Understanding How Disease Develops With Advances in Mass Spectrometry

As spatial omics and multiomics research continue to expand into larger cohorts and more complex biological questions, analytical technologies are under increasing pressure to deliver faster, deeper, and more integrated insights. Advanced mass spectrometry (MS) solutions are at the heart of these efforts, enabling researchers to probe proteins, metabolites, and lipids with unprecedented precision. However, long‑standing trade‑offs between acquisition speed, sensitivity, and data quality have historically constrained throughput and scalability.

At the 74th ASMS Conference on Mass Spectrometry and Allied Topics, Waters Corporation unveiled two new instruments geared towards accelerating multiomics and spatial omics research—the Xevo™ MRT P10 Mass Spectrometer and the Cyclic IMS P20 Mass Spectrometer. Both instruments offer stark improvements in sensitivity, enabling deeper biological insight to advance omics research.

These innovations could help researchers to detect previously unattainable signals for disease, according to James Hallam, Waters’ vice-president of the liquid chromatography-MS (LC-MS) business segment, and Gary Harland, portfolio owner for discovery, characterization, and imaging high-resolution-MS (HRMS). To learn more about how advances in MS could support the researchers furthering our understanding of disease development, Technology Networks sat down with Hallam and Harland at the event to discuss.

Eliminating the speed–sensitivity trade-off in multiomics workflows

What do faster acquisition speeds and improved sensitivity mean for real‑world multiomics and therapeutic applications?

Historically, researchers have had to balance acquisition speed against data quality when designing HRMS experiments. To conduct large-cohort biomedical research and epidemiology studies, researchers need to be able to acquire data quickly, to increase sample throughput while retaining very high resolution.

According to Hallam, recent instrumentation advances are removing this constraint: “For the Xevo MRT P10 MS, we can get 100,000 FWHM [full width at half maximum] resolution while also running at speeds of 200 Hertz. That means that researchers can run large cohort studies very quickly without sacrificing data quality, which was something that was not possible before.”

These advances are particularly relevant for metabolomics and lipidomics-type studies. But advancements in MS/MS sensitivity are also advancing proteomics studies.

“In MS/MS mode, we now have a 20x improvement in sensitivity versus the previous generation. That enables us to look at proteomics workflows as well and get much deeper proteomic coverage,” Hallam said. “Crucially, this means being able to run up to 300 samples per day and still get that depth of proteome coverage.”

Harland contextualized this broader challenge: “It’s the Holy Grail, isn’t it? Speed, sensitivity, and resolution. That performance envelope has always been the big analytical challenge in most of these experiments.”

There are other aspects of a workflow that can also speed up the overall time to results when working through a large volume of samples, Harland notes, such as improvements to sample preparation. But by “almost over-engineering performance capability, you give researchers more space to operate in, and this allows them to do things such as short gradients on their separations,” Harland said. “If you are able to use the performance of your mass spectrometer to offset against some of these things, it means you can create simpler methods and faster workflows without having to compromise your data quality; you can use the performance gain in one space to play off against other elements of your overall analysis.”

What this means for labs:

• High resolution (100,000 FWHM) and acquisition speeds (~200 Hz) support large cohort studies
• Sensitivity gains enable deeper proteomic profiling across high sample volumes
• Performance improvements can streamline upstream and downstream workflows

AI and hybrid acquisition strategies address the data bottleneck

How are vendors managing the surge in data generated by high‑throughput HRMS?

As throughput increases, data analysis becomes a major bottleneck. This means that, while advancements in hardware are extremely valuable to researchers, equal advances in data handling and analysis software are needed to truly unlock a new level of operation.

“Particularly when we first launched the [original] Xevo MRT, we announced a number of collaborations with third-party software providers, like MassMetaSite, to standardize workflows there,” Hallam said.

In addition to collaborating with software providers and developing in-house tools, Hallam is excited about the potential outcomes of integrating artificial intelligence (AI) tools into data analysis. “Everyone is talking about what AI can do in this space; in real terms, that means having machine learning (ML) algorithms that can better teach software about how to process data effectively, so you don’t need as much manual manipulation there,” Hallam explained. “When you’ve got this huge number of samples, you just cannot have that sort of manual intervention happening.”

As Harland added: “Doing more targeted analyses, knowing what you are looking for, can also reduce the overall volume of data you’re producing.”

At the acquisition level, Harland described a hybrid strategy designed to balance comprehensive data capture with manageable file sizes: “We have a new acquisition mode on the Xevo MRT P10, called SONAR Pulse, which allows us to do very fast DIA acquisition with fast chromatographic separations. It’s a kind of hybrid between DIA and DDA; it gives the data quality you would get with a DDA experiment, which is what everybody would like to try to run, but with a DIA setup.”

