Miniaturizing Sensor Active Areas to Enhance Analyte Surface Densities by Increasing “Effective” Analyte Concentrations

The drive to miniaturize sensing footprints to the micro- and nanoscale has been motivated by reduced sensor real estate, lower sample consumption, and quick response times. However, there remains a limited understanding of how reducing sensor active areas impacts analyte–sensor interactions at fixed analyte concentrations. Using gold nanoparticles as a model analyte, we demonstrate that diminishing sensor active areas are associated with a nonlinear enhancement of analyte surface densities without changing the solution concentration. This behavior is rationalized by correlating the reduced sensor dimensions to an increase in the “effective” analyte availability per surface site. Consequently, sensors with reduced footprints would require substantially fewer analyte molecules to achieve surface densities comparable to those of macroscopic sensors. The resulting increase in nanoparticle surface density further translates into enhanced signal intensities in surface-enhanced Raman detection, arising from the higher density of nanoparticle–substrate plasmonic hotspots within a fixed optical measurement footprint. Overall, the work highlights how micro- and nanoscale sensors with active areas approaching the dimensions of the measurement footprint of highly sensitive transducers (e.g., nanowires or plasmonic hotspots) maximize the benefits of sensor miniaturization.