Sample injection system

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.

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.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Having reference now toFIG. 1of the drawings, there is illustrated an automated liquid handler10. The liquid handler10is provided with a sample injection system generally designated as12and constructed in accordance with the principles of the present invention.

The liquid handler10includes a base14providing a work surface16for locating and supporting an array of many sample containers or receptacles18in which liquid samples are held. The containers can take many forms, including microplates, test tubes and bottles. A control housing20is located at one end of the base14. Liquid samples are aspirated from the containers18by a hollow probe22moved relative to the work surface14by a probe drive system24.

The probe drive system is a three axis X-Y-Z drive system. An X arm26extends horizontally in an X direction and is supported along the rear of the work surface16between the upstanding control housing20and a support pedestal28. A Y arm30extends horizontally in a Y direction from the X arm26. The base of the Y arm30is slideably supported on the X arm for movement across the work surface16in the X direction. An X motor32is coupled to the Y arm and drives it in the X direction.

A Z arm34extends vertically in a Z direction from the Y arm30. The base of the Z arm is slideably supported on the Y arm for movement in the Y direction across the work surface16. A Y motor36is coupled to the Z arm and drives it in the Y direction. The X and Y motors32and36are operated by a controller38(FIGS. 3 and 4) within the control housing20in order to precisely position the probe22above any selected sample container18.

The probe22is carried by a probe holder40. The probe holder40is mounted on the Z arm34for vertical sliding movement. A Z motor42is coupled to the probe holder40and drives it in the vertical Z direction. When the probe22is aligned with a selected sample container18, the Z motor42is operated by the controller38to lower the probe22into or raise the probe22upwardly from a liquid sample held in the sample container18.

The automated liquid handler10may 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 handler10beyond that needed for an understanding of the present invention.

A syringe probe pump44applies positive or negative pressure to the probe22for dispensing or aspirating liquid from or into the probe22. The pump44includes a pump piston46moved within a cylinder48by a syringe pump motor49(FIGS. 3 and 4) located within the control housing20and operated by the controller38. A three way syringe pump valve50is connected to the syringe pump44and is movable between one position in which the syringe pump44is able to communicate through a conduit52with the probe22and another position in which the syringe pump44communicates through a conduit54with a container56of dilutant or solvent (FIGS. 3 and 4). A syringe pump valve motor58(FIGS. 3 and 4) mounted within the control housing20operates the valve50between its alternate positions under the control of the controller38.

The sample injection system12includes an injection valve assembly60operated by an injection valve interface control module62in turn operated in accordance with operating instructions provided by the controller38. As seen inFIG. 2, the injection valve assembly60includes a valve operating motor64and a bearing support body66supporting a valve head68. These components are contained between upper and lower housing sections70and72. An internal mounting flange73holds the valve components in the housing.

In the illustrated sample injection system12, the valve head68includes a six port injection valve74having ports76,78,80,82,84and86(FIGS. 3 and 4). An external sample loop87is connected between injector valve ports78and84. 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 controller38and valve control62, the injector valve is operated by a motor88between 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 system12is a RHEODYNE™ RV700-100 injection valve sold by Rheodyne, L. P. Rohnert park, Calif. 94927.

The port76is connected to the probe22by a conduit90. A conduit92connects port82to a source of pressurized mobile phase. In the illustrated system, mobile phase is supplied from a container94by a high pressure precision pump96. 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 pump96beyond that needed for an understanding of the present invention. Port80is connected by a conduit98to a sample analyzer100. Analyzers of many types could be used with the sample injection system12. In the illustrated system, the analyzer includes a high pressure liquid chromatography (HPLC) column102communicating with a detector104. The detector104, for example, may be an ion detector, a mass spectrometer or other type.

In operation of the sample injection system12, the injection valve74is placed by motor88into the sample loading position ofFIG. 3. The probe drive system24positions the probe22over a selected sample container18. The Z drive motor42lowers the probe into the selected liquid sample. The syringe pump valve50is in the position seen inFIGS. 3 and 4. The syringe pump44communicates with the probe22through a flow path including valve50, conduit52, injection valve port86, the sample loop87, injection valve port76and conduit90. The syringe pump motor49operates to reduce pressure in the syringe pump44and liquid sample is aspirated through the probe22and into the sample loop87. During the sample loading operation, mobile phase travels from the pump94through injection valve ports82and80toward the HPLC column102.

The injection valve is then operated by motor88to the alternate, sample injection position ofFIG. 4. Pressurized mobile phase from the pump96and conduit92enters injection valve port82and forces the liquid sample in sample loop87along a flow path including the sample loop87, the injection valve port80and the conduit98toward the HPLC column102. The liquid sample from the sample loop is thus entrained in the liquid phase for analysis in the analyzer100. During the sample injection operation, the probe22is in communication with the syringe pump valve50through injection valve ports76and86.

Prior to the next sample loading operation, the probe22and conduit90are preferably rinsed to reduce cross sample contamination carryover. The probe22can be moved to a rinsing station and rinsed with solvent, and/or the probe may be rinsed with solvent provided by valve50and the syringe pump44from the dilutant container56.

In accordance with the invention, the injection valve74is mounted near the probe22, and the probe22and the injection valve74are connected directly and continuously by the short conduit90. The injection valve assembly60is attached to the drive system24, and preferably to the Z arm34near the top of the Z arm. In this mounting position, the injector valve74is close to the vertical axis of the probe22. The distance between the probe axis and the injector valve is only a few inches, preferably less than six inches. The conduit90is flexible to permit vertical motion of the probe22. The short separation distance between the probe axis and the injection valve74permits the conduit90to be only several inches long, and preferably less than twelve inches long.

Because the probe22and injection port76are continuously interconnected by the conduit90, 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.