Advanced Computational Techniques for Plasmonic Metasurfaces in the Detection of Neglected Infectious Diseases

Abstract

This tutorial delves into the integration of plasmonic metasurfaces as cutting-edge tools for creating highly sensitive diagnostic assays tailored to neglected infectious diseases. Plasmonic metasurfaces provide a transformative approach to diagnostics by addressing common limitations of traditional methods, including slow results and high costs. This tutorial explores their application in advancing sensitive and cost-effective solutions for neglected infectious diseases. This manuscript covers the complete cycle of developing optimized, AI-driven plasmonic metasurfaces, from biofunctionalization strategies and advanced fabrication techniques to addressing scalability, regulatory challenges, and point-of-care accessibility in resource-limited settings.

Figure 1

Illustration of the complete workflow for modeling plasmonic metasurfaces, from design and optimization to their integration into biodetection systems for enhanced diagnostic applications. Reprinted in part with permission from ref (25). Copyright 2024 ACS Publications.

Figure 2

Advanced techniques for designing plasmonic devices. (a) Procedure for shape (top) and topology (bottom) optimization. (b) Machine learning pipeline for analysis of data measured from plasmonic devices. (c) Prediction accuracy of DNA classification and detection in a plasmonic biosensor for different classifiers. Reprinted in part with permission from ref (46). Copyright 2022 Elsevier.

Figure 3

(a) Example of a fabricated pyramid array utilizing e-beam lithography. (b) Example of pyramidal nanoholes fabricated with e-beam lithography observed with scanning electron microscopy (SEM) and atomic force microscopy (AFM). (c) Example of nanoantennae fabricated with FIB lithography observed with scanning transmission electron microscopy (STEM) coupled with electron energy loss spectroscopy (EELS). Reproduced with permission from ref (25). Copyright 2024 ACS Publications. Reproduced with permission from ref (51). Copyright 2021 ACS Publications. Reproduced with permission from ref (53). Copyright 2024 ACS Publications.

Figure 4

Schematic representation of the functionalization of gold nanorods with biomolecules. (a) Gold nanorod synthesized by the seed-mediated growth method, coated with CTAB; (b) Gold nanorod coated with alpha-lipoic acid (LA); (c) Gold nanorod coated with LA and functionalized with a biomolecule. The sequence shown in this figure illustrates the functionalization process previously described. (Created in CorelDRAW Graphics Suite, by Raphael Gomes de Paula (2024), Used with permission).

Figure 5

Nanobiosensor assay development process. The three main branches of the development of a gold nanosensor for diagnostic application are particle functionalization, evaluation of proper biorecognition, and validation of the diagnostic tool. The flowchart describes experimental procedures and critical points to consider during the assay assessment. (Created in BioRender. Versiani, A. (2024) BioRender.com/f70w259).

Figure 6

(a) Difference in reflected intensity between s- and p-polarizations (I_S – I_P) for a nanopyramid array with a base of 388 nm, height 274 nm, and spacing of 69 nm. The inset shows a top-view electron microscopy image of the nanostructure. Vertical dashed lines indicate the λ₁₀^air and λ₁₀^sub diffraction edges at φ = 0. Arrows mark the spectral positions of the top mode (845 nm), edge modes (715 nm), and base mode (643 nm) scattered by the nanopyramids. (b) Relative phase shift between. (c) Incidence angle variation (15° to 55°) for a metasurface with gold nanopyramids. The resonance peak at 850 nm, selected for its stability, remains nearly constant between 25° and 50°, peaking at 41°, as indicated in the heat map. (d) Measured spectral response of the pyramidal nanoparticle lattice with albumin on its surface. Unlike a, in b, no SPP is observed; only the LSPRs excited in the said structure. This is because the albumin concentration, i.e., 5 mg/mL, saturates the surface, hindering the excitation of the propagating surface plasmons. (e) Measured spectral response of the pyramidal nanoparticle lattice as a function of the azimuthal angle of the incident beam. As shown in this figure, we have a periodic response, which is understandable due to the nature of our pyramidal lattice. Reprinted in part with permission from ref (25). Copyright 2024 ACS Publications.