Pushing the Boundaries in Mass Spectrometry
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At this year’s American Society for Mass Spectrometry Annual Conference (ASMS), Technology Networks spoke with Steve Smith, vice president of discovery and development at Waters Corporation, to learn more about the company’s latest innovative product launches.
In our conversation, we explored the many applications of Waters’ technologies, from mass spectrometry imaging (MSI) in spatial biology to combatting bottlenecks in biopharmaceutical development. Smith also discussed how the company continues to prioritize sustainability while pushing the boundaries of what’s possible for its customers.
Molly Campbell (MC): Can you discuss the core bottlenecks presented by customers that have led to the creation of new product launches shared at ASMS 2023?
Steve Smith (SS): Our spatial biology customers told us that they needed to:
- Visualize molecules at therapeutic dosage levels in tissue samples, with a more focused, sensitive and quantitative workflow compared to discovery visualization approaches
- Be able to better differentiate between compounds of similar size and structure (endogenous vs exogenous origin) in their discovery imaging experiments.
Further, when analyzing complex samples or spectra, our customers continued to face challenges in the confidence of small molecule compound identifications, even with a variety of scan types and fragmentation modes available to them. What they needed was greater mass accuracy (parts per billion) and more accurate fine isotope detail, importantly, when coupled with fast chromatographic separations.
MC: Waters Corporation announced new updates to its SELECT SERIES™ MRT System, increasing specificity and utility for metabolomics, drug discovery and mass spectrometry imaging (MSI) applications. Can you talk about the latest enhancements made to the system, and share case study examples of its use?
SS: For the SELECT SERIES™ MRT System (multi-reflecting time-of-flight) mass spectrometer, we introduced Resolution Enhancement Mode (REM). This novel acquisition mode doubles the length of the flight path and increases the resolving power by >50%, enabling >300,000 full width half maximum (FWHM). This allows us to access fine isotope detail, which in combination with the part per billion (ppb) mass accuracy of the MRT, provides unequivocal compound identification in liquid chromatography-mass spectrometry (LC-MS) applications.
The enhanced resolution increases specificity and can be particularly useful for imaging applications. We shared an example where an MS imaging experiment performed at 200,000 resolution (FWHM) enabled visualization of 1 lipid species, but when we employed 300K resolution using the new REM mode on the SELECT SERIES™ MRT, we could see that the one lipid-related species was comprised of two endogenous lipid species and across the tissue section we can observe the different spatial distribution of both these molecules. In addition to the improvements in resolution, we also increased the speed at which we can acquire data and have enabled a data dependent mode of acquisition (DDA).
For MSI applications, we introduced the first targeted MS imaging solution based on the Waters Xevo TQ Absolute tandem quadrupole mass spectrometer. Designed for highly sensitive, fast, and focused MS imaging. This allows the visualization of molecules that have been impossible to gain spatial distribution information about – until now!
Examples are novel radiopharmaceuticals at trace levels in brain tissue which were only possible to image at pharmacological doses previously via traditional high resolution MS imaging.
MC: Environmental analysis took center stage at ASMS 2023, with a particular focus on PFAS testing. Waters Corporation has been working in this space for some time now – can you talk about this history with PFAS testing and how the new products launched will continue to support these efforts? Can you also discuss how Water Corporation is working to support scientists that are in earlier stages of PFAS research, such as discovery?
SS: Waters has provided solutions for PFAS testing as far back as 2013 with the adoption of the United States EPA Unregulated Contaminant Monitoring Rule 3 (UCMR3). Six PFAS compounds (PFOS, PFOA, PFBS, PFHxS, PFHpA and PFNA) were part of the UCMR3 contaminant list. As concern increased around the prevalence of other PFAS compounds in drinking water and the environment, Waters continued to develop specific products to enable routine PFAS testing.
Waters looked at all aspects of the analytical workflow from sample preparation through to report generation. The outcome was a new PFAS workflow comprised of a Waters ACQUITY Premier UPLC System, a Xevo TQ Absolute tandem quadrupole mass spectrometer, Waters_connect for Quantitation Software, ACQUITY Premier BEH Columns, Oasis WAX sample preparation cartridges, PFAS analysis kit and ERA PFAS Proficiency Testing and Certified Reference Materials.
As scientists continue their work in understanding the prevalence and impact of PFAS compounds on our lives, Waters continues to develop products to aid in this endeavor.
MC: Waters and Sartorius also announced a novel collaboration to develop integrated analytical solutions for downstream biomanufacturing. Can you talk about how the integration of software and hardware will help researchers to improve yield, while reducing waste and costs? Can you also talk about the importance of industry collaboration?
SS: With our announcement at ASMS, Waters and Sartorius will focus efforts on implementing near real-time process analytical technologies (PAT) during the downstream purification of recombinant protein biotherapeutics to enable process developers and manufacturing engineers to detect quality deviations earlier and make timely decisions regarding continuous control of the process within the design space, resulting in more consistent drug substance quality, and less out of spec product waste.
To make this possible, Waters and Sartorius are working to more closely integrate the Waters PATROL UPLC Process Analysis System with the Sartorius Resolute® BioSMB multi-column chromatography system to rapidly and continuously monitor critical quality attributes, like aggregation and charge variant profiles in product streams.
The collaboration aimed at integrating these two products involves generating comprehensive application data and modifying the software of the Sartorius BioSMB Process Development (PD) to establish a feedback loop with the Waters PATROL System for dynamic loading.
MC: Can you talk about why sustainable practices are important at Waters Corporation, and discuss efforts that the company is undertaking to work sustainability?
SS: Waters’ approach to sustainability is driven by a combination of top-down and bottom-up initiatives. We have company-wide initiatives and goals, while also empowering individual functional units to achieve reductions in resource use that support those goals. For example, increasing the use of hybrid and electric vehicles in our Europe, the Middle East and Africa-based service fleet, and implementing design changes to increase the use of recycled and recyclable materials in our product packaging.
Another example is the development of Waters’ innovative mass spectrometer, the Xevo TQ Absolute system, which incorporates sustainable design elements. It takes less space and uses 50% less electricity and gas supply than other high-performance tandem quadrupole mass spectrometers available on the market, while also being the most sensitive benchtop tandem mass spectrometer in its class.
Waters has been publishing sustainability/ESG reports since 2009, and our mission is to leave the world better than we found it. Our approach to this is straightforward: we work to be more transparent, to align our disclosures with standardized frameworks, to identify and measure our biggest impacts, and to set quantitative, time-bound goals to drive improvements. In recent years, we have expanded this approach to include diversity, equity and inclusion, philanthropy, STEM education, and corporate governance as areas of focus.
MC: What does Waters foresee as the next “big challenges” that need to be overcome in the MS research space?
SS: The raw performance of MS systems is one thing, performance at speed and in a real-world analytical setting with real sample matrices is another. The analysis of mega-dalton sized molecular species and complexes in biomedical research and the biopharmaceutical discovery and development environment is something we hear about often. Further, the need to deliver high quality results for increasing sample cohort sizes in short time frames continues to pose omics researchers a dilemma in their MS system choices. Researchers are also pushing the boundaries surrounding where MS can be deployed – which is both exciting and extremely challenging at the same time.
Steve Smith, Vice President, Discovery and Development at Waters Corporation was speaking to Molly Campbell, Senior Science Writer at Technology Networks.