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Great Minds Shaping IMS

sponsored by Waters

Over the past century, we’ve seen the power that MS technologies bring to life-changing research. Now, as we transition into a new decade, it is important that we evaluate past successes, but also consider what can be achieved with future innovations. Ion mobility spectrometry–mass spectrometry (IMS-MS) has played a role in breakthroughs across fields – from drug discovery and development to food and environmental analysis. And yet, despite successes and gaining traction, there is a shared feeling in the analytical science community that we have barely scratched the surface of IMS-MS’ immense potential.

The IMS Great Minds Summits (GMS), hosted by Waters Corporation, brought together leading scientists from across the globe to discuss the latest IMS technologies and consider the path ahead. The events, which took place in Kerpen, Germany, and Indianapolis, USA, provided a unique opportunity for IMS-MS experts to help shape the instrumentation of the future.

Fundamentals of IMS

Matt Bush (University of Washington) and Erin Baker (North Carolina State University) explored the fundamentals of IMS-MS in Germany and the USA, respectively, each setting the stage for further discussion. Both Bush and Baker highlighted the key benefits of the method when interfaced with MS: a reduction in spectral complexity, maximized peak capacity, and enhanced selectivity. They also explored IMS-MS’ ability to measure an additional molecular identifier in the form of the collisional cross section (CCS), which offers a number of advantages, including greater confidence in analyte identification and structural elucidation of compounds. Finally, Baker and Bush touched upon the latest technology and current challenges – namely the need for improved software integration.

Recent technological innovations

Kevin Giles, from the Waters MS Research Team, expanded on the theme of technological development at both GMS events, with a presentation that explored the development of traveling wave ion mobility and the exciting capabilities of the first commercial Cyclic IMS instrument. Unveiled at ASMS 2019 and having earned a place on the 2019 Innovation Awards from The Analytical Scientist, the SELECT SERIES™ Cyclic IMS offers greater resolving power and the ability to perform IMSn experiments, enabling researchers to “zoom in” on a selected mobility range. Giles described that, as resolving power increases with the square root of the instrument’s pathlength, the cyclic design permits greater mobility resolution with each pass, while maintaining a compact instrument footprint.

From male infertility to food safety – applications from GMS Europe

The afternoon session on IMS-MS applications at the European GMS was kickstarted by Sheba Jarvis, Clinical Research Fellow at Imperial College London, whose talk focused on the use of IMS-MS in a study that assessed the impact of obesity on male infertility in animal models. The greater peak capacity permitted by IMS was critical for the confident identification of deregulated proteins in the testes associated with a chronic high fat diet, and the novel candidates that her team identified in the animal model study were found to have human relevance. Next: future studies in obese men presenting with infertility.

IMS-MS was able to distinguish human and synthetic insulins (which differ by only one or two amino acids) in just 10 minutes – standard analyses take three times as long.

The role of IMS-MS in sports doping analysis was explored by Mario Thevis from the German Sport University Cologne. He discussed the utility of CCS values as an additional confirmatory parameter in the screening of banned substances. Though not routinely applied in the field of doping control, his research suggests that CCS could provide crucial information to support investigations. A striking example highlighted during the lecture was the application of IMS-MS to doping control analysis of intact, rapid-acting insulin analogues; IMS-MS was able to distinguish human and synthetic insulins (which differ by only one or two amino acids) in just 10 minutes – standard analyses take three times as long.

Applications for IMS-MS in tissue imaging and drug metabolism were also demonstrated. Laura Cole of Sheffield Hallam University, UK, presented her research studying metabolite distribution across whole-body tissue sections – which were clearer than those obtained through autoradiography. And Jan Boerma from York Bioanalytical Solutions started the second day by highlighting how IMS-MS speeds up metabolite identification through enhancement of low- and high-energy mass spectra quality. The former work highlights the potential role of IMS-MS in image acquisitions without the need for radiolabeling of compounds of interest, potentially reducing the cost of drug development, while the latter demonstrates the utility of IMS in reducing noise and resolving co-eluting metabolites.

Perdita Barran from the University of Manchester, UK, delivered an engaging account of her work detecting Parkinson’s disease from sebum. Inspired by Joy Milne – a retired nurse with the ability to smell Parkinson’s disease – Barran is using IMS-MS to identify compounds found at higher-than-usual concentrations on the skin of Parkinson’s patients. IMS-MS is also being used to enhance food safety. Séverine Goscinny from Sciensano, Department of Food, Medicines and Consumer Safety in Belgium, outlined her progress in developing an extensive CCS library in collaboration with Michael McCullagh, Principal Scientist at Waters, to enable rapid detection of food additives. Both fortified and real substance samples have been identified using this method.

Bacterial “fight clubs,” polymer analysis and structural biology from GMS US

John McLean, Department Chair and Stevenson Professor of Chemistry at Vanderbilt University, Tennessee, opened the US GMS event with an inspiring lecture that emphasized how IMS-MS with improved mass resolving power helps solve the challenge of acquiring crucial biological data on short timescales. From aiding CRISPR gene editing experiments to creating bacterial “fight clubs” – that is, monitoring bacterial co-cultures with IMS-MS to discover new therapeutic compounds – the applications discussed were diverse and laid the foundations for another day of stimulating discussion.

From creating new research methods for Parkinson’s disease to developing bacterial “fight clubs” for the discovery of new biological compounds, the applications of IMS technology were shown to be wide-ranging

Chrys Wesdemiotis from the University of Akron, Ohio, shared his IMS-MS analysis of polymers and other materials. In particular, he noted how some bioconjugates were proving to be impossible to characterize with any other method (including
X-ray diffraction), and so IMS-MS represented a powerful technology in his toolbox.

Progress using IMS-MS in gas-phase structural biology was then explored by Brandon Ruotolo of the University of Michigan. His talk evaluated a new calibration method for CCS values to account for mass-to-charge ratio-dependent radial motion, and went on to discuss collision-induced unfolding – able to rapidly differentiate protein isoforms in gas phases based on differing unfolding patterns and stabilities. Potential applications, according to Ruotolo, include biosimilar studies and investigation of cell membrane-drug and cell membrane-protein interactions.

A fantastic finale

Both GMS events were concluded by David Clemmer from Indiana University, who delivered an energetic and informed review of the information that can be derived from studies of protein folding and dynamics. His presentation provided fascinating insight into the latest IMS-based methods for characterizing native and non-native proteins from solution. He also covered the use of IMS-MS for studying conformational changes in protein complexes and the extraordinary potential of charge detection MS, which can supply accurate information about the mass-to-charge ratio and charge of large bioparticles.

The future of IMS-MS – guided by great minds

The Waters IMS Great Minds Summits brought together leaders in the field and provided a forum at which to discuss a range of current topics surrounding IMS technology. From creating new research methods for Parkinson’s disease to developing bacterial “fight clubs” for the discovery of new biological compounds, the applications of IMS technology were shown to be wide-ranging – proof of the great technological gains that have been made.

What challenges remain? Experimental design, data management and data interpretation will all demand increased scrutiny as the technique evolves. And the discussions held at the GMS events helped identify IMS-MS standards, data formats and the application of CCS as three immediate areas for attention.

By facilitating discussion – and the sharing of ideas and challenges, the IMS Great Minds Summits achieved a core objective: to shape the future of IMS-MS instrumentation.

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