DNA nanoreactor-programmed interface modulation of Schottky junctions via etching for ultrasensitive dual-modal biosensing.

The sensitivity and accuracy of photoelectrochemical (PEC) biosensors are often constrained by high electron-hole recombination rates and reliance on a single detection mode. To address this limitation, an ultrasensitive PEC-colorimetric (CM) dual-mode biosensor has been designed based on DNA nanoreactor-programmed modulation of protonated g-C3N4/AuNPs (PCN/AuNPs) Schottky junctions via a target-triggered etching effect. The Schottky junction formed between AuNPs and PCN through electrostatic interactions effectively modulates the energy band structure, thereby enhancing electron-hole separation. Furthermore, the localized surface plasmon resonance (LSPR) effect of AuNPs broadens the light absorption range, enables a highly localized and intensified electromagnetic field, which promotes rapid interfacial charge transfer. Taking carcinoembryonic antigen (CEA) as a model target, a DNA nanoflower-based cascade nanoreactor integrated with glucose oxidase and horseradish peroxidase (DFs@GOx/HRP) is constructed via rolling circle amplification (RCA) with target-specific aptamer programming. Upon recognition of CEA, a sandwich-type composite forms, initiating a cascade catalytic reaction of the nanoreactor using glucose as the substrate to generate oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), thereby enabling CM detection. In the PEC detection mode, the generated oxTMB under acidic conditions further oxidizes to TMB2+, which etches the AuNPs on the PCN/AuNPs surface, further breaks the Schottky junctions and weakens electrical conductivity, resulting in a decrease in photocurrent. This dual-mode biosensor achieves remarkable detection limits of 16.8 pg mL-1 for PEC and 0.46 ng mL-1 for CM detection along with high specificity. The proposed programmable strategy establishes a universal platform for dual-mode biosensing, facilitating complementary information acquisition from distinct transducers for more comprehensive analytical applications.