This PDF file contains the front matter associated with SPIE Proceedings Volume 8933, including the Title Page, Copyright information, Table of Contents, Invited Panel Discussion, and Conference Committee listing.

Porous silicon structures have been demonstrated as effective biosensors due to their large surface area, size-selective filtering capabilities, and tunable optical properties. However, porous silicon surfaces are highly susceptible to oxidation and corrosion in aqueous environments and solutions containing negative charges. In DNA sensing applications, porous silicon corrosion can mask the DNA binding signal as the typical increase in refractive index that results from a hybridization event can be countered by the decrease in refractive index due to corrosion of the porous silicon matrix. Such signal ambiguity should be eliminated in practical devices. In this work, we carefully examined the influence of charge density and surface passivation on the corrosion process in porous silicon waveguides in order to control this process in porous silicon based biosensors. Both increased DNA probe density and increased target DNA concentration enhance the corrosion process, leading to an overall blueshift of the waveguide resonance. While native porous silicon structures degrade upon prolonged exposure to solutions containing negative charges, porous silicon waveguides that are sufficiently passivated to prevent oxidation/corrosion in aqueous solution exhibit a saturation effect in the corrosion process, which increases the reliability of the sensor. For practical implementation of porous silicon DNA sensors, the negative charges from DNA must be mitigated. We show that a redshift of the porous silicon waveguide resonance results from either replacing the DNA target with neutral charge PNA or introducing Mg2+ ions to shield the negative charges of DNA.

Our research demonstrates the design and fabrication of a biosensor based on the tapered optical fiber. The fiber is tapered biconically to a diameter of approximately 7 μm, which allows the evanescent field of propagating light to interact with molecules attached to the tapered surface. This sensing platform is capable of fast, continuous, specific, sensitive, and label-free molecular detection in the aqueous phase. Detection is demonstrated across multiple fibers, and the individual fibers are reusable. The system described previously has been modified for detection of volatile organic compounds. The fabrication of the modified design is also shown with preliminary results.

We present our developments on integrated optical waveguide based as well as on magnetic nanoparticle based label-free biosensor concepts. With respect to integrated optical waveguide devices, evanescent wave sensing by means of Mach- Zehnder interferometers are used as biosensing components. We describe three different approaches: a) silicon photonic wire waveguides enabling on-chip wavelength division multiplexing, b) utilization of slow light in silicon photonic crystal defect waveguides operated in the 1.3 μm wavelength regime, and c) silicon nitride photonics wire waveguide devices compatible with on-chip photodiode integration operated in the 0.85 μm wavelength regime. The nanoparticle based approach relies on a plasmon-optical detection of the hydrodynamic properties of magnetic-core/gold-shell nanorods immersed in the sample solution. The hybrid nanorods are rotated within an externally applied magnetic field and their rotation optically monitored. When target molecules bind to the surfaces of the nanorods their hydrodynamic volumes increase, which directly translates into a change of the optical signal. This approach possesses the potential to enable real-time measurements with only minimal sample preparation requirements, thus presenting a promising point-of- care diagnostic system.

Silicon micro-ring biosensors demonstrate great potential for high sensitivity and multiplexed lab-on-chip systems. In this work, we characterize the sensing performance of suspended TM-mode silicon micro-ring resonators, 5 μm in radius, and demonstrate an enhanced sensitivity to molecular binding on the ring after suspension. In the TM-mode, the overall field intensity exists primarily outside of the waveguide core, with high electric field intensities present near the top and bottom surfaces. In traditional micro-ring resonators, only the top surface of the ring is available for surface analyte attachment, while the electric field intensity near the bottom surface dissipates by leaking into the underlying silicon dioxide substrate. In our approach, we suspend the TM-micro ring resonators in order to increase the surface area for binding events and increase the light-matter interaction with analytes. The suspended rings demonstrate excellent mechanical stability to multiple rinsing, soaking and nitrogen drying steps during the sensing procedure. We show that the resonance shift achieved by the suspended micro-rings after attachment of small chemical molecules and DNA is at least twice that of micro-rings supported by the silicon dioxide substrate.

Optical sensor systems for biological and medical applications have been widely developed in order to satisfy the current requirements such as a miniaturization, cost reduction, label-free detection and fast response. Here, we demonstrate a highly sensitive optical sensor based on two cascaded microring resonators (MRRs) exploiting the Vernier effect. The architecture consists of a filter MRR connected to a sensor MRR via a common waveguide. The external medium of the filter MRR is isolated with a top cladding layer, while the sensor MRR interacts with the analyte sample via an opening. The sensor chip, that includes an array of five cascaded MRRs, was designed and fabricated on a silicon nitride platform. A first test has been performed with sodium chloride (NaCl) concentrations in deionized (DI) water providing a sensitivity of 1.03 nm/% (6317 nm/RIU). A limit of detection of 3.16 x 10^-6 RIU was demonstrated for the current sensor, respectively. Several concentrations of isopropanol in ethanol ranging from 0% to 10% were also investigated. These preliminary measurements show a sensitivity as high as 0.95 nm/% at ~1535 nm compared to 0.02 nm/% from a single sensor MRR. For a moderated alignment between the chip and cleaved optical fibers, tapered grating couplers are included at the ends of waveguides. Hence, by combining the Vernier effect and the silicon nitride material, cascaded MRRs will be a powerful optical configuration for biosensing applications in a wide operating wavelength range.

