The optical properties and surface-enhanced Raman scattering (SERS) of plasmonic nanodome array (PNA) substrates in air and aqueous solution are investigated. PNA substrates are inexpensively and uniformly fabricated with a hot spot density of 6.25 × 10(6) mm(-2) using a large-area nanoreplica moulding technique on a flexible plastic substrate. Both experimental measurement and numerical simulation results show that PNAs exhibit a radiative localized surface plasmon resonance (LSPR) due to dipolar coupling between neighboring nanodomes and a non-radiative surface plasmon resonance (SPR) resulting from the periodic array structure. The high spatial localization of electromagnetic field within the ∼10 nm nanogap together with the spectral alignment between the LSPR and excited and scattered light results in a reliable and reproducible spatially averaged SERS enhancement factor (EF) of 8.51 × 10(7) for Au-coated PNAs. The SERS enhancement is sufficient for a wide variety of biological and chemical sensing applications, including detection of common metabolites at physiologically relevant concentrations.

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.

This paper reports the design, fabrication and validation of a microfluidic well plate for combinatorial screening applications. Each well within the array is comprised of two 200 picoliter compartments that each contain a photonic crystal biosensor to enable the on-chip, in situ detection of (bio-) molecular binding events. This microfluidic chip utilizes arrays of Actuate-to-Open valves to isolate all compartments, which allows the chip to be decoupled from pneumatic control lines and thus to be transported freely between filling, sensing and characterization platforms. A proof-of-principle 4 x 4 protein/antibody binding assay was performed to demonstrate the discrete mixing and on-chip sensing capabilities.

A nanoreplica molding process has been used to produce polymer microfluidic channels, with integrated label-free photonic crystal biosensors as the bottom surface of the channels. Multiple flow channels are gathered in parallel so that an imaging detection instrument may simultaneously monitor the binding kinetics of many biomolecular interactions. In this work, the flow channel pattern has been adapted to a 96-well microplate format in which, for each 12-element row of the microplate, a single well serves as a common access port for 11 flow channels that are connected to separate microplate wells. Application of pneumatic pressure or suction to the common well serves to drive forward or backward flow to the channels. The system is demonstrated by measuring the kinetic binding interaction of protein A with IgG molecules of high, medium, and low affinity. The approach offers a means for minimizing the volume of reagent required to functionalize the biosensor surface, while retaining compatibility with the microplate assay fluid-handling methods that are most commonly used in biological research.

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A method for simultaneously integrating label-free photonic crystal biosensor technology into microfluidic channels by a single-step replica molding process is presented. By fabricating both the sub-micron features of the photonic crystal sensor structure and the >10 microm features of a flow channel network in one step at room temperature on a plastic substrate, the sensors are automatically self-aligned with the flow channels, and patterns of arbitrary shape may be produced. By measuring changes in the resonant peak reflected wavelength from the photonic crystal structure induced by changes in dielectric permittivity within an evanescent field region near its surface, detection of bulk refractive index changes in the fluid channel or adsorption of biological material to the sensor surface is demonstrated. An imaging detection instrument is used to characterize the spatial distribution of the photonic crystal resonant wavelength, gathering thousands of independent sensor readings within a single fluid channel.

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