This PDF file contains the front matter associated with SPIE Proceedings Volume 7888, including the Title Page, Copyright information, Table of Contents, and the Conference Committee listing.

Silicon photonic devices, such as SOI microring resonators, have optical properties that are incredibly responsive to changes in the local dielectric environment accompanying a biological binding event at or near the ring surface. We have developed a platform in which arrays of uniquely addressable microrings are functionalized with target-specific capture agents so as to create a powerful tool for multiplexed biomolecular detection. We will discuss applications of this technology to the multiplexed detection of DNA, RNA, and proteins in clinically-relevant matrices, and will also describe the rigorous empirical determination of key sensitivity metrics.

The development of label-free biosensors with high sensitivity and specificity is of significant interest for medical diagnostics and environmental monitoring, where rapid and real-time detection of antigens, bacteria, viruses, etc., is necessary. Ultra-high-Q optical microcavities are uniquely suited to sensing applications, but previous research efforts in this area have focused on the development of the sensor itself. While device sensitivity is crucial to sensor development, specificity is an equally important feature. Therefore, it is crucial to develop a high density, covalent surface functionalization process, which also maintains the device's performance. Here, we demonstrate a facile method to impart specificity to optical microcavities, without adversely impacting their optical performance. In this approach, we selectively functionalize the surface of the silica microtoroids with amine-terminated silane coupling agents, and examine the impact of differing reaction schemes on the overall quality of the devices. The chemistries investigated here result in uniform surface coverage, and no microstructural damage, and do not adversely impact the optical performance of the devices, as measured by their quality factors before and after functionalization. This work represents one of the first examples of non-physisorption-based bioconjugation of optical microtoroid resonators, which can be used for the label-free detection of biomolecules.

Detecting labeled or naturally-fluorescent biomolecules at very low concentrations is of a significant importance for health sciences, agricultural sciences, and security-related applications. Photonic crystals (PhC) are microfabricated nano-structures of periodic dielectric permittivity in one, two, or three dimensions that possess unique light manipulation properties. These include the ability to localize electromagnetic waves at particular PhC lattice locations. Ultra-sensitive detection using thin-film PhC structures fabricated in semiconductor materials has been demonstrated in both "active" and "passive" modalities. In the active modality, the adsorption of target molecules to the PhC surface causes a refractive index change that is translated into reflectance or transmission peak shifts. The passive modality demonstrated by our group utilizes the PhC structure to observe enhanced fluorescent emission within resonant defect cavities in a 2D PhC lattice. Integrating these semiconductor-based PhC structures with biocompatible microfluidic channels is a challenging task that can significantly increase the final cost of the sensor system. We demonstrate here soft lithographic nanomolding techniques for polymer-based PhC structures that are easily integrated with microfluidic channels to provide a portable means of biosensing. A TE bandgap of 2.857% for a 2D PhC fabricated in poly(dimethylsiloxane) (PDMS) will allow these lattices to become core structures in PhC-based biosensors incorporating both active and passive modalities. Modeling and initial optical characterization results of the Si- and PDMS-based PhC biosensor will also be presented.

We are developing a photonic wire evanescent field (PWEF) sensor chip using 260 nm x 450 nm cross-section silicon photonic wire waveguides. The waveguide mode is strongly localized near the silicon surface, so that light interacts strongly with molecules bound to the waveguide surface. The millimeter long sensor waveguides can be folded into tight spiral structures less than 200 micrometers in diameter, which can be arrayed at densities up to ten or more independent sensors per square millimeter. The long propagation length in each sensor element gives a response to molecular binding much better than currently available tools for label-free molecular sensing. Cost of instrumentation, cost per measurement, ease-of-use, and the number of sensors that can be simultaneously monitored on a sensor array chip are equally important in determining whether an instrument is practical for the end user and hence commercially viable. The objective of our recent work on PWEF sensor array chips and the associated instrumentation is to address all of these issues. This conference paper reviews our ongoing work on the photonic wire sensor chip design and layout, on-chip integrated fluidics, optical coupling, and chip interrogation using arrays of grating couplers formed using sub-wavelength patterned structures.

