Abstract

Use of Circulating Extracellular Vesicle Protein Biomarkers to Detect Disease Earlier

Jean Lewis, Director, Research, Biological Dynamics

Circulating extracellular vesicles (EVs) contain a wealth of biomarkers and are key to numerous emerging liquid biopsy approaches; information from these EV biomarkers can be harnessed for diagnosis of many different diseases.  For example, EVs released from tumors may carry biomarkers signaling the presence and type of cancer; EVs bearing markers of neurological damage can be found in circulating blood, and in the case of infectious disease, pathogen-related markers can be released on EVs from infected blood cells.  While there are multiple innovative, emerging technologies designed to measure EV biomarker levels, many rely on multi-step procedures for prior isolation of the EVs from plasma or serum or are very low throughput.  To advance EV biomarker analysis towards true point-of-care diagnostics, we have developed a lab-on-a-chip nanoparticle isolation platform (Verita™), designed to both isolate and immobilize extracellular vesicles directly from unprocessed blood fractions onto an AC Electrokinetics (ACE) microelectrode array.  The EV-associated biomarkers can be either eluted for further analysis or quantified directly on-chip, where the entire process takes less than an hour, showing the potential for point-of-care applications.  The Verita™ platform was used to screen clinical serum or plasma samples and demonstrated feasibility for detecting various disease types.  For example, performance of an assay using ACE-purified plasma EVs from stages I-II pancreatic cancer showed a sensitivity of 83% at 99% specificity.  EVs quantified directly on-chip can be probed with biomarkers related to early cancer or Alzheimer’s disease, and can be used to detect TB infection with an AUC of 1.00.