This PDF file contains the front matter associated with SPIE Proceedings Volume 8231, including the Title Page, Copyright information, Table of Contents, Introduction, and the Conference Committee listing.

Refractive index (RI) and its dispersion play a major role in interaction of electromagnetic wave with matter. Quantitative phase imaging (QPI) has proven to be a useful tool to estimate the RI from the sample-induced phase delay measurement at high spatio-temporal resolution. Here, we introduce near-infrared dispersive quantitative phase imaging (NIRD-QPI) of microscopic objects. The setup uses a new geometry for quantitative phase microscopy by use of spatial frequency filtering in Fourier plane. High resolution refractive index spectroscopic measurement over a range from 690 to 840nm in interval of 25nm is reported. This method could prove to be very useful for characterizing wide range of nano and biomaterials.

Medical applications of metal nanoparticles are the subject of intense research due to their unique properties which make them suitable for both diagnostic and therapeutic use. One such property is surface plasmon resonance which results in strong enhancement of the absorption and scattering of electromagnetic radiation. The combination of metal type, size, and shape characteristics provides unique tunability of a nanostructure's optical properties. Several types of nanoparticles have been explored for medical and biological applications. Here we present a theoretical investigation of novel metal nanostructures which have distinct absorption and scattering spectra. This could be beneficial for combined diagnostic and therapeutic applications since the diagnostic and therapeutic laser wavelengths can be decoupled for increased efficacy and safety. For this purpose, it is desirable to have the most intense scattering, with minimal absorption, in the near-infrared for imaging and the opposite in the red, for therapy. The efficiency factor for various metals, shapes and sizes was first calculated using the Discrete Dipole Approximation (DDA) method. From the results, nanostructures consisting of combinations of cubes and spheres were found to have the most appropriate scattering and absorption spectra and their optical properties were thoroughly investigated. The size, number and material (silver or gold) of the nanospheres and, to a lesser extent, the dimensions of the cubes were varied in order to obtain the optimum nanostructure with distinct absorption and scattering spectra. Given its properties, these nanostructures have the potential to be used for enhancement of various imaging and therapeutic methods.

We report our new discovery of the nanophenomenon called plasmonic nanobubbles to devise faster, safer and more accurate ways of manipulating the components of human tissue grafts. The reported work facilitates future cell and gene therapies by allowing specific cell subsets to be positively or negatively selected for culture, genetic engineering or elimination. The technology will have application for a wide range of human tissues that can be used to treat a multiplicity of human diseases.

Far-field microscopy techniques are routinely used for the visualization of biological systems, but are limited according to Abbe`s criteria to about λ/2. The objective of this work is to integrate a solid immersion lens (SIL) as a near-field probe into a standard microscope spectrophotometer in order to perform polychromatic illumination near-field microscopy as well as near-field spectroscopy. The SIL concept can achieve a higher resolution than expected by the increase of the numerical aperture. Even with a tip diameter of 700nm and a tip point angle of 130° the lateral resolution is in the range of about 30 nm, therefore overcoming the tradeoff between the resolution and intensity restrictions in aperture limited SNOM probes. In this paper the optical setup of the system is described and some images of biological samples on a nanoscale with high contrast are presented.

CARS is meritorious in its ability to perform chemical selective imaging, but its spatial resolution is limited by the diffraction limit of light; however, this limit can be broken by combining CARS and near-field scanning microscope. In this work, we report a novel radially polarized near-field coherent anti-Stokes Raman scattering microscopy (RP-NF-CARS), which uses radially polarized light as excitation to enhance the electric field enhancement under a metallic tip, and improves the signal to background ratio compared with that using linearly polarized excitations. We applied RP-NF-CARS to image nano-scale polystyrene beads and biological system.

The paper presents an image-oriented modality to functionally describe articially and biologically nanostruc- tured surfaces, which can be used for the characterization of the atom neighborhoods on the surface of proteins. The both properties,hydrophobicity and charge distribution on protein surface, are analyzed in this paper. The actual discrete hydrophobicity and charge distribution attached to the atoms that form a surface atom's vicinity is replaced by an approximately equivalent density distribution, computed in a standardized octagonal pattern around each atom. These representations of hydrophobicities and charges are used to compute the resemblance of surface atom neighborhoods belonging to a protein, dened as the sum of the products of hydrophobicity densities of the corresponding patches (the pattern's central circles or angular sectors having the same position). The similitude and the interaction of a pair of atom neighborhoods are dened as their resemblance for parallel, respectively, anti-parallel orientations of the normals on the molecular surfaces in the points where the central atoms are located. Surface atom neighborhoods have been classied in terms of both resemblance and vector description.

Nonlinear optical properties of barium titanate (BaTiO₃) nanoparticles are investigated as a function of size and shape. BaTiO₃ is an attractive option as a nonlinear material because it can exhibit a high second and third order electronic susceptibility even at the nanoscale. These particles are employed as contrast agents/biomarkers and phase conjugate nanomirrors in imaging, utilizing second harmonic generation for two-photon microscopy and four-wave mixing for three-photon microscopy and scattering reversal image enhancement. Silver is also used to create a shell around the BaTiO₃ nanoparticle to see if a core/shell structure enhances any of the nonlinear effects.

