Neuromorphic Processing for Optical Microbead Arrays: Dimensionality Reduction and Contrast Enhancement

This paper presents a neuromorphic approach for sensor-based machine olfaction that combines a portable chemical detection system based on microbead array technology with a biologically inspired model of signal processing in the olfactory bulb. The sensor array contains hundreds of microbeads coated with solvatochromic dyes adsorbed in, or covalently attached on, the matrix of various microspheres. When exposed to odors, each bead sensor responds with corresponding intensity changes, spectral shifts, and time-dependent variations associated with the fluorescent sensors. The bead array responses are subsequently processed using a model of olfactory circuits that capture the following two functions: chemotopic convergence of receptor neurons and center on-off surround lateral interactions. The first circuit performs dimensionality reduction, transforming the high-dimensional microbead array response into an organized spatial pattern (i.e., an odor image). The second circuit enhances the contrast of these spatial patterns, improving the separability of odors. The model is validated on an experimental dataset containing the responses of a large array of microbead sensors to five different analytes. Our results indicate that the model is able to significantly improve the separability between odor patterns, compared to that available from the raw sensor response     

Automated bead alignment apparatus using a single bead capturing technique for fabrication of a miniaturized bead-based DNA probe array

We have developed an automated bead alignment apparatus for fabricating a bead-based DNA probe array inside a capillary. The apparatus uses 16 micro vacuum tweezers to extract single beads from among a large amount of beads in bead stock wells. It then manipulates single beads into the probe array capillaries. Single 100-microm-diameter beads were successfully extracted from the water-contained bead-stock well by the vacuum tweezers, which have inner and outer diameters of 50 and 150 microm. An interesting aspect is that unexpected extra beads adsorbed on the outer wall of the vacuum tweezers can be removed using the surface tension force between the water and the atmosphere. In testing the total performance of this apparatus, the DNA probe arrays with 10 sets of probe-conjugated beads and 2 plain beads were produced in the intended order in the capillaries. The time needed to align the 12 beads was 10 min, and the 16 bead arrays were fabricated simultaneously. After hybridization experiments using these fabricated DNA probe arrays, fluorescence from each bead was clearly observed.     

Analysis of a hybrid micro/macro-optical method for distortion removal in free-space optical interconnections

Eikonal analyses are applied to a hybrid micro/macro-optical shuffle interconnection approach that minimizes distortion in a multichip smart-pixel shuffle interconnection system. The optical system uses off-axis imaging elements to link clusters of dense arrays of vertical-cavity surface-emitting laser (VCSEL) sources to matching clusters within arrays of detectors. A critical requirement for such a system is that the images of the two-dimensional arrays of the VCSELs must be registered on their associated detector arrays with a precision of the order of 10 microm across the entire multichip array. The hybrid approach exploits the typical narrow-beam cone angles of VCSELs by use of beam-deflecting micro-optics to create a distortion-canceling symmetry about a central aperture in the optical system for each VCSEL-detector link. The second- and third-order aberrations of the plane-symmetric system created by the global off-axis imaging system are analyzed. The results prove that the hybrid concept cancels distortion and minimizes the spot size at the detector array plane.     

High-throughput nanohole array based system to monitor multiple binding events in real time

We have developed an integrated label-free, real-time sensing system that is able to monitor multiple biomolecular binding events based on the changes in the intensity of extraordinary optical transmission (EOT) through nanohole arrays. The core of the system is a sensing chip containing multiple nanohole arrays embedded within an optically thick gold film, where each array functions as an independent sensor. Each array is a square array containing 10 x 10 nanoholes (150 nm in diameter), occupying a total area of 3.3 mum x 3.3 mum. The integrated system includes a laser light source, a temperature-regulated flow cell encasing the sensing chip, motorized optics, and a charge-coupled detector (CCD) camera. For demonstration purposes, sensing chips containing 25 nanohole arrays were studied for their use in multiplexed detection, although the sensing chip could be easily populated to contain up to 20 164 nanohole arrays within its 0.64 cm2 sensing area. Using this system, we successfully recorded 25 separate binding curves between glutathione S-transferase (GST) and anti-GST simultaneously in real time with good sensitivity. The system responds to binding events in a concentration-dependent manner, showing a sharp linear response to anti-GST at concentrations ranging from 13 to 290 nM. The EOT intensity-based approach also enables the system to monitor multiple bindings simultaneously and continuously, offering a temporal resolution on milliseconds scale that is decided only by the camera speed and exposure time. The small footprint of the sensing arrays combined with the EOT intensity-based approach enables the system to resolve binding events that occurred on nanohole sensing arrays spaced 96 mum apart, with a reasonable prediction of resolving binding events spaced 56 mum apart. This work represents a new direction that implements nanohole arrays and EOT intensity to meet high-throughput, spatial and temporal resolution, and sensitivity requirements in drug discovery and proteomics studies.     

