Automated system for sample preparation and analysis

Abstract

A sample preparation and analysis system. The system 10 includes a sample preparation system 12 and a sample analysis system 14 . The sample preparation system 12 prepares samples in accordance with an assay that is selected from a database containing a plurality of unique assays. The sample analysis system 14 includes an analyzer 110 that is dynamically reconfigurable based on the selected assay so as to analyze the prepared sample in accordance with that selected assay. A data communication link 27 communicates data from the sample preparation system 12 to the sample analysis system 14 to reconfigure the analyzer 110 in accordance with the selected assay.

What is claimed is: 
     
         1 . An automated sample preparation system for preparing a sample of a biological fluid specimen for analysis by LCMS, the sample preparation system comprising:
 a specimen rack configured to hold one or more specimen containers;   a reagent rack configured to hold one or more reagent containers;   a movable automated liquid handler operable to aspirate and dispense a volume of fluid;   a reaction vessel for receiving a first aliquot comprising a volume of a fluid specimen and a second aliquot comprising a volume of at least one reagent, the first and second aliquots forming a reaction mixture;   a gripper movable between at least a first position and a second position and configured to grip and transport the reaction vessel;   a mixer configured to receive the reaction vessel for mixing the reaction mixture;   a filtration station configured to filter precipitated particles from the reaction mixture to produce a supernatant liquid;   an incubation station configured to heat the supernatant liquid to a specified temperature between about 27° C. to about 70° C.;   a waste chute configured to transport a used reaction vessel to a waste container; and   a controller operable to control the movable automated liquid handler to aspirate the first aliquot from a specimen container and dispense the first aliquot into the reaction vessel.   
     
     
         2 . The system of  claim 1 , wherein the filtration station comprises a vacuum filtration system. 
     
     
         3 . The system of  claim 1 , wherein the controller comprises a database containing stored information about a plurality of reagents that can be used to prepare a specimen that has been loaded into the system. 
     
     
         4 . The system of  claim 1 , further comprising a user input interface configured to receive identification information associated with each specimen loaded into the specimen rack, including whether the specimen is a priority specimen, wherein the controller is configured to dynamically adjust the order in which specimens are prepared based on the information received from the user input interface. 
     
     
         5 . The system of  claim 1 , further comprising a reagent container containing a protein precipitation reagent. 
     
     
         6 . The system of  claim 1 , further comprising a plurality of protein precipitation reagents stored in the reagent rack. 
     
     
         7 . The system of  claim 1 , further comprising an information acquisition device configured to identify the location of a reagent container in the reagent rack. 
     
     
         8 . The system of  claim 7 , wherein the information acquisition device is further configured to monitor the quantity of a reagent in the reagent container. 
     
     
         9 . An automated sample preparation system for preparing samples of biological fluid specimens for analysis by LCMS, the sample preparation system comprising:
 a specimen rack configured to hold a plurality of specimen containers;   a reagent rack configured to hold a plurality of reagent containers;   a reaction vessel rack configured to hold a plurality of reaction vessels;   an automated pipetting assembly configured to aspirate a sample of a fluid specimen from a specimen container in the specimen rack and dispense the sample into a reaction vessel;   a mixing station comprising a mixer configured to receive the reaction vessel;   a filtration station configured to pass the sample from the reaction vessel through a filter membrane;   a waste chute configured to receive a used reaction vessel;   an automated transport assembly operable to grip and transport the reaction vessel from the mixing station to the filtration station and from the filtration station to the waste chute;   a database containing stored information about a plurality of sample preparation operations, including information about a plurality of protein precipitation reagents that can be used to prepare a specimen for analysis;   a user input interface; and   a controller connected to the user input interface and the database and configured to operate the automated pipetting assembly and the automated transport assembly in accordance with a selected sample preparation operation.   
     
     
         10 . The system of  claim 9 , wherein the filtration station comprises a vacuum filtration system. 
     
     
         11 . An automated sample preparation system for preparing samples of biological fluid specimens for analysis by LCMS, the sample preparation system comprising:
 a specimen rack configured to hold a plurality of specimen containers containing biological fluid specimens;   a reagent rack configured to hold a plurality of reagent containers;   a liquid level sensor operable to determine the presence of a reagent in one or more reagent containers that have been loaded into the reagent rack;   a reaction vessel rack configured to hold a plurality of reaction vessels;   a pipetting assembly configured to aspirate a sample of a biological fluid specimen from a specimen container in the specimen rack and dispense the sample into a reaction vessel;   a mixing station comprising a mixer configured to receive the reaction vessel;   a filtration station configured to apply a vacuum to the reaction vessel; and   a display operatively connected to the liquid level sensor and operable to report the presence of a reagent in the one or more reagent containers that have been loaded into the reagent rack.   
     
     
         12 . The system of  claim 11 , further comprising a controller operatively connected to the liquid level sensor and operable to prevent the preparation of a sample if insufficient reagent is detected. 
     
