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A series of Dmt-Tic analogues with substitution on the Tic aromatic ring has been synthesized and evaluated for opioid receptor affinity and activation. Incorporation of large hydrophobic groups at position 7 of Tic did not greatly alter the delta opioid receptor binding affinities of the dipeptides whereas substitution at position 6 substantially diminished their affinity. These modified Dmt-Tic peptides showed binding affinities as low as 2.5 nM with up to 500-fold selectivity for the delta versus mu opioid receptor and proved to be delta receptor antagonists.

Photonic wire evanescent field (PWEF) sensor chips have been developed for multiplexed label free molecular detection. The sensors are made using 260 nm ×450 nm cross-section silicon waveguides folded into spirals less than 200 μm in diameter, but with an overall sensor length of more than a millimeter. The long propagation length gives a response to molecular binding much better than currently available tools for label-free molecular sensing. These sensors can be arrayed at densities up to ten or more per square millimeter. This talk 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 goal is to develop a commercially viable sensor platform by addressing cost-of-instrumentation, cost per measurement, ease-of-use, and by increasing the number of sensors that can be simultaneously monitored. © 2011 IEEE., 2011 ICO International Conference on Information Photonics, IP 2011, 18 May 2011 through 20 May 2011, Ottawa, ON

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. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE)., SPIE BiOS, January 22-23, 2011, San Francisco, CA, USA, Series: Proceedings of SPIE; no. 7888

A series of Dmt-Tic analogues with substitution on the Tic aromatic ring has been synthesized and evaluated for opioid receptor affinity and activation. Incorporation of large hydrophobic groups at position 7 of Tic did not greatly alter the delta opioid receptor binding affinities of the dipeptides whereas substitution at position 6 substantially diminished their affinity. These modified Dmt-Tic peptides showed binding affinities as low as 2.5 nM with up to 500-fold selectivity for the delta versus mu opioid receptor and proved to be delta receptor antagonists.

Photonics is playing an increasingly important role in the field of medical diagnostics, genomics and drug discovery. With the advances in molecular biology which gives insight to the processes underlying diseases and drug response, there is a need for new biological sensors to rapidly detect and quantify these processes. Sensing of biological events using planar waveguide evanescent field (EVF) detection offers label-free, high sensitivity, and real time monitoring [1-4]. This is a competing technology with the commercially pervasive SPR (surface plasmon resonance) method, but with the advantage of portability and low cost.

Silicon photonic wire waveguides have a remarkably high response to surface molecular binding. Evanescent field waveguide sensors based on silicon can be interrogated using Mach-Zehnder interferometers, ring resonators, or by probing surface gratings in a reflection geometry. This paper compares these approaches from a theoretical viewpoint and through recent experimental results, with the goal of defining a path from our existing individual sensors to practical biosensor array chips.

We review our work developing label-free molecular sensors using silicon nanophotonic waveguides. We show that the high index contrast of these waveguides provides high surface sensitivity and enables compact sensor designs to be realized. We also describe new waveguide circuit geometries that allow photonic wire waveguide sensors to be conveniently arrayed in two dimensions for compatibility with commercial spotting tools, while simultaneously providing long interaction length and improved molecular capture efficiency. These sensor designs are shown to provide a practical route to the development of label-free, microarrayed biochips for multiparameter analysis.

Methods and devices relating to a sensor for use in detecting and monitoring molecular interactions. A silicon waveguide sensing element is provided along with a layer of silicon. A silicon oxide layer is also provided between the waveguide element and the layer of silicon. The sensing element is adjacent to an aqueous solution in which the molecular interactions are occurring. A light beam travelling in the silicon waveguide creates an evanescent optical field on the surface of the sensing element adjacent to the boundary between the sensing element and the aqueous medium. Molecular interactions occurring on this surface affect the intensity or the phase of the light beam travelling through the waveguide by changing the effective refractive index of the medium. By measuring the effect on the intensity, phase, or speed of the light beam, the molecular interactions can be detected and monitored in real time.

We present experimental and theoretical results of label-free molecular sensing with the TM mode of a 0.22 µm thick silicon slab waveguide used in a guided mode resonance configuration. Due to the strong overlap of the evanescent field of the waveguide mode with a molecular layer attached to the surface, these sensors exhibit high sensitivity, while their fabrication and packaging requirements are minimal. Experimentally, we demonstrate a resonance wavelength shift of ~1 nm when a monolayer of streptavidin is attached to the surface, in good agreement with calculations based on rigorous coupled wave analysis.

Using silicon photonic wire waveguides we demonstrate highly sensitive and ultra-compact optical circuits for molecular sensing. The high-index-contrast of these structures is exploited to fabricate new folded waveguide geometries beneficial for sensing, as well as optical switching applications.

We review our work developing optical waveguide-based evanescent field sensors for the label-free, specific detection of biological molecules. Using high-index-contrast silicon photonic wire waveguides of submicrometer dimension, we demonstrate ultracompact and highly sensitive molecular sensors compatible with commercial spotting apparatus and microfluidic-based analyte delivery systems. We show that silicon photonic wire waveguides support optical modes with strong evanescent field at the waveguide surface, leading to strong interaction with surface bound molecules for sensitive response. Furthermore, we present new sensor geometries benefiting from the very small bend radii achievable with these high-index-contrast waveguides to extend the sensing path length, while maintaining compact size. We experimentally demonstrate the sensor performance by monitoring the adsorption of protein molecules on the waveguide surface and by tracking small refractive index changes of bulk solutions.