Rapid melting curve analysis on monolayered beads for high-throughput genotyping of single-nucleotide polymorphisms

This report describes a rapid solid-phase melting curve analysis method for single-nucleotide polymorphism (SNP) genotyping. The melting curve analysis is based on dynamic allele-specific hybridization (DASH). The DNA duplexes are conjugated on beads that are immobilized on the surface of a microheater chip with integrated heaters and temperature sensors. SNP on PCR products were scored, illustrating the sensitivity and robustness of the system. The method is based on random bead immobilization by microcontact printing. Single-bead detection and multiplexing were performed with a heating rate more than 20 times faster than conventional DASH. Analyses that took more than 15 min could be performed in less that 1 min, enabling ultrarapid SNP analysis. In addition, an array version of the chip was implemented enabling the preparation of an array of bead arrays for high-throughput and rapid SNP genotyping.     

Demonstration and architectural analysis of complementary metal-oxide semiconductor /multiple-quantum-well smart-pixel array cellular logic processors for single-instruction multiple-data parallel-pipeline processing

We present an optoelectronic-VLSI system that integrates complementary metal-oxide semiconductor/multiple-quantum-well smart pixels for high-throughput computation and signal processing. The system uses 5 x 10 cellular smart-pixel arrays with intrachip electrical mesh interconnections and interchip optical point-to-point interconnections. Each smart pixel is a fine grain microprocessor that executes binary image algebra instructions. There is one dual-rail optical modulator output and one dual-rail optical detector input in each pixel. These optical input-output arrays provide chip-to-chip optical interconnects. Cascading these smart-pixel array chips permits direct transfer of two-dimensional data or images in parallel. We present laboratory demonstrations of the system for digital image edge detection and digital video motion estimation. We also analyze the performance of the system compared with that of conventional single-instruction-multiple-data processors.     

Patterning of multilayer dielectric optical coatings for multispectral CCDs

The development of optical sensors for spacecraft applications requires that all components be as lightweight as possible. One method to reduce the weight of a multispectral optical system is to eliminate beamsplitting optics and multiple detectors by patterning a filter array directly onto a CCD. However, techniques commonly used in the production of these filter arrays result in decreased image resolutions. This can greatly impact the performance of sensors used for applications such as planetary probes. To address this issue, we have studied the patterning of multilayer dielectric optical coatings in a small scale, two dimensional array, which will allow development of a four color sensor with a resolution one-half that of monochromatic sensors (compared to one-fourth or less for a four color striped array). We have developed ion milling techniques for the preparation of optical filter arrays which are patterned on a scale as small as 7.5 μm, enabling each pixel of a CCD to have its own associated filter. This paper presents details of the fabrication of these multispectral arrays, and discusses problems associated with pixel-sized filters.     

Magnetic assembly of high-density DNA arrays for genomic analyses

A method for rapidly assembling high-density DNA arrays with near-perfect order is described. Photolithography is used to generate a wafer-scale array of microwells in a layer of photoresist on a chemically functionalized glass coverslip. The array is enclosed within a microfluidic device, and a suspension of superparamagnetic microbeads conjugated to DNA molecules is introduced into the chamber. A permanent magnet is used to direct the rapid assembly of the beads into the wells, with each well containing a single bead. These beads are immobilized on the glass surface via affinity binding, and excess beads can be recycled or washed away. Nonspecifically bound beads are removed by dissolving the photoresist. The result is a high-density array of beads with virtually no background. This method can be used to produce protein arrays for chip-based assays and DNA arrays for genotyping or genome sequencing.     

