Detection of lung cancer poses a great challenge as symptoms often manifest late, at advanced stages. Extracellular vesicles (EV) offer novel targets for early detection as they carry transmembrane proteins inherited from their parent cells. As they were found in exhaled breath, they could provide a non-invasive diagnostic approach.
In this project, we devised an electrochemical biosensor to capture EVs by immobilising an aptamer, a bioreceptor specific for CD44, on gold surfaces. Modified gold plates were used as sensing electrodes in electrochemical impedance spectroscopy (EIS) measurements. Using optimised platforms, EVs isolated from non-small cell lung cancer (NSCLC) were captured, generating successive calibrations with low detection limits. Complementary data using surface plasmon resonance (SPR) and circular dichroism further confirmed EV-aptamer binding, indicating a target-induced mechanism.
Finally, a portable prototype was fabricated via lithography which transferred this platform to a planar electrochemical biosensor. The microfabricated sensor chips required shorter incubation time (15 min) of a tiny sample volume (10 µL) to detect NSCLC EVs. Our results showcase the potential of EVs as alternative biomarkers for rapid, affordable and non-invasive lung cancer screening, a paradigm shift from traditional biomarkers and/or current diagnoses using biopsy and bronchoscopy. Future efforts targeting a cocktail of biomarkers are expected to improve sensitivity and selectivity, removing cross-sensitivity to other diseases. The sensor is highly adaptable for integration into a portable POC nanofluidic device, potentially transforming the aptasensor into a breathalyser for lung cancer.