The aim of this work was to investigate the possibilities to support device functionality that includes strongly confined and localized light emission and detection processes within nano/micro-structured semiconductors for biosensing applications. The interface between biological molecules and semiconductor surfaces, yet still under-explored is a key issue for improving biomolecular recognition in devices. We report on the use of adhesion peptides, elaborated via combinatorial phage-display libraries for controlled placement of biomolecules, leading to user-tailored hybrid photonic systems for molecular detection. An M13 bacteriophage library has been used to screen 10¹⁰ different peptides against various semiconductors to finally isolate specific peptides presenting a high binding capacity for the target surfaces. When used to functionalize porous silicon microcavities (PSiM) and GaAs/AlGaAs photonic crystals, we observe the formation of extremely thin (<1nm) peptide layers, hereby preserving the nanostructuration of the crystals. This is important to assure the photonic response of these tiny structures when they are functionalized by a biotinylated peptide layer and then used to capture streptavidin. Molecular detection was monitored via both linear and nonlinear optical measurements. Our linear reflectance spectra demonstrate an enhanced detection resolution via PSiM devices, when functionalized with the Si-specific peptide. Molecular capture at even lower concentrations (femtomols) is possible via the second harmonic generation of GaAs/AlGaAs photonic crystals when functionalized with GaAs-specific peptides. Our work demonstrates the outstanding value of adhesion peptides as interface linkers between semiconductors and biological molecules. They assure an enhanced molecular detection via both linear and nonlinear answers of photonic crystals.

Optical biosensors can detect biomarkers in the blood serum caused by either infections or exposure to toxins. Until now, most work on the micro-cavity biosensors has been based on measurement of the resonant frequency shift induced by binding of biomarkers to a cavity. However, frequency domain measurements are not precise for such high Q micro-cavities. We hypothesize that more accurate measurements and better noise tolerance can be achieved by the application of the ring down measurement approach to the micro-cavity in a biosensor. To test our hypothesis, we have developed a full vectorial finite element model of a silica toroidal micro-cavity immersed in water. Our modeling results show that a toroidal cavity with a major diameter of 70μm and a minor diameter of 6μm can achieve a sensitivity of 28.6μs/RIU refractive index units (RIU) at 580nm. Therefore, our sensor would achieve the resolution of 5 x 10^-8 RIU by employing a detector with picosecond resolution. Hence we propose a micro-cavity ring down biosensor with high sensitivity which will find wide applications in real time and label free bio-sensing.

We report on a new type of whispering gallery mode (WGM) resonator made of out of low-loss polymer poly (methyl methacrylate) (PMMA). These optical cavities are fabricated using standard semiconductor processing methods in combination with a specific thermal reflow process. During this subsequent thermal treatment, surface tension leads to the goblet like geometry of the resonator and to an ultra smooth surface. The Q-factor of these goblet resonators is above 2·10⁶ in the 1310 nm wavelength range. In order to demonstrate the applicability of the goblet resonators for bio sensing, Bovine Serum Albumin was detected by monitoring the shift of resonator modes due to protein adsorption.

Implemented through a confocal microscope, Raman spectroscopy has been used to distinguish between biofilm samples of two common oral bacteria species, Streptococcus sanguinis and mutans, which are associated with healthy and cariogenic plaque, respectively. Biofilms of these species are studied as a model of dental plaque. A prediction model has been calibrated and validated using pure biofilms. This model has been used to identify the species of transferred and dehydrated samples (much like a plaque scraping) as well as hydrated biofilms in situ. Preliminary results of confocal Raman mapping of species in an intact two-species biofilm will be shown.

Arrayed imaging reflectometry (AIR) has been previously demonstrated as a highly sensitive biosensing technique, with picomolar limits of detection observed for certain cytokines and growth factors. However, the implementation of AIR has so far been on dry chip surfaces in an end-point sensor format that precludes real-time monitoring of interactions. The simple substrate format used for dry AIR (a thermally grown oxide film on silicon) is unsuitable for imaging in an aqueous medium due to near grazing angles of incidence required to achieve total destructive interference of reflected light, the foundation of AIR. Hence, a new substrate was identified that would allow practically realizable incidence angles. Here, the substrate proposed for AIR imaging under an aqueous environment has been described, and its ability to detect Angstrom level thickness differences has been demonstrated. This substrate consisted of a two-layer stack on silicon: a silicon nitride film followed by a sputtered oxide film, which produced the total destructive interference condition required for AIR for an operating wavelength of 632.8 nm and an angle of incidence of ~52°. The apparatus used for imaging substrates in an aqueous environment was essentially the same as that used for dry AIR, modified by the incorporation of a flow cell. Several chips were patterned with oxide posts such that the background yielded minimum reflectance while the post heights were varied to test the thickness sensitivity of the new sensor configuration. Detectable contrast from substrates bearing oxide posts with a 0.2 nm thickness was observed using pure water or aqueous solutions of sucrose. This substrate can thus be used to monitor biomolecular interactions in real time with a high sensitivity.

In recent studies, optical forces have been exploited to guide particles along waveguides and to trap particles near refractive index sensors. But the ability of photonic devices to bind a freely flowing particle from an adjacent microfluidic channel has yet to be fully characterized. In order to determine the ability of a given device to trap an arbitrary particle, we develop a method to numerically calculate the trajectory of a particle flowing near a model system. We determine the trajectories of 50 nm radius particles in a fluid flowing at an average velocity of 1 cm/s near a photonic crystal resonator pumped at 1 W. The finite element method is used to calculate the force of the fluid on the particles and finite-difference time-domain simulations are used to calculate optical forces. The particle equation of motion is solved using the adaptive Runge-Kutta method.