In the interest of generating new biomedical sensing techniques as well as improving those that currently exist, a great deal of attention has been given to upconverting lanthanide nanoparticles in recent years. In order to develop these nanoparticles for use in multiplexed and ratiometric sensing techniques, many recent studies have focused on experimental control of their emission wavelengths. Here we describe a new method for controlling the relative intensity of green and red emission bands in NaYF4:Yb3+,Er3+ nanoparticles via control of the excitation pulse repetition rate. Using this method, particles of the same composition may be tuned to produce red and green light in user-defined ratios. We discuss the mechanism behind this control as well as potential applications that could make use of this property, specifically in super resolution imaging techniques.

The cost of fabrication and instrumentation presents a significant barrier to uptake of optical mapping as a tool for genomic investigation. Here a low cost optical instrumentation system to perform optical genomic mapping of DNA fragment restriction digestion by nanochannel confinement is presented. Specifically, the system is used for the detection of YOYO-1 labeled DNA within chemically formed nanochannels on a polystyrene chip. The formation of nanochannels on the polystyrene chip is achieved by solvent swelling of an injection moulded polystyrene substrate. The inverted microscope based system is compact and of low-cost but offers the sensitivity to detect individual fragments ranging from 0.56Kb to 9.4Kb of the λ-phage genome within a channels. Conformation of DNA within nanochannels driven by capillary flow is most consistent with modeled polymer extension in nanoslit.

We present a rigorous electromagnetic theory of the electromagnetic power emitted by a dipole located in the vicinity of a multilayer stack. We applied this formalism to a luminescent molecule attached to a CMOS photodiode surface and report light collection efficiency larger than 80% toward the CMOS silicon substrate. We applied this result to the development of a low-cost, simple, portable device based on CMOS photodiodes technology for the detection and quantification of biological targets through light detection, presenting high sensitivity, multiplex ability, and fast data processing. The key feature of our approach is to perform the analytical test directly on the CMOS sensor surface, improving dramatically the optical detection of the molecule emitted light into the high refractive index semiconductor CMOS material. Based on adequate surface chemistry modifications, probe spotting and micro-fluidics, we performed proof-of-concept bio-assays directed against typical immuno-markers (TNF-α and IFN-γ). We compared the developed CMOS chip with a commercial micro-plate reader and found similar intrinsic sensitivities in the pg/ml range.

The development of miniature and label-free optical sensors is very critical for applications in a wide range of areas such as medicine, environment, forensic and food quality control. In this report, a Bragg-grating air-slot waveguide is designed (using Finite Domain Time Difference modeling (FDTD)) and fabricated (using Electron beam lithography and Reactive ion etching) on a silicon-on-insulator substrate to develop a label-free optical sensor. The Bragg gratings constitute of recesses in the 140 nm wide air-slot waveguide. The grating structures generate a band-gap for certain frequencies and the spectral shift of the lower band-edge is used as the mechanism to sense fluids or bio-molecules in the air-slot. Based on the 3-D FDTD and experimental results, the sensitivity of the device is 620 nm/RIU, which is higher than other recently reported sensors. Due to the high electric field intensity in the air slot, this area becomes very sensitive to index variations caused by bio-molecules or fluids in the air-slot.

In previous work, we demonstrate a simple approach to creating a plasmonic polymer. Reflecting upon the need for greater spot density while still maintaining the objective of low cost analysis, the next generation of device is described where density up to 24000 sensing spots is achievable. A localized surface plasmon micro-array is described formed by single or multiple deposition of a nanorod plasmonic polymer by micro-contact printing. The structure of the polymer can be made micro-porous and thickness can be controlled by a cyclical deposition and rapid heat cure protocol. The consistency of feature deposition is assessed. The resulting micro-structure provides a large surface area for immobilization of biomolecules for assay development. Dark-field analysis of the polymer demonstrates complex microstructure and intense Mie Scattering as expected from gold nanorods. Using fluorescence confocal analysis images of the polymer demonstrates two independent photo-luminescent emission spectra. The two independent emission spectra are linked to the positions of the localized surface plasmons of the nanorods, using a pump source of 543nm excites the transverse plasmon (peak at 550nm)and it's commensurate emission, but doesn't excite the longer emission around 700nm that is linked to the longitudinal Plasmon around 737nm. The different emissions are demonstrated in the illumination of different portions of the polymer matrix under each pump source excitation. The potential for multiple spectroscopic biosensor analysis is discussed.

