Plasmonics-Enhanced Dual-Modal Colorimetric and Photothermal Lateral Flow Immunoassay Using Gold Nanocages
Supriya Atta, Yuanhao Zhao, Sebastian Sanchez, Sabina V. Yampolsky, Tuan Vo‐Dinh
Abstract
Lateral flow immunoassays (LFIA) are widely recognized as cost-effective point-of-care diagnostic tools (POCT) for infectious disease diagnosis. Despite their widespread use, traditional colorimetric LFIAs, which rely on gold nanospheres (GNP), are constrained by a limited sensitivity. To overcome this challenge, we have engineered gold nanocages (GNCs) with optimized core-to-shell morphologies, achieving significant amplification of both colorimetric and photothermal LFIA readout signals. The distinctive morphology of GNCs, featuring adjustable core-to-shell gap thicknesses, enables fine-tuning of the localized surface plasmon resonance (LSPR) peak across a broad spectral range from 600 to 1200 nm. Among the GNC morphologies evaluated, the optimized GNC (GNC-4), characterized by its larger size and maximal core-to-shell gap thickness, exhibited superior color brightness and enhanced photothermal efficiency compared to other GNC morphologies and traditional GNP. The enhanced performance of GNC-4 enabled the detection of influenza A (H1N1), used as the model analyte, achieving a limit of detection (LOD) of 1.8 ng/mL via colorimetric analysis and 1.51 pg/mL using photothermal LFIA. Compared to traditional GNP-based colorimetric LFIA detection, the colorimetric sensitivity of the GNC-4-based LFIA was enhanced by 7-fold, while the photothermal detection sensitivity showed an improvement of over 8000-fold. By incorporating a portable smartphone-based photothermal LFIA platform, our dual-modal LFIA exhibits high sensitivity, practicality in detecting H1N1 in spiked saliva samples, and long-term stability over five months, making it a promising tool for infectious disease detection and a potential model for diagnosing other pathogens.