Integration of a high duty cycle SLIM mobility filter with a triple quadrupole mass spectrometer for targeted quantitative analysis

A high sensitivity, high-resolution platform using a structures for lossless ion manipulation (SLIM) ion mobility (IM) filter in conjunction with a triple quadrupole mass spectrometer (QQQ-MS) was developed and implemented as a means to enhance performance for targeted quantitative analysis using ion mobility mass spectrometry (IMMS). Differential mobility spectrometry (DMS) and field asymmetric ion mobility spectrometry (FAIMS) have previously been integrated with QQQ-MS but both typically suffer from limited resolution and ion transmission efficiency (i.e., sensitivity). This new approach uses SLIM to combine mobility pre-filtering, ion enrichment functionality with high-resolution parallelized mobility filtering on multiple ion paths to improve the analytical duty cycle. Multiple samples including aldosterone and cortisone as the demonstration of value on a relevant clinical application were analyzed on a standalone SLIM mobility filter as well as a SLIM-QQQ system employed in various operating modes to evaluate the duty cycle (i.e., sensitivity) improvement. 100% duty cycle SLIM mobility filtering for Agilent tuning mix ions was achieved with two identical ion paths implemented to allow for parallelization of the analysis. A ~30-80% practical ion utilization efficiency was measured on the SLIM-QQQ system in mobility and m/z two-dimensional filtering mode for various analytes from standard mixtures, improving selectivity while also realizing a modest increase in detection/quantification limits (1.5-3x improvement). We believe this new SLIM-QQQ approach will provide a fast, high sensitivity, and high specificity targeted quantitative analysis tool which dramatically improves the ion utilization efficiency as compared to previous IMS-enabled mass spectrometry approaches.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

A new high sensitivity, high-resolution platform was developed using SLIM ion mobility filter with QQQ-MS to enhance performance for targeted quantitative analysis. The experimental results demonstrated that the SLIM-QQQ approach significantly improved ion utilization efficiency and detection/quantification limits in various operating modes.