Diagnosis is the key component in disease elimination to improve global health. However, there is a tremendous need for diagnostic innovation for neglected tropical diseases that largely consist of mosquito-borne infections and bacterial infections. Early diagnosis of these infectious diseases is critical but challenging because the biomarkers are present at low concentrations, demanding bioanalytical techniques that can deliver high sensitivity with ensured specificity. Owing to the plasmonic nanomaterials-enabled high detection sensitivities, even up to single molecules, surface-enhanced Raman spectroscopy (SERS) has gained attention as an optical analytical tool for early disease biomarker detection. In this mini-review, we highlight the SERS-based assay development tailored to detect key types of biomarkers for mosquito-borne and bacterial infections. We discuss in detail the variations of SERS-based techniques that have developed to afford qualitative and quantitative disease biomarker detection in a more accurate, affordable, and field-transferable manner. Current and emerging challenges in the advancement of SERS-based technologies from the proof-of-concept phase to the point-of-care phase are also briefly discussed.

Plasmonic-polymer nanocomposites can serve as a multifunctional platform for a wide range of applications such as biochemical sensing and photothermal treatments, where they synergistically benefit from the extraordinary optical properties of plasmonic nanoparticles (NPs) and biocompatible characteristics of biopolymers. The field translation of plasmonic-polymer nanocomposites requires design rules for scalable and reproducible fabrication with tunable and predictable optical properties and achieving the best performance. The optical properties of NPs and the optimal analytical performance of nanocomposites could be affected by many fabrication parameters, but a fundamental understanding of such parameters is still minimal. Herein, we systematically investigated the NP distribution and their optical properties in gold nanostar (GNS)-polymer nanocomposites as a function of GNS concentration, polymer identity, and the method of GNS incorporation into a polymer matrix. We performed a comprehensive analysis of the single-particle scattering spectra of GNS incorporated into agarose gel and chitosan hydrogels via embedding and surface deposition, using dark-field spectroscopy. While relative GNS concentration affects the GNS scattering property distribution in both polymer matrices, chemical interactions between a polymer matrix and GNS is the key determinant of the GNS stability and homogenous distribution in nanocomposites. When GNS are embedded in a polymer matrix and there are stronger chemical interactions between GNS and a polymer, significantly less aggregation and a more homogenous distribution of GNS, which leads to a larger percentage of GNS optical property preservation, were observed at all the concentrations. In a proof-of-concept surface-enhanced Raman spectroscopy (SERS) study, we observed that the SERS detection efficiency is dictated by the analyte accessibility of GNS, which is governed by the polymer matrix porosity, polymer-GNS interactions, and other polymer physical characteristics. This work presents the interplay between key fabrication parameters and foundational design parameters for more predictable and reliable fabrication of plasmonic-polymer nanocomposites as an optical platform.