“…Currently, many isolation methods (e.g., ultracentrifugation, coprecipitation, and size exclusion), and detection techniques, such as optical, electrical, and acoustic sensors, − have been broadly deployed in EV assays, whereas they stress on either EV enrichment or quantification. , Although bioaffinity magnetic particles and microfluidics have advanced EV isolation and detection, − they usually require costly antibodies (e.g., antibody cocktail) and are heavily relied on microfabrication or external forces, , thus limiting the usage of EVs in clinical settings in a more competent fashion. In comparison, transition-metal elements show cost-effective coordinative affinity toward EVs. − Based on such affinities, Ti-based metal oxides (TiO 2 ) and Zr-based metal–organic frameworks (Zr-MOFs) have been exploited for EV capture, − whereas the unordered accumulation or overdispersion of these particles largely degrades downstream in situ, on-site, and multiplexed EV analysis. Despite the progress, developing clinically feasible EV tests, however, is still hampered by several technical challenges, including (i) multistep manual sample separation, (ii) low enrichment efficiency, (iii) limited sensitivity and readout, (iv) costly multiple antibody pairs, and (v) over-reliance on external force or microfabrication.…”