Plasmonic Absorption in Antigen-Induced Aggregated Gold Nanoparticles: Toward a Figure of Merit for Optical Nanosensors

Carlo Bravin,Vincenzo Amendola

doi:10.1021/acsanm.1c03380

Abstract

Gold nanoparticles (Au NPs) have been extensively used for colorimetric and optical detection of various analytes, exploiting the difference in optical properties when the NPs are dispersed or aggregated. The properties of Au NPs-based optical sensors depend strongly on the particle size, spacing, number, and disposition in the aggregate, which explains the different performances reported so far for this class of sensors. Here, we investigated the optical response of a model Au NP immunosensor and the correlation of its plasmonic absorption with the analyte-dependent aggregation state, supported by transmission electron microscopy and numerical calculations. The antigen–antibody system used for this study is the C-reactive protein (CRP)/anti-CRP couple, well-established and of great applicative interest. The results provide several insights into the evaluation of the extent and type of antigen-induced aggregation for receptor-conjugated Au NPs and point toward the identification of a figure of merit of great utility in the development of particle aggregates with the optimal structure for desirable nanosensor response.

Highlights

While the working principle of Au NP optical sensors is simple and general, there is a list of parameters which influence their response, such as the particle size and shape, interparticle distance, and number and disposition of particles in the aggregate.[14−18] The variety of these parameters has a direct correspondence with the different responses reported so far for this class of detection systems
The optical properties of a model nanosensor based on the immunocomplexation of anti-C-reactive protein (CRP)-PEG-SHcoated Au NPs in the presence of CRP were studied
The aggregation of NPs is associated with a change in the plasmon peak position and optical density in the 500−800 nm range, with optimal effects in terms of sensitivity and the signal-tonoise ratio depending on the observation wavelength, which is the first relevant parameter for optical sensing

Summary

Introduction

Gold nanoparticles (Au NPs) are chemically stable, not toxic, photostable, surface functionalizable in one step with any thiolated ligand,[1,2] and synthesizable even at very low cost.[3,4] Most importantly, Au NPs exhibit an intense coloration due to the plasmon resonance band, which is shape-dependent and aggregation-dependent.[5,6] This set of deeply investigated features has been exploited for decades in colorimetric and optical sensing to detect a variety of analytes such as biomolecules, organic compounds, and metal ions.[1,5] The typical Au NP optical sensor is based on the specific molecular recognition between a receptor bound to the particle surface and an antigen to be detected.[1,7−9] The receptor can be an antibody, scFv, nanobody, aptamer, or any other chemical function selective for the analyte.[1,7,8,10−12] When Au NPs are conjugated with antibodies, the binding of the antigen will induce specific particle aggregation by immunocomplexation.[1,5,7,12,13]While the working principle of Au NP optical sensors is simple and general, there is a list of parameters which influence their response, such as the particle size and shape, interparticle distance, and number and disposition of particles in the aggregate.[14−18] The variety of these parameters has a direct correspondence with the different responses reported so far for this class of detection systems. Several examples of colorimetric sensors based on Au NPs have been proposed in recent times.[19−21] For instance, a colorimetric serological assay to detect SARS-CoV-2 IgG antibodies was developed by coating Au NPs with epitopes located on the spike and nucleocapsid proteins of the virus.[22] Another example consists in the evolution of the optical properties of Au NPs functionalized with a red blood cell membrane, which has been assessed over time in the presence of the antigen fibrinogen to identify the best timing and spectroscopic features for analytical applications.[23] Aptamer-conjugated Au NPs showed reversible aggregation in the presence of analyte thrombin and external physical stimuli such as ultrasound.[24] In a model albumin assay, a mixture of 20 and 50 nm Au NPs was shown to enhance the signal compared to the single-sized 20 nm Au NP samples and to provide acceptable colloidal stability compared to the single-sized 50 nm Au NPs.[15]

Methods

Results

Discussion

Conclusion