Label-free protease sensors based on optical microsphere resonators

Simple and effective sensors for proteolytic activity are of interest to clinical diagnosis, homeland security, and nanofabrication. We demonstrate a novel label-free sensor for proteolytic activity utilizing an optical microsphere resonator that relies on circulation of the light to enhance the interaction with analytes. As a model, we employ the protease trypsin and a monolayer of BSA as a substrate on the sphere surface. We show a trypsin detection limit of approximately 10(-4) Units/ml, corresponding to removal of 0.6% of each BSA molecule on the sphere surface. The detection limit obtained in this work indicates that a microsphere sensor with specificity for a protease of interest can be designed using synthesized peptides and a functionalized microsphere.