7-(Diethylamino)coumarin-3-carboxylic acid functionalized aptamers induced photoelectrochemical/fluorescence dual-mode microfluidic sensor for integrated detection of three liver cancer biomarkers.

Single-mode biosensor is prone to external interference, and detection of a single biomarker is insufficient for accurate diagnosis of liver cancer. Herein, we report a 7-(Diethylamino)coumarin-3-carboxylic acid (7DCCA) functionalized aptamers induced photoelectrochemical(PEC)/fluorescence(FL) dual-mode aptasensor integrated into a three-channel microfluidic chip for multiplexed detection of three liver cancer biomarkers: alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and Golgi protein 73 (GP73). A robust PEC sensing platform was established using I/S co-doped oxygen-vacancy bismuth oxybromide (ISBO-OVs) modified with gold nanoparticles (Au NPs), with 7DCCA-labeled aptamers (7DCCA-Apt) serving as the unified recognition probes. In the presence of target analytes, 7DCCA-Apts bind to their corresponding targets, dissociating from the complementary strand and releasing into the electrolyte to activate the FL signal; simultaneously, this dissociation reduces the insulating layer thickness and restores the photocurrent response. Furthermore, superoxide anions (•O2-) are generated through the dissolution of oxygen by photogenerated electrons, which reacts with luminol to produce chemiluminescence that as an internal light source to further amplify the PEC signal. The integrated microfluidic aptasensor exhibits a wide linear range (1.0 × 102 fg/mL - 1.0 × 102 ng/mL), low detection limits (31 - 37 fg/mL across the three biomarkers), excellent specificity, stability, and reproducibility for both modes. This strategy enables integrated detection of liver cancer biomarkers, holding great promise for early clinical point-of-care screening.