Hsin Yu Wu

Plasmonic nanogap-enhanced Raman scattering using a resonant nanodome array.

We investigate the optical properties and surface-enhanced Raman scattering (SERS) of plasmonic nanodome array substrates that are demonstrated to provide a reproducible SERS enhancement factor of 1.18×1010 for detection of a urinary metabolite used to monitor kidney function.

Surface-enhanced Raman nanodomes

We demonstrate a surface-enhanced Raman scattering (SERS) substrate consisting of a closely spaced metal nanodome array fabricated on flexible plastic film. We used a low-cost, large-area replica molding process to produce a two-dimensional periodic array of cylinders that is subsequently overcoated with SiO(2) and silver thin films to form dome-shaped structures. Finite element modeling was used to investigate the electromagnetic field distribution of the nanodome array structure and the effect of the nanodome separation distance on the electromagnetic field enhancement. The SERS enhancement from the nanodome array substrates was experimentally verified using rhodamine 6G as the analyte. With a separation distance of 17 nm achieved between adjacent domes using a process that is precisely controlled during thin film deposition, a reproducible SERS enhancement factor of 1.37 × 10(8) was demonstrated. The nanoreplica molding process presented in this work allows for simple, low-cost, high-throughput fabrication of uniform nanoscale SERS substrates over large surface areas without the requirement for high resolution lithography or defect-free deposition of spherical microparticle monolayer templates.

Improved Sensitivity of DNA Microarrays Using Photonic Crystal Enhanced Fluorescence

DNA microarrays are used to profile changes in gene expression between samples in a high-throughput manner, but measurements of genes with low expression levels can be problematic with standard microarray substrates. In this work, we expand the detection capabilities of a standard microarray experiment using a photonic crystal (PC) surface that enhances fluorescence observed from microarray spots. This PC is inexpensively and uniformly fabricated using a nanoreplica molding technique, with very little variation in its optical properties within- and between-devices. By using standard protocols to process glass microarray substrates in parallel with PCs, we evaluated the impact of this substrate on a one-color microarray experiment comparing gene expression in two developmental stages of Glycine max. The PCs enhanced the signal-to-noise ratio observed from microarray spots by 1 order of magnitude, significantly increasing the number of genes detected above substrate fluorescence noise. PC substrates more than double the number of genes classified as differentially expressed, detecting changes in expression even for low expression genes. This approach increases the dynamic range of a surface-bound fluorescence-based assay to reliably quantify small quantities of DNA that would be impossible with standard substrates.

Plasmonic coupling of SiO2 -Ag "post-cap" nanostructures and silver film for surface enhanced Raman scattering

We demonstrate a surface-enhanced Raman scattering (SERS) substrate consisting of SiO<inf>2</inf>-Ag “post-cap” nanostructures with an underlying silver film. Optimized coupling between freestanding Ag caps and the underlying silver film results in a maximum enhancement factor of 2.38×10⁹.

Employing two distinct photonic crystal resonances to improve fluorescence enhancement

Surface-bound fluorescence assays such as microarrays have emerged as a prominent technology in current life sciences research and are currently performed on optically passive substrates such as glass microscope slides. We present an alternative approach using photonic crystal substrates exhibiting resonant reflections. In this work, we design and fabricate a photonic crystal with a TM-polarized resonance at the cyanine-5 excitation wavelength and a TE-polarized resonance spectrally overlapping this fluorophores emission spectrum. The former resonance increases the excitation of the fluorophore through enhanced electric field intensities, while the latter resonance redirects a proportion of emitted light toward the detection instrumentation. Spots of cyanine-5 conjugated streptavidin on the photonic crystal demonstrate a 60-fold increase in fluorescence intensity and a 42-fold increase in signal-to-noise ratio relative to a glass slide.

Label-Free Prehybridization DNA Microarray Imaging Using Photonic Crystals for Quantitative Spot Quality Analysis

Technical variability during DNA capture probe printing remains an important obstacle to obtaining high quality data from microarray experiments. While methods that use fluorescent labels for visualizing printed arrays prior to hybridization have been presented, the ability to measure spot density using label-free techniques would provide valuable information on spot quality without altering standard microarray protocols. In this study, we present the use of a photonic crystal biosensor surface and a high resolution label-free imaging detection instrument to generate prehybridization images of spotted oligonucleotide microarrays. Spot intensity, size, level of saturation, and local background intensity were measured from these images. This information was used for the automated identification of missed spots (due to mechanical failure or sample depletion) as well as the assignment of a score that reflected the quality of each printed feature. Missed spots were identified with >95% sensitivity. Furthermore, filtering based on spot quality scores increased pairwise correlation of posthybridization spot intensity between replicate arrays, demonstrating that label-free spot quality scores captured the variability in the microarray data. This imaging modality can be applied for the quality control of printed cDNA, oligonucleotide, and protein microarrays.

Biochemical sensor tubing for point-of-care monitoring of intravenous drugs and metabolites

In medical facilities, there is strong motivation to develop detection systems that can provide continuous analysis of fluids in medical tubing used to either deliver or remove fluids from a patients body. Possible applications include systems that increase the safety of intravenous (IV) drug injection and point-of-care health monitoring. In this work, we incorporated a surface-enhanced Raman scattering (SERS) sensor comprised of an array of closely spaced metal nanodomes into flexible tubing commonly used for IV drug delivery and urinary catheters. The nanodome sensor was fabricated by a low-cost, large-area process that enables single use disposable operation. As exemplary demonstrations, the sensor was used to kinetically detect promethazine (pain medication) and urea (urinary metabolite) within their clinically relevant concentration ranges. Distinct SERS peaks for each analyte were used to demonstrate separate detection and co-detection of the analytes.

Magnification of photonic crystal fluorescence enhancement via TM resonance excitation and TE resonance extraction on a dielectric nanorod surface

We experimentally demonstrate that a 1D photonic crystal surface incorporating a nanorod-structured layer reveals a 588-fold enhancement in fluorescence intensity through the use of resonance-enhanced excitation of Cy5 and resonance-enhanced extraction of Cy5 emission.

Deposited nanorod films for photonic crystal biosensor applications

Planar photonic crystals have been used as the basis of many biological sensing devices. Here, the authors successfully demonstrated that the combination of the photonic crystal structures and a dielectric nanorod coating prepared by the glancing-angle deposition technique can lead to significant increases in the device sensitivity. By incorporating a TiO2 nanorod coating onto the label-free photonic crystal biosensor structure, the surface area of the device is increased. The results for detection of polymer films and proteins indicate up to a 5.5 fold enhancement of detected adsorbed mass density.

Surface-enhanced Raman scattering nanodomes fabricated by nanoreplica molding

We demonstrate a surface-enhanced Raman scattering substrate consisting of a closely spaced metal nanodome array fabricated on flexible plastic film. We used a low cost, large area replica molding process to produce a 2-dimensional periodic array of cylinders that is subsequently overcoated with SiO2 and silver thin films to form dome-shaped structures. Finite element modeling was used to investigate the electromagnetic field distribution of the nanodome array structure and the effect of the nanodome separation distance on the electromagnetic field enhancement. The SERS enhancement from the nanodome array substrates was experimentally verified using rhodamine 6G as the analyte. With a separation distance of 17 nm achieved between adjacent domes using a process that is precisely controlled during thin film deposition, a reproducible SERS enhancement factor of 1.37×108 was demonstrated. The nanoreplica molding process presented in this work allows for simple, low cost, high-throughput fabrication of uniform nanoscale SERS substrates over large surface areas without the requirement for high resolution lithography or defect-free deposition of spherical microparticle monolayer templates.