IEEE Journal of Selected Topics in Quantum Electronics

Continuous and longitudinal monitoring of cerebral blood flow (CBF) in animal models provides information for studying the mechanisms and interventions of various cerebral diseases. Since anesthesia may affect brain hemodynamics, researchers have been seeking wearable devices for use in conscious animals. We present a wearable diffuse speckle contrast flowmeter (DSCF) probe for monitoring CBF variations in mice. The DSCF probe consists of a small low-power near-infrared laser diode as a point source and an ultra-small low-power CMOS camera as a 2D detector array, which can be affixed on a mouse head...

Fluorescence acquisition and image display over a high dynamic range is highly desirable. However, the limited dynamic range of current photodetectors and imaging CCDs impose a limit on the fluorescence intensities that can be simultaneously captured during a single image acquisition. This is particularly troublesome when imaging biological samples, where protein expression fluctuates considerably. As a result, biological images will often contain regions with signal that is either saturated or hidden within background noise, causing information loss...

Endoscopic integrated photoacoustic and ultrasound imaging has the potential for early detection of the cancer in the gastrointestinal tract. Currently, slow imaging speed is one of the limitations for clinical translation. Here, we developed a high speed integrated endoscopic PA and US imaging system, which is able to perform PA and US imaging simultaneously up to 50 frames per second. Using this system, the architectural morphology and vasculature of the rectum wall were visualized from a Sprague Dawley rat in-vivo ...

This paper reports the application of endoscopic light scattering spectroscopy (LSS) with light gating to detect malignancies in the biliary and pancreatic ducts, and also reviews the application of endoscopic LSS for differentiating cystic neoplasms in the pancreas and detecting invisible dysplasia in Barrett's esophagus. Information about tissue structure within the superficial epithelium where malignancy starts is present within the spectra of reflected light. Fortunately, this component of the reflected light is not yet randomized...

We report on SwissSPAD2, an image sensor with 512×512 photon-counting pixels, each comprising a single-photon avalanche diode (SPAD), a 1-bit memory, and a gating mechanism capable of turning the SPAD on and off, with a skew of 250ps and 344ps, respectively, for a minimum duration of 5.75ns. The sensor is designed to achieve a frame rate of up to 97,700 binary frames per second and sub-40ps gate shifts. By synchronizing it with a pulsed laser and using multiple successive overlapping gates, one can reconstruct a molecule's fluorescent response with picosecond temporal resolution...

We report a plasmonic interferometer array (PIA) sensor and demonstrate its ability to detect circulating exosomal proteins in real-time with high sensitivity and low cost to enable the early detection of cancer. Specifically, a surface plasmon wave launched by the nano-groove rings interferes with the free-space light at the output of central nano-aperture and results in an intensity interference pattern. Under the single-wavelength illumination, when the target exosomal proteins are captured by antibodies bound on the surface, the biomediated change in the refractive index between the central aperture and groove rings causes the intensity change in transmitted light...

Magnetic iron-oxide nanoparticles have been developed as contrast agents in magnetic resonance imaging (MRI) and as therapeutic agents in magnetic hyperthermia. They have also recently been demonstrated as contrast and elastography agents in magnetomotive optical coherence tomography and elastography (MM-OCT and MM-OCE, respectively). Protein-shell microspheres containing suspensions of these magnetic nanoparticles in lipid cores, and with functionalized outer shells for specific targeting, have also been demonstrated as efficient contrast agents for imaging modalities such as MM-OCT and MRI, and can be easily modified for other modalities such as ultrasound, fluorescence, and luminescence imaging...

Dual-axis confocal (DAC) microscopy is an optical imaging modality that utilizes simple low-numerical aperture (NA) lenses to achieve effective optical sectioning and superior image contrast in biological tissues. The unique architecture of DAC microscopy also provides some advantages for miniaturization, facilitating the development of endoscopic and handheld DAC systems for in vivo imaging. This article reviews the principles of DAC microscopy, including its differences from conventional confocal microscopy, and surveys several variations of DAC microscopy that have been developed and investigated as non-invasive real-time alternatives to conventional biopsy and histopathology...

Planar optofluidics provide a powerful tool for facilitating chip-scale light-matter interactions. Silicon-based liquid core waveguides have been shown to offer single molecule sensitivity for efficient detection of bioparticles. Recently, a PDMS based planar optofluidic platform was introduced that opens the way to rapid development and prototyping of unique structures, taking advantage of the positive attributes of silicon dioxide-based optofluidics and PDMS based microfluidics. Here, hydrodynamic focusing is integrated into a PDMS based optofluidic chip to enhance the detection of single H1N1 viruses on-chip...

We present a multiwavelength, multichannel, time-domain near-infrared spectroscopy system named MAESTROS. This instrument can measure absorption and scattering coefficients and can quantify the concentrations of oxy- and deoxy-haemoglobin ([HbO2 ], [HHb]), and oxidation state of cytochrome-c-oxidase ([oxCCO]). This system is composed of a supercontinuum laser source coupled with two acousto-optic tuneable filters. The light is collected by four photomultipliers tubes, connected to a router to redirect the signal to a single time-correlated single-photon counting card...

