This paper presents a self-powered biosensing platform based on graphdiyne@Au (2D GDY@Au) nanoparticles and rolling circle-hybridization chain (RC-HC) dual linear cascade amplification technology, which significantly enhances target recognition and signal amplification efficiency for miRNA-141. Specifically, the target on bioanode outputs a large amount of single-stranded DNA (T1) through the strand displacement amplification (SDA) mechanism. This efficient target recycling process triggers RC-HC dual linear cascade reaction. The RCA product and H2 form the L-Liner/H2 hybridized chain through a hybridization chain reaction, and then are immobilized on a flexible electrode using a Y-DNA capture handle. [Ru(NH3)6]3+ is precisely anchored in the grooves of the DNA double helix. The 2D GDY@Au enhances the electron mobility of the system to form a rich electron-donating center. The [Ru(NH3)6]3+ on the biocathode receives electrons and is reduced to [Ru(NH3)6]2+, producing a significantly amplified open-circuit voltage signal. Dual linear cascade amplification technology realizes precise target recognition, exponential amplification, and efficient conversion of biological signals. This technique displays an extensive linear range (0.0001–10000 pM) with a detection limit of 25.9 aM (S/N = 3), and it provides an innovative method for developing sensors based on nucleic acid amplification and presents a promising novel approach for the sensitive and precise detection of low-abundance target molecules, highlighting a new tactic for the creation of compact and portable analytical devices.
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