Acoustic Ejection Mass Spectrometry Empowers Ultra-Fast Peptide Biomarker Quantification... A Paradigm shift

ABSTRACT: There is an urgent need for increased capacity of accurate quantification of proteins to better understand health and disease. Mechanistically, higher throughput is needed to cope with biological variation; clinically the COVID-19 pandemic has underscored the critical demand for high throughput methods for measuring e.g. acute phase response (APR) proteins or the SARS-CoV-2 viral proteins to characterize infection dynamics. Conventional protein biomarker screening approaches generally rely on capture reagents with colorimetric detection strategies (e.g., immunoassays) which are parallelized to allow for rapid throughput. An alternative detection strategy is mass spectrometry coupled with liquid chromatography (LC-MS). However, this is done sequentially, challenging throughput. Acoustic ejection mass spectrometry (AEMS) has emerged as a potential paradigm shift for ultra-fast screening by MS, at throughputs as fast as 1-2 seconds per analyte per sample. Here, we present the first quantitative AEMS assays utilizing peptide immunocapture to enrich 10 APR protein markers from plasma. We quantified 10 proteins from 267 plasma samples in triplicate in 4.8 hours with %CV between 4.2 and 10.5%, representing a 20-fold speed increase over LC-MS. Similarly, we show the capability of direct SARS-CoV-2 peptide quantification in nasopharyngeal swabs. By leveraging the speed of AEMS technology, combined with the enrichment and selectivity provided by peptide immunocapture, this generalizable approach enables both biomarker screening and diagnostic detection on very large cohorts, accelerating our ability to translate biological discoveries into future clinical use.

ORGANISM(S): Homo Sapiens Severe Acute Respiratory Syndrome Coronavirus 2

SUBMITTER: Bart Van Puyvelde  

PROVIDER: PXD046249 | panorama | Tue Jul 02 00:00:00 BST 2024

REPOSITORIES: PanoramaPublic