- Photoelectrochemical (PEC) biosensors, with optical biasing and electrochemical readout, are expected to enhance the limit-of-detection of electrochemical biosensors by lowering their background signals. However, when PEC transducers are functionalized with biorecognition layers, their current significantly decreases, which reduces their signal-to-noise ratio and dynamic range. Here, we develop and investigate a wrinkled conductive scaffold for loading photoactive quantum dots into an electrode. The wrinkled photoelectrodes demonstrate an order of magnitude enhancement in the magnitude of the transduced PEC current compared to their planar counterparts. We engineer PEC biosensors by functionalizing the wrinkled photoelectrodes with nucleic acid capture probes. We challenge the sensitivity of the wrinkled and planar biosensors with various concentrations of DNA target and observe a 200 times enhancement in the limit-of-detection for wrinkled versus planar electrodes. In addition to enhanced sensitivity, the wrinkled PEC biosensors are capable of distinguishing between fully complementary and targets with a single base-pair mismatch, demonstrating the suitability of these biosensors for use in clinical diagnostics.