Publications

Achieving 4-fold Greater Sensitivity with MOBILion's SLIM Technology

Separation of β-Amyloid Tryptic Peptide Species with Isomerized and Racemized L-Aspartic Residues with Ion Mobility in Structures for Lossless Ion Manipulations.

Author(s)

Gabe Nagy, Komal Kedia, IsaacK. Attah, Sandilya V. B. Garimella, Yehia M. Ibrahim, Vladislav A. Petyuk, Richard D. Smith.

Abstract

Accumulation of β-amyloid (β) is one of the hallmarks of Alzheimer's disease. The deposition of β-amyloid plaques is likely to start years in advance of manifestation of clinical symptoms, although the exact timing is unknown. Over the years, b peptides undergo both post-translational modification and stereoisomerization. Analysis of the resulting stereoisomers is particularly challenging because of their identical elemental composition and similar physicochemical properties. This paper explores how MOBILion's SLIM HRIM-MS can be used for characterization of β stereoisomers.

Customer Intro

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Conclusions

Abstract

The paper, published in Analytical Chemistry concludes:

In this paper, MOBILion's SLIM technology was used for resolving four challenging sets of AÎ² peptide epimers incorporating two Asp residues labile to racemization/ isomerization.
The ever-growing suite of available MS fragmentation techniques has given rise to the more confident characterization of structurally similar biomolecules but this comes at the cost of significantly reduced sensitivity and precision in quantification.
Present techniques are ultimately limited by the separation prior to fragmentation because differences are typically small, making deconvolution of overlapping peaks challenging, and potentially leading to the inaccurate identification and reduced effectiveness of quantification for L- and D- and iso-aspartic acid residues in epimeric mixtures.
In an effort to address these analytical challenges associated with limited resolution of conventional IM approaches, a higher resolution traveling wave (TW)-based HRIM-MS platform built upon MOBILion's SLIM and SLIM serpentine ultralong path with extended routing (SUPER) IM-MS was used in this study.
In this paper, significant differences in protonated versus sodiated peptide mobility peak widths (sodiated ones being far narrower than their protonated counterparts) that would not be evident with lower resolution platforms were noted using MOBILion's SLIM.
âˆ¼4-fold greater sensitivity was achieved because of the combination of in-SLIM ion accumulation followed by a subsequent CRIMP step as compared to ion introduction via the ion funnel trap, increasing the signal-to-noise ratios of measurements.
The MOBILion SLIM-IM technology has broad utility for the separation of other challenging peptide epimers and, more specifically, for clinical applications in probing AÎ² accumulation in AD patients as a complementary technique to existing, classical, biochemical techniques.

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