Plasmonic biosensors: Immunoassay and glucose

Noble metal nanoparticles exhibit a localized surface plasmon resonance (LSPR) that is strongly dependent on their size, shape, material, and the local dielectric environment. As a consequence of LSPR, extinction of the electromagnetic frequency occurs that couples with the oscillation of the electrons, and the localized electromagnetic field is enhanced, contributing to surface-enhanced Raman spectroscopy (SERS). The research presented herein demonstrates efforts toward developing biological sensors using two detection techniques: (1) detection of proteins using LSPR spectroscopy and (2) detection of glucose using SERS. In the first part of this work, nanosphere lithography (NSL) fabricated Ag nanoparticles are used to exploit this LSPR sensitivity as a signal transduction method in biosensing applications. First, a comparative analysis of the properties of two optical biosensor platforms is performed: (1) a propagating surface plasmon resonance (SPR) sensor based on a planar, thin film gold surface and (2) an LSPR sensor based on surface confined Ag nanoparticles fabricated by nanosphere lithography (NSL). The binding of Concanavalin A (ConA) to mannose-functionalized self-assembled monolayers (SAMs) was chosen to highlight the similarities and differences between the responses of the real-time angle shift SPR and wavelength shift LSPR biosensors. Then, an elementary (2x1) multiplexed version of an LSPR carbohydrate sensing chip has been demonstrated to probe the simultaneous binding of ConA to mannose and functionalized SAMs. Additionally, LSPR biosensing for the anti dinitrophenyl (antiDNP) immunoassay system was also demonstrated.; The second part of this work updates the progress made toward fabricating a real-time, quantitative, and biocompatible glucose sensor based on SERS. The sensor design relies on a self-assembled monolayer (SAM) that consists of both hydrophobic and hydrophilic components, which allow glucose to partition and departition based on the solution concentration. The glucose sensor is fabricated by vapor depositing ∼200 nm of metal on a polystyrene nanosphere mask followed by functionalizing the metal surface with SAM. The SERS glucose sensor demonstrates several days of temporal stability, rapid and reversible glucose partitioning and departitioning, and quantitative glucose detection in a complex biological medium. Moreover, the glucose sensor was subcutaneously implanted in a rat model to demonstrate quantitative detection of glucose in the interstitial fluid. This is the first in vivo application of SERS.