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Liquid chromatography–mass spectrometry (LC-MS) has been the backbone of modern analytical workflows for decades — but what if one of its most trusted components is also its biggest bottleneck? In Episode 50 of Concentrating on Chromatography, host Dave Oliva sits down with Daniel DeBord, Chief Technology Officer at MOBILion Systems, to explore how high-resolution ion mobility may be changing the way scientists think about precursor isolation in tandem MS. Traditional MS/MS workflows rely on quadrupole filtering to isolate precursor ions prior to fragmentation. But because quadrupoles operate as mass filters, they routinely discard the vast majority of incoming ions — often more than 99% — contributing to signal loss, slower acquisition speeds, and chimeric spectra in complex mixtures. Daniel explains how Structures for Lossless Ion Manipulations (SLIM) technology introduces an additional gas-phase separation step between LC and MS — enabling: Near-lossless ion transmission through the instrument Separation based on size-to-charge rather than mass-to-charge Cleaner MS/MS spectra with reduced spectral chimerism LC gradient compression without sacrificing analytical resolution Peak capacities comparable to 20–30 minute LC separations — achieved in milliseconds For chromatographers, this raises an important question: If critical separations can occur in the mobility domain, how much chromatography do we actually need? Daniel also discusses: Whether HRIM could supplement or replace quadrupoles in future instruments Applications in proteomics, metabolomics, and environmental analysis Integrating ion mobility into triple quadrupole workflows Challenges around method development and data processing What the next generation of LC-ion mobility-MS platforms may look like Thank you @SeparationScience for collaborating with me on this episode! --- 🎧 Guest: Daniel DeBord, CTO, MOBILion Systems 🎙 Podcast: Concentrating on Chromatography 📌 Episode 50