An indium phosphide (InP)-based photonic integrated circuit (PIC) transmitter for free space optical communications was demonstrated. The transmitter consists of a sampled grating distributed Bragg reflector (SGDBR) laser, a high-speed semiconductor optical amplifier (SOA), a Mach-Zehnder modulator, and a high-power output booster SOA. The SGDBR laser tunes from 1521 nm to 1565 nm with >45 dB side mode suppression ratio. The InP PIC was also incorporated into a free space optical link to demonstrate the potential for low cost, size, weight and power...

Single-molecule and single-nanoparticle biosensors are a growing frontier in diagnostics. Digital biosensors are those which enumerate all specifically immobilized biomolecules or biological nanoparticles, and thereby achieve limits of detection usually beyond the reach of ensemble measurements. Here we review modern optical techniques for single nanoparticle detection and describe the single-particle interferometric reflectance imaging sensor (SP-IRIS). We present challenges associated with reliably detecting faint nanoparticles with SP-IRIS, and describe image acquisition processes and software modifications to address them...

Silicon-based optofluidic devices are very attractive for applications in biophotonics and chemical sensing. Understanding and controlling the properties of their dielectric waveguides is critical for the performance of these chips. We report that thermal annealing of PECVD-grown silicon dioxide (SiO2) ridge waveguides results in considerable improvements to optical transmission and particle detection. There are two fundamental changes that yield higher optical transmission: (1) propagation loss in solid-core waveguides is reduced by over 70%, and (2) coupling efficiencies between solid- and liquid-core waveguides are optimized...

Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Optical coherence tomography (OCT) is an optical biomedical imaging modality that relies on the detection of backscattered light to generate high-resolution cross-sectional images of biological tissue. MNPs have been utilized as imaging contrast and perturbative mechanical agents in OCT in techniques called magnetomotive OCT (MM-OCT) and magnetomotive elastography (MM-OCE), respectively...

Optical coherence tomography (OCT) is a promising research tool for brain imaging and developmental biology. Serving as a three-dimensional optical biopsy technique, OCT provides volumetric reconstruction of brain tissues and embryonic structures with micrometer resolution and video rate imaging speed. Functional OCT enables label-free monitoring of hemodynamic and metabolic changes in the brain in vitro and in vivo in animal models. Due to its non-invasiveness nature, OCT enables longitudinal imaging of developing specimens in vivo without potential damage from surgical operation, tissue fixation and processing, and staining with exogenous contrast agents...

In the past two decades significant advances have been made in single-molecule detection, which enables the direct observation of single biomolecules at work in real time and under physiological conditions. In particular, the development of single-molecule tracking (SMT) microscopy allows us to monitor the motion paths of individual biomolecules in living systems, unveiling the localization dynamics and transport modalities of the biomolecules that support the development of life. Beyond the capabilities of traditional camera-based tracking techniques, state-of-the-art SMT microscopies developed in recent years can record fluorescence lifetime while tracking a single molecule in the 3D space...

Simultaneous imaging of cerebral hemodynamic changes in response to functional activation during drug intoxication provides a valuable strategy to assess cocaine induced neurovascular dysfunction. However, this requires tools with sufficient spatiotemporal resolution and adequate signal to noise ratio (SNR). Though several technologies have been developed to address this demand during functional brain activation, their spatiotemporal resolution has been compromised to preserve SNR. In this study, we combine spatiotemporal-domain laser speckle contrast analysis and image correlation techniques to integrate multi-wavelength spectroimaging and laser speckle contrast imaging (MW-LSCI)...

Mechanical flexibility and the advent of scalable, low-cost, and high-throughput fabrication techniques have enabled numerous potential applications for plasmonic sensors. Sensitive and sophisticated biochemical measurements can now be performed through the use of flexible plasmonic sensors integrated into existing medical and industrial devices or sample collection units. More robust sensing schemes and practical techniques must be further investigated to fully realize the potentials of flexible plasmonics as a framework for designing low-cost, embedded and integrated sensors for medical, environmental, and industrial applications...

We present fluorescence detection of single H1N1 viruses with enhanced signal to noise ratio (SNR) achieved by multi-spot excitation in liquid-core anti-resonant reflecting optical waveguides (ARROWs). Solid-core Y-splitting ARROW waveguides are fabricated orthogonal to the liquid-core section of the chip, creating multiple excitation spots for the analyte. We derive expressions for the SNR increase after signal processing, and analyze its dependence on signal levels and spot number. Very good agreement between theoretical calculations and experimental results is found...

The imaging of dysregulated cell-surface receptors (or biomarkers) is a potential means of identifying the presence of cancer with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Recently, surface-enhanced Raman-scattering (SERS) nanoparticles (NPs) have attracted wide interest due to their potential for sensitive and multiplexed biomarker detection...