Chip-Scale Aptamer Sandwich Assay Using Optical Waveguide-Assisted Surface-Enhanced Raman Spectroscopy.

Chip-scale optical waveguide-assisted surface-enhanced Raman spectroscopy (SERS) that used nanoparticles (NPs) was demonstrated. The Raman signals from Raman reporter (RR) molecules on NPs can be efficiently excited by the waveguide evanescent field when the molecules are in proximity to the waveguide surface. The Raman signal was enhanced by plasmon resonance due to the NPs close to the waveguide surface. The optical waveguide mode and the NP-induced field enhancement were calculated using a finite difference method (FDM). The sensing performance of the waveguide-assisted SERS device was experimentally characterized by measuring the Raman scattering from various RRs, including 4-mercaptobenzoic acid (4-MBA), 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB), and malachite green isothiocyanate (MGITC). The observed Raman spectral features were identified and assigned to the complex vibrational modes associated with different reporters. A low detection limit of 1 nM was achieved. In addition, the device sensing method was applied to the detection of the biomarker cardiac troponin I (cTnI) using an aptamer sandwich assay immobilized on the device surface. Overall, the optical waveguides integrated with SERS show a miniaturized sensing platform for the detection of small molecules and large proteins, potentially enabling multiplexed detection for clinically relevant applications.