High-Sensitive Detection and Quantitative Analysis of Thyroid-Stimulating Hormone Using Gold-Nanoshell-Based Lateral Flow Immunoassay Device

Abstract

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.

Sensitive dipstick assays for lectin detection, based on glycan–BSA conjugate immobilisation on gold nanoparticles

“…In addition, 150 nm NHS ester-activated AuNSs were chosen to investigate the effect that the size has on the detection system, as these exhibit a 14 times bigger surface area than 40 nm AuNPs, which can lead to up to 25 times improved sensitivity in immunochromatographic assays. 74,75 Propyl-AuNSs (25) were prepared as negative controls by quenching AuNSs in absence of the galactoside, to study non-specific interactions with RCA 120 and WGA. Non-specific interactions were observed between the nanoshells and both RCA 120 and WGA, which was overcome by the addition of a combination of 1% Triton X100 and 1% BSA to the dipstick buffer.…”

Optical biosensing systems for a biological living body

“…Although many forms of NPs including nanopillar, 35 nanostar, 36,37 and core‐shell structure, 38–40 are used in colorimetric biosensing systems, nanosphere is the most common form because of its isotropy 41,42 . NP accumulation reactions are also applied in point‐of‐care devices including lateral flow assay (LFA) and paper‐based colorimetric biosensing systems 43–47 …”

“…41,42 NP accumulation reactions are also applied in point-of-care devices including lateral flow assay (LFA) and paper-based colorimetric biosensing systems. [43][44][45][46][47] In order to overcome the disadvantage of the narrow analytical spectrum of colorimetric biosensors, it is an excellent extension to introduce the application of fluorescence biosensing systems. Unlike colorimetric biosensors, fluorescence biosensors reflect changes in the concentration of the analyte mainly by differences in the intensity of fluorescence-containing optical-sensing molecules, with the advantages of high sensitivity and fast real-time monitoring.…”

Nanomaterial and Interface Advances in Immunoassay Biosensors

“…Gold nanoshell particles (AuNSs), which are 150 nm gold coated silica particles, absorb light more strongly than smaller spherical Au NPs because of their larger size and large scattering cross-sections . Substituting AuNSs for the probe could improve detection of serum thyroid stimulating hormone (TSH) with a 26× decrease in LOD . Carbon nanotubes also possess strong optical features, have a black color because of their broad absorbance, and are similarly used as a label to detect rabbit IgG down to 1.3 pg/mL, an LOD 1000× lower compared to that for assays with Au NPs …”

“…21 Substituting AuNSs for the probe could improve detection of serum thyroid stimulating hormone (TSH) with a 26× decrease in LOD. 22 Carbon nanotubes also possess strong optical features, have a black color because of their broad absorbance, and are similarly used as a label to detect rabbit IgG down to 1.3 pg/mL, an LOD 1000× lower compared to that for assays with Au NPs. 16 The plasmonic properties of Au NPs have been investigated in the literature for decades, where the factors influencing their absorption spectra are now well understood.…”