Detection of pathogens from infected biological samples through conventional process involves cell lysis and purification. The main objective of this work is to minimize the time and sample loss, as well as to increase the efficiency of detection of biomolecules. Electrical lysis of medical sample is performed in a closed microfluidic channel in a single integrated platform where the downstream analysis of the sample is possible. The device functions involve, in a sequence, flow of lysate from lysis chamber passed through a thermal denaturation counter where dsDNA is denatured to ssDNA, which is controlled by heater unit. A functionalized binding chamber of ssDNA is prepared by using ZnO nanorods as the matrix and functionalized with bifunctional carboxylic acid, 16-(2-pyridyldithiol) hexadecanoic acid (PDHA) which is further attached to a linker molecule 1-ethyl-3-(3-dimethylaminopropyl) (EDC). Linker moeity is then covalently bound to photoreactive protoporphyrin (PPP) molecule. The photolabile molecule protoporphyrin interacts with -NH2 labeled single stranded DNA (ssDNA) which thus acts as a probe to detect complimentary ssDNA from target organisms. Thereafter the bound DNA with protoporphyrin is exposed to an LED of particular wavelength for a definite period of time and DNA was eluted and analyzed. UV/Vis spectroscopic analysis at 260/280 nm wavelength confirms the purity and peak at 260 nm is reconfirmed for the elution of target DNA. Quantitative and qualitative data obtained from the current experiments show highly selective detection of biomolecule such as DNA which have large number of future applications in Point-of-Care devices.

We present a novel strategy for label-free detection of glucose based on CdSe/ZnS core/shell quantum dots (QDs). We exploit the concentration-dependent, narrowband absorption of the hexokinase-glucose 6-phosphate dehydrogenase enzymatic assay to selectively filter a 365-nm excitation source, leading to a proportional decrease in the photoluminescence intensity of the QDs. The visible wavelength emission of the QDs enables quantitative readout using standard visible detectors (e.g., CCD). Experimental results show highly linear QD photoluminescence over the clinically relevant glucose concentration range of 1-25mM, in excellent agreement with detection methods demonstrated by others. The method has a demonstrated limit of detection of 3.5μM, also on par with the best proposed methods. A significant advantage of our strategy is the complete elimination of QDs as a consumable. In contrast with other methods of QD-based measurement of glucose, our system does not require the glucose solution to be mixed with the QDs, thereby decreasing its overall cost and making it an ideal strategy for point-of-care detection of glucose in low-resource areas. Furthermore, readout can be accomplished with low-cost, portable detectors such as cellular phones, eliminating the need for expensive and bulky spectrophotometers to output quantitative information. The general strategy we present is useful for other biosensing applications involving chemistries with unique absorption peaks falling within the excitation band of available QDs.

Integrated fluorescent waveguide biosensors have had a substantial impact on the field of biodetection. Many types of waveguide sensors have been developed, but most of them rely on evanescent field excitation of fluorophores, whose emission is then detected directly or indirectly. A sensor device which performs detection by measuring the fluorescent light that back-couples into the device was recently demonstrated. The work for this device did not compare the efficiency of their detection method with traditional detection methods, nor did they develop a rigorous theoretical model for understanding the efficiency of the device. Using finite difference time domain simulations and complementary experiments, we develop and verify a model which can predict the performance of the sensor in air and aqueous environments. Additionally, we perform spatiotemporal fluorescence measurements using the waveguide device which allow us to sample the magnitude of the fluorescence along the device at every point in space and time that we recorded.

Accurate monitoring of microbial viability plays an essential role in pharmacodynamic studies such as in estimating the efficiency of antimicrobial agents. Traditionally, bacterial viability is determined by their ability to form colonies on solid growth medium or to proliferate in liquid nutrient broths but, with these culture-based methods, the live bacterial population can only be estimated retrospectively. To address this challenge, we have employed differential fluorescence staining and an all-fiber optical system developed by our group. The detection is based on the collection of the fluorescence from commercial dyes that produce a substantially increased signal upon binding with bacterial nucleic acids. The dyes allow discrimination between alive and dead cells through differential membrane permeability and fluorescence wavelength. The respective fluorescence signal is correlated to the number of bacterial cells present in the sample. Our setup uses DPSS lasers and a sensitive CCD-based spectrometer over the 400-800 nm wavelength range. A laser shutter allows the sample exposure time and acquisition time to be synchronized to minimize the effect of photobleaching. As a model, bacteria (Escherichia coli or Staphylococcus aureus) killed with isopropyl alcohol were mixed with live cells at different ratios. The population ratios of alive and dead cells were accurately quantified by our optical setup providing a rapid method for the estimation of bactericidal treatments. In summary, our optical system may offer a robust, accurate and fast alternative for detection of dead/alive bacteria in turbid solution opening the new avenues for pharmacodynamic studies.

