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Publication Date: 2015-Sep-03
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The Prior Art Database

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Multiplexed Thermal Gradient Chromatography

I.          Background

Gas chromatography (GC) entails the analytical separation of a vaporized or gas-phase sample that is injected into a chromatographic column containing a stationary phase.  The column is typically housed in a thermally controlled oven.  A chemically inert carrier gas, such as helium, nitrogen, argon, or hydrogen, is utilized as the mobile phase for elution of the analyte sample in the column.  The sample and carrier gas are introduced into a GC inlet coupled to the column head.  In the GC inlet, the sample is injected into the carrier gas stream and the resulting sample-carrier gas mixture flows through the column.  During column flow the sample encounters the stationary phase, which causes different compounds of the sample to separate according to different affinities with the stationary phase.  The separated compounds elute from the column exit and are measured by a detector, producing data (e.g., peaks) from which a chromatogram or spectrum identifying the compounds may be constructed.  The detector may be a stand-alone detector such as a flame ionization detector (FID), or may be part of an analytical instrument such as a mass spectrometer (MS).

In GC there are two commonly implemented techniques for controlling GC column temperature:  isothermal GC and temperature-programmed GC.  In isothermal GC, the column temperature is uniform and constant throughout the analysis.  In temperature- programmed GC, the column temperature is still uniform, but it is gradually increased during the analysis.  This allows the analysis of compounds with widely varying retention times to be performed more quickly than by isothermal GC.  The disadvantage of temperature-programmed GC is that increasing the temperature rapidly does not make effective use of long columns, due to some compounds being virtually unretained by the time they reach the end of the column.  Temperature-programming, therefore, represents a compromise between speed and resolution.

Recently there have been experiments in thermal gradient-programmed GC (TGPGC).  In this case, the column temperature is raised non-uniformly, such that the front of the column, nearest the GC inlet, rises in temperature earlier than the back of the column.  If done correctly, each compound is subject to approximately the same temperature, and therefore the same retention, as that compound travels down the column.  In this way the full length of the column is utilized more effectively, even though the temperature is raised fairly rapidly.  Moreover, there is a secondary effect that involves non-ideal injections.  If the injected sample is initially distributed over some length of the column instead of being initially confined to a very small distance, the thermal gradient can effectively “focus” the peaks to correct, to some extent, the problem.  This correction to a non-ideal injection will never be as good as an id...