Circulating exosomes and extracellular vesicles (EVs) present in bodily fluids carry biomarkers that may enable minimally invasive diagnosis through liquid biopsies. Isolation of exosomes, however, has proven challenging. In order to help pave the way of clinical applications of exosomes, we have developed a lab-on-a-chip technology (nanoDLD) which efficiently separates and concentrates exosomes. I will show that nanoDLD compares favorably with other standard isolation techniques in terms of yield, concentration and reproducibility. To study the type of transcriptomics cargo carried by nanoDLD isolated exosomes we collaborated with the NIH Extracellular RNA Communication Consortium, which has recently categorized RNA carried in biofluids as cargo of 6 different types of carriers such as EVs, lipoproteins and ribonucleoproteins. We found that nanoDLD isolated exosomes carry one of the six specific cargo types which is reproducible and similar in the serum of different subjects. Finally, we studied the tissue of origin in the mixture of all EVs isolated from serum and urine, by analyzing the transcriptome of matched exosomes and prostatic tissue in prostate cancer patients.

We found dozens of RNA markers which are common (and some exclusive) to their prostate tissue of origin and coincident across patients, indicating the prostatic origin of a subset of circulating EVs.