Single Circulating Vesicle Analysis for Early Cancer Detection

Analysis of circulating extracellular vesicles (EV) have advanced over the last several years but challengesremain to reproducibly analyze samples in a clinical setting. If more sensitive and reproducible methods couldbe established, they would have far reaching applications in early cancer detection, measuring patientresponse to drugs, understanding tumor heterogeneity and discriminating different diseases. The problem ispotentiated in pancreatic cancer (PDAC), where early detection methods are lacking, reproducibility ofmeasurements has been a problem and an understanding of vesicle heterogeneity is missing. Furthermore,most existing technologies rely on bulk measurements which are inherently less sensitive since markers ofinterest are diluted (Yang et al., 2017, Sci Transl Med, 9). The goal of this proposal is to explore a novel singleEV analysis (SEA) method (Lee et al, 2018, ACSnano, in press) to shed light on tumor EV (TEV) biomarkercomposition in PDAC. Specifically, we propose to i) integrate the method with on-chip microfluidics for improvedsample handling while adding a MAb-DNA barcoding step for signal amplification and multiplexing (aim 1) and ii)expand and test the approach for point-of-care analyses of TEV in clinical samples (aim 2). The proposed singlevesicle method has the potential to transform PDAC cancer research and clinical practice. It will allow us to discoverthe make-up of TEV in clinical specimen with far reaching applications for early detection (analysis of rare proteins)and treatment t evaluation in different types of cancers.