April 5 @12:30pm

Dr. John Sausen, Agilent Technologies, Director of Strategic Initiatives — Mass Spectrometry

“Advancing Ion Mobility into Lipidomics, Metabolomics, Exposomics, and Protein Characterization”

Date: Friday, April 5, 2024
Time: 12:30pm
Location: 014 University Hall

Laboratories conducting Multi-Omics analysis have challenging requirements to better define isomeric and isoberic structures across a broad mass range in a relatively short time scale – increasing throughput and reducing cost per sample. This applies to Lipidomics, Metabolomics and Proteomics as well as Protein characterization. Specifically with Native Protein Structures, it would be helpful to determine if there are multiple proteoforms present in putative proteomics biomarkers and therapeutic biomolecules. Recent advancements in Ion Mobility are making this possible. Multiplexing improves Sensitivity, dynamic range, extends the mass range to lower mass. It also enables added statistical significance enabling High Resolution Demultiplexing which can dramatically increase Drift Resolution of Isomers and Isobars while maintaining fast UHPLC acquisition rates as well as a wide mass range – single injection with both high drift resolution and excellent chromatographic fidelity. In addition, Ion Mobility can be predictive in assisting with identifications of unknowns not found in a data base. For example, leveraging high precision CCS Collisional Cross Sections of a homologous series of Lipids or PFAS subunits, or enabling Machine Learning to better predict which unknown isomer hypothesis has the most likelihood of being accurate. The better the precision in the training set, the more accurate the prediction of the putative unknown isomer – will show PFAS as an example, could apply to many isomeric compound classes. We can now achieve and leverage precision of the CCS (0.4 – 0.2%RSD – great precision in the CCS) enabling better accuracy in the predictions. Another important subject is Protein Characterization. Several techniques and assist in helping to determine if there are multiple protoeforms present – Collision Induced Unfolding, being one – compare profiles of a putative protein marker in disease Vs not diseased, or a therapeutic in a bioreactor as one optimizes changing feedstocks – quickly determine if something changed. Agilent has improved the precision to both the CCS and CIU50 Voltage values of native protein unfolding, enabling more confidence in rapidly determining if the protein structure has changed. In addition, with newer electrodes used in the CIU experiments, we are now able to work with larger native protein structures, as large as GroEL. Realtime Microdroplet flash characterization can also offer interesting tools to better rapidly characterize higher order structures.

John has been a part of Agilent Technologies and Hewlett Packard for the past 41 years. He is currently Director of Strategic Initiatives – Mass spectrometry, supporting the America’s field organization. He works with thought leaders in a a business development capacity, building collaborations and collecting customer feedback on changing requirements in the life science markets, with a focus toward triple quad, QTOF, and Ion  Mobility technology and applications.