Rapid analyte recognition in a device based on optical sensors and the olfactory system

We report here the development of a new vapor sensing device that is designed as an array of optically based chemosensors providing input to a pattern recognition system incorporating artificial neural networks. Distributed sensors providing inputs to an integrative circuit is a principle derived from studies of the vertebrate olfactory system. In the present device, primary chemosensing input is provided by an array of fiber-optic sensors. The individual fiber sensors, which are broadly yet differentially responsive, were constructed by immobilizing molecules of the fluorescent indicator dye Nile Red in polymer matrices of varying polarity, hydrophobicity, pore size, elasticity, and swelling tendency, creating unique sensing regions that interact differently with vapor molecules. The fluorescent signals obtained from each fiber sensor in response to 2-s applications of different analyte vapors have unique temporal characteristics. Using signals from the fiber array as inputs, artificial neural networks were trained to identify both single analytes and binary mixtures, as well as relative concentrations. Networks trained with integrated response data from the array or with temporal data from a single fiber made numerous errors in analyte identification across concentrations. However, when trained with temporal information from the fiber array, networks using "name" or "characteristic" output codes performed well in identifying test analytes.     

Sparse 2-D array design for real time rectilinear volumetric imaging

Several sparse 2-D arrays for real time rectilinear volumetric imaging were investigated. All arrays consisted of 128x128=16,384 elements with lambda spacing operating at 5 MHz. Because of system limitations, not all of the elements could be used. From each array, 256 elements were used as transmitters, and 256 elements were used as receivers. These arrays were compared by computer simulation using Field II. For each array, beamplots for the on-axis case and an illustrative off-axis case were obtained. For the off-axis case, the effects of receive mode dynamic focusing were studied to maintain the beam perpendicular to the transducer face. Main lobe widths, side lobe heights, clutter floor levels, and pulse-echo sensitivities were quantified for each array. The sparse arrays, including a vernier periodic array, a random array, and a Mills cross array, were compared with a fully sampled array that served as the "gold standard". The Mills cross design showed the best overall performance under the current system constraints.     

DNA hybridization and discrimination of single-nucleotide mismatches using chip-based microbead arrays

The development of a chip-based sensor array composed of individually addressable agarose microbeads has been demonstrated for the rapid detection of DNA oligonucleotides. Here, a "plug and play" approach allows for the simple incorporation of various biotinylated DNA capture probes into the bead-microreactors, which are derivatized in each case with avidin docking sites. The DNA capture probe containing microbeads are selectively arranged in micromachined cavities localized on silicon wafers. The microcavities possess trans-wafer openings, which allow for both fluid flow through the microreactors/analysis chambers and optical access to the chemically sensitive microbeads. Collectively, these features allow the identification and quantitation of target DNA analytes to occur in near real time using fluorescence changes that accompany binding of the target sample. The unique three-dimensional microenvironment within the agarose bead and the microfluidics capabilities of the chip structure afford a fully integrated package that fosters rapid analyses of solutions containing complex mixtures of DNA oligomers. These analyses can be completed at room temperature through the use of appropriate hybridization buffers. For applications requiring analysis of < or = 10(2) different DNA sequences, the hybridization times and point mutation selectivity factors exhibited by this bead array method exceed in many respects the operational characteristics of the commonly utilized planar DNA chip technologies. The power and utility of this microbead array DNA detection methodology is demonstrated here for the analysis of fluids containing a variety of similar 18-base oligonucleotides. Hybridization times on the order of minutes with point mutation selectivity factors greater than 10000 and limit of detection values of approximately 10(-13) M are obtained readily with this microbead array system.     

