Precise Molecular Profiling of Circulating Exosomes Using a Metal–Organic Framework-Based Sensing Interface and an Enzyme-Based Electrochemical Logic Platform

Exosomes have emerged as a promising circulating tumor biomarker; however, it is a big challenge for convenient, multiparametric, and accurate profiling of tumorous exosomes due to their unique structure and heterogeneity. To address these problems, we develop a highly integrated electrochemical platform for molecular profiling of tumor exosomes. A metal–organic framework-functionalized sensing interface is fabricated through a simple self-growth process, which collects exosomes from biofluids without additional separation steps. Meanwhile, a sensing strategy is designed to analyze both exosomal protein and RNA markers on a single chip based on the unique sensor architecture, allowing detection of low-abundance targets (∼250 vesicles in a 10 μL sample) using an integrated microfluidic electrochemical device. Furthermore, a multiple-input, protein enzyme-based logic gate is introduced into the system to accurately identify breast cancer patients with 100% sensitivity and specificity, thus revealing the advantageous role of logical profiling of exosomes in early diagnostics of tumor.