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. [Display omitted] •High sensitivity and high-resolution SLIM-based ion mobility filter was integrated with a QQQ mass spectrometer.•100% duty cycle was achieved for various compounds in high duty cycle mobility filtering mode.•1.5-3x sensitivity improvement was achieved on the integrated SLIM-QQQ platform compared to the QQQ system.