Sculpting the analytical volume in and around nanoparticle sensors using a multilayer geometry.

The use of structured nanoparticles as optical contrast agents has led to new sensing opportunities in localizing the analytical volume within or outside the particle. Here we examine the use of structured nanoparticles for controlling the sensed analytical volume and figures of merit for their use. Nanolayered alternating metal-dielectric particles (nanoLAMPs), consisting of metal-dielectric nanospheres, are a flexible and highly tunable structure and used here to illustrate the concept of sculpting the analytical volume associated with a nanoparticle. The alternating metal and dielectric shells in LAMPs are designed such that, when illuminated, the plasmonic coupling of metal shells results in amplified electric fields in specific volumes. The strength and extent of regions with amplified fields (hot spots) in and around a LAMP are at the expense of other regions with depleted fields. A rigorous Mie theory formulation is used to model electric field redistributions. A genetic algorithm-based strategy is then employed to design LAMPs that selectively enhance the response of analyte molecules located either outside or in various dielectric layers through electric field redistribution. We demonstrate that it is possible to localize the analytical volume to within or outside the particle quite efficiently. Further, the analytical figures of merit (localization and amplification of signal as well as contrast between sensed species and background) are optimized and limits to the same are described. The strategy proposed here is a general route to engineer a palette of probes with highly specific detection capabilities using spectroscopy techniques based on surface-enhanced scattering, absorption, or emission processes.

Optimized nanospherical layered alternating metal-dielectric probes for optical sensing.

Multishell nanospheres have been proposed as a class of layered alternating metal-dielectric probes (LAMPs) that can greatly enhance sensitivity and multiplexing capabilities of optical molecular imaging . Here we theoretically demonstrate that the interplasmonic coupling within these spheres and hence their spectral responses can be tuned by a rational selection of layer thicknesses. As a proof-of-concept, layered Mie theory calculations of near- and far-field characteristics followed by a genetic algorithm-based selection are presented for gold-silica, silver-silica and copper-silica LAMPs. The results demonstrate that the optical tunability available allows for design of application (excitation wavelength)-specific probes of different sizes. The tunability further increases with number of layers and within a particular allowable probe size provides for structures with distinct resonances at longer wavelengths. The concept of scaling internal field resonances is also shown theoretically and the range over which the magnitudes can be tuned are presented.

Optimally designed nanolayered metal-dielectric particles as probes for massively multiplexed and ultrasensitive molecular assays.

An outstanding challenge in biomedical sciences is to devise a palette of molecular probes that can enable simultaneous and quantitative imaging of tens to hundreds of species down to ultralow concentrations. Addressing this need using surface-enhanced Raman scattering-based probes is potentially possible. Here, we theorize a rational design and optimization strategy to obtain reproducible probes using nanospheres with alternating metal and reporter-filled dielectric layers. The isolation of reporter molecules from metal surfaces suppresses chemical enhancement, and consequently signal enhancements are determined by electromagnetic effects alone. This strategy synergistically couples interstitial surface plasmons and permits the use of almost any molecule as a reporter by eliminating the need for surface attachment. Genetic algorithms are employed to optimize the layer dimensions to provide controllable enhancements exceeding 11 orders of magnitude and of single molecule sensitivity for nonresonant and resonant reporters, respectively. The strategy also provides several other opportunities, including a facile route to tuning the response of these structures to be spectrally flat and localization of the enhancement within a specific volume inside or outside the probe. The spectrally uniform enhancement for multiple excitation wavelengths and for different shifts enables generalized probes, whereas enhancement tuning permits a large dynamic range by suppression of enhancements from outside the probe. Combined, these theoretical calculations open the door for a set of reproducible and robust probes with controlled sensitivity for molecular sensing over a concentration range of over 20 orders of magnitude.

Narrowband midinfrared reflectance filters using guided mode resonance.

There is a need to develop mid-infrared (IR) spectrometers for applications in which the absorbance of only a few vibrational mode (optical) frequencies needs to be recorded; unfortunately, there are limited alternatives for the same. The key requirement is the development of a means to discretely access a small set of spectral positions from the wideband thermal sources commonly used for spectroscopy. We present here the theory, design, and practical realization of a new class of filters in the mid-infrared (IR) spectral regions based on using guided mode resonances (GMR) for narrowband optical reflection. A simple, periodic surface-relief configuration is chosen to enable both a spectral response and facile fabrication. A theoretical model based on rigorous coupled wave analysis is developed, incorporating anomalous dispersion of filter materials in the mid-IR spectral region. As a proof-of-principle demonstration, a set of four filters for a spectral region around the C-H stretching mode (2600-3000 cm(-1)) are fabricated and responses compared to theory. The reflectance spectra were well-predicted by the developed theory and results were found to be sensitive to the angle of incidence and dispersion characteristics of the material. In summary, the work reported here forms the basis for a rational design of filters that can prove useful for IR absorption spectroscopy.

Dark field Raman microscopy.

Confocal Raman microscopy is often used for optical sectioning but is problematic when the sample plane of interest has a weak Raman cross-section/signal relative to areas that are out-of-focus. This is especially true for clinical samples in pathology, which consist of a thin tissue (approximately 5 microm) sample placed on a thick glass slide. Here, we recognize that the problem is the result of the extent of the illumination at the confocal plane being larger than the size of the sample and propose a dark field illumination scheme to efficiently reject substrate signals. The ability of several optical configurations in rejecting out-of-plane signal is investigated for two model systems: SU-8 photo resist over Teflon and SU-8 photo resist over polystyrene. The proposed reflective dark field approach, in which excitation converged to a focal point slightly above the focal plane of the collection optics, was found to be most effective in recording data from the sample. The proposed approach is validated by the rejection of substrate response (fluorescence) in spectra acquired from approximately 4 microm of breast tissue on a glass microscope slide. The proposed approach is easy to implement on existing confocal systems, has a straightforward optimization in acquiring data, and is not expected to result in loss of lateral resolution in mapping experiments.

An inverse problem for reduced-encoding MRI velocimetry in potential flow.

We propose a computational technique to reconstruct internal physiological flows described by sparse point-wise MRI velocity measurements. Assuming that the viscous forces in the flow are negligible, the incompressible flow field can be obtained from a velocity potential that satisfies Laplace's equation. A set of basis functions each satisfying Laplace's equation with appropriately defined boundary data is constructed using the finite-element method. An inverse problem is formulated where higher resolution boundary and internal velocity data are extracted from the point-wise MRI velocity measurements using a least-squares method. From the results we obtained with approximately 100 internal measurement points, the proposed reconstruction method is shown to be effective in filtering out the experimental noise at levels as high as 30%, while matching the reference solution within 2%. This allows the reconstruction of a high-resolution velocity field with limited MRI encoding.