Ultrasensitive Photoelectrochemical Biosensor Based on DNA Tetrahedron as Nanocarrier for Efficient Immobilization of CdTe QDs-Methylene Blue as Signal Probe with Near-Zero Background Noise.

Usually, photoelectrochemical (PEC) assays were devoted to the direct modification of photoactive materials on sensing interface, thereby producing high initial signal and unneglected background noise, which could further result in low sensitivity and restricted detection limit during the detection of targets. In this work, a PEC biosensor with near-zero background noise was established for ultrasensitive microRNA-141 (miRNA-141) detection based on DNA tetrahedron (TET) as nanocarrier for efficient immobilization of CdTe quantum dots (QDs)-Methylene Blue (MB) (TET-QDs-MB complex) as signal probe. First, CdTe QDs as PEC signal indicator was bound to the TET through DNA hybridizations. Then, massive MB as PEC signal enhancer was attached to DNA duplex of the TET immobilized with CdTe QDs via intercalation. Thereafter, the as-prepared TET-QDs-MB complex was considered as an efficient PEC signal probe owing to its excellent photovoltaic properties, thereby avoiding direct modification of photoactive materials on sensing interface and producing a near-zero background noise to improve the sensitivity of this PEC biosensor. Besides, the detection sensitivity could be further improved with the help of the duplex specific nuclease (DSN) enzyme-assisted target cycling amplification strategy. The proposed PEC biosensor performs a wide linear range from 50 aM to 50 pM with a low detection limit of 17 aM for miRNA-141, paving a new and promising horizon for highly accurate and ultrasensitive monitoring of multifarious analytes such as proteins, DNAs, and miRNAs in bioanalysis and disease diagnosis.