Cantilever arrays with self-aligned nanotips of uniform height

Cantilever arrays are employed to increase the throughput of imaging and manipulation at the nanoscale. We present a fabrication process to construct cantilever arrays with nanotips that show a uniform tip-sample distance. Such uniformity is crucial, because in many applications the cantilevers do not feature individual tip-sample spacing control. Uniform cantilever arrays lead to very similar tip-sample interaction within an array, enable non-contact modes for arrays and give better control over the load force in contact modes. The developed process flow uses a single mask to define both tips and cantilevers. An additional mask is required for the back side etch. The tips are self-aligned in the convex corner at the free end of each cantilever. Although we use standard optical contact lithography, we show that the convex corner can be sharpened to a nanometre scale radius by an isotropic underetch step. The process is robust and wafer-scale. The resonance frequencies of the cantilevers within an array are shown to be highly uniform with a relative standard error of 0.26% or lower. The tip-sample distance within an array of up to ten cantilevers is measured to have a standard error around 10 nm. An imaging demonstration using the AFM shows that all cantilevers in the array have a sharp tip with a radius below 10 nm. The process flow for the cantilever arrays finds application in probe-based nanolithography, probe-based data storage, nanomanufacturing and parallel scanning probe microscopy.     

High frequency optoacoustic arrays using etalon detection

Two-dimensional phased arrays for high frequency (>30 MHz) ultrasonic imaging are difficult to construct using conventional piezoelectric technology. A promising alternative involves optical detection of ultrasound, where the array element size is defined by the focal spot of a laser beam. Element size and spacing on the order of a few microns are easily achieved, suitable for imaging at frequencies exceeding 100 MHz. We have previously shown images made from a receive-only, two-dimensional optoacoustic array operating at 10 to 50 MHz. The main drawback of optical detection has been poor sensitivity when compared with piezoelectric detection. In this paper, we explore a different form of optical detection demonstrating improved sensitivity and offering a potentially simple method for constructing two-dimensional arrays. Results from a simple experiment using an etalon sensor confirm that the sensitivity of etalon detection is comparable with piezoelectric detection. This paper concludes with a proposal for a high frequency optoacoustic array system using an etalon.     

Board-to-Board Free-Space Optical Interconnections Passing through Boards for a Bookshelf-Assembled Terabit-Per-Second-Class ATM Switch

We propose free-space optical interconnections for a bookshelf-assembled terabit-per-second-class ATM switch. Thousands of arrayed optical beams, each having a rate of a few gigabits per second, propagate vertically to printed circuit boards, passing through some boards, and are connected to arbitrary transmitters and receivers on boards by polarization controllers and prism arrays. We describe a preliminary experiment using a 1-mm-pitch 2 x 2 beam-collimator array that uses vertical-cavity surface-emitting laser diodes. These optical interconnections can be made quite stable in terms of mechanical shock and temperature fluctuation by the attachment of reinforcing frames to the boards and use of an autoalignment system.     

Sparse random ultrasound phased array for focal surgery

Ultrasound phased arrays offer several advantages over single focused transducer technology, enabling electronically programmable synthesis of focal size and shape, as well as position. While phased arrays have been employed for medical diagnostic and therapeutic (hyperthermia) applications, there remain fundamental problems associated with their use for surgery. These problems stem largely from the small size of each array element dictated by the wavelength employed at surgical application frequencies (2-4 MHz), the array aperture size required for the desired focal characteristics, and the number of array elements and electronic drive channels required to provide RF energy to the entire array. The present work involves the theoretical and experimental examination of novel ultrasound phased arrays consisting of array elements larger than one wavelength, minimizing the number of elements in an aperture through a combination of geometric focusing, directive beams, and sparse random placement of array elements, for tissue ablation applications. A hexagonally packed array consisting of 108 8-mm-diameter circular elements mounted on a spherical shell was modeled theoretically and a prototype array was constructed to examine the feasibility of sparse random array configurations for focal surgery. A randomly selected subset of elements of the prototype test array (64 of 108 available channels) was driven at 2.1 MHz with a 64-channel digitally controlled RF drive system. The performance of the prototype array was evaluated by comparing field data obtained from theoretical modeling to that obtained experimentally via hydrophone scanning. The results of that comparison, along with total acoustic power measurements, suggest that the use of sparse random phased arrays for focal surgery is feasible, and that the nature of array packing is an important determinant to observed performance     

Digital optical computing with magneto-optic spatial light modulators: a new and efficient multiplication algorithm

Digital optical computing executed on arrays of binary data can offer parallel processing and multivalued output, which permits more flexibility in algorithm development. The hardware used consists of two computer-controlled magneto-optic spatial-light-modulator arrays in conjunction with a CCD detector array as the computational hardware. Algorithms for binary-processing tasks are presented. We used magneto-optic spatial light modulators for parallel processing in a way that exploits multivalued output. Also, in carrying this evaluation out, we developed a new and efficient multiplication algorithm. Multiplication is an important operation in many digital systems, and the design of fast multipliers is of great interest to computer scientists and engineers. The speed of this computing system is evaluated.     