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In addition to easier setup, this process also results in smaller file sizes, Harland noted, which can further improve the ease of data analysis.

Key implications for data workflows:

• AI could reduce the need for manual intervention in large datasets
• SONAR Pulse acquisition modes minimize file size without sacrificing insight

Cyclic IMS unlocks subtle molecular differences in disease biology

Where can cyclic IMS provide new biological insights?

By spinning ions multiple times around a circular path, multipass cyclic ion mobility spectrometry (cIMS) can achieve extremely high separation resolution. The new Cyclic IMS P20 platform now also features integrated and interchangeable matrix-assisted laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI) imaging, to offer a comprehensive solution for structural and spatial omics studies.

“Having a deeper understanding of the way proteins fold, misfold, and unfold, that is a significant area,” Hallam said. As a part of the Waters ASMS 2026 events, Prof. Konstantinos (Kostas) Thalassinos, University College London, a long-time user of Waters instruments, took part in a fireside chat-style interview where he shared more about his research using MS-based structural proteomics to investigate the dynamics and causes of protein misfolding diseases.

“Kostas talked a lot about his research, protein misfolding, and how this is linked to neurodegenerative diseases,” Hallam summarized. “These are such subtle molecular differences, and if you identify those, then it gives you a much deeper understanding of what is happening within those disease states. That is one example.”

Harland expanded on the importance of resolving isomeric and low‑abundance species for disease research.

“Within a protein structure, you can have a very simple modification, a small change on an amino acid, or isomerism. That can be very difficult to distinguish with traditional MS techniques,” Harland said. “Kostas has been working on this for more than 20 years with us, through generations of technology. Now, they have the sensitivity to see these really rare, low-abundance changes. This new level of analytical performance is making a big difference.”

Scientific impact highlights:

• Improved sensitivity enables the detection of subtle molecular changes
• Supports characterization of protein misfolding in diseases
• Expands the observable dynamic range for low‑abundance species

Expanding access to therapies through analytical advancements

What are the key challenges in translating these advances into healthcare impact?

Despite technical progress, accessibility remains a major challenge in modern therapeutics. Hallam emphasized the role that analytical technologies can play in improving this accessibility, for example, by enabling biosimilars development.

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“Some modern medicines are very expensive, and so they are only accessible to a very small proportion of the population,” Hallam said. “We are working with generics companies and giving them access to our instrumentation so that biosimilars can be developed faster. With biosimilars, this enables better access to more medicines for a much larger proportion of the population who don’t necessarily have the wealth of other regions or nations.”

“That is probably what drives Waters the most—that vision of making medicines more accessible.” — James Hallam.

Harland framed the broader mission: “I think it is a very personal thing. Everybody shares a vision around trying to solve these problems and benefit human health.”

Broader industry takeaways:

• Biosimilars development is key to improving therapy accessibility
• HRMS platforms can support the development of biosimilars

Integrating multiomics layers: The strategic impact of the BDS combination

How does the combination with BD Biosciences and Diagnostic Solutions (BDB and DS) business expand Waters’ capabilities?

At the start of 2026, Waters announced it had completed its combination with the Biosciences & Diagnostic Solutions businesses of Becton, Dickinson and Company (BD). Following this, four new divisions were formed: Waters Analytical Sciences, Waters Biosciences, Waters Advanced Diagnostics, and Waters Materials Sciences.

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This combination has resulted in a new, expanded scope that can support more layers of omics research, Hallam and Harland explained.

“With access to the technologies of BD Biosciences, we have access to cellular-level information as well as Waters’ molecular-level information; it gives a deeper understanding on a biological level,” Hallam said. “Some of these technologies are things we previously didn’t have access to, so this combination is a really powerful thing for the customer base.”

Harland also emphasized its potential impact for precision medicine: “In the space that my team works in, with multiomics, I think of the health services industry, the move towards precision medicines and predictive cancer diagnostics. This type of move to understand the population ahead of time is a part of the genomics and transcriptomics layer of multiomics, where BD really excels. Then, with protein expression, you start to get into the LC-MS analytical technologies with proteomics, lipidomics, and metabolomics. At each of these layers—from molecular to structural—we have the opportunity as a combined organization to maximize the expertise there and bring that to healthcare.”

“Another example—BD has a very strong presence in diagnostics,” Hallam added. “For a number of years, Waters has been pursuing LC-MS in the diagnostics space very successfully. This [combination] gives a much bigger footprint in the diagnostics space that we can use to continue to develop LC-MS as a technique for this space.”

The combination of Waters with BD’s BDS business:

• Combines cellular and molecular data for holistic multiomics analysis
• Supports predictive and precision medicine initiatives

This content includes text that has been created with the assistance of generative AI and has undergone editorial review before publishing. Technology Networks' AI policy can be found here.