Self-assembled colloidal gold superparticles to enhance the sensitivity of lateral flow immunoassays with sandwich format

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Abstract

Background: Traditional lateral flow immunoassay (LFIA) based on 20-40 nm gold nanoparticles (AuNPs) as signal reporter always suffers from relatively low detection sensitivity due to its insufficient brightness, severely restricting its wide-ranging application in the detection of target analytes with trace concentration.

Methods: To address this problem, the self-assembled colloidal gold superparticles (GSPs) were synthesized as an improved absorption-dominated labeling probe for improving the sensitivity of sandwich LFIA. Five kinds of GSPs with the size ranging from 100 nm to 400 nm were synthesized by embedding hydrophobic AuNPs of size 12 nm as building blocks into the polymer nanobeads. The as-prepared GSPs were suggested as novel labeling probes of LFIA. The effects of the size of assembled GSPs on the sensitivity of sandwich LFIA was assessed, and the detection performance of GSPs-LFIA was further compared with traditional AuNPs-LFIA.

Results: The resultant GSPs showed extremely high light absorption but very low light scattering, which favor the absorption-dominated signal output in LFIA. Among them, the GSP ₂₇₀-LFIA (size 270 nm) exhibits the highest sensitivity for human chorionic gonadotropin and hepatitis B surface antigen detection in real serum sample, which are approximate 39.79- and 13.8-fold higher than that of traditional AuNP ₄₀-LFIA.

Conclusions: The proposed research demonstrated that the current GSPs can provide an ultrasensitive and quantitative detection for disease biomarkers in real serum samples as promising reporters of sandwich LFIA platform.

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Most cited references 44

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Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine.

Prashant Jain, Kyeong Seok Lee, Ivan El-Sayed … (2006)

The selection of nanoparticles for achieving efficient contrast for biological and cell imaging applications, as well as for photothermal therapeutic applications, is based on the optical properties of the nanoparticles. We use Mie theory and discrete dipole approximation method to calculate absorption and scattering efficiencies and optical resonance wavelengths for three commonly used classes of nanoparticles: gold nanospheres, silica-gold nanoshells, and gold nanorods. The calculated spectra clearly reflect the well-known dependence of nanoparticle optical properties viz. the resonance wavelength, the extinction cross-section, and the ratio of scattering to absorption, on the nanoparticle dimensions. A systematic quantitative study of the various trends is presented. By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of extinction as well as the relative contribution of scattering to the extinction rapidly increases. Gold nanospheres in the size range commonly employed ( approximately 40 nm) show an absorption cross-section 5 orders higher than conventional absorbing dyes, while the magnitude of light scattering by 80-nm gold nanospheres is 5 orders higher than the light emission from strongly fluorescing dyes. The variation in the plasmon wavelength maximum of nanospheres, i.e., from approximately 520 to 550 nm, is however too limited to be useful for in vivo applications. Gold nanoshells are found to have optical cross-sections comparable to and even higher than the nanospheres. Additionally, their optical resonances lie favorably in the near-infrared region. The resonance wavelength can be rapidly increased by either increasing the total nanoshell size or increasing the ratio of the core-to-shell radius. The total extinction of nanoshells shows a linear dependence on their total size, however, it is independent of the core/shell radius ratio. The relative scattering contribution to the extinction can be rapidly increased by increasing the nanoshell size or decreasing the ratio of the core/shell radius. Gold nanorods show optical cross-sections comparable to nanospheres and nanoshells, however, at much smaller effective size. Their optical resonance can be linearly tuned across the near-infrared region by changing either the effective size or the aspect ratio of the nanorods. The total extinction as well as the relative scattering contribution increases rapidly with the effective size, however, they are independent of the aspect ratio. To compare the effectiveness of nanoparticles of different sizes for real biomedical applications, size-normalized optical cross-sections or per micron coefficients are calculated. Gold nanorods show per micron absorption and scattering coefficients that are an order of magnitude higher than those for nanoshells and nanospheres. While nanorods with a higher aspect ratio along with a smaller effective radius are the best photoabsorbing nanoparticles, the highest scattering contrast for imaging applications is obtained from nanorods of high aspect ratio with a larger effective radius.

