This PDF file contains the front matter associated with SPIE Proceedings Volume 7397, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing.

Single polystyrene nanoparticles are detected from resonance wavelength fluctuations in toroidal and spherical microcavities. The magnitude of the wavelength-shift signal follows a reactive mechanism with inverse dependence on mode volume. By reducing the size of a microsphere cavity we demonstrate sensitivity to single Influenza A virions. Furthermore, we introduce a novel mechanism for trapping and accumulation of nanoparticles at the microcavity-sensorregion by utilizing light-force exerted in evanescent field gradients.

Mesoporous silicon (PSi) photonic crystals have attracted interest as biosensing transducers owing to their high quality optics and sensitivity in optical characteristics to changes in refractive index. We describe progress our group has made derivatizing PSi towards devices for biology and medicine. PSi rugate filters display a high reflectivity resonant line in the reflectance spectrum. As an example for biosensing, immobilization of peptides and biopolymers within the PSi is demonstrated for detecting protease enzymes. Secretion of matrix metalloproteases from live cells was detected as a blue shift in the photonic resonance within hours, demonstrating the promise of this biosensor.

Diabetes Mellitus is a common chronic disease that has become a public health issue. Continuous glucose monitoring improves patient health by stabilizing the glucose levels. Optical methods are one of the painless and promising methods that can be used for blood glucose predictions. However, having accuracies lower than what is acceptable clinically has been a major concern. Using lasers along with multivariate techniques such as Partial Least Square (PLS) can improve glucose predictions. This research involves investigations for developing a novel optical system for accurate glucose predictions, which leads to the development of a small, low power, implantable optical sensor for diabetes patients.

We studied the thermal characteristics and analysis of InGaAs/InAlAs quantum cascade lasers (QCLs) in terms of internal temperature distribution, heat flux, and thermal conductance from the heat transfer simulation. The heat source densities were obtained from threshold power densities measured experimentally for QCLs under room-temperature continuous-wave operation. The use of a thick electroplated Au around the laser ridges helps increase the heat removal from devices. The two-dimensional anisotropic heat dissipation model was used to analyze the thermal behaviors inside the device. The simulation results were also compared with those estimated from experimental data.

A compact fiber optic sensor is described using Incoherent Broad-Band Cavity Enhanced Absorption Spectroscopy for sensitive detection of nanoliter samples of aqueous chemicals and microorganisms in capillaries. Absorption was measured in a 70 μm gap, comparable to the inside diameter of a capillary used for electrophoresis, between the ends of two short segments of multimode fiber. The other ends of the fibers were optically contacted to dielectric mirrors to form an 11-cm cavity resonator. Light from a superluminescent diode (λ=1054 nm, BW=35 nm FWHM) was coupled into one end of the cavity, and transmission through the cavity was measured using a silicon photodiode. Dilute aqueous solutions of near infrared dye were used to determine the minimum detectable absorption change of 4x10^-6 for 10 second integration and unity signal-to-noise ratio, which is approximately two orders of magnitude more sensitive than previously published results for systems with comparable sample path lengths.

Nanotechnology has recently been applied to a wide range of biological systems. In particular, there is a current push to examine the interface between the biological world and micro/nano-scale systems. Our research in this field has led to the development of novel strategies for spatial patterning of biomolecules, electrical and optical biosensing, nanomaterial delivery systems, single-cell manipulation, and the study of cellular interactions with nano-structured surfaces. Current work on these topics will be presented, including work on novel, semiconductor-based DNA detection methods and mechanical, atomic force microscopy (AFM)-based characterization of bacterial biofilms in threedimensional microfluidic systems.

This paper reviews recent progress in the design and fabrication of bio-inspired gradient index lenses. Inspired by the gradient index distributions of the protein layers in biological eyes, we employ nested layers of polymer composites to create smoothly-varying index distributions within bulk lens substrates. Because the fabrication technique allows for independent control of the index layers, the index contours, and the final lens surfaces, optical power can be combined with aberration control in a single element. Gradient-index singlets which correct for spherical aberration and singlets which correct for chromatic aberration are described as examples of the utility of this class of optics.

