This PDF file contains the front matter associated with SPIE Proceedings Volume 7574, including the Title Page, Copyright information, Table of Contents, and the Conference Committee listing.

A novel fluidic actuator that is simple to fabricate, integrate, and operate is demonstrated for use within microfluidic systems. The actuator is designed around the use of trapped air bubbles in lateral cavities and the resultant acoustic streaming generated from an outside acoustic energy source. The orientation of the lateral cavities to the main microchannel is used to control the bulk fluid motion within the device. The first order flow generated by the oscillating bubble is used to develop a pumping platform that is capable of driving fluid within a chip. This pump is integrated into a recirculation immunoassay device for enhanced biomolecule binding through fluid flow for convection limited transport. The recirculation system showed an increase in binding site concentration when compared with traditional passive and flow-through methods. The acoustic cavity transducer has also been demonstrated for application in particle switching. Bursts of acoustic energy are used to generate a second order streaming pattern near the cavity interface to drive particles away or towards the cavity. The use of this switching mechanism is being extended to the application of sorting cells and other particles within a microfluidic system.

P53 is a tumor suppressor used as marker for early cancer diagnosis and prognosis. We have studied constructs based on gold nanoparticles (NPs) decorated with specific anti-p53 antibodies and with a fluoresceine derivative, FITC. The interaction of gold surface plasmons with fluorophores bound within few nanometers from the surface, likely induces changes in the fluorophore excited state lifetime. Indeed we found previously that this parameter follows linearly the p53 concentration in solutions (in vitro conditions) up to 200-400 pM, depending on the size of the NP, with a 5 pM uncertainty. We have evaluated here the nanosensor specificity for p53 by testing it in-vitro against bovine serum albumine, beta-lactolglobulin and lysozyme. Moreover, the titration of total cell extracts from p53+/+ or p53-/- cells with the p53antibody decorated gold NPs, indicates that this construct can also be used to detect the presence of p53 in total cell extracts and it will be therefore a valuable tool also for in vivo screening.

Photothermal therapy is a laser-based non-invasive technique for cancer treatment. Photothermal therapy can be enhanced by employing metal nanoparticles that absorb the radiant energy from the laser leading to localized thermal damages. Targeting of nanoparticles leads to more efficient uptake and localization of photoabsorbers thus increasing the effectiveness of the treatment. Moreover, efficient targeting can reduce the required dosage of photoabsorbers; thereby reducing the side effects associated with general systematic administration of nanoparticles. Magnetic nanoparticles, due to their small size and response to an external magnetic field gradient have been proposed for targeted drug delivery. In this study, we investigate the applicability of multifunctional nanoparticles (e.g., magneto-plasmonic nanoparticles) and magneto-motive ultrasound imaging for image-guided photothermal therapy. Magneto-motive ultrasound imaging is an ultrasound based imaging technique capable of detecting magnetic nanoparticles indirectly by utilizing a high strength magnetic field to induce motion within the magnetically labeled tissue. The ultrasound imaging is used to detect the internal tissue motion. Due to presence of the magnetic component, the proposed multifunctional nanoparticles along with magneto-motive ultrasound imaging can be used to detect the presence of the photo absorbers. Clearly the higher concentration of magnetic carriers leads to a monotonic increase in magneto-motive ultrasound signal. Thus, magnetomotive ultrasound can determine the presence of the hybrid agents and provide information about their location and concentration. Furthermore, the magneto-motive ultrasound signal can indicate the change in tissue elasticity - a parameter that is expected to change significantly during the photothermal therapy. Therefore, a comprehensive guidance and assessment of the photothermal therapy may be feasible through magneto-motive ultrasound imaging and magnetoplasmonic nanoparticles.

