Automated capillary liquid chromatography small volume analysis system
First Claim
1. An automatic capillary liquid chromatography chemical analysis system comprising, in combination, a capillary defining a fluid passageway having an inlet end, and outlet end, and an intermediate branch outlet, said capillary being filled with a porous material to form a trapping pre-concentration column between said inlet end and said intermediate branch outlet and a separation column between said branch outlet and said outlet end, loading flow control means coupled to said inlet end and to said branch outlet for passing a liquid sample through said trapping pre-concentration column, analysis flow control means for terminating the further introduction of said liquid sample into said pre-concentration column via said inlet end and for thereafter passing a concentrated liquid sample from said pre-concentration column through said separation column at a separation flow rate between 10 and 1,000 nanoliters per minute to deliver chromatography eluent through said outlet end, and an analyzer positioned at said outlet end for receiving and analyzing said chromatography eluent delivered from said separation column via said outlet end.
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Accused Products
Abstract
A system for automatically performing liquid chromatography analysis of low volume liquid chemical samples at nanosecond flow rates using an analysis column that integrates a pre-concentration trapping column and a chromatography separation column terminating at an electrospray nozzle of an online mass spectrometer. The analysis column consists of a capillary having an inside diameter of between 75 and 125 microns packed throughout with a porous bed of micron particles. A branch outlet positioned 10 to 16 centimeters upstream from the nozzle divides the analysis column into an upstream pre-concentration trap and a downstream separation column. An autosampler delivers low volume liquid samples to the upstream inlet via a two-position valve. Feed connections couple the autosampler to upstream inlet when the valve is open to inject a liquid sample into the pre-concentration trap at a maximum loading flow rate in the range from 0.5 to 50 microliters/minute. Thereafter, when the valve closes, it terminates the further injection the sample, and a concentrated portion of the sample then passes though the chromatography separation column at a much slower flow rate between 10 and 1,000 nanoliters per minute. Throughput can be doubled by coupling two such analysis columns to a single autosampler using a ten-port, two position valve. A single column can be supplied through a six port two-position valve.
46 Citations
20 Claims
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1. An automatic capillary liquid chromatography chemical analysis system comprising, in combination,
a capillary defining a fluid passageway having an inlet end, and outlet end, and an intermediate branch outlet, said capillary being filled with a porous material to form a trapping pre-concentration column between said inlet end and said intermediate branch outlet and a separation column between said branch outlet and said outlet end, loading flow control means coupled to said inlet end and to said branch outlet for passing a liquid sample through said trapping pre-concentration column, analysis flow control means for terminating the further introduction of said liquid sample into said pre-concentration column via said inlet end and for thereafter passing a concentrated liquid sample from said pre-concentration column through said separation column at a separation flow rate between 10 and 1,000 nanoliters per minute to deliver chromatography eluent through said outlet end, and an analyzer positioned at said outlet end for receiving and analyzing said chromatography eluent delivered from said separation column via said outlet end.
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14. A system for automatically analyzing a plurality of liquid chemical samples comprising, in combination,
a first capillary having an inside diameter of between 50 and 150 microns packed with a porous bed of particles to form an analysis column having an upstream inlet, a downstream outlet, and a branch outlet positioned between said inlet and said outlet at a distance between 10 and 16 centimeters from said outlet, said analysis column forming a pre-concentration trap between said upstream inlet and said branch outlet and forming a chromatography separation column between said branch outlet and said downstream outlet, a mass spectrometer positioned to receive chromatography eluent from said downstream outlet, an autosampler for delivering said plurality of liquid samples, a two-position valve having an open position and a closed position, and feed connections coupling said autosampler to said upstream inlet via said two-position valve for injecting one of said liquid samples into said pre-concentration trap via said upstream inlet at a maximum loading flow rate in the range from 0.5 to 50 microliters/minute when said two-position valve is in said open position, for thereafter terminating the further injection of said one of said liquid samples via said upstream inlet when said two-position valve moves to said closed position, and for permitting the passage of a concentrated portion of said one of said liquid samples though said chromatography separation column at a lower flow rate between 10 and 1,000 nanoliters per minute to thereby deliver chromatography eluent through said downstream outlet to said mass spectrometer when said two position valve is in said closed position.
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19. A system for automatically analyzing a plurality of liquid chemical samples comprising, in combination,
first and second analysis columns each of which comprises capillary having an inside diameter of between 50 and 150 microns packed with a porous bed of particles to form an analysis column having an upstream inlet, a downstream outlet, and a branch outlet positioned between said inlet and said outlet at a distance between 10 and 16 centimeters from said outlet, said analysis column forming a pre-concentration trap between said upstream inlet and said branch outlet and forming a chromatography separation column between said branch outlet and said downstream outlet, and a mass spectrometer positioned to receive chromatography eluent from said downstream outlet of each of said analysis columns an autosampler for delivering said plurality of liquid samples, a valve having first and second positions, a first set of feed connections coupling said autosampler to said upstream inlet of first analysis column via said two-position valve for injecting a second one of said liquid samples into the pre-concentration trap of said first analysis column via said upstream inlet of said first analysis column at a maximum loading flow rate in the range from 0.5 to 50 microliters/minute when said two-position valve is in said first position, for thereafter terminating the further injection of said first one of said liquid samples via said upstream inlet of said first analysis column when said two-position valve moves from said first to said second position, and for permitting the passage of a concentrated portion of said first one of said liquid samples though said chromatography separation column of said first analysis column at a lower flow rate between 10 and 1,000 nanoliters per minute to thereby deliver chromatography eluent derived from said first one of said liquid samples to said mass spectrometer positioned to receive chromatography eluent from said downstream outlet of said first analysis column when said two position valve is in said second position.
Specification