Bacteria proliferation-mediated cascade amplification for visually ultrasensitive detection of extracellular vesicles

Abstract

In molecular diagnostics, there exist challenges in effectively isolating and sensitively detecting biomarkers such as extracellular vesicles (EVs)11Extracellular vesicles (EVs) visually. Within this study, we propose a highly sensitive and specific point-of-care testing (POCT)22Point-of-Care testing (POCT) strategy that utilizes the rapid capture of E. coli as a surrogate, coupled with volumetric bar-chart chips (V-chip)33volumetric bar-chart chips (V-chip) for EVs markers quantification. Firstly, the signals of EVs markers are transformed to bacteria numbers and exponentially amplified by exploiting the rapid self-proliferative ability of bacteria within a short timeframe. Secondly, the V-chip leverages the catalase activity of platinum nanoparticles (Pt NPs)44platinum nanoparticles (Pt NPs) to achieve further amplification of the bacterial signal. Consequently, integration of both techniques via a cascade amplification strategy significantly enhances the detection sensitivity for EVs biomarkers, enabling a limit of detection (LOD)55limit of detection (LOD) as low as 100 EVs/mL under optimal conditions. Additionally, the entire process of separation and detection is both facile and expeditious. The strategy also exhibits commendable specificity and reliability, making it applicable in the analysis of EVs within clinical samples. Overall, through the amalgamation of bacteria proliferation-mediated cascade amplification, this endeavor furnishes a sensitive and user-friendly platform to enhance EVs detection for POCT diagnostics.