Nanofluidic Photoelectrochemical Biosensors for Ultrasensitive Detection of Prostate Cancer Biomarkers

Significant advances have been made in nanofluidic biosensors for the highly efficient detection of disease biomarkers in complex biofluids. However, most research efforts have primarily focused on external voltage-driven sensing mechanisms. Despite their promise, the practical applications of these biosensors are sometimes limited by operational complexity and insufficient sensitivity governed by an interfacial charge-modulated ionic current. Here, we report a novel nanofluidic photoelectrochemical (NPEC) biosensor that integrates the advantages of both nanofluidic and photoelectrochemical biosensors. The NPEC biosensor operates on the principle of target-induced changes of light-driven ion currents across a TiO₂ nanofluidic membrane with nano-in-nano channel structures. NPEC biosensors show several distinct advantages: (1) simplified operation by replacing external voltage with light, as opposed to traditional nanofluidic biosensors; (2) enhanced probe-target interactions by confining and enriching analytes at the entrance of nanochannels, thereby improving detection sensitivity; and (3) reduced interference from nontarget molecules through recording non-Faradaic ionic current signals, thereby promoting selectivity. Accordingly, this biosensor exhibits an excellent sensing performance in detecting protein and small-molecule analytes associated with prostate cancer in complex samples. This study not only presents a novel paradigm for unconventional NPEC biosensors applicable to general biochemical sensing purposes but also suggests that the new concept of nanofluidic photoelectrochemistry marks a significant step toward innovative bioanalytical applications.