Gold-Nanoparticle-Based Localized Surface Plasmon Resonance Sensor Integrating Microfluidics for Dual Cardiovascular Disease Biomarker Detection

High Resolution Image Download MS PowerPoint Slide Localized surface plasmon resonance (LSPR) technique shows a notable potential for biosensing applications, primarily due to its compact, real-time, label-free and highly sensitive features. In this study, we propose a nanofabrication process that involves two gold deposition steps, followed by rapid thermal annealing (RTA) processing, defining as dual RTA-treated LSPR sensor fabrication. This fabrication process allows gold layer optimization for dense and uniform nanoparticle redistribution, leading to a high LSPR effect. The nanoparticle distribution and extinction spectra of each fabrication case are analyzed by scanning electron microscopy (SEM) images and UV–vis spectroscopy, respectively. Based on the surface morphology, we propose two nanoparticle growth mechanisms, particle coalescence and nucleation, to explain the nanoparticle formation. Then, the spectra of 12 cases are compared. The results showed that a first 8-nm gold layer followed by the second 4-nm gold layer (8 + 4 nm) RTA LSPR sensor can achieve the highest sensitivity and figure of merit (FOM). Finally, we assembled the 8 + 4 nm RTA LSPR sensor with microfluidics to perform the measurement of two cardiovascular disease (CVD) biomarkers: cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The results showed a real-time and continuous cTnI and NT-proBNP measurement from 1 pg/mL to 10 ng/mL and 10 pg/mL to 10 ng/mL, respectively, which fall into the clinical threshold. Based on the above features, we envision the dual RTA-treated LSPR sensor can enable a label-free, highly sensitive, yet simple optical sensing method for point-of-care based CVD diagnostic applications.