Detection of chemical processes on a single molecule scale is the ultimate goal of sensitive analytical assays. We have explored methods to detect chemical analytes in solution using synthetic derivatives of gramicidin A (gA). We exploited the functional properties of an ion channel-forming peptideg—gA—to report changes in the local environment near the opening of these semi-synthetic nanopores upon exposure to specific external stimuli. These peptide-based nanosensors detect reaction-induced changes in the chemical or physical properties of functional groups presented at the opening of the pore. This paper discusses the development of gA-based sensors for detecting external factors such as metal ions in solution or for detecting specific wavelengths of light. We propose that gA-based ion channel sensors offer tremendous potential for ultra sensitive functional detection since a single chemical modification of each individual sensing element can lead to readily detectable changes in channel conductance.

Multi-modal sensing scheme significantly improves the detection accuracy but can also introduce extra complexity in the overall design of the sensor. We overcome this difficulty by utilizing the plasmonic properties of metallic nanoparticles. In this study, we will present a simple dual optical sensing mechanism which harvests signals of the resonantly excited metallic nanostructure in the form of surface enhanced Raman scattering (SERS) and resonant Rayleigh scattering. Silver and gold nanoparticles labeled with appropriate antibodies act as signal transduction units and upon exposure to the targeted pathogen render the targeted species optically active. We demonstrate that detection of a single pathogen cell is easily attainable with the dual detection scheme. Furthermore, we explore the markedly different SERS intensity observed from the use of two very different antibody recognition units during the pathogen labeling process.

Surface Enhanced Raman Scattering (SERS) technique is used as an indispensable and sensitive modality for bio-sensing due to its ability to distinguish the analyte molecules based on their distinct 'fingerprint' spectra. One of the most promising SERS substrates for biosensing was fabricated by coating noble metal film over orderly packed nanospheres. However, the major challenge in developing such a sensor is to achieve reproducible SERS substrate. Here, we report a new class of SERS substrate with ordered 3D nanostructures fabricated on silicon wafer by deep UV lithography technique followed by bi-metallic coating of silver and gold. Compared to the substrate fabricated by conventional nanosphere lithography, this approach allows better control of the nanostructures, which in turn gives uniform surface roughness for the metal film to provide adequate SERS enhancement with high reproducibility. Significance of this substrate for biomedical application was demonstrated by glucose sensing under physiologically relevant conditions. Partitioning and localization of glucose molecules within the first few nanometers of active SERS substrate was achieved by a self assembled monolayer (SAM) on the surface of substrate.

The development of air-tight buildings to significantly reduce the carbon emissions from buildings is a relatively new building technique. However the side effects of the new approach have not been fully investigated. One potential issue arising is from insufficient ventilation resulting in an increase in poor indoor air quality from exacerbated microbial growth through elevated humidity and temperature. At the moment there is no in situ real-time sensor for the detection of multiple microbes within the built environment. Developing a sensor utilizing the phenomena of Surface Plasmon Resonance as its detection method to continuously monitor in situ multiple microbial species and fungi is being undertaken. The research involves the refinement of the specialised instruments commercially available, simplifying the components and advancing the architecture of the interface allowing for the monitoring of multiple species and a novel output detection method.

The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of <200-nm bilayer vesicles composed of anionic and neutral lipids as well as cholesterol. Vesicle disruption, or peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

Tear fluid offers a potential route for non-invasive sensing of physiological parameters. Utilization of this potential depends on the ability to manufacture sensors that can be placed on the surface of the eye. A contact lens makes a natural platform for such sensors, but contact lens polymers present a challenge for sensor fabrication. This paper describes a microfabrication process for constructing sensors that can be integrated into the structure of a functional contact lens in the future. To demonstrate the capabilities of the process, an amperometric glucose sensor was fabricated on a polymer substrate. The sensor consists of platinum working and counter electrodes, as well as a region of indium-tin oxide (ITO) for glucose oxidase immobilization. An external silver-silver chloride electrode was used as the reference electrode during the characterization experiments. Sensor operation was validated by hydrogen peroxide measurements in the 10- 20 μM range and glucose measurements in the 0.125-20 mM range.

