Differential photoelectrochemical biosensor and methods of use thereof

A biosensor for detecting a target analyte in a sample comprising:

• a) a photoelectrode comprising a conductive substrate and a photoactive material;
• b) a population of capture probes functionalized on the photoelectrode, wherein the capture probes are configured to bind to the target analyte and a reporter moiety;
• and c) the reporter moiety comprising a detectable label and a capture probe binding portion;
• wherein exposure of the target analyte to the population of the capture probes of b) is configured to result in binding of the target analyte to a fraction of the population of capture probes, which thereby results in a decrease in the intensity of detection signal compared to the intensity of detection signal in the absence of exposure of the target analyte, and wherein the binding of the target analyte to a fraction of the population of capture probes of b) is configured to result in a population of remaining unbound capture probes, and wherein subsequent binding of the reporter moiety to the population of remaining unbound capture probes of c) is configured to result in an increase in intensity in detection signal that is less than an increase in intensity in detection signal from binding of the reporter moiety to a population of capture probes that has not been exposed to the target analyte.