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Gold nanoparticle-enabled biological and chemical detection and analysis.

Hilde Jans, Qun Huo (2012)

Gold nanoparticles (AuNPs) are some of the most extensively studied nanomaterials. Because of their unique optical, chemical, electrical, and catalytic properties, AuNPs have attracted enormous amount of interest for applications in biological and chemical detection and analysis. The purpose of this critical review is to provide the readers with an update on the recent developments in the field of AuNPs for sensing applications based on their optical properties. An overview of the optical properties of AuNPs is presented first, followed by a more detailed literature survey. As the last part of this review, we compare the advantages and disadvantages of each technique, briefly discuss their commercialization status, and some technical issues that remain to be solved in order to move the technique forward (151 references).

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Platinum Nanocatalyst Amplification: Redefining the Gold Standard for Lateral Flow Immunoassays with Ultrabroad Dynamic Range

Colleen Loynachan, Michael Thomas, Eleanor R. Gray … (2017)

Paper-based lateral flow immunoassays (LFIAs) are one of the most widely used point-of-care (PoC) devices; however, their application in early disease diagnostics is often limited due to insufficient sensitivity for the requisite sample sizes and the short time frames of PoC testing. To address this, we developed a serum-stable, nanoparticle catalyst-labeled LFIA with a sensitivity surpassing that of both current commercial and published sensitivities for paper-based detection of p24, one of the earliest and most conserved biomarkers of HIV. We report the synthesis and characterization of porous platinum core–shell nanocatalysts (PtNCs), which show high catalytic activity when exposed to complex human blood serum samples. We explored the application of antibody-functionalized PtNCs with strategically and orthogonally modified nanobodies with high affinity and specificity toward p24 and established the key larger nanoparticle size regimes needed for efficient amplification and performance in LFIA. Harnessing the catalytic amplification of PtNCs enabled naked-eye detection of p24 spiked into sera in the low femtomolar range (ca. 0.8 pg·mL–1) and the detection of acute-phase HIV in clinical human plasma samples in under 20 min. This provides a versatile absorbance-based and rapid LFIA with sensitivity capable of significantly reducing the HIV acute phase detection window. This diagnostic may be readily adapted for detection of other biomolecules as an ultrasensitive screening tool for infectious and noncommunicable diseases and can be capitalized upon in PoC settings for early disease detection.

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Author and article information

Journal

Journal ID (nlm-ta): Theranostics

Journal ID (iso-abbrev): Theranostics

Journal ID (publisher-id): thno

Title: Theranostics

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1838-7640

Publication date Collection: 2020

Publication date (Electronic): 19 February 2020

Volume: 10

Issue: 8

Pages: 3737-3748

Affiliations

[1 ]State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China;

[2 ]School of Food Science and Technology, Nanchang University, Nanchang 330047, P. R. China;

[3 ]Jiangxi-OAI Joint Research Institute, Nanchang University, Nanchang 330047, P. R. China.

Author notes

✉ Corresponding authors: Dr. Xiaolin Huang and Dr. Yonghua Xiong, State Key Laboratory of Food Science and Technology, and Jiangxi-OAI Joint Research Institute, Nanchang University. Address: 235 Nanjing East Road, Nanchang 330047, P.R. China. Phone: +0086-791-8833-4578. Fax: +0086-791-8833-3708. E-mail: hxl19880503@ 123456163.com (X. H.); yhxiongchen@ 123456163.com (Y. X.)

* These authors contributed equally to this work.

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: thnov10p3737

DOI: 10.7150/thno.42364

PMC ID: 7069069

PubMed ID: 32206119

SO-VID: 54ccd837-f844-4251-86c2-7dfbc6747061

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Self-assembled colloidal gold superparticles to enhance the sensitivity of lateral flow immunoassays with sandwich format

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Most cited references 44

Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine.

Gold nanoparticle-enabled biological and chemical detection and analysis.

Platinum Nanocatalyst Amplification: Redefining the Gold Standard for Lateral Flow Immunoassays with Ultrabroad Dynamic Range

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