     
         13 . An automated sample preparation system for preparing samples of biological fluid specimens for analysis by LCMS, the sample preparation system comprising:
 specimen rack configured to hold a plurality of specimen containers;   a reagent rack configured to hold a plurality of reagent containers;   a reaction vessel;   a prepared sample vessel;   an automated pipetting assembly configured to transfer a sample of a biological fluid specimen from a specimen container in the specimen rack to the reaction vessel;   a mixing station comprising a mixer configured to receive the reaction vessel;   a filtration station configured to pass the sample through a filter membrane into the prepared sample vessel;   an automated transport assembly comprising a gripper, the transport assembly configured to grip and transport the reaction vessel from the mixing station to the filtration station; and   a controller configured to control the movement of the transport assembly.   
     
     
         14 . The system of  claim 13 , further comprising an incubation station configured to heat the prepared sample vessel to a specified temperature between about 27° C. to about 70° C., wherein the transport assembly is configured to grip and transport the prepared sample vessel from the filtration station to the incubation station. 
     
     
         15 . An automated sample preparation system capable of performing a plurality of different matrix interference removal operations for preparing samples of biological fluid specimens for analysis my LCMS, the sample preparation system comprising:
 a specimen rack holding a first specimen container containing a first biological fluid specimen and a second specimen container containing a second biological fluid specimen;   a reagent rack holding a first reagent container containing a first protein precipitation reagent and a second reagent container containing a second protein precipitation reagent;   an information acquisition device configured to identify and/or monitor the location of the first reagent container in the reagent rack and the location of the second reagent container in the reagent rack;   a first reaction vessel for mixing a sample of the first biological fluid specimen with an aliquot of the first protein precipitation reagent to form a first reaction mixture;   a second reaction vessel for mixing a sample of the second biological fluid specimen with an aliquot of the second protein precipitation reagent to form a second reaction mixture;   an automated pipetting assembly configured to transport the aliquot of the first protein precipitation reagent from the first reagent container to the first reaction vessel and transport the aliquot of the second protein precipitation reagent from the second reagent container to the second reaction vessel;   a mixing station configured to receive the first and second reaction vessels for mixing the first and second reaction mixtures;   a filtration station configured to receive the first and second reaction vessels for filtering precipitated solids from the first and second reaction mixtures;   an automated transport assembly comprising a gripper, the transport assembly configured to grip and transport the first reaction vessel from the mixing station to the filtration station and to grip and transport the second reaction vessel from the mixing station to the filtration station;   a database containing stored information about a plurality of sample preparation operations comprising matrix interference removal;   a controller configured to operate the automated pipetting assembly to perform first and second matrix interference removal operations, the first matrix interference removal operation using the first protein precipitation reagent and the second matrix interference removal operation using the second protein precipitation reagent.   
     
     
         16 . The system of  claim 15 , wherein the controller is configured to carry out the first and second matrix interference removal operations in series and in parallel. 
     
     
         17 . The system of  claim 15 , further comprising a user input interface configured to identify a specimen container loaded into the specimen rack as containing a priority specimen, wherein the controller is configured to dynamically reorder the first and second matrix interference removal operations based on the identification of a specimen container as containing a priority specimen. 
     
     
         18 . The system of  claim 15 , further comprising:
 a user input interface configured to input identification information associated with each of a plurality of specimen containers loaded into the specimen rack; and   a display operatively connected to the user input interface and configured to graphically display the position of each specimen container loaded into the specimen rack.   
     
     
         19 . An automated sample preparation system for preparing samples of biological fluid specimens for analysis by LCMS, the sample preparation system comprising:
 a specimen container containing a biological fluid specimen;   a first reagent container holding a first protein precipitation reagent;   a second reagent container holding a second protein precipitation reagent;   a reaction vessel for receiving a first aliquot comprising a sample of the biological fluid specimen and a second aliquot comprising at least one reagent, the first and second aliquots forming a reaction mixture;   an automated liquid handler operable to aspirate a volume of the first protein precipitation reagent from the first reagent container or a volume of the second protein precipitation reagent from the second reagent container and dispense the aspirated volume into the reaction vessel;   a mixing station comprising a mixer configured to receive the reaction vessel;   a filtration station configured to pass the reaction mixture through a filter membrane;   an automated transport assembly configured to transport the reaction vessel from the mixing station to the filtration station;   an information acquisition device configured to monitor the quantity of the first protein precipitation reagent in the first reagent container and the quantity of the second protein precipitation reagent in the second reagent container;   electronic memory containing stored information about the minimum volume of the first protein precipitation reagent required to perform a first sample preparation operation and the minimum volume of the second protein precipitation reagent required to perform a second sample preparation operation; and   a controller connected to the information acquisition device and configured to prevent the automated liquid handler from aspirating the first protein precipitation reagent if the quantity of the first protein precipitation reagent in the first reagent container is less than the minimum volume required to perform the first sample preparation operation.