valve motor  58  ( FIGS. 3 and 4 ) mounted within the control housing  20  operates the valve  50  between its alternate positions under the control of the controller  38 . 
     The sample injection system  12  includes an injection valve assembly  60  operated by an injection valve interface control module  62  in turn operated in accordance with operating instructions provided by the controller  38 . As seen in  FIG. 2 , the injection valve assembly  60  includes a valve operating motor  64  and a bearing support body  66  supporting a valve head  68 . These components are contained between upper and lower housing sections  70  and  72 . An internal mounting flange  73  holds the valve components in the housing. 
     In the illustrated sample injection system  12 , the valve head  68  includes a six port injection valve  74  having ports  76 ,  78 ,  80 ,  82 ,  84  and  86  ( FIGS. 3 and 4 ). An external sample loop  87  is connected between injector valve ports  78  and  84 . However the principles of the invention can be applied to other injector valve systems, such as four port injector valves having an internal sample loop. Under the control of the controller  38  and valve control  62 , the injector valve is operated by a motor  88  between a sample loading position ( FIG. 3 ) and an alternate sample injection position ( FIG. 4 ). One commercially available injection valve suitable for use in the sample injection system  12  is a RHEODYNE™ RV700-100 injection valve sold by Rheodyne, L. P. Rohnert park, Calif. 94927. 
     The port  76  is connected to the probe  22  by a conduit  90 . A conduit  92  connects port  82  to a source of pressurized mobile phase. In the illustrated system, mobile phase is supplied from a container  94  by a high pressure precision pump  96 . One suitable pump is disclosed in Gilson et al. U.S. Pat. No. 4,326,837, incorporated herein by reference. The disclosure of that patent may be referred to for a description of the pump  96  beyond that needed for an understanding of the present invention. Port  80  is connected by a conduit  98  to a sample analyzer  100 . Analyzers of many types could be used with the sample injection system  12 . In the illustrated system, the analyzer includes a high pressure liquid chromatography (HPLC) column  102  communicating with a detector  104 . The detector  104 , for example, may be an ion detector, a mass spectrometer or other type. 
     In operation of the sample injection system  12 , the injection valve  74  is placed by motor  88  into the sample loading position of  FIG. 3 . The probe drive system  24  positions the probe  22  over a selected sample container  18 . The Z drive motor  42  lowers the probe into the selected liquid sample. The syringe pump valve  50  is in the position seen in  FIGS. 3 and 4 . The syringe pump  44  communicates with the probe  22  through a flow path including valve  50 , conduit  52 , injection valve port  86 , the sample loop  87 , injection valve port  76  and conduit  90 . The syringe pump motor  49  operates to reduce pressure in the syringe pump  44  and liquid sample is aspirated through the probe  22  and into the sample loop  87 . During the sample loading operation, mobile phase travels from the pump  94  through injection valve ports  82  and  80  toward the HPLC column  102 . 
     The injection valve is then operated by motor  88  to the alternate, sample injection position of  FIG. 4 . Pressurized mobile phase from the pump  96  and conduit  92  enters injection valve port  82  and forces the liquid sample in sample loop  87  along a flow path including the sample loop  87 , the injection valve port  80  and the conduit  98  toward the HPLC column  102 . The liquid sample from the sample loop is thus entrained in the liquid phase for analysis in the analyzer  100 . During the sample injection operation, the probe  22  is in communication with the syringe pump valve  50  through injection valve ports  76  and  86 . 
     Prior to the next sample loading operation, the probe  22  and conduit  90  are preferably rinsed to reduce cross sample contamination carryover. The probe  22  can be moved to a rinsing station and rinsed with solvent, and/or the probe may be rinsed with solvent provided by valve  50  and the syringe pump  44  from the dilutant container  56 . 
     In accordance with the invention, the injection valve  74  is mounted near the probe  22 , and the probe  22  and the injection valve  74  are connected directly and continuously by the short conduit  90 . The injection valve assembly  60  is attached to the drive system  24 , and preferably to the Z arm  34  near the top of the Z arm. In this mounting position, the injector valve  74  is close to the vertical axis of the probe  22 . The distance between the probe axis and the injector valve is only a few inches, preferably less than six inches. The conduit  90  is flexible to permit vertical motion of the probe  22 . The short separation distance between the probe axis and the injection valve  74  permits the conduit  90  to be only several inches long, and preferably less than twelve inches long. 
     Because the probe  22  and injection port  76  are continuously interconnected by the conduit  90 , it is not necessary for the probe to aspirate liquid sample from a sample container and then dispense the liquid sample into an injection port at a remote location. It is not necessary for the probe to be driven from a selected sample container to a remote injection port. Sample throughput rates are maximized and sample carryover is minimized. High injection reproducibility is achieved. 
     While the present invention has been described with reference to the details of the embodiment of the invention shown in the drawing, these details are not intended to limit the scope of the invention as claimed in the appended claims.