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Review
. 2023 Mar 22;13(3):411.
doi: 10.3390/bios13030411.

Gold Nanoparticle-Based Plasmonic Biosensors

Enrico Ferrari  1
Affiliations
Review

Gold Nanoparticle-Based Plasmonic Biosensors

Enrico Ferrari. Biosensors (Basel). .

Abstract

One of the emerging technologies in molecular diagnostics of the last two decades is the use of gold nanoparticles (AuNPs) for biosensors. AuNPs can be functionalized with various biomolecules, such as nucleic acids or antibodies, to recognize and bind to specific targets. AuNPs present unique optical properties, such as their distinctive plasmonic band, which confers a bright-red color to AuNP solutions, and their extremely high extinction coefficient, which makes AuNPs detectable by the naked eye even at low concentrations. Ingenious molecular mechanisms triggered by the presence of a target analyte can change the colloidal status of AuNPs from dispersed to aggregated, with a subsequent visible change in color of the solution due to the loss of the characteristic plasmonic band. This review describes how the optical properties of AuNPs have been exploited for the design of plasmonic biosensors that only require the simple mixing of reagents combined with a visual readout and focuses on the molecular mechanisms involved. This review illustrates selected examples of AuNP-based plasmonic biosensors and promising approaches for the point-of-care testing of various analytes, spanning from the viral RNA of SARS-CoV-2 to the molecules that give distinctive flavor and color to aged whisky.

Keywords: molecular diagnostics; naked-eye detection; point-of-care testing.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Bibliometric analysis of articles featuring AuNP-based biosensors (data from Scopus). (a) Articles per year that have “gold nanoparticle biosensor” or “detection” in the title, abstract, or keywords, excluding the words “lateral flow”, and limited to the “article” document type. The red bars refer to the years 2020–2022 characterized by the COVID-19 pandemic, with the yellow portion of the bars representing the articles mentioning “SARS-CoV-2” in the title, abstract, or keywords. (b) Venn diagram of the 2020–2022 articles from panel a grouped based on the presence or absence of the words DNA or RNA (nucleic acids) and protein in the title, abstract, or keywords.
Figure 2
Figure 2
Optical properties of spherical AuNPs. (a) Extinction spectra (1 cm pathlength) of commercial 50 μg/mL citrate-capped AuNP colloids (nanoComposix, San Diego, CA, USA). (b) Photograph of the AuNP solutions from panel a.
Figure 3
Figure 3
Change in AuNP optical properties due to aggregation. (a) Extinction spectra of dispersed 20 nm citrate-capped AuNPs (solid line) and of the same solution after adding NaCl (dashed line). The presence of charged ions destabilizes the colloid via screening of negative charges with consequent aggregation and loss of the SPR band. (b) Photograph of the AuNP solutions from panel a (dispersed, left; aggregated, right).
Figure 4
Figure 4
The principle of sandwich hybridization for the detection of nucleic acids using AuNP–ASOs. On the left, two distinct sets of AuNP–ASOs are represented by the blue and green ssDNA molecules conjugated via a thiol–gold bond to the AuNPs at the 5′ or 3′ end. In presence of a target DNA complementary to both ASOs and a temperature T below the melting temperature Tm of the ASOs, the AuNPs undergo aggregation, and the red color typical of a dispersed solution of AuNPs shifts towards the blue (right).
Figure 5
Figure 5
The principle of AuNP-enhanced LAMP assays. (a) Schematic of the main steps involved in the amplification of DNA by LAMP. Light and dark blue represent complementary strands. Green, orange, and yellow rectangles represent the forward (solid outline) and backward (dashed outline) primers’ target sequences and their complements identified by the letter ‘c’. (b) Detection of LAMP amplicons by hybridization of a pair of AuNP–ASOs to complementary regions on the target DNA (orange and green rectangles).
Figure 6
Figure 6
Dispersion of AuNPs mediated by the target-specific activation of a split DNAzyme (purple). The hybridization of designer arms to the target DNA (orange) triggers the assembly of the DNAzyme and the activation of the catalytic arms that selectively cleave a complementary DNA sequence within the linker (DNA substrate in yellow). The cleavage of the linker promotes the dispersion of the otherwise complexed AuNPs. As the target DNA and the split DNAzyme are available for another cleavage cycle, the dispersion of AuNPs is sustained.
Figure 7
Figure 7
Schematic of the working principle of plasmonic ELISA. The assay is similar to a conventional double-sandwich ELISA; however, the readout is based on the in situ synthesis of AuNPs by gold (Au) reduction due to hydrogen peroxide (H2O2). The synthesized AuNPs confer a bright-red color to the test solution. Instead, when the target protein is present, the enzyme catalase is retained in the test well and catalyzes the removal of H2O2, causing the formation of an aggregated blue colloid.
Figure 8
Figure 8
Schematic of the working principle of the wash-free plasmonic immunoassay. The method relies on the growth of antibody-conjugated core AuNPs as a dispersed colloidal suspension (negative sample) or aggregated clusters (positive samples).
Figure 9
Figure 9
Schematic of the working principle of the aptamer-based plasmonic assay. The method uses DNA aptamers hybridized to DNA oligos on two sets of AuNPs. The aptamer undergoes a conformational change when bound to the analyte, which causes the de-hybridization of one of the complementary DNA oligos and the subsequent dispersion of the AuNPs.
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References

    1. Saha K., Agasti S.S., Kim C., Li X., Rotello V.M. Gold Nanoparticles in Chemical and Biological Sensing. Chem. Rev. 2012;112:2739–2779. doi: 10.1021/cr2001178. - DOI - PMC - PubMed
    1. Jans H., Huo Q. Gold Nanoparticle-Enabled Biological and Chemical Detection and Analysis. Chem. Soc. Rev. 2012;41:2849–2866. doi: 10.1039/C1CS15280G. - DOI - PubMed
    1. Aldewachi H., Chalati T., Woodroofe M.N., Bricklebank N., Sharrack B., Gardiner P. Gold Nanoparticle-Based Colorimetric Biosensors. Nanoscale. 2018;10:18–33. doi: 10.1039/C7NR06367A. - DOI - PubMed
    1. Tang L., Li J. Plasmon-Based Colorimetric Nanosensors for Ultrasensitive Molecular Diagnostics. ACS Sens. 2017;2:857–875. doi: 10.1021/acssensors.7b00282. - DOI - PubMed
    1. Sun J., Xianyu Y., Jiang X. Point-of-Care Biochemical Assays Using Gold Nanoparticle-Implemented Microfluidics. Chem. Soc. Rev. 2014;43:6239–6253. doi: 10.1039/C4CS00125G. - DOI - PubMed

Grants and funding

This research received no external funding.