Spatial Ion Compression without Loss of Resolution on a Cyclic Ion Mobility Spectrometry–Mass Spectrometry Platform

Traveling wave-based ion mobility spectrometry-mass spectrometry (IMS-MS) has emerged as an analytical technique, particularly because of technological improvements for enabling the scalable resolution of challenging biomolecules. However, IMS-MS remains limited by peak broadening from diffusion in extended separations, thus precluding further gains in sensitivity and resolution. Previous efforts have attempted to overcome these issues through the development of peak compression strategies, such as compression ratio ion mobility programming (CRIMP) and temporal compression. Unfortunately, both previous compression strategies suffer from certain drawbacks related to resolution. Herein, we present a new reinjection-based spatial ion compression strategy implemented on a commercially available cyclic IMS-MS platform without hardware or software modifications. Our method involves slicing a portion of a mobility peak, storing it in the prestore, and reinjecting it under conditions ensuring a gentle transition back to separation conditions as well optimizing timing for the remerging (i.e., spatial compression) step. Our spatial ion compression approach enables reduction in peak widths, improved sensitivity without any ion losses during reinjection, and allows continued separation after the compression event. We highlight how this compression strategy can enable better feature finding by improving peak intensity and signal-to-noise of a low abundance species as well as achieving near baseline resolution of previously partially resolved compounds. Overall, our reinjection-based spatial ion peak compression strategy can be readily adaptable on any traveling wave-based IMS-MS platforms with ion storage regions (i.e., traps) and is an added one to the suite of existing compression strategies in IMS-MS measurements.