Three dimensional particle tracking is useful technology to characterize live cell or surrounding environment by tracing small particles such as fluorescence beads or polystyrene beads which adhered to objective samples. In microscopy imaging system, the longitudinal(z axis) tracking of the particle is essential for implementation of three-dimensional particle tracking, however it's been still a challenging topic to find the exact position of the particle in z axis with high precision. In this study, we present that a novel technique to find the longitudinal position of the particle, as well as the transverse position(x,y axis) by applying the numerical reconstruction and focusing with digital holographic microscope. Transmission type off-axis digital holographic microscope is implemented for this experiment, based on Mach-Zehnder interferometer and 632.8nm HeNe laser is used as a coherent light source of the microscope and high-speed CMOS camera is utilized for acquiring the hologram. Digital holographic microscope makes it possible to record and reconstruct the phase and amplitude image of the sample. In order to find the position of the particle in z axis, we apply the numerical focusing algorithm, which enables the translation of the imaging focus without actual longitudinal movement of the sample. To demonstrate the presented method, Brownian movement of 3μm polystyrene sphere suspended in water is investigated in this experiment.

A nonlinear theory for the optical properties of gold nanorods is presented. The refractive index sensitivity of the associated surface plasmon resonance is calculated to be 100-1000 nm/RIU for the aspect ratio range of 1-10. According to Gan's theory, the figure of merit, defined by the refractive index sensitivity divided by the FWHM value of the extinction coefficient, is calculated to be 1.0-12.0, which has a maximum value at the optimum aspect ratio of 3.5-4.5 depending on refractive index the surrounding medium.

Carboxylic acid functionalized multi-walled carbon nanotubes (COOH-MWCNTs) have been studied as macromolecular carriers for pH indicators to be used inside cells. The activation of carboxylic groups with thionyl chloride (SOCl2) followed by the reaction with a family of fluorescein ethylen glycol derivatives led to dyes covalently anchored to the MWCNT surface. Such a functionalization was found to preserve wholly the fluorescence properties of the dye ultimately providing higher water solubility to the modified macromolecular systems. Moreover, the use of a polyether spacer between the dye and the MWCNT surface preserved from undesired florescence quenching effects. The pH dependence of the modified nanotubes was investigated interrogating a solution of MWCNTs, the pH of which was adjusted in the range 4-9 pH units by adding drops of hydrochloric acid and sodium hydroxide. Light from LED was suitably filtered at 480 nm with a high pass-band filter and coupled to an optical fiber which illuminates the solution containing the fluorescein-functionalised MWCNTs. An optical fiber, at 90° with respect to the LED illumination, is connected with a Hamamtsu spectrum analyzer for the recording of the fluorescence spectra. The modified MWCNTs exhibited linear pH dependence in the range between 6 and 8 pH units with a sensitivity less than 0.1 pH units.

Biomolecules, such as DNA and cytoskeleton proteins, self-assemble in long-range-ordered nano-aggregates. The process of formation of these long-range ordered nanostructures have large biological interest but, increasingly, they also offer good inspiration for bottom-up 'fabrication' processes leading to large nanostructured areas with the design embedded in their smaller components, as opposed to the classical top-down nanofabrication. To this end, we report here an atomic force microscopy (AFM) study of the high order self assembly of F-actin on mica. AFM is a classical tool for elucidating the topography of biomolecules-covered surfaces, including proteins, and mica is commonly used as a substrate for AFM imaging at molecular resolution due to its atomically-flat surface. Beyond this classical aspects, the most interesting aspect of our work was the capability of fabrication ordered patterns formed by F-actin filaments, through the tuned interplay between F-actin self-assembly forces and forces applied by the AFM tip in a contact mode. More specifically, increasing the force applied by the AFM tip we could observe the shift from the visualisation of individual actin filaments to parallel actin filaments 'rafts'. Thus we could produce ordered hybrid nano-structured surfaces through a mix-and-match nanofabrication technology.

The paper presents a methodology using atom or amino acid hydrophobicities to describe the surface properties of proteins in order to predict their interactions with other proteins and with artificial nanostructured surfaces. A standardized pattern is built around each surface atom of the protein for a radius depending on the molecule type and size. The atom neighborhood is characterized in terms of the hydrophobicity surface density. A clustering algorithm is used to classify the resulting patterns and to identify the possible interactions. The methodology has been implemented in a software package based on Java technology deployed in a Linux environment.

