M. Selim Ünlü

Resonant cavity enhanced photonic devices

We review the family of optoelectronic devices whose performance is enhanced by placing the active device structure inside a Fabry‐Perot resonantmicrocavity. Such resonantcavity enhanced (RCE) devices benefit from the wavelength selectivity and the large increase of the resonant optical field introduced by the cavity. The increased optical field allows RCE photodetector structures to be thinner and therefore faster, while simultaneously increasing the quantum efficiency at the resonant wavelengths. Off‐resonance wavelengths are rejected by the cavity making RCE photodetectors promising for low crosstalk wavelength division multiplexing(WDM) applications. RCE optical modulators require fewer quantum wells so are capable of reduced voltage operation. The spontaneous emission spectrum of RCE light emitting diodes(LED) is drastically altered, improving the spectral purity and directivity. RCE devices are also highly suitable for integrated detectors and emitters with applications as in optical logic and in communication networks. This review attempts an encyclopedic overview of RCE photonicdevices and systems. Considerable attention is devoted to the theoretical formulation and calculation of important RCE device parameters. Materials criteria are outlined and the suitability of common heteroepitaxial systems for RCE devices is examined. Arguments for the improved bandwidth in RCE detectors are presented intuitively, and results from advanced numerical simulations confirming the simple model are provided. An overview of experimental results on discrete RCE photodiodes, phototransistors, modulators, and LEDs is given. Work aimed at integrated RCE devices,optical logic and WDM systems is also covered. We conclude by speculating what remains to be accomplished to implement a practical RCE WDM system.

Label-free and dynamic detection of biomolecular interactions for high-throughput microarray applications

Direct monitoring of primary molecular-binding interactions without the need for secondary reactants would markedly simplify and expand applications of high-throughput label-free detection methods. A simple interferometric technique is presented that monitors the optical phase difference resulting from accumulated biomolecular mass. As an example, 50 spots for each of four proteins consisting of BSA, human serum albumin, rabbit IgG, and protein G were dynamically monitored as they captured corresponding antibodies. Dynamic measurements were made at 26 pg/mm2 SD per spot and with a detectable concentration of 19 ng/ml. The presented method is particularly relevant for protein microarray analysis because it is label-free, simple, sensitive, and easily scales to high-throughput.

Single nanoparticle detectors for biological applications

Nanoparticle research has become increasingly important in the context of bioscience and biotechnology. Practical use of nanoparticles in biology has significantly advanced our understanding about biological processes in the nanoscale as well as led to many novel diagnostic and therapeutic applications. Besides, synthetic and natural nanoparticles are of concern for their potential adverse effect on human health. Development of novel detection and characterization tools for nanoparticles will impact a broad range of disciplines in biological research from nanomedicine to nanotoxicology. In this article, we discuss the recent progress and future directions in the area of single nanoparticle detectors with an emphasis on their biological applications. A brief critical overview of electrical and mechanical detection techniques is given and a more in-depth discussion of label-free optical detection techniques is presented.

High-speed 90% Quantum-Efficiency p-i-n Photodiodes with a Resonance Wavelength Adjustable in the 795-835 nm Range

We report GaAs/AlGaAs-based high-speed, high-efficiency, resonant cavity enhanced p–i–n photodiodes. The devices were fabricated by using a microwave-compatible fabrication process. By using a postprocess recess etch, we tuned the resonance wavelength from 835 to 795 nm while keeping the peak efficiencies above 90%. The maximum quantum efficiency was 92% at a resonance wavelength of 823 nm. The photodiode had an experimental setup-limited temporal response of 12 ps. When the system response is deconvolved, the 3 dB bandwidth corresponds to 50 GHz, which is in good agreement with our theoretical calculations.

Single nanoparticle detection for multiplexed protein diagnostics with attomolar sensitivity in serum and unprocessed whole blood.

Although biomarkers exist for a range of disease diagnostics, a single low-cost platform exhibiting the required sensitivity, a large dynamic-range and multiplexing capability, and zero sample preparation remains in high demand for a variety of clinical applications. The Interferometric Reflectance Imaging Sensor (IRIS) was utilized to digitally detect and size single gold nanoparticles to identify protein biomarkers in unprocessed serum and blood samples. IRIS is a simple, inexpensive, multiplexed, high-throughput, and label-free optical biosensor that was originally used to quantify biomass captured on a surface with moderate sensitivity. Here we demonstrate detection of β-lactoglobulin, a cows milk whey protein spiked in serum (>10 orders of magnitude) and whole blood (>5 orders of magnitude), at attomolar sensitivity. The clinical utility of IRIS was demonstrated by detecting allergen-specific IgE from microliters of characterized human serum and unprocessed whole blood samples by using secondary antibodies against human IgE labeled with 40 nm gold nanoparticles. To the best of our knowledge, this level of sensitivity over a large dynamic range has not been previously demonstrated. IRIS offers four main advantages compared to existing technologies: it (i) detects proteins from attomolar to nanomolar concentrations in unprocessed biological samples, (ii) unambiguously discriminates nanoparticles tags on a robust and physically large sensor area, (iii) detects protein targets with conjugated very small nanoparticle tags (~40 nm diameter), which minimally affect assay kinetics compared to conventional microparticle tagging methods, and (iv) utilizes components that make the instrument inexpensive, robust, and portable. These features make IRIS an ideal candidate for clinical and diagnostic applications.