This paper reports the progress (design, fabrication and measurement) in label-free biological sensors based on ring resonator technology originally developed for telecommunication. These sensors are made in silicon-on-insulator (SOI), a high index contrast material platform that provides enhanced sensitivity and allows compact waveguide geometries by employing very small bend radii. A double spiral shape allows designing millimetre-long resonator in a compact size (100-150 mum) compatible with spotting technology used for large biochip assays. The detection limit estimated from the resonance shift measurement is ~5 fg of streptavidin adsorbed on the sensor surface functionalised with biotin.

We demonstrate Mach-Zehnder interferometer and ring resonator evanescent field sensors fabricated on the silicon-on-insulator material platform. These devices exploit the strong evanescent field of the transverse magnetic mode of a high index contrast, submicron dimension waveguide to obtain strong interaction of the guided mode with biomolecules adsorbed to the waveguide surface. We utilize the extremely small bend radius achievable with silicon photonic wire waveguides to fabricate spiral and folded waveguide sensors that maintain the high sensitivity of a long waveguide, while providing compact footprint. These devices offer a suitable geometry for the development of sensor arrays and provide compatibility with commercial spotting functionalization systems. We demonstrate sensors containing waveguides of up to 5.5 mm length that are contained within a 150 μm × 150 μm area.

We demonstrate a new silicon photonic wire waveguide evanescent field (PWEF) sensor that exploits the strong evanescent field of the transverse magnetic mode of this high-index-contrast, submicrometer-dimension waveguide. High sensitivity is achieved by using a 2 mm long double-spiral waveguide structure that fits within a compact circular area of 150 microm diameter, facilitating compatibility with commercial spotting apparatus and the fabrication of densely spaced sensor arrays. By incorporating the PWEF sensor element into a balanced waveguide Mach-Zehnder interferometer circuit, a minimum detectable mass of approximately 10 fg of streptavidin protein is demonstrated with near temperature-independent response.

We present recent theoretical and experimental results on silicon photonic wire evanescent field (PWEF) sensors that show such PWEF sensors have the highest response to bulk index change as well as surface molecular adsorption.

We present experimental and theoretical results of label-free molecular sensing using the transverse magnetic mode of a 0.22 mum thick silicon slab waveguide with a surface grating implemented in a guided mode resonance configuration. Due to the strong overlap of the evanescent field of the waveguide mode with a molecular layer attached to the surface, these sensors exhibit high sensitivity, while their fabrication and packaging requirements are modest. Experimentally, we demonstrate a resonance wavelength shift of approximately 1 nm when a monolayer of the protein streptavidin is attached to the surface, in good agreement with calculations based on rigorous coupled wave analysis. In our current optical setup this shift corresponds to an estimated limit of detection of 0.2% of a monolayer of streptavidin.

We demonstrate folded waveguide ring resonators for biomolecular sensing. We show that extending the ring cavity length increases the resonator quality factor, and thereby enhances the sensor resolution and minimum level of detection, while at the same time relaxing the tolerance on the coupling conditions to provide stable and large resonance contrast. The folded spiral path geometry allows a 1.2 mm long ring waveguide to be enclosed in a 150 microm diameter sensor area. The spiral cavity resonator is used to monitor the streptavidin protein binding with a detection limit of approximately 3 pg/mm(2), or a total mass of approximately 5 fg. The real time measurements are used to analyze the kinetics of biotin-streptavidin binding.

This Article describes a strategy to stabilize a phospholipid monolayer directly on the surface of a H-terminated silicon substrate in order to provide a useful platform for silicon based biosensors. The stabilization of an acrylated phospholipid monolayer is obtained by two-dimensional chain polymerization. As the formation of the lipid monolayer in aqueous solution competes with the oxidation of the silicon surface, several cycles of oxide removal and lipid exposure are necessary to densify the lipid layer. Lipid monolayer formation is followed by Fourier transform infrared spectroscopy. The resulting monolayer is denser than corresponding alkyl monolayers formed on H-terminated silicon via photochemical or thermally initiated reactions.

A silicon waveguide evanescent field molecular sensor interrogated by reflection from a surface grating is demonstrated. The sensor is probed by a beam of light incident at θ = 45° through the backside of the silicon-on-insulator (SOI) wafer. The reflected power shows a strong resonant feature near λ = 1532 nm, arising from resonant coupling of incident beam, guided mode, and the reflected beam. The resonant wavelength is very sensitive to molecular surface coverage. We have measured a Δλ = 1.0 nm resonance shift when a monolayer of streptavidin protein is bound to the sensor surface, or a 60% reflectivity change when measured at a fixed wavelength.

We demonstrate silicon photonic wire evanescent field sensors formed by folding long photonic wire waveguides into dense spiral paths that occupy spot sizes less than 150 mum in diameter, and are hence suitable for biochip array formats. These sensors are incorporated into both ring resonator and Mach-Zehnder interferometer (MZI) interrogation circuits, and tested by monitoring streptavidin protein adsorption. The level of detection is less than 1% of a monolayer in either configuration. Using a balanced MZI design, we show that the sensors can be insensitive to temperature and wavelength, while retaining a very high sensitivity to molecular adsorption.

Densely folded silicon wire waveguide evanescent field sensors demonstrate high sensitivity and compact foot-print. Real time monitoring of molecular binding resolves ~0.2% of a protein monolayer, corresponding to a mass of ~5 femtograms.