This paper presents a label-free biosensor using two Light Emitting Diodes (LEDs) as light sources and a photo detector as a receiver. The sensor uses a silica-on-silicon wafer with PMMA [Poly(methyl methacrylate)] as the functional layer. The principle of this biosensor is based on the Fabry Perot (FP) interferometer. A thickness of a 100 nm PMMA layer is spin-coated on the silicon wafer, which has a thin thermal oxide layer of 500 nm. In such a configuration, the PMMA layer and silica layer function as an FP cavity. When a light illuminates the surface of the sensor, the reflections from the PMMA-air and silica-silicon interfaces will interfere with each other. Consequently, the change of the cavity length, which is caused by biomaterial binding on the PMMA layer, will result in a red shift in the reflection spectrum. An intensity change of the reflection light will be observed on an individual wavelength. In order to eliminate environment noise and to enhance the sensitivity of the sensor, two LEDs, whose center wavelength is chosen on either side of the spectrum notch, are introduced in the system. A photo detector will alternatively obtain the intensities of the two individual reflected lights, and collect the signal via a data acquisition system. Long-term tests have shown that the sensor is resistant to environmental fluctuation. Biolinker Protein G' was used for binding tests. The sensor shows great potential in biosensor applications due to its compact size and low cost.

A nanoarray, integrated with an electrophoretic system, was developed to trap nanoparticles into their corresponding nanowells. This nanoarray overcomes the complications of losing the function and activity of the protein binding to the surface in conventional microarrays by using minimum amounts of sample. The nanoarray is also superior to other biosensors that use immunoassays in terms of lowering the limit of detection to the femto- or atto-molar level. In addition, our electrophoretic particle entrapment system (EPES) is able to effectively trap the nanoparticles using a low trapping force for a short duration. Therefore, good conditions for biological samples conjugated with particles can be maintained. The channels were patterned onto a bi-layer consisting of a PMMA and LOL coating on conductive indium tin oxide (ITO)-coated glass slide by using e-beam lithography. The suspensions of 170 nm-nanoparticles then were added to the chip that was connected to a positive voltage. On top of the droplet, another ITO-coated-glass slide was covered and connected to a ground terminal. Negatively charged fluorescent nanoparticles (blue emission) were selectively trapped onto the ITO surface at the bottom of the wells by following electric field lines. Numerical modeling was performed by using commercially available software, COMSOL Multiphysics to provide better understanding about the phenomenon of electrophoresis in a nanoarray. Simulation results are also useful for optimally designing a nanoarray for practical applications.

Motility assays are the tools of choice for the studies regarding the motility of protein molecular motors in vitro. Despite their wide usage, some simple, but fundamental issues still need to be specifically addressed in order to achieve the best and the most meaningful motility analyses. An analysis of the errors in the calculation of the average velocity and of the fluctuations of velocity due to pixel size is presented here. The magnitude of the fluctuations is correlated with the resolution of the objective lens used in observing the motility assays and with the parameters of the camera used for digitizing the images. Also, the errors in the angular distribution of velocities due to pixel size are characterized and discussed.

We report a numerical study on the frequency property of a system composed of an optical antenna array placed on the surface of a dielectric grating. Such a periodic structure is designed for Raman spectroscopy application because of its advantages over the conventional rough-surface based surface enhanced Raman spectroscopy: the position of the high field intensity and the exact field magnitude is well controlled by the design, and the constructive interference from the elements placed in periodic array may form a collective resonance and provide a further enhancement to the field intensity. By integrating and weakly coupling the guided mode resonance (GMR) of a dielectric grating with optical nano-antennas made of plasmonic materials that are also field-enhancing devices, it provides a further enhanced local field around the antenna. We specifically studied the behavior of the device under oblique incidence, and show that multiple resonant peaks are observed in the spectrum. The application of the device in a Raman process is discussed in details.

Three types of photo-responsive nano-architectures -nano-gatekeepers, nanovalves and nanoimpellers- were synthesized based on azobenzene derivatives tethered in and on mesporous silica nanoparticles. The light responsive nature of these materials enables them to be externally controlled such that transport of the cargo molecules from mesopores can be regulated. In particular, nanoimpellers have shown to successfully release anti-cancer drug, camptothecin, upon photoactivation and ultimately led to cell apoptosis.