We report the synthesis and characterization of a novel nanoparticle formulation designed for skin penetration for the purpose of skin imaging. Solid lipid nanoparticles (SLNs), a drug delivery vehicle, were used as the matrix for targeted delivery of peroxide-sensitive chemiluminescent compounds to the epidermis. Luminol and oxalate were chosen as the chemiluminescent test systems, and a formulation was determined based upon non-toxic components, lotion-like properties, and longevity/visibility of a chemiluminescent signal. The luminescence lifetime was extended in the lipid formulation in comparison to the chemiluminescent system in solution. When applied to porcine skin, our formulation remained detectable relative to negative and positive controls. Initial MTT toxicity testing using HepG2 cells have indicated that this formulation is relatively non-toxic. This formulation could be used to image native peroxides present in tissue that may be indicative of skin disease.

Recently there has been a rapid growth in a new area of research known asWireless Health.¹ By leveraging stateof- the-art microelectronics and wireless technology, novel biosensing platforms can potentially be widely deployed in various healthcare applications that involve long-term patient monitoring. This paper provides a summary on the development and application of a specific type of biosensing platform known as wearable sensors.

The skin care product market is growing due to the threat of ultraviolet (UV) radiation caused by the destruction of the ozone layer, increasing demand for tanning, and the tendency to wear less clothing. Accordingly, there is a potential demand for a personalized UV monitoring system, which can play a fundamental role in skin cancer prevention by providing measurements of UV radiation intensities and corresponding recommendations. Furthermore, the need for such device becomes more vital since it has turned out that in some places (e.g., on snowy mountains) the UV exposure gets doubled, while individuals are unaware of this fact. This paper highlights the development and initial validation of a wireless and portable embedded system for personalized UV monitoring which is based on a novel software architecture, a high-end UV sensor, and conventional PDA (or a cell phone). In terms of short-term applications, by calculating the UV index, it informs the users about their maximum recommended sun exposure time by taking their skin type and sun protection factor (SPF) of the applied sunscreen into consideration. As for long-term applications, given that the damage caused by UV light is accumulated over days, it is able to keep a record of the amount of UV received over a certain course of time, from a single day to a month. Low energy consumption and high accuracy in estimating the UV index are salient features of this system.

Biological systems contain a multitude of molecules with specific functions and three-dimensional shapes that enable them to selectively interact with other molecules in a coordinated fashion. Engineering, on the other hand, has produced devices that operate on the micron-scale and that combine electronic and mechanical systems. Microelectromechanical Systems (MEMS) offer advantages such as the integration of a variety of functions into a single device (i.e. "lab-on-a-chip" platforms) and portability for "point-of-care" diagnostics. This study utilizes a microscale electrochemical sensor for detecting BoNT apatamer hybridization, in which we first used top-down lithographic processing to define the pattern of the electrodes and then used bottom-up manufacturing to modify the surface molecular properties for reducing non-specific binding. The goal was to systemically examine the effects of the design parameters of an electrochemical DNA sensor. Four key design parameters were examined: the area of the working electrode, the area of the counter electrode, the separation distance between the working and counter electrodes, and the overlap length between the working and counter electrodes. Through a log-log analysis of the current generated, representing the signal or noise, across variations of the different parameters, the significance of each parameter in sensor performance was determined. We found that the area of the working electrode was important in the performance optimization of the sensor, while the performance seemed to be independent of the other three parameters. The output signal level increased with the area of the working electrode and the signal-to-noise ratio was about constant in the tested range.

