Methods for Operating a System Comprising a Coupled Mass Spectrometer and Ion Mobility Spectrometer

Abstract

A method of operating a system comprising a chromatograph, an ion source, a mass spectrometer having a mass analyzer and an ion mobility spectrometer interposed between the ion source and the mass analyzer, comprising: performing a first chromatographic and mass analysis of a sample while operating the ion mobility spectrometer in non-dispersive mode, wherein a respective ion-signal-acquisition time (AT) and a corresponding loss-of-ion-signal time (LT) are identified for each detected m/z ratio that corresponds to a precursor-ion m/z ratio of interest; and performing a second chromatographic and mass analysis of the sample during which, for each identified AT and LT, the corresponding respective precursor ion is fragmented to generate product ions and the product ions are detected by the mass analyzer, wherein the ion mobility spectrometer is operated in dispersive mode such that ions of said each respective precursor-ion species are preferentially transmitted therethrough spectrometer to the mass analyzer.

What is claimed is: 
     
         1 . A method of operating a system comprising a chromatograph, a mass spectrometer and an ion mobility spectrometer interposed between an ion source and a mass analyzer of the mass spectrometer, the method comprising:
 performing a first chromatography and mass spectrometry analysis of the sample, wherein:
 the ion source generates a first plurality of ions from a chromatographic eluate and the ion mobility spectrometer is operated in non-dispersive mode to transmit the first plurality of ions to the mass spectrometer, 
 the mass analyzer detects m/z values and abundances of the ions, and 
 a respective ion-signal-acquisition time (AT) and a corresponding loss-of-ion-signal time (LT) are identified, from the detected m/z values and abundances, for each detected m/z value that corresponds to a precursor-ion species of interest, wherein each AT and LT are referenced with respect to a start time of the first chromatography and mass spectrometry analysis; and 
   performing a second chromatography and mass spectrometry analysis of the sample, wherein:
 the ion source generates a second plurality of ions from a second chromatographic eluate, and 
 wherein, for each time period between an identified AT and its corresponding LT, each AT and LT taken with respect to a start time of the second chromatography and mass spectrometry analysis:
 the ion mobility spectrometer is operated in dispersive mode such that ions of the corresponding precursor-ion species of interest are preferentially transmitted through the ion mobility spectrometer to the mass spectrometer, and 
 the ions of the corresponding precursor-ion of interest are fragmented in the mass spectrometer to generate product ions that are detected by the mass analyzer. 
 
   
     
     
         2 . A method as recited in  claim 1 , wherein the transmitting of the first plurality of ions through the ion mobility spectrometer operated in non-dispersive mode comprises transmitting said first plurality of ions through a high field asymmetric waveform ion mobility spectrometry (FAIMS) spectrometer. 
     
     
         3 . A method as recited in  claim 2 , wherein the operating of the FAIMS spectrometer in dispersive mode during the second chromatography and mass spectrometry analysis comprises transmitting the precursor-ion species of interest within a gas having a gas flow rate through an annular separation region of the FAIMS spectrometer from an ion inlet port to an ion exit port, wherein the gas flow rate and a flow path length between the ion inlet and ion exit ports are such that a residence time of the precursor-ion species within the FAIMS spectrometer is less than or equal to 10 milliseconds. 
     
     
         4 . A method as recited in  claim 2 , further comprising providing a list having a respective entry for each of one or more precursor ion species of interest wherein each entry includes FAIMS parameters necessary for causing the FAIMS spectrometer to preferentially transmit the respective precursor ion species therethrough when operated in dispersive mode. 
     
     
         5 . A method of operating a system comprising a chromatograph operable to separate sample solutions into fractions, an ion source operable to ionize components of the fractions and a mass spectrometer operable to detect the ions, the method comprising:
 (a) providing a list comprising respective entries for each of two or more precursor ion species of interest comprising respective precursor-ion m/z ratios;   (b) performing a first analysis of a sample comprising:
 (b1) separating the sample into sample fractions using the chromatograph; 
 (b2) generating a plurality of fraction ion species from each fraction using an ion source; 
 (b3) transmitting the plurality of fraction ion species through an ion mobility spectrometer operated in non-dispersive mode to the mass spectrometer; and 
 (b4) detecting an ion abundance at each of a plurality m/z ratios within each fraction using a mass analyzer of the mass spectrometer; 
   (c) identifying, from the first analysis, a respective ion-signal-acquisition time (AT) and a corresponding loss-of-ion-signal time (LT), for each m/z ratio that corresponds to a precursor-ion m/z ratio, wherein each AT and LT is referenced to a first-analysis start time taken as time zero; and   (d) performing a second analysis of the sample comprising:
 (d1) establishing a second analysis start time taken as time zero for referencing time periods during the second analysis; 
 (d2) separating the sample into second sample fractions using the chromatograph; 
 (d3) generating a respective plurality of second-sample-fraction ion species from each second sample fraction using the ion source and inletting each plurality of second-sample-fraction ion species to the ion mobility spectrometer; and 
 (d4) for each precursor-ion species of interest for which the respective m/z ratio corresponds to a respective identified AT and LT:
 operating the ion mobility spectrometer, during a time period occurring at or after said respective identified AT and at or before said respective identified LT, in dispersive mode such that ions of said each precursor-ion species are preferentially transmitted through the ion mobility spectrometer to the mass spectrometer; 
 fragmenting the preferentially transmitted ion species in the mass spectrometer so as to generate product ions; and 
 detecting the product ions using the mass analyzer.