Au nanoparticles (AuNPs) have been used as signal reporters in colorimetric lateral flow immunoassays (LFAs) for decades. However, it remains a major challenge to significantly improve the detection sensitivity of traditional LFAs due to the low brightness of AuNPs. As an alternative approach, we overcome this problem by utilizing 150 nm gold nanoshells (AuNSs) that were engineered by coating low-density silica nanoparticles with a thin layer of gold. AuNSs are dark green, have 14 times larger surface area, and are approximately 35 times brighter compared to AuNPs. In this study, we used detection of thyroid-stimulating hormone (TSH) in a proof-of-concept assay. The limit of detection (LOD) with AuNS-based LFA was 0.16 µIU/mL, which is 26 times more sensitive than the conventional colorimetric LFA that utilizes AuNP as a label. The dynamic range of the calibration curve was 0.16–9.5 µIU/mL, making it possible to diagnose both hyperthyroidism (<0.5 µIU/mL) and hypothyroidism (>5 µIU/mL) using AuNS-based LFA. Thus, the developed device has a strong potential for early screening and diagnosis of diseases related to the thyroid hormone.
We report a self-sufficient microfluidic paper-based lateral flow immunoassay device (μLFD) for highly sensitive detection of the thyroid-stimulating hormone (TSH). Fabrication of the paper microchannels involves engraving the nitrocellulose membrane with a CO2 laser to create narrow flow paths, which constrain the fluid flow over the test zone. The proposed microchannel modified devices were studied for detection of the TSH using gold nanoparticles as labels. The effect of such microchannel modified LFDs has led to an improvement in sensitivity by nine times and the limit of detection by 6.6 times due to the slow flow rate of the sample compared with the traditional LFD. In addition, the binding of gold nanoparticles over the test line is more uniform in the case of the μLFD, thus minimizing leading-edge effects, resulting in more accurate quantitative analysis. The proposed strategy offers great potential for multiplex detection of biomarkers with increased sensitivity without introducing any hydrophobic materials to the LFD.
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