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.
Yang et al. (Thu,) studied this question.