CLN Daily

Mass Spec Arrives for the Large Masses

Joe El-Khoury, PhD

The introduction of mass spectrometry into the clinical laboratory space has completely revolutionized the field, with applications ranging from toxicology to microbiology. However, one area where its use has not proliferated as rapidly in most clinical labs is protein measurement. Recognizing that a lack of expertise has been one of the major contributors to the slow adoption of mass spectrometry for protein applications, speakers Mari DeMarco, PhD, and Junyan Shi, PhD, are teaming up for a session today that offers a step-by-step guide on how to design your first protein mass spectrometry assay.

More education is needed on this topic to translate advances in research to patient care, according to Shi. “Protein biomarkers have been studied extensively using proteomics approaches, yet there is a big gap between proteomics discoveries and clinical applications,” Shi said. According to DeMarco, the speakers developed today’s session with the aim of lowering the barrier for clinical laboratories to employ mass spectrometry for qualitative and quantitative peptide and protein analysis.

It was the invention of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) in the late 1980s that afforded mass spectrometry the ability to analyze macro-molecules such as proteins. These advancements were a significant milestone, with the inventors of MALDI and ESI being jointly awarded the 2002 Nobel Prize in Chemistry. For clinical labs, this meant we were no longer limited by our immunoassays to measure proteins. We finally had a new tool that promised superior sensitivity and selectivity to existing platforms (or at least another option when needed).

New applications have emerged since then, with the most prominent being thyroglobulin (Tg) testing by liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, the cost and complexity of developing these assays meant that they were only offered by a few reference labs and academic medical centers in the country. This may seem surprising considering how many labs have adopted mass spec for other applications, but in reality, the workflow for development of protein assays is much different than that of small molecules.

This workflow issue is a major impetus for DeMarco in presenting today’s session. “We were motivated by discussions with colleagues who were experts in small molecule mass spectrometry who expressed apprehension about attempting protein workflows,” she said.

Interested in finding out how to design your first protein assay using mass spectrometry? Learn more about the steps to take at today’s morning session, “Quantitative Protein Mass Spectrometry: A Step-by-Step Guide to Designing Your First Assay.” Shi and DeMarco will cover how to determine if a peptide or protein is a good candidate for a mass spectrometry method and all the front end in silico work that goes into developing that method.