1 Inverse Sensitivity in Plasmonic Nanosensors via Enzyme-Guided Crystal Growth

Lowering the limit of detection is a fundamental aspect in the design of sensors important to food safety regulations,1-2 environmental policies3-5 and the diagnosis of severe diseases.6-10 However, conventional transducers generate a signal that is directly proportional to the concentration of the target molecule. As such, the presence of chemical species at ultralow concentrations results in tiny variations in the physical properties of the sensor and these are difficult to detect with confidence. Here we redefine the limit of detection of nanoparticle sensors by presenting a signal generation mechanism that induces a larger signal when the target molecule is less concentrated. The key step to achieve this inverse sensitivity is to use an enzyme in order to control the rate of nucleation of silver nanocrystals on plasmonic transducers. The outstanding sensitivity and robustness of this approach was demonstrated by detecting the cancer biomarker prostate specific antigen (PSA) down to 10-18 g·mL-1 (4·10-20 M) in whole serum. Metal nanoparticles are outstanding building blocks for the fabrication of biosensors when their surface plasmon resonance (LSPR) shifts in response to a biorecognition event.11 I