Zika and dengue are mosquito-borne diseases that present similar nonspecific symptoms but possess dramatically different outcomes. The first line of defense in epidemic outbreaks are rapid point-of-care diagnostics. Because many outbreaks occur in areas that are resource poor, assays that are easy to use, inexpensive, and require no power have become invaluable in patient treatment, quarantining, and surveillance. Paper-based sandwich immunoassays such as lateral flow assays (LFAs) are attractive as point-of-care solutions as they have the potential for wider deployability than lab-based assays such as PCR. However, their low sensitivity imposes limitations on their ability to detect low biomarker levels and early diagnosis. Here, we exploit the high sensitivity of surface-enhanced Raman spectroscopy (SERS) in a multiplexed assay that can distinguish between Zika and dengue nonstructural protein 1 (NS1) biomarkers. SERS-encoded gold nanostars were conjugated to specific antibodies for both diseases and used in a dipstick immunoassay, which exhibited 15-fold and 7-fold lower detection limits for Zika NS1 and dengue NS1, respectively. This platform combines the simplicity of a LFA with the high sensitivity of SERS and could not only improve Zika diagnosis but also detect diseases sooner after infection when biomarker levels are low.
The unique size and material dependent properties of nanoparticles have made them highly attractive for biological and medical applications. However, combining nanoparticles with biomolecules and biological environments has faced many challenges. These interface issues often involve protein denaturation, steric hindrance, and orientational issues for the biomolecule, which can impair function and decrease overall performance of the nanoparticle-biomolecule conjugate. Historically, our understanding of the physical and chemical properties of nanoparticle-biomolecule conjugates as appropriate tools and experimental techniques had to be determined. We discuss here selected examples investigating the fundamental physical properties of the interface between nanoparticles and DNA and proteins and protein coronas and how they have provided insight into the properties of the biomolecule when it is interfaced to a nanoparticle.
We report a quantitative
evaluation of the choice of reporters
for multiplexed surface-enhanced Raman spectroscopy (SERS). An initial
library consisted of 15 reporter molecules that included commonly
used Raman dyes, thiolated reporters, and other small molecules. We
used a correlation matrix to downselect Raman reporters from the library
to choose five candidates: 1,2-bis(4-pyridyl)ethylene, 4-mercaptobenzoic
acid, 3,5-dichlorobenzenthiol, pentachlorothiophenol, and 5,5′-dithiobis(2-nitrobenzoic
acid). We evaluated the ability to distinguish the five SERS reporters
in a dipstick immunoassay for the biomarker human IgG. Raman nanotags,
or gold nanostars conjugated to the five reporters and anti-human
IgG polyclonal antibodies were constructed. A linear discriminant
analysis approach was used to evaluate the separation of the nanotag
spectra in mixtures of fixed ratios.
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