Prof Ray ILES, Keynote Speaker

PROFESSOR & CHIEF SCIENTIFIC OFFICER @ MAPSciences Ltd and University of Cambridge, Laboratory of Viral Zoonotics


Ray Iles has a BSc in Bioanalysis, MSc in Applied Immunology and PhD in Molecular Pathology from Barts and the London Hospital Medical School. He is a clinical scientist, former University Dean and author of 150+ peer-reviewed publications spanning reproduction to cancer. Through recent advances in mass spectrometry his team has developed techniques and expertise in proteomics and metabolomics as applied to laboratory medicine. Many of these are now patented and form the basis of biomedical start-up companies pioneering post-genomic, faster, efficient and cheaper diagnostic/screening tests.

Rapid viral infection detection and screening by MALDI-ToF MS – how, why and what is next!

The mass spectral approach to the detection of viral particles is distinct from that of bacteria as the marker proteins are several orders of magnitude larger than the house keeping ribosomal proteins exploited as the target high abundance protein biomarkers in MALDI-ToF bacterial identification. Furthermore, these viral proteins can often be glycosylated or otherwise post translationally modified. Thus the  biochemistry of Virus detection is completely different.

There are three distinct elements to virus detection by MALDI-ToF.  1) is rapid and cost effective enrichment /concentration of viral particles within the clinical sample. 2) Chemical liberation of viral proteins in a mass spectrometry friendly manner 3) Suitable matrix formulation and laser, pulse extraction & detector setting for optimal detection of the viral particle proteins.

An optimised methodology was developed primarily for detection of SARS-CoV-2 but which identifies other viral infections. Simple acetone precipitation from biological fluids effectively enriched and concentrate viral particles. A series of mass spectrometry compatible detergents and reducing agents were developed that liberated virion particle proteins for mass spectrometric analysis. The size range of characteristic virion proteins monitored was between 10,000m/z and 100,000m/z. Characteristic patterns can be seen for various enveloped and non -enveloped viruses.

In addition, unlike classical pre-analysis tryptic digest of proteins for liquid chromatography ESI mass analysis, this approach facilitated rapid- direct identification of endogenous and biologically functional cleavage sites of key viral spike/adhesion invasion complexes proteins.  The changes in endogenous cleavage sites of these viral attachment and invasion protein complexes are not only distinguishing mass characteristics, but can also indicate changes in viral pathogenic activity.

The development of clinical MALDI-ToF mass spectrometry will advance through automated bioinformatic analysis of spectra but also improved enrichment chemistries and MALDI matrices. The mass of proteins and viral protein-complexes detected will also increase with improved detector design.

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