Chemometric Data Analysis for Deconvolution of Overlapped Ion Mobility Profiles

Abstract

We present the details of a data analysis approach for deconvolution of the ion mobility (IM) overlapped or unresolved species. This approach takes advantage of the ion fragmentation variations as a function of the IM arrival time. The data analysis involves the use of an in-house developed data preprocessing platform for the conversion of the original post-IM/collisioninduced dissociation mass spectrometry (post-IM/CID MS) data to a Matlab compatible format for chemometric analysis. We show that principle component analysis (PCA) can be used to examine the post-IM/CID MS profiles for the presence of mobility-overlapped species. Subsequently, using an interactive self-modeling mixture analysis technique, we show how to calculate the total IM spectrum (TIMS) and CID mass spectrum for each component of the IM overlapped mixtures. Moreover, we show that PCA and IM deconvolution techniques provide complementary results to evaluate the validity of the calculated TIMS profiles. We use two binary mixtures with overlapping IM profiles, including (1) a mixture of two non-isobaric peptides (neurotensin (RRPYIL) and a hexapeptide (WHWLQL)), and (2) an isobaric sugar isomer mixture of raffinose and maltotriose, to demonstrate the applicability of the IM deconvolution.

Competing Noncovalent Host-guest Interactions and H/D Exchange: Reactions of Benzyloxycarbonyl-Proline Glycine Dipeptide Variants with ND3

“…We also used a previously reported post-IM/CID-chemometric approach to examine the presence of potential IM overlapped conformers [59]. Results from post-IM/CID-chemometric studies further confirmed the absence of resolvable multiple IM overlapped conformers for any of the protonated Z-PG and [Z-PG + alkali metal] + species.…”

Determination of ion mobility collision cross sections for unresolved isomeric mixtures using tandem mass spectrometry and chemometric deconvolution

“…TWIM-MS experiments were performed as previously described 37,39,42–44,46 using Synapt G1 (for the pentapeptide binary mixture) and G2-S (for the hexapeptide quaternary mixture) systems (Waters Corporation, Milford, MA, USA). Experimental details on collection of TWIM-MS data reported in this manuscript are included in the supporting information, Table S1.…”

“…Previously, we introduced a chemometric data deconvolution technique 37 based on SIMPLe-to-use Interactive Self-modeling Mixture Analysis (SIMPLISMA) 38 which allowed the extraction of “pure” IM and post-IM/CID mass spectra for IM-unresolved species. Subsequently, we integrated SIMPLISMA into an automated IM deconvolution (AIMD) software, which improved the speed and accuracy of IM-MS analyses.…”

“…39 Moreover, we showed that chemical rank determination techniques 40,41 could be used to identify the number of IM-unresolved species without prior knowledge of the sample composition. 37,39,42–44 …”

Collision-energy resolved ion mobility characterization of isomeric mixtures

“…[30][31][32][33][34] Although these valuable developments have generated impressive results, it may be challenging to implement them in shared instruments, such as in core facilities, or for the everyday user. 8,29,[31][32][33][34][35][36][37] Hence, it is desirable to complement instrument development efforts by designing improved methods for IM-MS data acquisition and interpretation that are independent of the IMS and/or IM-MS instrumental hardware. 8,29,[31][32][33][34][35][36][37] Hence, it is desirable to complement instrument development efforts by designing improved methods for IM-MS data acquisition and interpretation that are independent of the IMS and/or IM-MS instrumental hardware.…”