Optical imaging fiber-based single live cell arrays: a high-density cell assay platform

A high-density, ordered array containing thousands of microwells is fabricated on an optical imaging fiber. Each individually addressable microwell is used to accommodate a single living cell. A charged coupled device (CCD) detector is employed to monitor and spatially resolve the fluorescence signals obtained from each individual cell, allowing simultaneous monitoring of cellular responses of all the cells in the array using reporter genes (lacZ, EGFP, ECFP, DsRed) or fluorescent indicators. Yeast and bacteria cell arrays were fabricated and used to perform multiplexed cell assays with resolution at the single-cell level. Monitoring gene expression in single yeast cells carrying a two-hybrid system was used to detect in vivo protein-protein interactions. The single-cell array technology provides a new platform for monitoring the unique multiple responses of large populations of individual cells from different strains or cell lines. The rich data acquired by the cell array has the potential to be employed as a new tool for cell biology research as well as to improve cell-based high-throughput screening (HTS) applications, such as the validation of new disease-associated cellular targets and the early-stage evaluation of potential drug candidates.     

Analysis and application of multiframe superresolution processing for conventional imaging systems and lenslet arrays

Low-cost compact sensors for ultrasmall systems are a pressing need in many new applications. One potential solution is a shallow aspect ratio system using a lenslet array to form multiple undersampled subimages of a scene on a single focal plane array, where processing techniques then produce an upsampled restored image. We have investigated the optimization and theoretical limits of the performance of such arrays. We have built a hardware simulator and developed algorithms to process imagery similar to that of a full lenslet imaging sensor, which allowed us to quickly test optical components, algorithms, and complete system designs for future lenslet imaging systems.     

Electromagnetic field enhancement and spectrum shaping through plasmonically integrated optical vortices

We introduce a new design approach for surface-enhanced Raman spectroscopy (SERS) substrates that is based on molding the optical powerflow through a sequence of coupled nanoscale optical vortices "pinned" to rationally designed plasmonic nanostructures, referred to as Vortex Nanogear Transmissions (VNTs). We fabricated VNTs composed of Au nanodiscs by electron beam lithography on quartz substrates and characterized their near- and far-field responses through combination of computational electromagnetism, and elastic and inelastic scattering spectroscopy. Pronounced dips in the far-field scattering spectra of VNTs provide experimental evidence for an efficient light trapping and circulation within the nanostructures. Furthermore, we demonstrate that VNT integration into periodic arrays of Au nanoparticles facilitates the generation of high E-field enhancements in the VNTs at multiple defined wavelengths. We show that spectrum shaping in nested VNT structures is achieved through an electromagnetic feed-mechanism driven by the coherent multiple scattering in the plasmonic arrays and that this process can be rationally controlled by tuning the array period. The ability to generate high E-field enhancements at predefined locations and frequencies makes nested VNTs interesting substrates for challenging SERS applications.     

Coherent coupling of vertical-cavity surface-emitting laser arrays and efficient beam combining by diffractive optical elements: concept and experimental verification

A phase-locked diode-laser system based on master-slave coupling of two-dimensional vertical-cavity surface-emitting laser (VCSEL) arrays by injection locking is presented. Frequencies and phases are adjusted by laser-trimmed microresistors. Additional beam-transformation optics consisting of two diffractive optical elements (DOEs) and a Fourier lens concentrates most of the far-field power in a nearly diffraction-limited beam. Both the VCSEL array and the microlens array are monolithically integrated and mounted in a compact module. With an array of 21 slave lasers a system coherence of 95% (for several hours) and of nearly 90% (for several months) has been demonstrated without any active phase control. The scalability of the output power has been verified by locking of an array of 77 slave lasers with a system coherence of 78%. The optical system efficiency is 20-23%; with beam-transformation optics this efficiency could be improved to 44%.