Article pubs.acs.org/ac
Evaluation of Hadamard Transform Atmospheric Pressure Ion Mobility Time-of-Flight Mass Spectrometry for Complex Mixture Analysis Xing Zhang,† Richard Knochenmuss,‡ William F. Siems,*,† Wenjie Liu,† Stephan Graf,‡ and Herbert H. Hill, Jr.† †
Department of Chemistry, Washington State University, Pullman, Washington 99164, United States Tofwerk, AG, Thun, Switzerland
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S Supporting Information *
ABSTRACT: Ion mobility mass spectrometry (IMMS) has gained popularity in the analysis of complex mixtures such as those encountered in metabolomics and proteomics. However, the challenge that exists in conventional pulsed IMMS is its inherent low duty cycle. The first application of Hadamard transform (HT)-type signal coupled with atmospheric pressure IMMS to complex mixtures is presented. Performance of the prototype was assessed by the analysis of metabolite standard mixture. With 200 times increased IMS duty cycle in HT mode compared with conventional pulsed mode, the limit of detection (LOD) was decreased by ∼10 times. Evaluation for application to complex mixtures was achieved using the NIST Standard Reference Material 1950 Metabolites in Human Plasma. Approximately 180 metabolite ions were detected within 1 min with an IMS resolving power (Rp) of ∼100. Rapid chromatographic separation prior to IMMS analysis was also demonstrated for improving the response of metabolite ions in rat brain tissue extract.
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on mobility spectrometry (IMS)1 is a gas-phase separation technique, which has been widely used for rapid detection of explosives, drugs, and chemical warfare agents as a screening method in homeland security.2,3 It has gained increased popularity mainly because of its portability and reasonable low detection limit in the field. Internal ionizations sources such as 63 Ni are efficient and stable,4 which have been most commonly used in IMS for gas phase target detection. In the past decades, the development of alternative ionization methods such as electrospray ionization (ESI)5 and matrix-assisted laser desorption ionization (MALDI)6 has enabled the use of IMS devices for liquid and solid phase targets analysis. In addition, the success of coupling ion mobility spectrometers to various types of mass spectrometers has further extended the IMS capabilities to a wide range of analytes, especially complex mixtures.7 The most recent applications of IMMS include proteomics,8 metabolomics,9 and organic reaction monitoring.10 Interfacing of an ion mobility spectrometer to a mass spectrometer has not only expanded the application fields but also provided value-added data with reduced chemical noise.11 Rapid sample analysis on the minute time scale, separation of isomers and isobars, and two-dimensional identifications based on ion size-to-charge ratio and ion massto-charge ratio (m/z) have made IMMS a natural fit for complex mixture analysis. However, the inherent high Rp of atmospheric pressure IMS has been limited due to low duty-cycle operation. © 2013 American Chemical Society
As a pulsed analytical technique, the traditional way of initiating an IMS experiment is by pulsing open an ion gate for a short time (100−200 μs), admitting a spatially confined packet of ions into the drift region, where the ions disperse in time based on their collision-cross-section-to-charge ratios (Ω/z).12 This “pulse-and-wait” approach only pulses the ion gate one time within an experimental cycle, then an average of multiple experimental cycles yield an ion mobility spectrum. The simplicity of the experiment provides accurate and reproducible measurement of ion signals. However, with continuous ionization sources such as ESI, 63Ni, and corona discharge, this pulsed mode of operation results in low ion usage because the ion gate cannot be open during the time when the previous ion packet disperses in the drift region. For a traditional IMS experiment, the duty cycle is usually
