Video

Rethinking MS/MS with High-Resolution Ion Mobility

Daniel DeBord explains how SLIM-based high-resolution ion mobility challenges quadrupole isolation, accelerates separations, and reshapes LC-MS workflows.
Written byAimee Cichocki
InterviewingDaniel DeBord
Presented byDavid Oliva

Analytical laboratories face constant pressure to increase throughput without sacrificing confidence in complex LC–MS workflows. That tension often exposes the limits of traditional precursor isolation and long chromatographic gradients. High-resolution ion mobility offers another path. By adding rapid gas-phase separation between liquid chromatography (LC) and mass spectrometry (MS), it can improve selectivity, reduce spectral interferences, and ease reliance on extended LC methods. Concentrating on Chromatography's David Oliva speaks with Daniel DeBord, Chief Technology Officer at MOBILion Systems, about how SLIM-based ion mobility aims to reshape MS/MS performance and future LC–MS workflows.

SLIM Technology and Why It Matters

At the heart of MOBILion’s approach is structures for lossless ion manipulations (SLIM), a high-resolution ion mobility platform that introduces an additional gas-phase separation between LC and MS.

Unlike traditional ion mobility methods, SLIM separates ions based on size-to-charge ratio rather than mass-to-charge. This separation occurs rapidly—often in a few hundred milliseconds—compared with 20–30 minutes for typical LC runs. The mobility dimension acts like an additional chromatography spectrum, offering a new layer of separation without sacrificing speed or sensitivity.

DeBord likens SLIM separations to chromatography analogies familiar to LC-MS users: peak capacity correlates with arrival times, and voltage ramps mimic gradient elution. But because the separation occurs in the gas phase, kinetics differ significantly, enabling much faster analysis while preserving precision.

Beyond the Quadrupole: Faster, Cleaner MS/MS

A compelling theme of the interview is how high-resolution ion mobility challenges conventions in tandem mass spectrometry (MS/MS). Quadrupoles, long the workhorse of precursor ion isolation, filter 99% of ions and can generate chimeric spectra when co-isolating molecules with similar mass-to-charge ratios.

SLIM takes a different approach. Through a mode called parallel accumulation mobility-aligned fragmentation (PAMAF), ion mobility separates ions before fragmentation. This allows:

  • Near-lossless ion transmission, meaning nearly all ions introduced at the front end reach detection
  • Faster acquisition rates, now demonstrated at over 1,300 Hz—more than five times faster than leading quadrupole systems
  • Cleaner MS/MS spectra, because mobility resolves isobars and isomers that quadrupoles would co-isolate

DeBord emphasizes that, while quadrupoles retain utility—especially in targeted workflows—high-resolution ion mobility can supplement or, in some designs, replace quadrupole isolation entirely. In workflows where mobility precedes the quadrupole, labs can set wider windows without losing specificity, preserving more ions for analysis and improving quantitative confidence.

Shorter LC Gradients and More Robust Workflows

One of the biggest practical advantages of adding high-resolution ion mobility is the potential to relax reliance on chromatographic separation. In many LC-MS methods, analysts optimize long gradients to resolve challenging compounds. But when mobility provides an orthogonal separation, those constraints lessen.

DeBord explains that SLIM’s gas-phase separations can achieve similar peak capacities to 20–30 minute LC runs in a fraction of the time. This allows:

  • Shortened chromatographic methods with equivalent specificity
  • Reduced method development time
  • Greater robustness against retention time variability
  • Better reproducibility across instruments and labs

High-resolution mobility can also help streamline workflows that previously required multiple injections or distinct chromatographic conditions by capturing additional separation in the ion mobility domain.

Applications and Adoption

MOBILion’s commercial product, MOBI, is already finding traction in life sciences, environmental analysis, and food and beverage testing. DeBord notes that ion mobility’s impact extends wherever complex mixtures and unknown compounds pose analytical challenges. Examples include:

  • Proteomics, where mobility supports deeper peptide characterization
  • Metabolomics, where dynamic, unpredictable metabolite profiles benefit from enhanced separation specificity
  • Environmental studies, where unknown analytes and broad dynamic ranges are common

He foresees broader adoption of ion mobility across both high-end discovery platforms and routine analytical labs. While mobility has been more prevalent in high-end systems like timsTOF, DeBord believes the technology will increasingly influence even triple-quadrupole workflows, improving robustness and lowering barriers to reproducible quantitative results.

Explore Additional Resources

Learn More:

  • Explore the Concentrating On Chromatography podcast to dive into the frontiers of chromatography, mass spectrometry, and sample preparation with host David Oliva.

Connect with Daniel:


Add Separation Science as a preferred source on Google

Add Separation Science as a preferred Google source to see more of our trusted coverage

Meet the Author(s):

  • Aimee Cichocki is the Editorial Director at Separation Science and Chromatography Forum. Aimee brings a broad range of experience in creating, editing, and formatting scientific content. With a degree in medicinal chemistry, a 10-year background in formulation chemistry, an MBA, and a diverse background in publishing, Aimee guides editorial initiatives at Separation Science and Chromatography Forum. Aimee is dedicated to ensuring the delivery of informative, reliable, and practical content to our audience of analytical scientists.

    View Full Profile

Interviewing

  • Separation Science Placeholder Image
    Daniel DeBord, PhD, is the Chief Technology Officer for MOBILion Systems, Inc. He leverages his 15 years of experience developing novel analytical instrumentation to address challenges across a range of application spaces. For the past 10 years, DeBord’s work has focused on developing ion mobility technologies, including trapped ion mobility spectrometry (TIMS) and structures for lossless ion manipulation (SLIM), and exploring how these new techniques can be coupled to mass spectrometry instruments to access higher performance in fields such as proteomics and biopharma characterization.View Full Profile

Speaker

  • Separation Science Placeholder Image

    David Oliva

    David Oliva is the General Manager at Organomation and the producer of the Concentrating on Chromatography podcast.

    View Full Profile

Here are some related topics that may interest you:

Loading Next Article...
Loading Next Article...