Ultrahigh sensitivity made simple: nanoplasmonic label-free biosensing with an extremely low limit-of-detection for bacterial and cancer diagnostics

Abstract
We present a simple and robust scheme for biosensing with an ultralow limit-of-detection down to several pg cm(-2) (or several tens of attomoles cm(-2)) based on optical label-free biodetection with localized surface plasmon resonances. The scheme utilizes cost-effective optical components and comprises a white light source, a properly functionalized sensor surface enclosed in a simple fluidics chip, and a spectral analyzer. The sensor surface is produced by a bottom-up nanofabrication technique with hole mask colloidal lithography. Despite its simplicity, the method is able to reliably detect protein-protein binding events at low picomolar and femtomolar concentrations, which is exemplified by the label-free detection of the extracellular adherence protein (EAP) found on the outer surface of the bacterium Staphylococcus aureus and of prostate-specific antigen (PSA), which is believed to be a prostate cancer marker. These experiments pave the way towards an ultra-sensitive yet compact biodetection platform for point-of-care diagnostics applications.