Synchronized Stepped Frequency Modulation for Multiplexed Ion Mobility Measurements.

Implementation of frequency-encoded multiplexing for ion mobility spectrometry (e.g., Fourier transform ion mobility spectrometry (FT-IMS)) has facilitated the direct coupling of drift tube ion mobility instrumentation with ion-trap mass analyzers despite their duty cycle mismatch. Traditionally, FT-IMS experiments have been carried out to utilize continuous linear frequency sweeps that are independent of the scan rate of the ion-trap mass analyzer, thus creating a situation where multiple frequencies are swept over two sequential mass scans. This in turn creates a degree of ambiguity in which the ion current derived from a single modulation frequency cannot be assigned to a single data point in the frequency-modulated signal. In an effort to eliminate this ambiguity, this work describes a discrete stepwise function to modulate the ion gates of the IMS while synchronization between the generated frequencies and the scan rate of the linear ion trap is achieved. While the number of individual frequencies used in the stepped frequency sweeps is less than in continuous linear modulation experiments, there is no loss in performance and high levels of precision are maintained across differing combinations of terminal frequencies and scan lengths. Furthermore, the frequency-scan synchronization enables further data-processing techniques such as linear averaging of the frequency modulated signal to drastically improve signal-to-noise ratio for both high and low intensity analytes.