Applications of Gold Nanoparticles in Plasmonic and Nanophotonic Biosensing

Abstract

The unique properties of plasmonic nanoparticles and nanostructures have enabled a broad range of applications in a diverse set of fields, ranging from biological sensing, cancer therapy, to catalysis. They have been some of the most studied nanomaterials due in part to their chemical stability and biocompatibility as well as supporting theoretical efforts. The synthesis and fabrication of plasmonic nanoparticles and nanostructures have now reached high precision and sophistication. We review here their fundamental optical properties, discuss their tailoring for biological environments, and then detail examples on how they have been used to innovate in the biological and biomedical fields.

Keywords: Gold nanoparticles; Photothermal; Plasmon-enhanced fluorescence; Plasmonics; Surface plasmon resonance; Surface-enhanced Raman spectroscopy.

Figure 1.

The field of biosensing with plasmonics has been supported by the pillars of robust theory and simulation, synthesis and fabrication, and bioconjugation and biocompatibility strategies

Figure 2.

Oscillations in a spherical particle induced by an electromagnetic wave. B) simulations of NR absorption spectra, exhibiting an LSPR maxima shift with the aspect ratio R of the particle. From [2]

Figure 3.

a) solution of colloidal gold nanoparticles, exhibiting a strong red color due to their SPR. b) LaMer theory of the nucleation and growth.

Figure 4.

Different structures of nanoparticles that can be synthesized by solution synthesis. A) gold nanostars of different arm lengths, which can shift the SPR throughout the visible, and result in different colors. B) gold nanoshells synthesized by Au coating of dielectric templates, where the absorption spectra shifts with increasing core:shell thickness, from [8], c) gold nanorods of different aspect ratios shift the LSPR to the red with increasing aspect ratio From [9]

Figure 5.

a) Lithography techniques and the resolution and throughput they can achieve.. SPL:scanning probe lithography, EBL/IBL: electron/ion beam lithography, NIL: nanoimprint lithography. From [25]b) approach for ea-beam lithography that use the beam to write directly, or to remove the photoresist. c) SEM of structures of gold made by liftoff and d) plasma etching [26] e) NSL lithography using colloids to create ordered masks through which the gold can be evaporated. From [27]

Figure 6.

Strategies to modify the particle surfaces, by addition of surface capping ligands such as PEG-SH or BPS, silica coating by the Stöber process, coating with amphiphilic molecules such as CTAB, which form a bilayer on the surface, or surface blocking with proteins such as BSA to prevent non-specific adsorption

Figure 7.

Bioconjugation strategies to link nanoparticles to proteins and DNA. A) thiols on DNA can form a covalent bond, and then be used to capture the complementary strand, b) biotin-streptavidin can be used to append biotin-functionalized proteins or DNA, c) click chemistry such as NHS-esters can link to primary amines on proteins or DNA

Figure 8.

Colorimetric readouts of nanoparticles. A) the SPR of spherical red NPs has been exploited as the visible color in rapid tests. The target antigen, if present, binds to antibodies conjugated to nanoparticles and also antibodies immobilized on the paper strip. B) multicolor immunoassays for yellow fever virus (YFV), Ebola virus (ZEBOV), and Dengue virus (DENV) using silver nanoplates, which exhibit different colors due to their different sizes. C) aggregation-based colorimetric changes result from DNA linked to DNA that binds to a complementary strand, bringing the nanoparticles in proximity, and shifting the absorption spectra. This results in a color change from red to blue. D) Multicolor nanoparticles in immunoassays can enable repurposing of antibodies to detect antigens that the antibodies were not raised against. This can be achieved by hacking existing tests for Dengue so that they can detect yellow fever, with machine learning analysis

Figure 9.

a) SERS occurs on metal nanostructures, which enhances the Raman spectra by several orders of magnitude. B) Periodic nanoholes in substrates have been used for the detection of hepatitis A virus. From [66] c) Crescent structures engineered for SERS hotspots. From [67]

Figure 10.

a) Structure of a SERS Nanotag b)SERS barcoding to identify peptides. From [77], c) SERS nanotags for multiplexed detection of zika and dengue in an immunoassay. From [75], d) correlation matrix for choosing multiple reporters based on their spectra. Yellow indicates high overlap, blue low overlap. From [73]

Figure 11.

Photothermal mechanism upon irradiation of a nanoparticle with an ultrafast laser pulse. B)ultrafast irradiation at the LSPR of nanorods induces a shape change, and a decrease in the LSPR peak. From [86]; c) tissue window relative to the visible and NIR spectrum, d) nanords of two different aspect ratios have LSPR that can be selectively excited at two different wavelengths, 800 nm (blue) and 1100 nm (red). From [12] e) Selective release of thrombin binding aptamer (TBA) and its complement can be used to switch blood clotting on and off. From [87]