The surface plasmon resonance reflectance changes measured with a circularly polarized ellipsometry and an electrochemical impedance spectroscopy were identified to be able to characterize the critical roles of biomolecules for vastly different biological functions and processes. Throughout the course of this study, interferon-gamma (IFN-γ) was chosen as the biomarker to test and to verify the performance of this newly developed system for Tuberculosis detection. The interactions of IFN-γ with immobilized anti-IFN-γ antibody at various concentrations were interrogated both optically and electrochemically. A semi-conductive linker bis-thiophene was thiolated to ensure the cross-linked monoclonal human IFN-γ antibody got self-assembled onto the gold thin film and form a label-free biosensor. The functional features of the bis-thiophene coated-gold film were characterized by cyclic voltammetry and impedance spectroscopy methods. The association of IFN-γ to the bis-thiophene bridging units via antibody-antigen interactions provided the basis for ultrasensitive detection of IFN-γ by tracking the conformation changes in surface-bound protein molecules. The phase shift can be attributed to the average thickness and the real-time index of refraction of the protein layer in different protein layer. Experimental results obtained by impedance spectroscopy and by phase-interrogation SPR showed linear dynamic range. Our experimental results verified that an increase in the concentration of the IFN-γ usually accompanied by phase increase in SPR and an impedance decrease in EIS. These results indicated that our newly developed integrated biosensing system can potentially provide new insight into various conjugate phenomena and interfacial processes for observing molecular conformation changes.

We report on the first polarimetric plasmonic biosensor based on arrays of bowtie nanoantennas. Using the Finite Element Method (FEM) the phase retardation between the components of light polarized parallel and perpendicular to the axis of the nanoantennas is studied. After optimizing them for high volumetric sensitivity at a wavelength of 780 nm, sensitivities ~5 rad/RIU are obtained, corresponding to a detection limit ~10^-7 RIU when using the polarimetric readout platform. Surface sensitivity values resulted from studies of phase retardation changes from a coverage of bioreceptors and analytes.

Diatoms are single-celled algaes that make photonic-crystal-like silica shells or frustules with hierarchical micro- and nano-scale features consisting of two-dimensional periodic pores. In this paper, we present an innovative label-free optical sensor based on a biological-plasmonic hybrid nanostructure by self-assembling silver (Ag) nanoparticles into diatom frustules. The photonic-crystal-like diatom frustules provide a spatially confined electric field with enhanced intensity that can form hybrid photonic-plasmonic modes through the optical coupling with Ag nanoparticles. The experimental results demonstrate 4-6x and 9-12x improvement of sensitivities to detect the Raman dye for resonance and nonresonance SERS sensing, respectively.

We present a widefield microscopy system for imaging super-paramagnetic nanoparticles (SPNs), and propose to use it as a bio-sensing system wherein SPNs are used as tags. Potential advantages of magnetic tags over conventional fluorescent tags include the elimination of noise from auto-fluorescence, optical isolation of the biological system from the measurement apparatus, and the potential for magnetic removal of non-specifically bound material. The microscope magnetic sensing surface is composed of a thin layer of nitrogen-vacancy defect centers in the top 200 nm of a diamond substrate. Nitrogen-vacancy centers in diamond have been shown to be suitable for use as highly sensitive magnetometers due to their long spin-coherence time at room temperature. Furthermore, spin-dependent photoluminescence allows for simple far-field optical readout of the spin state, which in turn allows for opticallydetected magnetic resonance measurements. We will present our results detecting a single, lithographically defined 50 nm diameter by 100 nm thick iron nanodot. With the current sensitivity of 9 μT⋅Hz^-1/2, we expect to be able to detect single 20 nm magnetite SPNs, our proposed tags, in less than one minute. By further optimizing the sensor surface, we predict DC magnetic sensitivities as low as 1 μT⋅Hz^-1/2.

Digital enzyme linked immunosorbent assay (ELISA) is an ultra-sensitive technology for detecting biomarkers and viruses etc. As a conventional ELISA technique, a target molecule is bonded to an antibody with an enzyme by antigen-antibody reaction. In this technology, a femto-liter droplet chamber array is used as reaction chambers. Due to its small volume, the concentration of fluorescent product by single enzyme can be sufficient for detection by a fluorescent microscopy. In this work, we demonstrate a miniaturized lensless imaging device for digital ELISA by using a custom image sensor. The pixel array of the sensor is coated with a 20 μm-thick yellow filter to eliminate excitation light at 470 nm and covered by a fiber optic plate (FOP) to protect the sensor without resolution degradation. The droplet chamber array formed on a 50μm-thick glass plate is directly placed on the FOP. In the digital ELISA, microbeads coated with antibody are loaded into the droplet chamber array, and the ratio of the fluorescent to the non-fluorescent chambers with the microbeads are observed. In the fluorescence imaging, the spatial resolution is degraded by the spreading through the glass plate because the fluorescence is irradiated omnidirectionally. This degradation is compensated by image processing and the resolution of ~35 μm was achieved. In the bright field imaging, the projected images of the beads with collimated illumination are observed. By varying the incident angle and image composition, microbeads were successfully imaged.