Gold nanoparticle/MXene for multiple and sensitive detection of oncomiRs based on synergetic signal amplification

Multiple and sensitive detection of oncomiRs for accurate cancer diagnostics is still a challenge. Here, a synergetic amplification strategy was introduced by combining a MXene-based electrochemical signal amplification and a duplex-specific nuclease (DSN)-based amplification system for rapid, attomolar and concurrent quantification of multiple microRNAs on a single platform in total plasma. Synthesized MXene-Ti₃C₂T_x modified with 5 nm gold nanoparticles (AuNPs) was casted on a dual screen-printed gold electrode to host vast numbers of DNA probes identically co-immobilized on dedicated electrodes. Interestingly, presence of MXene provided biofouling resistance and enhanced the electrochemical signals by almost 4 folds of magnitude, attributed to its specious surface area and remarkable charge mobility. The 5 nm AuNPs were perfectly distributed within the whole flaky architect of the MXene to give rise to the electrochemical performance of MXene and provide the thiol-Au bonding feature. This synergetic strategy reduced the DSN-based biosensors' assay time to 80 min, provided multiplexability, antifouling activity, substantial sensitivity and specificity (single mutation recognition). The limit of detection of the proposed biosensor for microRNA-21 and microRNA-141 was respectively 204 aM and 138 aM with a wide linear range from 500 aM to 50 nM. As a proof of concept, this newly-developed strategy was coupled with a 96-well adaptive sensing device to successfully profile three cancer plasma samples based on their altered oncomiR abundances.