Porous silicon is an attractive platform for the encapsulation of chemical and biological recognition elements. We demonstrate fabrication of porous silicon using a dry etching technique. The Xenon Difluoride etching technique allows selective formation of porous silicon with a standard photoresist layer as mask. We demonstrate free standing 5μm thick porous silicon films for biological sample filtering. Further, we employ the porous silicon as a substrate for the immobilization of xerogel thin films that encapsulate specific analyte responsive luminophores in their pores. The porous silicon behaves as an optical interference filter which allows selective enhancement of the wavelengths of interest.

In this paper, we describe the development of a novel, retina-like neuromorphic chip that has an array of two types of retina 'cells' arranged to mimic the fovea structure in certain animals. One of the two retina cell types performs irradiance detection and the other can perform color detection. Together, via the two parallel pathways the retina chip can perform color change intensity change disambiguation (CCICD). The irradiance detection cell has a wide-dynamic detection range that spans almost 3 orders of magnitude. The color detection cell has a buried double junction (BDJ) photodiode as the photoreceptor followed by two parallel logarithmic I-V convertors. The output from this is a color response which has at least a 50nm resolution for wavelengths from 400nm to 900nm. With these two cells, the array can perform color change -intensity change disambiguation (CCICD) to determine if a change in the output of the irradiance pathway is because of irradiance change, color change, or both. This biological retina-like neuromorphic sensor array is implemented in ON-SEMI 0.5μm technology, a standard CMOS fabrication process available at MOSIS.

Gold nanorods (GNRs) exhibit intense localized plasmon resonances at optical frequencies in the near infrared (NIR), which is the window where the penetration of light into the body is maximal. Upon excitation with a NIR laser, a strong photothermal effect is produced, which can be exploited to develop minimally invasive therapies. Here we prove the use of chitosan-GNRs films as a novel NIR sensitive nanocomposite for the photothermal conversion of NIR laser light during surgical interventions of tissue welding. Chitosan is an attractive biomaterial due to its biodegradability, biocompatibility, hemostatic, antimicrobial and wound healing-promoting activity. Colloidal GNRs were embedded in chitosan based, highly stabilized, flexible and easy-to-handle films, which were stored in water until the time of surgery. The chitosan-GNRs films were first positioned on freshly explanted rabbit tendon samples. Then, by administration of single pulses ranging from 80 to 140 ms duration and 0.5 to 1.5 W power delivered by a 300-μm optic fiber coupled with a 810 nm diode laser, spots of local thermally-induced adhesion characterized by a tensile strength of ~ 10 kPa were obtained. The present results are encouraging toward the development of a novel minimally-invasive technology based on the application of bioderived nanoplasmonic materials to biomedical optics.

Scattering from noble metallic nanoparticles with specific structures are strongly depolarized in contrast to dielectric particles. The effect depends on the shape and symmetry of the nanoparticles and can be explained by induced plasmonic multi-resonances along different axes of symmetry. In our experiments we found that the scattering from 'nanorod' structures of silver is more polarized than globular colloidal silver nanostructures. The depolarized scattering can be tuned to the near-infrared region by using proportionate mixture of the colloids and nanorods. We demonstrate this effect in solution as well as in polymer films where nanoparticles were immobilized. This phenomenon of depolarized scattering is promising for designing dye-less sensing devices useful in diagnostics. We show scattering polarization profile from asymmetric nanostructures changes during their aggregation. Modulating the rate of aggregation of these nanostructures by 'receptor - ligand'-like interactions can be successfully utilized for sensitive 'dye-less' diagnostics.

Diffraction-based biosensors that rely on optical scattering are a sensitive approach for biomolecular detection. We present a Mie surface double-interaction computer study of the in situ assembly of bead-based diffraction gratings on a gold substrate. The limit of detection for a system having 26 stripes is calculated to be approximately 25 beads in total, or approximately one bead per stripe in an immunoassay experiment. This sensitivity limit is orders of magnitude better than label-free molecular sensors, and is consistent with high-speed scanning for high-throughput assays.