US scientists are developing mass spectroscopy technology to focus on developing and translating new assays for protein biomarkers related to cancer, diabetes and heart disease.
At the Biodesign Institute’s Molecular Biomarkers Laboratory at Arizona State University, US scientists are developing mass spectrometric immunoassay (MSIA) technology - a high-throughput protein quantification technique that also provides detailed protein information including post-translation modifications and genetic variants.
During initial research, the team developed a high-throughput method for quantifying and characterising insulin-like growth factor 1 (IGF1) at a rate of around 1,000 human samples a day.
“From our knowledge, this is the first demonstration of a mass spectroscopy-based targeted-proteomics assay for IGF1 – or any protein for that matter – capable of running at this,” said lead researcher Paul Oran.
The method being developed has been dubbed a “top-down” approach to protein quantification.
Instead of digesting the protein by means of proteases like trypsin and extracting the resulting peptide fragments for analysis by mass spectroscopy, a top down method captures a full length protein and any protein variants in their entirety, enabling rapid analysis of a protein and its variants.
“Other competing bottom-up approaches struggle to identify and thus ignore micro-heterogeneity, cost substantially more and require more time and labour per sample,” Oran said.
In its current study, the research team quantified 1,054 human samples in 9 hours – a throughput rate on a par with ELISA – while providing more detailed information on the IGF1 protein, available only through mass spectroscopy. The new method also detected mutations in roughly 1 percent of the samples tested.
Future research will entail a larger validation study intended to support clinical adoption of the assay, the team claims.
“This is really the first viable option for routine analysis in a clinical laboratory that meets cost and time requirements while taking advantage of mass spectroscopy to quantify proteins,” Oran added.