Protein function is reliant on structural flexibility and this flexibility is slaved to the surrounding solvent. Here we discuss how the exposed surface of the protein influences the solvent dynamics and thereby influences the protein's own structural dynamics. We discuss measurements of the THz absorption of water in the presence of hydrophilic and hydrophobic surfaces.

A dynamic surface-plasmon-resonance (SPR) imaging sensor was developed to realize high-resolution high-throughput applications. The SPR device consisted of a half-cylinder prism, 47.5nm-thick gold thin film and a custom-designed flow cell to construct the Kretschmann configuration. A cylindrical lens pair in conjunction with the half-cylinder prism was used to simplify the optical alignment procedure and to ensure plane-wave propagation inside the prism. Phase-shifting interferometry was implemented by using a piezoelectric transducer (PZT) driven by a triangular voltage waveform. A CCD camera was employed to acquire the sequential interference patterns required for phase calculations. A reference signal obtained from a photodiode before the SPR device was used to compensate the system instability from the laser intensity, environmental disturbances, and mechanical vibrations from the PZT. Integrating-bucket data acquisition was realized with the synchronization between the photodiode and the CCD camera to preserve the dynamic capability of the SPR sensor. System evaluations were performed by salt-water mixture measurements and gold-spot array imaging. The achieved phase-measurement stability was 0.40 degrees and the system sensitivity was 5.14×10⁴ degree/RIU (refractive index unit). The corresponding system resolution was 7.8×10^-6 RIU. This SPR imager is anticipated to find applications in studying biomolecular interactions with high resolution, stability, throughput and dynamic capability.

The connection of biomolecules like DNA to a micro scale environment such as microarrays and Lab-on-a-chip systems is an imminent task in biochip technology. Especially in Lab-on-a-chip systems microscopic forces are used to separate the analyte from a complex mixture for further analysis [1]. In this contribution the sorting and manipulation of DNA using dielectrophoresis (DEP) on micro structured chips was investigated [2]. DEP represents an interesting approach to manipulate and control objects at the micro- [3, 4] and nanoscale range [5-7], and especially to position them at controlled locations in microelectrode arrangements. It could be shown that DNA can be reversible arranged but also permanently immobilized in micro scale electrode gaps. It was also demonstrated that it is possible to stretch and align DNA from a single molecule level to high DNA concentration in a parallel manner between microelectrodes [8]. Furthermore DNA was stretched between moveable electrodes.

An electroless-microwave method is described here in order to synthesize electrically conductive gold nano-wires on a DNA. The electrical characterization shows that the gold wires were formed on the DNA. The nanowires were continuous, having low contact resistance, and exhibited the Ohmic behavior of electrodes. These nanowires were found to be in a few micrometers long having the diameter of 10-15 nm in solution and 20-30 nm in immobilized DNA with resistivity comparable to pure metal. The nanowires fabricated here could be used as building blocks for functional nanodevices, sensors, and optoelectronics.

In this work we summarize the main results obtained with the portable surface plasmon resonance (SPR) device developed in our group (commercialised by SENSIA, SL, Spain), highlighting its applicability for the real-time detection of extremely low concentrations of toxic pesticides in environmental water samples. In addition, we show applications in clinical diagnosis as, on the one hand, the real-time and label-free detection of DNA hybridization and single point mutations at the gene BRCA-1, related to the predisposition in women to develop an inherited breast cancer and, on the other hand, the analysis of protein biomarkers in biological samples (urine, serum) for early detection of diseases. Despite the large number of applications already proven, the SPR technology has two main drawbacks: (i) not enough sensitivity for some specific applications (where pM-fM or single-molecule detection are needed) (ii) low multiplexing capabilities. In order solve such drawbacks, we work in several alternative configurations as the Magneto-optical Surface Plasmon Resonance sensor (MOSPR) based on a combination of magnetooptical and ferromagnetic materials, to improve the SPR sensitivity, or the Localized Surface Plasmon Resonance (LSPR) based on nanostructures (nanoparticles, nanoholes,...), for higher multiplexing capabilities.

