title: Method for assessing the reliability of molecular diagnostics based on multiplexed SERS-coded nanoparticles.
abstract: Surface-enhanced Raman scattering (SERS) nanoparticles have been engineered to generate unique fingerprint spectra and are potentially useful as bright contrast agents for molecular diagnostics. One promising strategy for biomedical diagnostics and imaging is to functionalize various particle types ("flavors"), each emitting a unique spectral signature, to target a large multiplexed panel of molecular biomarkers. While SERS particles emit narrow spectral features that allow them to be easily separable under ideal conditions, the presence of competing noise sources and background signals such as detector noise, laser background, and autofluorescence confounds the reliability of demultiplexing algorithms. Results obtained during time-constrained in vivo imaging experiments may not be reproducible or accurate. Therefore, our goal is to provide experimentalists with a metric that may be monitored to enforce a desired bound on accuracy within a user-defined confidence level. We have defined a spectral reliability index (SRI), based on the output of a direct classical least-squares (DCLS) demultiplexing routine, which provides a measure of the reliability of the computed nanoparticle concentrations and ratios. We present simulations and experiments to demonstrate the feasibility of this strategy, which can potentially be utilized for a range of instruments and biomedical applications involving multiplexed SERS nanoparticles.
authors.affiliation: Stony Brook University (SUNY), Department of Biomedical Engineering, Stony Brook, New York, USA.
authors.forename: Steven Y
authors.initials: SY
authors.lastname: Leigh
authors.forename: Madhura
authors.initials: M
authors.lastname: Som
authors.forename: Jonathan T C
authors.initials: JT
authors.lastname: Liu
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D016018:Least-Squares Analysis; D053758:Nanoparticles; D057089:Pathology, Molecular / Q000379:methods*; D015203:Reproducibility of Results; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013499:Surface Properties