Accurate and portable tumor exosomes detection based on manganese dioxide and aptamer-functionalized fluorescent microspheres mediated dual-mode lateral flow assay

As biomarkers for liquid biopsy, tumor exosomes play a key role in the early tumor diagnosis and postoperative monitoring. However, the accurate and portable detection of exosomes remains a big challenge. Here, a novel lateral flow test strips based on manganese dioxide (MnO2) and aptamer-functionalized fluorescent microspheres (FMs-aptamer) was developed for colorimetry/fluorescence dual-mode sensing of cancer-associated exosomes (using MCF-7 cells derived exosomes as model) in serum samples. Various characterizations (including UV-vis, FTIR, SEM, TEM, DLS, XRD and XPS) were first carried out to demonstrate the successful preparation of test strips. In this work, the size advantage of exosomes is skillfully used to mediate the fluorescence resonance energy transfer (FRET) between FMs (donors) and MnO2 (acceptor), thus a dual-mode output platform was constructed. Compared to the single-readout test strips, our proposed method could reduce the false positive via recording the change of two different signals. This test strip realized sensitive and accurate detection of MCF-7 exosomes, with a detection limit of 2.5x103 particles/mL. Importantly, the platform enables direct and rapid detection of cancer exosomes in serum samples without tedious sample pretreatment process, showing its great potential for point-of-care tests.