To come up to the demand for extremely sensitive biosensors for parallel real-time bioanalyses, we present several configurations of label-free biosensors on Silicon-on-Insulator (SOI) optical chips. We discuss results on microring resonators with a non-fouling polymer coating, increased sensitivity with slotted wire resonators and the design and fabrication of an integrated surface plasmon resonance interferometer. The high refractive index contrast of SOI offers submicron-size features with high quality for dense integration, high sensitivity and detection with very low analyte volumes. The fabrication method, 193nm deep-UV lithography, allows for mass production of cheap disposable biochips.

A hybrid CMOS/Microfluidic microsystem is presented. The microsystem integrates a soft polymer microfluidic network with a 64x128 pixel imager fabricated in low-cost standard 0.35 micron CMOS technology. The multiple microfluidic channels facilitate in-situ photochemical reactions of analytes and their detection directly on the surface of the CMOS photosensor array. The promixity between the analyte and the photosensor enhances the microsystem sensitivity, thus requiring only microliter volumes of the sample. Circuit techniques such as pixel binning and a two transistor reset path technique are employed to improve the imager sensitivity. The integrated microsystem is validated in on-chip chemiluminescence detection of luminol for the two microfluidic network prototypes designed.

Intensity interrogation of SPR biosensor owns high sensitivity, and is generally used as SPR microscopy due to the optical intensity variation. Therefore, it is substantial to improve its sensitivity to have a better sensing ability and image quality. In this paper, we discussed numerically and experimentally the influence of sensitivity by metal thickness, and provide a design rule of manifesting optimized thickness to maximize sensitivity in intensity interrogation.

A successful detection of inherently weak Raman signal from molecules is possible with giant enhancement of signal by the process of surface-enhanced Raman scattering (SERS). The SERS-induced enhancement is typically achieved when the molecules adsorbed onto the surface of a noble-metal substrate with nanometric roughness. Such SERS-substrate could be economically fabricated by convective assembly of polystyrene beads followed by metal deposition. The characterization of mono-metallic substrate showed that the SERS enhancement factor increases with increasing thickness of Ag or Au, with Ag-substrate giving the greatest SERS enhancement. However, the formation of silver oxide layer could reduce the shelf-life of the Ag-substrate. Alternatively, Au is also used as the coating material owing to its chemical inertness and biocompatibility. Despite the decent enhancement of the Au-substrate, Au-layer was found to be unstable after prolonged incubation in crystal violet solution. The inherent deficiency in adhesiveness of Au to the glass limits its use as a reliable and cost-effective substrate. In an attempt to improve the SERS-substrate, bimetallic substrate was fabricated by depositing the Au-film, as a protective layer, on the Ag-substrate. In this case, the top layer of Au of the bimetallic substrate remained intact after chemical treatment. Furthermore, the bimetallic substrate was shown to give comparable level of enhancement as an Ag-substrate by choosing a proper thickness ratio of the bimetallic layers. The result suggests that the design of bimetallic substrate could be optimized to maximize the SERS enhancement while retaining a decent stability after laser illumination and chemical treatment. Our findings suggest that bimetallic substrates are potentially useful for a reliable SERS-based biosensing.

Blood is a limited resource that supplies neurons and glia with nutriments. How is blood distributed both in a fail-safe way and in response to changing metabolic loads? We examine this issue in rodent cortex. First, in terms of topology, all-optical histology is used to reconstruct the vasculature network. Second, in terms of dynamics, the flux of blood cells in individual vessels is measured in response to neuronal activation and/or the perturbation of flow of a targeted vessel via plasma-mediated ablation. Lastly, in terms of control, optical indicators of neurovascular signaling molecules that alter vessel diameter are measured.