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Next-generation LC-MS technologies enable robust, high-quality proteome profiling

Beyond the Boundaries of LC-MS for Large Sample Proteomic Studies

Next-generation LC-MS technologies enable robust, high-quality proteome profiling

Alexander Boychenko, PhD

Alexander Boychenko, PhD, is a product marketing manager in the chromatography and mass spectrometry group at Thermo Fisher Scientific, Inc. focused on bringing innovative applications and life science technologies to market. He holds a PhD in analytical chemistry, and before joining the company, worked as a postdoctoral researcher at the University of Groningen, The Netherlands, where he developed LC-MS techniques for discovery and validation of protein biomarkers in cervical cancer diagnostics. With a strong scientific background in chromatography, mass spectrometry, physical chemistry, chemometrics, and bioinformatics Alexander is a subject matter expert in LC-MS analysis and theory, new separation technologies, multidimensional separations, LC-MS data analysis and data interpretation in proteomics, and biomarker discovery and validation. He utilizes his passion for translating scientists’ technology and application requirements into novel nano-, capillary-, and micro-flow LC-MS workflows and LC products seamlessly hyphenated with mass spectrometry instruments.


The search for regulated proteins that differ between cases and controls is the primary goal of biomarker discovery studies, biopharmaceutical development, translational proteomics, and precision medicine [1]. However, the multiple sources of variation in these studies are limiting factors for scientists and could lead to erroneous conclusions.

The challenges of variation can be effectively overcome using innovative high-pressure liquid chromatography-mass spectrometry (LC-MS). LC-MS is often deployed in the discovery and early validation phases of proteomics studies to find more specific and sensitive biomarkers associated with a particular state [2]. 

When paired with advanced software and automated data analysis workflows, LC-MS also has the potential to be used for routine applications in clinical research. Advanced LC-MS workflows offer a range of advantages for large sample cohort analysis, including enhanced reproducibility and automation, and could ultimately enable proteomics to become a key technology in clinical settings.

Next-generation technologies offer new capabilities

High-throughput capillary and micro-flow LC-MS methods have gained traction for profiling proteomes, including in biological fluids and tissues. Increased manufacturing reproducibility for LC and MS instrumentation, long-lasting columns and stable electrospray ionization interfaces, together with high loading capacity and low overhead times [3-5] are pushing proteomics beyond the realm of traditional research laboratories.

The almost unlimited possibilities of MS for label or label-free quantification with data-dependent and data-independent acquisition are complemented by LC’s capabilities for nonstop operation. As a result, proteomics is experiencing rapid expansion across many routine application areas, accelerated by the possibility of obtaining reproducible data from laboratories across continents.

Courtesy of thermo fisher scientific

Improving reproducibility and robustness

Standardized LC-MS workflows produce accurate, precise, and reproducible results [4]. They also offer the advantages of multiplexing, high analytical sensitivity, and unsurpassed target selectivity. This opens the door to obtaining clinically relevant results from large sample cohort analyses, enabling translational proteomics to complement other -omics disciplines, such as genomics, transcriptomics, and metabolomics.

However, there can be multiple sources of variation in an LC-MS experiment (biological, analytical and sample related), which might lead to irreproducible results. A thorough understanding of the analytical process, how to standardize procedures, and how to reduce uncertainty within experiments by LC and MS technology manufactures becomes essential to help researchers achieve high-quality results. 

Achieving reproducibility across laboratories, combined with high sensitivity analysis and high-throughput methods, will enable researchers to collect large datasets, merge data from multiple sites, and ultimately draw statistically significant conclusions. Thus, the next-generation instrumentation can enable LC-MS proteomics to transition from pure academic research into a reliable tool for day-to-day use in clinical contexts.

Transforming the landscape of proteomics

Intelligent and versatile LC-MS systems with a high level of standardization offer the ability to process hundreds of samples per day, allowing biological and clinical questions to be answered faster. This means scientists can focus on generating results, increasing the productivity of their work and reducing cost-per-sample.

Recent advances in LC-MS have skyrocketed the possibilities of translational proteomics and improved understanding of health and disease. Looking to the future, LC-MS has the potential to become a core technology in clinical research and routine clinical analysis. It could even be used to track patient response to treatment, allowing therapeutic regimens to be adjusted for optimum effect and maximizing patient benefit.

References:

  1. Expert Review of Proteomics, 2021 DOI: 10.1080/14789450.2021.1980387
  2. Analytical Chemistry 2021, 93, 28, 9663-9668 DOI: 10.1021/acs.analchem.1c01291
  3. Nature Communications volume 11, Article number: 157 (2020) DOI: 10.1038/s41467-019-13973-x
  4. Analytical Chemistry 2021, 93, 8, 3686-3690 DOI: 10.1021/acs.analchem.1c00257
  5. Analytical Chemistry 2021, 93, 25, 8687-8692 DOI: 10.1021/acs.analchem.1c00738