Is Ion Mobility Mass Spectrometry Child’s Play?


On Wednesday evening after dinner and my usual digestif, I was watching the webcast “Making Ion Mobility Mass Spectrometry Routine” when my son walked by. “Wow dad, that’s kind of cool! What the heck is it?” he asked.

Collision cross section (CCS) measurements by ion mobility drift times (dt) resolving isomeric metabolites with the same retention time and m/z.
Collision cross-section (CCS) measurements by ion mobility drift times (dt) resolving isomeric metabolites with the same retention time and m/z.

“It’s ion mobility!! It’s an orthogonal and complementary resource for chromatography and mass spectrometry…” The digestif was already working but not enough to miss the blank look on his face. I tried again. “Zach, it’s a different, easy way of getting at an answer or result you obtained from another, somewhat unrelated method.”

“Oh, I see! It’s like solving a math problem in two different ways but I get the same answer so I know my answer is right.” He was so much more succinct.

“Yes, that works. You want to be a business development manager?” I joked. “No thanks!” He shouted as he moved on.

 

The number of peer reviewed papers published annually (to end of 2013). Data generated using web of Science, SCI-expanded between 1985 and 2013 search terms “ion mobility” and “mass spectrometry”. From Lanucara et al, Nature 2014

Indeed, ion mobility mass spectrometry (IMS-MS) is exploding and capturing the interest of the scientific community, with the number of publications in peer-reviewed journals in 2013 increasing to 250 submissions reported by Lanucara, et al., in their Nature 2014 submission. IMS-MS measures the collision cross-section (CCS) of molecules as they move through a drift tube with an inert gas.

The collision cross-section is an inherent property of a molecule in the gas phase and thus affords a complementary technique for characterizing an analyte. CCS is calculated from the three-dimensional shape of the molecule and its chemical structure in the gas phase.  Innovation around IMS-MS has been focused toward research applications, and ion mobility is having impact in many areas including non-targeted discovery proteomics.

By observing changes in mobility and thus conformation and CCS, properties such as conformational dynamics, folding and unfolding intermediates, ligand‑induced conformational changes, aggregation intermediates and quaternary structures (topology) can be determined. However, recent breakthroughs in instrumentation and informatics have brought IMS-MS into laboratories conducting routine analyses and these labs are now also able to realize the benefits of IMS-MS.

The implications of IMS-MS for routine use are significant. The technique is fast. The information garnered significantly outweighs the millisecond time scale of the analysis step.

It effectively reduces chemical noise, and investigators have reported a subsequent 10-fold improvement in sensitivity due to this removal of background interference. CCS measurements provide an additional parameter that can be used for detecting compounds with confidence, which is particularly useful when sample variation and complexity cause retention-time shifting. It can be used to identify isobaric analytes and spectral interferences.

As described by Emma, Nick and Jason in their webinar and related white paper, using ion mobility is now no more complicated than understanding how to use your remote control or hand held device. Understanding the inner workings… well let’s talk about that after the digestif is fully absorbed.

Check out the webinar here:

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Check out the white paper here:

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Delve more into the instrumentation for ion mobility here:

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Vion IMS QTof, one of several IMS-MS systems from Waters.

 

 

 

 

 

 

If you’re interested in how to manage the data that comes out of ion mobility experiments, listen to Dr. Russell Mortishire-Smith, Senior Consulting Scientist at Waters, discuss pivotal advancements in informatics: