2025 ASMS: New Mass Spectrometry Technologies to Confront the Next Wave of Complex Challenges

The 2025 American Society of Mass Spectrometry (ASMS) conference was held June 1-5^th in Baltimore Maryland. This year’s exhibitions, press conferences, and hospitality suites provided abundant opportunities to learn about new trends in the industry and innovations evolving meet the next series of challenges.

From Bottom-Up to Top-Down Analysis

One trend that stood out at this year’s ASMS focused on the evolution of top-down proteomic approaches to solve intact protein size and complexity. The mass spectrometry industry has focused in recent years on bottom-up proteomics due to the accuracy of the approach in providing peptide sequencing information in a range of sample backgrounds. Over this time, bottom-up proteomics grew to become the de facto technique for protein confirmation, protein identification and quantification, quality control, discovery proteomics, and other important applications. Mass spectrometers and data analysis solutions took aim at determining peptide sequence with incredible accuracy, sensitivity, and resolution and relating this by proxy to intact protein characterization.

As mentioned at the conference, we are now approaching the top of the s-curve for bottom-up proteomics where new developments are based on incremental advancements. Technology development has pushed the mass spectrometry field into faster analysis with broader coverage and depth of confidence for protein identification. While this is great progress for proteomics, the bottom-up approach has limitations. For instance, disclosing intact protein structure and post-translational modifications, particularly those that result in similar or identical masses as unmodified proteins, can be difficult if not impossible. Protein modifications including proteoforms that act during signaling and disease processes can escape the eye of bottoms-up methods. Determining the yield of intact proteins can be challenging without the ability to quantify small but significant populations of side products or fragments. These limitations have bearing on therapeutic antibody development, vaccine research, cell and gene therapy, and other important fields.

Although traditional ultra-high-resolution systems such as Fourier-transform mass spectrometers were intact protein pioneers, these systems suffered from rich data capture and the need complex spectral deconvolution. Refined top-down proteomic technologies with significantly enhanced capabilities and have now emerged as front runners in a new wave of innovation.

The Balance of Size and Performance

For many years now the industry has sought to reduce size requirements for mass spectrometers. Innovations have included benchtop triple quads, qTOFs, diminutive MALDI devices, and a range of others. While remarkable devices, a struggle became apparent between pressures to maintain the performance seen in larger instruments while reducing complexity and size. This included front-end separations and ionization technologies for LC-MS platforms and other related tools.

This year’s conference showed a different look to this balance. While size efficiency is a continued theme, size reduction does not seem to correlate with compromises in new technology performance. In fact, in many cases the exact opposite is true. A remarkable shift of this balancing act, companies are now pushing the boundaries of speed and performance through state-of-the-art engineering combined with design of smaller more efficient instruments.

Progress Towards Higher Workflow Efficiency

The advancement in workflow efficiency has been a recurrent theme over recent years as well. Technologies such as on-board maintenance and diagnostics programs aim to reduce downtime. Smart analytics serve to address and correct system inconsistencies. Innovative data capture and analysis strategies seek to reduce cycle time and increase throughput.

This year’s conference showed a continuation of that theme, with many new products designed to enhance analytical capabilities while improving workflow efficiency. This is reflected in many new partnerships introduced between technology vendors -- pushing the needle of performance and productivity.

New Top-Down Performance

• Bruker announced a new initiative in “proteoformics” and has released several new instruments based on their trapped ion mobility spectrometry TOF (timsTOF) technology.
• The timsOmni incorporates several advanced capabilities, including ion enrichment mode and machine learning isotope resolution features, making the system ideal for functional, therapeutic, and pathological protein isoform analysis.
• The timsMetabo merges rich metabolite detection with a digital metabolome archive for current and future mining experiments. Applications of such approaches may involve monitoring metabolite repositories including bile acids and microbiomes and how they change over time or in response to treatment.
• The timsUltraAIP system is designed to probe deeper inter a wider array of sample types offering increased sensitivity, robustness, and overall performance compared to previous high-resolution instruments with complicated workflows.
• Thermo - building on the success of the Orbitrap Astral system which to this point has helped drive research to rates of nearly a publication per day - announced release of the next generations of Orbitrap Astral technologies.
• The Thermo Orbitrap Excedion Pro MS combines Orbitrap Astral analyzers with alternative fragmentation technologies. Together this approach is exceedingly effective for analysis of complex biomolecules, with applications in biotherapeutics and monoclonal antibody development.

Smaller and More Powerful

• Waters announced the Xevo Absolute XR benchtop tandem quadrupole which exhibits a 6-fold increase in reproducibility as tested in over 20,000 injections of crashed human plasma, a number that is still climbing. All while using 50% less power and gas, 50% less bench space, and minimized downtime.
• The benchtop Xevo MRT MS from Waters combines ultra-high 100k resolution with sub-ppm sensitivity using multi-reflectron qTOF technology. Compared to the original MRM qTOF floor device, this is a significant decrease in size and space without sacrificing performance.
• Agilent showcased their pioneering development of a significantly smaller single quadrupole platform that can achieve the performance required for accurate and sensitive protein identification. The Infinity Lab ProIQ and IQPlus mass detectors fit within the Agilent Infinity HPLC stack footprint offering increased range and upper detection limits over previous instruments quadrupole protein detectors.

Building Out Workflow Efficiency

• The new Thermo Orbitrap Astral Zoom demonstrates 30% faster scan speeds, 40% higher throughput, and 50% expanded multiplexing capabilities.
• Thermo also showcased the Optispray column and ion source cartridges which are designed to offer plug and play front-end versatility, while minimizing downtime by avoiding offline column maintenance and source cleaning.
• SCIEX announced the ZenoTOF 8600 qTOF which incorporates AI-enabled software Scan DIA 2.0 and new data conversion tools to perform high-resolution accurate mass analysis with 10-fold higher sensitivity.
• Evosep announced the new Evosep Eno, the next generation of the Evosep One LC separations platform. The new instrument boasts 40% improved throughput evidenced by the ability to process over 2000 proteins per minute and a rate of 500 samples per day. The product release was accompanied by announcements of a partnership with SCIEX for extended reach in the biopharma space.
• Shimadzu showcased the LCMS-2050 as a space-saving single quadrupole combining the accessibility of an LC detector with the performance of an MS. The system enables enhanced detection by combining heated electrospray (HESI) and atmospheric pressure chemical ionization (APCI) in a dual ion source.

Summary

The mass spectrometry industry will continue to see the development of top-down technologies, particularly for expanded applications in single cells, small tissue-specific cells, as well as biopharma workflows. Size and workflow efficiency will continue to be areas of focus as well, as labs look to increase analytical power while continuing to face space and resource limitations. New software solutions with artificial intelligence and machine learning (AI/ML) features will make data access and analysis easier and more efficient. Sustainability will continue to be a growing theme with new processing efficiency and resource usage at the forefront.

It's an exciting time to witness the forefront of unprecedented increases in analytical power balanced with solid enhancements in resource and workflow efficiency. The technologies announced at this year’s ASMS may bring more comprehensive insight into novel therapeutic strategies -- faster and more efficiently.