An Acoustofluidic Device for Sample Preparation and Detection of Small Extracellular Vesicles

Small extracellular vesicles (sEVs) have emerged as powerful vectors for liquid biopsy, offering a noninvasive window into the dynamic physiological and pathological states of the body. However, to fully leverage the clinical potential of sEV biomarkers, it is imperative to develop robust and efficient technologies for their isolation and analysis. In this study, we introduce a novel sharp-edge acoustofluidic platform designed for rapid and effective sample preparation, coupled with sensitive detection of specific sEV populations based on their surface markers. Our approach utilizes acoustically activated sharp-edge microstructures to concentrate bead-bound sEVs within the microfluidic device, facilitating immediate visualization by fluorescence microscopy. As a proof of principle, we demonstrate the capability of this portable acoustofluidic chip to selectively isolate and detect epidermal growth factor receptor (EGFR)-expressing vesicles, achieving nearly a 6-fold signal enhancement in EGFR-positive sEVs compared to EGFR-negative populations from sample volumes as small as 50 μl. This advancement not only underscores the potential of our platform for high-sensitivity biomarker detection but also paves the way for its application in isolating organ-specific sEVs. Such capability could be transformative for real-time monitoring of organ function and the simultaneous detection of multiple sEV markers, thereby broadening the scope of diagnostic precision and therapeutic decision-making in clinical practice.