Integrated photoelectrochemical-organic electrochemical transistor biosensor based on AS1411 aptamer and n-GaN/Au electrode for nucleolin detection.

Nucleolin (NCL) is a critical biomarker for early cancer diagnosis and prognostic evaluation. To overcome the limitations of existing detection methods, such as insufficient sensitivity and cumbersome procedures, this study reports an ultrasensitive biosensing platform based on an organic photoelectrochemical transistor (OPECT). The biosensor employs a guanine-rich DNA aptamer, AS1411, immobilized on an n-GaN/Au gate electrode. Specific binding to NCL induces AS1411 to fold into a G-quadruplex (G4) structure, whose intrinsic π-π stacking interactions are proposed to establish an efficient charge transport channel. This effect substantially promotes the separation of photogenerated holes, and combining this with the intrinsic gain of the OPECT transconductance mechanism yields notable signal amplification. As a result, the proposed sensor exhibits ultrahigh sensitivity with a limit of detection (LOD) of 0.28 pM (S/N = 3) and a wide linear range from 1 pM to 100 nM. The excellent analytical performance originates from the synergistic effect of OPECT amplification, G4-mediated charge transport, efficient photoelectric conversion of the GaN/Au gate, and minimal signal loss. Moreover, the biosensor demonstrates high selectivity against potential interfering proteins and reliable quantitative accuracy in complex biological matrices. In the analysis of breast cancer cell lysates, recoveries range from 96.4% to 97.6%, consistent with the standard ELISA method. This work establishes a label-free detection strategy wherein ultrasensitive signal transduction is achieved exclusively through aptamer conformational switching-without requiring heterojunction engineering enabling point-of-care NCL analysis.