Accelerating Biomarker Discovery and Validation: From Discovery to Clinical Utility

At MSACL 2025, a Thermo Fisher Scientific–sponsored workshop led by Qin Fu addressed one of the most persistent challenges in proteomics: how to efficiently and reproducibly translate biomarker discoveries into clinically meaningful assays. Drawing on experience spanning academia and industry—including prior work in Jennifer Van Eyk’s lab—Fu shared practical insights into building a scalable, end-to-end biomarker discovery-to-validation pipeline.

mass spectrometry solutions for clinical research and toxicology

The session highlighted how emerging mass spectrometry technologies, automation, and informatics are reshaping biomarker research—reducing complexity, improving reproducibility, and accelerating the path to clinical utility.

The three tiers of biomarker assays

The workshop opened with a review of the widely accepted three-tier framework that guides biomarker development from early discovery through clinical validation:

Tier 3 – discovery
Exploratory, untargeted workflows such as data-dependent acquisition (DDA) and data-independent acquisition (DIA). These approaches prioritize breadth, enabling the identification of large-magnitude biological changes across hundreds to thousands of analytes, typically with low-to-moderate precision and without internal standards.

Tier 2 – verification
Research-grade targeted assays, including parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM). These methods focus on tens to hundreds of analytes, delivering improved precision and repeatability to confirm trends observed during discovery.

Tier 1 – validation
Clinically validated assays designed to meet rigorous quality and regulatory standards. These workflows incorporate internal standards and strict quality controls to ensure quantitative reproducibility suitable for clinical and translational use.

Each tier represents a critical step toward ensuring that biomarker candidates can ultimately deliver reliable patient benefit.

The central challenge: from sample to signal

Reliable biomarker development depends on consistency across the entire analytical workflow—from biological sample preparation to mass spectrometry data acquisition and downstream analysis. Every step introduces potential sources of variability, and minimizing this analytical noise while preserving biological signal is essential.

Automation emerged as a central theme of the workshop. Beyond improving throughput, automation fundamentally enhances reproducibility. Robotic sample preparation reduces variability associated with digestion, pipetting, and handling—enabling consistent performance across hundreds or thousands of samples, a scale that is difficult to achieve manually.

Technological innovation powering a paradigm shift

Recent advances in mass spectrometry are enabling researchers to bridge the gap between discovery and validation more efficiently than ever before. The workshop highlighted several Thermo Fisher Scientific platforms driving this shift:

Thermo Scientific Orbitrap Astral mass spectrometer
Optimized for discovery workflows, the Astral system delivers rapid acquisition and deep proteome coverage while maintaining high precision across large cohorts.
Thermo Scientific Stellar platform
Designed for high-throughput targeted quantification, the Stellar platform supports scalable PRM workflows. Features such as PRM Conductor enable adaptive retention time tracking, which is essential for robust performance in large studies.
Thermo Scientific OptaSpray Ion Source (under evaluation)
A hands-free ionization source designed to deliver consistent spray performance with simplified maintenance, supporting reproducibility across thousands of injections.

Together, these technologies create a smoother continuum across assay tiers, shortening timelines and reducing barriers to clinical translation.

Case study: Inflammatory bowel disease (IBD) cohort

A key highlight of the presentation was a large-scale biomarker study in inflammatory bowel disease (IBD). The team conducted a 500-sample discovery analysis, followed by validation in a 1,000-sample cohort. Discovery was performed using the Orbitrap Astral system, while targeted validation employed the Stellar platform.

This integrated approach successfully confirmed established biomarkers such as C-reactive protein (CRP) while also identifying novel protein candidates with strong translational potential. Importantly, these markers demonstrated consistency across discovery and validation data sets—underscoring the power of advanced instrumentation combined with robust workflows and informatics.

From high quantity to high quality

Historically, biomarker discovery has involved a tradeoff between throughput and data quality. The workshop demonstrated that this compromise is no longer necessary. By integrating automated sample preparation, optimized informatics, and next-generation mass spectrometry, researchers can now generate high-quality, high-throughput data that is both scalable and reproducible.

This shift enables faster discovery while increasing confidence that candidate biomarkers are ready for downstream validation and clinical follow-up.

The future of biomarker translation

The workshop concluded on an optimistic note. Innovations in proteomics are fundamentally transforming biomarker development—shortening timelines, reducing costs, and accelerating the transition from discovery to clinical application.

By integrating platforms such as Orbitrap Astral, Stellar, and OptaSpray, Thermo Fisher Scientific is helping advance a new era of translational biomarker science—where precision, scalability, and reliability work together to deliver meaningful clinical impact.

Watch the full workshop recording to explore the data, workflows, and results behind this end-to-end approach to biomarker discovery and validation.

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