In recent years a variety of studies has demonstrated that artificially generated microenvironments can exert a strong influence on cell growth, cell adhesion, proliferation, and differentiation behavior in the culture dish. In particular, cells tend to adapt themselves to elongated micro- and nanostructures. Thus, nanostructured substrates are of significant interest in the biological and biomedical sciences as adhesion and development of cells can be controlled via the topological surface properties. In contrast to earlier approaches relying on electron beam or nanoimprint lithography, nanostructures were produced on Si(100) surfaces using sub-15 femtosecond high-resolution laser scanning microscopy. Laser processing was performed with the silicon surface immersed in water followed by hydrofluoric acid etching in order to remove silicon oxide residues. Ripples of at a periodicity of 150 nm as well as random nanoporous surface arrangements were generated by Ti:Sapphire laser light of centre wavelength 800 nm (bandwidth 120 nm, repetition rate 85 MHz) at picojoule pulse energies. Growth of Chinese hamster ovary (CHO) cells revealed good adhesion to the silicon substrates. Importantly, alignment of cells along the direction of ripples was observed, whereas randomly nanoporous surfaces did not induce any preferences in cell orientation.

Two-dimensional, large-area, periodic mushroomlike metallodielectric nanostructures have been simulated, fabricated, and characterized for biosensing applications. Simulations show high electrical field around the tips of the structure. The fabrication process consists of using holographic lithography to create 2-D periodic nanohole array. Subsequently, oblique metal deposition on the nanohole array results in mushroomlike nanostructure with a cavity underneath the void space. The precise geometry of the nanocavity is dependent on the deposition time (thickness). The periodicity of the array was designed to excite propagating surface plasmon resonance (SPR) modes, while the geometric shape of the nanostructure excites localized plasmons on its edges. The coupling between these two phenomena results in higher electric field and thus higher enhancement factor than conventional nanohole array over the whole substrate area ( > 4 cm²). By analyzing the Raman mode of the adsorbed benzenethiol on the surface, the surface enhanced Raman scattering (SERS) enhancement factor of greater than 10⁶ has been measured. Due to its moderately-high enhancement factor, large-area array, and low-cost fabrication method, this nanostructure can be used for future SERS biosensing applications.

A new type of Raman spectroscopy hyperspectral imager based on Bragg tunable filter has been developed by University of Montreal and Photon etc. The technology of Bragg tunable filter significantly reduces the acquisition time by selecting a single wavelength in a full camera field and scanning the wavelength with a high efficiency. The transmission is continuously tunable over 400 nm range with a spectral resolution of 0.2 nm. We here present the principle of this novel Raman imaging system as well as hyperspectral images of Si taken with a spectral resolution of 0.2 nm on the whole field of view of the microscope.

Computer simulation of lipid bilayer detection using ion-sensitive field-effect transistors (ISFETs) is presented. Based on a previous work addressing DNA sensing using ISFETs, lipid bilayers on ISFET sensor surface is modeled. The model consists of (a) sensor surface, (b) Stern layer, (c) thin electrolytic layer, (d) lipid bilayer, and (e) semi-infinitely-extended electrolyte domain. Poisson-Boltzmann equation is solved to determine electrostatics taking into account mobile ion charges in electrolyte and lipid charges. The simulation successfully reproduces experimental results of output signal change due to positively-charged lipid molecular concentration, as well as salt ion concentration.

Zero-mode waveguides (ZMWs) are optical nanostructures to confine fluorescent excitation within sub-diffraction volumes and are commonly used for single-molecule analysis. However, the conventional ZMWs with aluminum film on fused silica have limitations on living cell studies. The same surfaces composed of hydroxyl group inside and outside each ZMW restrict specific surface functionalization. The sharp-cylinder shaped and rough edge of each ZMW produces a steric interference of molecular dynamics on cell membrane. In this study, selectively surface functionalization inside and outside of each ZMW was achieved with tri-metal-layer film on fused silica. Moreover, bowl-shaped and smooth edge of each ZMW was manufactured in large area. The improvement of ZMWs provides a broad way for monitoring molecular dynamics in living cells.

This study investigated a method that simultaneously detects three bacteria, Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus via an approach that combines un-immunized magnetic nanoparticles for the enrichment and antibody-conjugated quantum dots (QDs) as fluorescence markers, by using a laboratory-made system. In the enrichment procedure, the un-immunized superparamagnetic polymer nanoparticles and the three bacteria formed "beadcell" complex. Magnetic nanoparticles with different size were used and some interferents were added into the bacteria suspension respectively to check the influence on concentration efficiency. In the immuno-fluorescence labeling procedure, QDs with different emission wavelenghs were immobilized with antibody. Antibody conjugated QDs capture the bacteria selectively and specifically so that "sandwich" complex were formed. The suspension of the labeled bacteria was trickled onto a microporous membrane. A 450nm semiconductor laser was used as a part of the laboratory-made system to excite the QDs. Three PMT detectors were utilized to detect the fluorescence intensity. These un-immunized magnetic nanoparticles can be applied in nonspecific separation and enrichment of bacteria from environmental samples, and this method, of which the detection procedures are completed within 2 h, can be applied to the cost-effective and rapid detecting of bacterial contamination.