Utility Of Ion Mobility Spectrometry Research Articles

Improving the Speed and Selectivity of Newborn Screening Using Ion Mobility Spectrometry-Mass Spectrometry.

Detection and diagnosis of congenital disorders is the principal aim of newborn screening (NBS) programs worldwide. Mass spectrometry (MS) has become the preferred primary testing method for high-throughput NBS sampling because of its speed and selectivity. However, the ever-increasing list of NBS biomarkers included in expanding panels creates unique analytical challenges for multiplexed MS assays due to isobaric/isomeric overlap and chimeric fragmentation spectra. Since isobaric and isomeric systems limit the diagnostic power of current methods and require costly follow-up exams due to many false-positive results, here, we explore the utility of ion mobility spectrometry (IMS) to enhance the accuracy of MS assays for primary (tier 1) screening. Our results suggest that ∼400 IMS resolving power would be required to confidently assess most NBS biomarkers of interest in dried blood spots (DBSs) that currently require follow-up testing. While this level of selectivity is unobtainable with most commercially available platforms, the separations detailed here for a commercially available drift tube IMS (Agilent 6560 with high-resolution demultiplexing, HRdm) illustrate the unique capabilities of IMS to separate many diagnostic NBS biomarkers from interferences. Furthermore, to address the need for increased speed of NBS analyses, we utilized an automated solid-phase extraction (SPE) system for ∼10 s sampling of simulated NBS samples prior to IMS-MS. This proof-of-concept work demonstrates the unique capabilities of SPE-IMS-MS for high-throughput sample introduction and enhanced separation capacity conducive for increasing speed and accuracy for NBS.

Adding a new separation dimension to MS and LC–MS: What is the utility of ion mobility spectrometry?

Ion mobility spectrometry is an analytical technique known for more than 100 years, which entails separating ions in the gas phase based on their size, shape, and charge. While ion mobility spectrometry alone can be useful for some applications (mostly security analysis for detecting certain classes of narcotics and explosives), it becomes even more powerful in combination with mass spectrometry and high-performance liquid chromatography. Indeed, the limited resolving power of ion mobility spectrometry alone can be tackled when combining this analytical strategy with mass spectrometry or liquid chromatography with mass spectrometry. Over the last few years, the hyphenation of ion mobility spectrometry to mass spectrometry or liquid chromatography with mass spectrometry has attracted more and more interest, with significant progresses in both technical advances and pioneering applications. This review describes the theoretical background, available technologies, and future capabilities of these techniques. It also highlights a wide range of applications, from small molecules (natural products, metabolites, glycans, lipids) to large biomolecules (proteins, protein complexes, biopharmaceuticals, oligonucleotides).

Ion Mobility Spectrometry: Ion Source Development and Applications in Physical and Biological Sciences

The utility of ion mobility spectrometry (IMS) has been steadily growing, and it cuts across diverse areas in physical and biological sciences. The development of ion sources, particularly in the context of IMS, is described. IMS ion sources operate efficiently in ambient environment and yield ions for a wide range of complex molecules including biological materials. While significant progress has been made in this area through the development of a variety of ion sources, further research to address several key issues, namely, ionization processes, reaction chemistry, and overall system miniaturization for field deployment of IMS, is the primary focus of current activities. Aside from reviewing the present state of the art of ion sources for IMS, this paper has discussed the wide range of applications and current trends of research in the field.

The Utility of Ion Mobility Spectrometry to Separate Candidate Precursors from Background Ions and Species of Different Charge States in Tandem MS Experiments

As a technique for characterising proteins, tryptic digestion followed by data dependant LC-MS/MS is well established. However, in complex biological mixtures, with a wide dynamic range, the majority of the peptides observed are in the lowest order of magnitude that can be detected, and despite tandem MS experiments, singly charged chemical noise present in the MS/MS spectrum can hinder precursor identification. In addition, cross-linked peptides containing >2 charges are often at low stoichiometry compared with tryptic peptides, and as such it may be difficult for the mass spectrometer to identify these in the MS survey as candidate precursors.

High-sensitivity ion mobility spectrometry/mass spectrometry using electrodynamic ion funnel interfaces.

The utility of ion mobility spectrometry (IMS) for separation of mixtures and structural characterization of ions has been demonstrated extensively, including in biological and nanoscience contexts. A major attraction of IMS is its speed, several orders of magnitude greater than that of condensed-phase separations. Nonetheless, IMS combined with mass spectrometry (MS) has remained a niche technique, substantially because of limited sensitivity resulting from ion losses at the IMS-MS junction. We have developed a new electrospray ionization (ESI)-IMS-QTOF MS instrument that incorporates electrodynamic ion funnels at both front ESI-IMS and rear IMS-QTOF interfaces. The front funnel is of the novel "hourglass" design that efficiently accumulates ions and pulses them into the IMS drift tube. Even for drift tubes of 2-m length, ion transmission through IMS and on to QTOF is essentially lossless across the range of ion masses relevant to most applications. The rf ion focusing at the IMS terminus does not degrade IMS resolving power, which exceeds 100 (for singly charged ions) and is close to the theoretical limit. The overall sensitivity of the present ESI-IMS-MS system is comparable to that of commercial ESI-MS, which should make IMS-MS suitable for analyses of complex mixtures with ultrahigh sensitivity and exceptional throughput.