MRI of the lung gas-space at very low-field using hyperpolarized noble gases

In hyperpolarized (HP) noble-gas magnetic resonance imaging, large nuclear spin polarizations, about 100,000 times that ordinarily obtainable at thermal equilibrium, are created in 3He and 129Xe. The enhanced signal that results can be employed in high-resolution MRI studies of void spaces such as in the lungs. In HP gas MRI the signal-to-noise ratio (SNR) depends only weakly on the static magnetic field (B(0)), making very low-field (VLF) MRI possible; indeed, it is possible to contemplate portable MRI using light-weight solenoids or permanent magnets. This article reports the first in vivo VLF MR images of the lungs in humans and in rats, obtained at a field of only 15 millitesla (150 Gauss).

Label-free multiplexed virus detection using spectral reflectance imaging

We demonstrate detection of whole viruses and viral proteins with a new label-free platform based on spectral reflectance imaging. The Interferometric Reflectance Imaging Sensor (IRIS) has been shown to be capable of sensitive protein and DNA detection in a real time and high-throughput format. Vesicular stomatitis virus (VSV) was used as the target for detection as it is well-characterized for protein composition and can be modified to express viral coat proteins from other dangerous, highly pathogenic agents for surrogate detection while remaining a biosafety level 2 agent. We demonstrate specific detection of intact VSV virions achieved with surface-immobilized antibodies acting as capture probes which is confirmed using fluorescence imaging. The limit of detection is confirmed down to 3.5 × 10(5)plaque-forming units/mL (PFUs/mL). To increase specificity in a clinical scenario, both the external glycoprotein and internal viral proteins were simultaneously detected with the same antibody arrays with detergent-disrupted purified VSV and infected cell lysate solutions. Our results show sensitive and specific virus detection with a simple surface chemistry and minimal sample preparation on a quantitative label-free interferometric platform.

Floating light-activated microelectrical stimulators tested in the rat spinal cord

Microelectrodes of neural stimulation utilize fine wires for electrical connections to driving electronics. Breakage of these wires and the neural tissue response due to their tethering forces are major problems encountered with long-term implantation of microelectrodes. The lifetime of an implant for neural stimulation can be substantially improved if the wire interconnects are eliminated. Thus, we proposed a floating light-activated microelectrical stimulator (FLAMES) for wireless neural stimulation. In this paradigm, a laser beam at near infrared (NIR) wavelengths will be used as a means of energy transfer to the device. In this study, microstimulators of various sizes were fabricated, with two cascaded GaAs p-i-n photodiodes, and tested in the rat spinal cord. A train of NIR pulses (0.2 ms, 50 Hz) was sent through the tissue to wirelessly activate the devices and generate the stimulus current. The forces elicited by intraspinal stimulation were measured from the ipsilateral forelimb with a force transducer. The largest forces were around 1.08 N, a significant level of force for the rat forelimb motor function. These in vivo tests suggest that the FLAMES can be used for intraspinal microstimulation even for the deepest implant locations in the rat spinal cord. The power required to generate a threshold arm movement was investigated as the laser source was moved away from the microstimulator. The results indicate that the photon density does not decrease substantially for horizontal displacements of the source that are in the same order as the beam radius. This gives confidence that the stimulation threshold may not be very sensitive to small displacement of the spinal cord relative to the spine-mounted optical power source.

Fabrication of high-speed resonant cavity enhanced Schottky photodiodes

We report the fabrication and testing of a GaAs-based high-speed resonant cavity enhanced (RCE) Schottky photodiode. The top-illuminated RCE detector is constructed by integrating a Schottky contact, a thin absorption region (In/sub 0.08/Ga/sub 0.92/As) and a distributed AlAs-GaAs Bragg mirror. The Schottky contact metal serves as a high-reflectivity top mirror in the RCE detector structure. The devices were fabricated by using a microwave-compatible fabrication process. The resulting spectral photo response had a resonance around 895 nm, in good agreement with our simulations. The full-width-at-half-maximum (FWHM) was 15 nm, and the enhancement factor was in excess of 6. The photodiode had an experimental setup limited temporal response of 18 ps FWHM, corresponding to a 3-dB bandwidth of 20 GHz.

Widefield subsurface microscopy of integrated circuits

We apply the numerical aperture increasing lens technique to widefield subsurface imaging of silicon integrated circuits. We demonstrate lateral and longitudinal resolutions well beyond the limits of conventional backside imaging. With a simple infrared widefield microscope (lambda(0) = 1.2 microm), we demonstrate a lateral spatial resolution of 0.26 microm (0.22 lambda(0)) and a longitudinal resolution of 1.24 microm (1.03 lambda(0)) for backside imaging through the silicon substrate of an integrated circuit. We present a spatial resolution comparison between widefield and confocal microscopy, which are essential in integrated circuit analysis for emission and excitation microscopy, respectively.