Multiplexed Ion Mobility Spectrometry-Orthogonal Time-of-Flight Mass Spectrometry

Belov, Mikhail E.; Buschbach, Michael A.; Prior, David C.; Tang, Keqi; Smith, Richard D.

doi:10.1021/ac0617316

Cited by 68 publications

(75 citation statements)

References 41 publications

(67 reference statements)

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“…Thus, for a continuous ion source, the introduction of a short pulse of ions upon initiation of experiments often limits duty cycles. Researchers have used a number of approaches (including utilizing multiple injections, as well as Fourier and Hadamard transform approaches) to improve duty cycles (100)(101)(102). Alternatively, at low pressures, it is possible to store ions for extended times to accumulate continuous signals into concentrated packets.…”

Section: Peak Shape and Resolving Power Considerationsmentioning

confidence: 99%

Biomolecule Analysis by Ion Mobility Spectrometry

Bohrer

Merenbloom

Koeniger

et al. 2008

Annual Rev. Anal. Chem.

449

429

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Although nonnative protein conformations, including intermediates along the folding pathway and kinetically trapped misfolded species that disfavor the native state, are rarely isolated in the solution phase, they are often stable in the gas phase, where macromolecular ions from electrospray ionization can exist in varying charge states. Differences in the structures of nonnative conformations in the gas phase are often large enough to allow different shapes and charge states to be separated because of differences in their mobilities through a gas. Moreover, gentle collisional activation can be used to induce structural transformations. These new structures often have different mobilities. Thus, there is the possibility of developing a multidimensional separation that takes advantage of structural differences of multiple stable states. This review discusses how nonnative states differ in the gas phase compared with solution and presents an overview of early attempts to utilize and manipulate structures in order to develop ion mobility spectrometry as a rapid and sensitive technique for separating complex mixtures of biomolecules prior to mass spectrometry.

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Section: Peak Shape and Resolving Power Considerationsmentioning

confidence: 99%

Biomolecule Analysis by Ion Mobility Spectrometry

Bohrer

Merenbloom

Koeniger

et al. 2008

Annual Rev. Anal. Chem.

449

429

View full text Add to dashboard Cite

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“…To address this constraint, a multiplexing approach based on the Hadamard transform was developed so that discreet packets of ions could co-exist in the drift cell as long as they did not overlap due to diffusional broadening ( Fig. 1B and 1C) (15). This approach substantially circumvents space charge limitations, allows much higher IMS duty cycle, significantly increases measurement sensitivity, and deconvolution of its pseudorandom sequence has been shown to greatly reduce the noise in the spectra allowing a much higher signal to noise ratio for the resulting ions (16).…”

Section: Ims-ms Developments and Improvements To Increasementioning

confidence: 99%

Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry

Baker

Burnum-Johnson

Jacobs

et al. 2014

Molecular & Cellular Proteomics

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Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput To date pre-clinical and clinical applications of MS-based proteomic techniques analyzing complex biofluids have fallen short of expectations, largely due to deficiencies in both analytical sensitivity and throughput. These deficiencies result in measurements typically failing to confidently detect and quantify proteins at moderate to low concentrations, or not providing sufficient sample analysis throughput for statistical relevance. Targeted MS analyses with higher sensitivity are currently utilized to address these shortcomings (1, 2); however, these studies often only analyze a small list of proteins identified as biologically significant. While targeted MS measurements are increasingly common in clinical applications (3, 4), the limited number of proteins they examine does not necessarily reflect the biodiversity across a population, making broad untargeted measurements essential in developing individual disease metrics for diagnosis (5). As the future of medicine proceeds toward a personal profiling approach (6, 7), the potential for robust high throughput clinical measurements based upon MS is highly attractive, though only if its deficiencies can be addressed. MSAn initial step in attaining broad untargeted measurements that increasingly retain the benefits of targeted analyses exploits technological advances such as faster separations, more effective ion sources, detectors with greater dynamic range, and MS measurements with both higher resolution and accuracy. Advanced liquid-phase separations have already

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“…In theory, ESI-IMMS spectra can be obtained in a few milliseconds with high resolution, providing a rapid multidimensional separation of the sample components (Belov et al 2007;Merenbloom et al 2006;Steiner et al 2001). The separation potential of ESI-IMMS, however, has not been characterized as has those of chromatography or mass spectrometry.…”

Section: Introductionmentioning

confidence: 99%

Metabolic profiling by ion mobility mass spectrometry (IMMS)

et al. 2007

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Ion Mobility Mass Spectrometry (IMMS) was evaluated as an analytical method for metabolic profiling. The specific instrument used in these studies was a direct infusion (DI)-electrospray ionization (ESI)-ambient pressure ion mobility spectrometer (APIMS) coupled to a timeof-flight mass spectrometer (TOFMS). The addition of an ion mobility spectrometer to a mass spectrometer had several advantages over direct infusion electrospray mass spectrometry alone. This tandem instrument (ESI-IMMS) added a rapid separation step with high-resolution prior to mass spectrometric analysis of metabolite mixtures without extending sample preparation time or reducing the high through put potential of direct mass spectrometry. Further, IMMS also reduced the baseline noise common with ESI-MS analyses of complex samples and enabled rapid separation of isobaric metabolites. IMMS was used to analyze the metabolome of Escherichia coli (E. coli), containing a collection of extremely diverse chemical compounds including hydrophobic lipids, inorganic ions, volatile alcohols and ketones, amino and non-amino organic acids, and hydrophilic carbohydrates. IMMS data were collected as twodimensional spectra showing both mobility and mass of each ion detected. Using direct infusion ESI-IMMS of a nonderivatized methanol extract of an E. coli culture, more than 500 features were detected, of which over 200 intracellular metabolites were tentatively assigned as E. coli metabolites.This analytical method also allowed simultaneous separation of isomeric metabolic features.

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Multiplexed Ion Mobility Spectrometry-Orthogonal Time-of-Flight Mass Spectrometry

Cited by 68 publications

References 41 publications

Biomolecule Analysis by Ion Mobility Spectrometry

Biomolecule Analysis by Ion Mobility Spectrometry

Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry

Metabolic profiling by ion mobility mass spectrometry (IMMS)

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