DNA-Driven Photothermal Amplification Transducer for Highly Sensitive Visual Determination of Extracellular Vesicles

Extracellular vesicles (EVs) are crucial focus of currentbiomedicalresearch and future medical diagnosis. However, the requirement forspecialized sophisticated instruments for quantitative readouts haslimited the sensitive measurement of EVs to specialized laboratorysettings, which in turn has limited bench-to-bedside translation ofEV-based liquid biopsies. In this work, a straightforward temperature-outputplatform based on a DNA-driven photothermal amplification transducerwas developed for the highly sensitive visual detection of EVs usinga simple household thermometer. The EVs were specifically recognizedby the antibody-aptamer sandwich immune-configuration that was constructedon portable microplates. Via a one-pot reaction, cutting-mediatedexponential rolling circle amplification was initiated in situ onthe EV surface, generating substantial G-quadruplex-DNA-hemin conjugates.Significant amplification in temperature was achieved from the effectivephotothermal conversion and regulation guided by the G-quadruplex-DNA-heminconjugates in the 3,3 ',5,5 '-tetramethylbenzidine-H2O2 system. Through obvious temperature outputs,the DNA-driven photothermal transducer enabled highly sensitive EVdetection at close to the single-particle level and supported thehighly specific identification of tumor-derived EVs directly in serumsamples, without the requirement of any sophisticated instrument orlabeling process. Benefiting from highly sensitive visual quantification,an easy-to-use readout, and portable detection, this photothermometricstrategy is expected to be deliverable across professional on-sitescreening to home self-testing as EV-based liquid biopsies.