Photoelectrochemical detection of let-7a based on toehold-mediated strand displacement reaction and Bi2S3 nanoflower for signal amplification

•The nanoflower-shaped Bi2S3 had a high photoelectric activity and large specific surface area.•Toehold-mediated strand displacement reaction without enzyme was used to recycle target for signal amplification.•TSDR strategy improved the sensitivity and reaction efficiency of the biosensor. Herein, a photoelectrochemical (PEC) biosensor we proposed was used to detect let-7a via studying the photocurrent response change resulted from the change of the toehold-mediated strand displacement reaction (TSDR) between the AuNPs-H2 (a conjugate of gold nanoparticles and DNA strand H2) and let-7a. Without the participation of let-7a, after the alkaline phosphatase (ALP) were immobilized at Bi2S3 surface through modified on the AuNPs-H2, ALP converted the ascorbic acid 2-phosphate (AAP) to produce ascorbic acid (AA), AA could be catalytically oxidized to provide electrons, resulting in the enhancement of photocurrent signal on the Bi2S3. In contrast, the conjugate of ALP@AuNPs-H2 (a conjugate of ALP and AuNPs-H2) were compelled away from Bi2S3 surface when the let-7a participated in the process and hybridized with H1. The fuel DNA assisted the recycling of the let-7a via another TSDR, the recovered let-7a could participate in the next enzyme-free cycle. The PEC biosensor not only exploited TSDR signal amplification strategy, but also achieved good linearity in the range of 0.01 nM-1000 nM with a low detection limit of 6.7 pM. Due to the excellent performance, we believe it will offer more opportunities for bioanalysis and clinical biomedicine.