Photonic crystal (PC) biosensing platforms have the potential to achieve single-pathogen detection using nanoscale optical resonant cavities. Real-time sample analysis requires the PC sensor to be interfaced with a fluidic environment, but current practical fluidic structures typically have dimensions much larger than the PC sensing cavities. To enhance sensing probability, an on-chip optofluidic structure is being developed to concentrate target material within a narrow sensing region of the microfluidic channel. The device relies on fluid drag forces to propel material along the microfluidic channel. Dielectric material is guided transversely within the microfluidic channel by optical gradient forces due to the evanescent field surrounding a ridge waveguide within the channel. Results of computational modeling are presented.

Optical fiber provides a unique and versatile platform for developing point-of-care optical sensing systems. Here we first propose a Fabry-Pérot (FP) based flow-through optofluidic biosensor, and then construct an all-fiber system which fully utilizes optical fibers to achieve rapid, sensitive, label-free biomolecular detection. This sensor consists of two single mode fibers (SMFs) with reflecting surfaces and a photonic crystal fiber (PCF) vertically sandwiched by them. Firstly, the SMFs act as waveguides for delivering light into and out of an optofluidic device (like PCF); secondly, instead of using the optical properties of the PCF, we take advantage of its inherent multiple fluidic channels and large sensing surface; thirdly, the two reflective surfaces and the PCF form a Fabry-Pérot microresonator and its resonance mode is sensitive to the change in the fluidic channels, which can be used to detect the substances flowing through the fluidic channels or adsorbing on the channel surface. In this paper, we explore the operating principle of the FP-based optofluidic biosensor, theoretically and experimentally investigate its feasibility and capability. The results show that the all-fiber optofluidic sensor is a promising technology platform for rapid, sensitive and high-throughput biological and chemical sensing.

Superparamagnetic nanoparticles (NPs) coated with surface ligands are shown to be an effective means to impart magnetic field modulation to optical signals from targeted receptor complexes. The modulated signals they produce can be used for a number of important high throughput applications in bio-sensing including: detecting (weaponized) viruses, screening recombinant libraries of proteins, identifying pathogenic conversions of microbes, and monitoring gene amplification. We compare the results of two dynamic methods of measuring target binding to NPs: birefringence and field modulated light scattering (FMLS). These measurements reflect complementary manifestations of NP alignment (orientation) and de-alignment (relaxation) dynamics. Birefringence originates from the specific crystalline properties of a small subset of paramagnetic NPs (for example, maghemite) when oriented in a magnetic field. Upon quenching the field, it decays at a rate exhibiting the Debye-Stokes-Einstein rotational relaxation constant of target-NP complexes. Birefringence relaxation reflects the particle dynamics of the mixed suspension of NPs, with signal components weighted in proportion to the free and complexed NP size distributions. FMLS relaxation signals, on the other hand, originate predominately from the inherent optical anisotropy of the target complexes, show little contribution from non-complexed NPs when the targets are more optically anisotropic than the NPs, and provide a more direct and accurate method for determining target receptor concentrations. Several illustrations of the broad range of applications possible using these dynamic measurements and the kind of information to be derived from each detection modality will be discussed.

The rapid detection of foodborne pathogens is of vital importance to keep the food supply rid of contamination. Previously we have demonstrated the design of a hybrid optical device that performs real-time surface plasmon resonance (SPR) and epi-fluorescence imaging. Additionally we have developed a biosensor array chip that is able to specifically detect the presence of two known pathogens. This biosensor detects the presence of the pathogen strains by the selective capture of whole pathogens by peptide ligands functionalized to the spots of the array. We have incorporated this biosensor array into a self contained PDMS microfluidic chip. The enclosure of the biosensor array by a PDMS microfluidic chip allows for a sample to be screened for many strains of pathogens simultaneously in a safe one time use biochip. This disposable optical biochip is inserted into with the hybrid SPR/epi-fluorescence imaging device to form an integrated system for the detection of foodborne pathogens. Using this integrated system, we can selectively detect the presence of E. coli 0157:H7 or S. enterica in a simultaneously in real-time. Additionally, we have modeled the mechanical properties of the microfluidic biochip in order to manipulate the flow conditions to achieve optimal pathogen capture by the biosensor array. We have developed an integrated system that is able to screen a sample for multiple foodborne pathogens simultaneously in a safe, rapid and label-free manner.

The paper will introduce the quaternary, or radix 4, based system for use as a fundamental standard beyond the traditional binary, or radix 2, based system in use today. A greater level compression is noted in the radix 4 based system when compared to the radix 2 base as applied to a model of information theory. The application of this compression algorithm to both DNA and RNA sequences for compression will be reviewed in this paper.