Experts pioneer protein analysis technique

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.