Real-time Low-background Digital Liquid Biopsy for Cancer Diagnosis


Liquid biopsies are a small volume (~mL) sample collected from blood and urine for cancer diagnostics. Compared to traditional tissue biopsy, liquid biopsies have the advantage of being rapid, precise, and less invasive. Small extracellular vesicles (sEVs) are small vesicles (< 120 nm) secreted by cells into all biofluids. sEVs are diagnostically valuable because they are secreted by tumor cells in large amounts and carry biomarkers unique to both the tumor and tissue of origin. Thus, the detection of tumor biomarkers in blood or urine on sEVs is a promising avenue for the development of ‘liquid biopsies.’ Current bulk analysis techniques for identifying sEVs suffer from very high background noise because relevant sEVs represent only a very small fraction of all sEVs in biofluids and there is colocalization of multiple biomarkers on single sEVs. The alternatives of single sEV analysis are inefficient given the size limitation of sEVs and tumor heterogeneity. Thus, there is an unmet need to develop new methods for bulk analysis of sEVs.

Technology Overview

Researchers have developed a microfluidic method for isolating sEVs in the pores of ultrathin nanoporous silicon nitride membranes (NPN) we call catch-and-display for liquid biopsy (CAD-LB). Biomarker-tagged serum or urine is injected into a microfluidic device containing an NPN membrane which captures millions of sEVs within seconds. The spatially isolated sEVs are then imaged with fluorescence microscopy and quantified with particle counting software. Our system is sensitive to even a single target sEV. Detection of rare biomarkers in human samples has been demonstrated experimentally.


The new detection method 1) has a very simple sample preparation process, 2) rapidly displays with low background sEVs carrying relevant biomarkers, 3) uses standard fluorescence microscopy techniques, and 4) enables the detection of rare biomarkers, even those comprising less than 1% of the sEV population.


  • EV biogenesis
  • EV heterogeneity
  • Cancer/tumor diagnostics
URV Reference Number: 2-20064
Patent Information:
For Information, Contact:
McKenna Geiger
Licensing Manager
University of Rochester
James McGrath
Richard Waugh
Julie Kuebel
Michael Klaczko