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IEEE Journal Of Selected Topics In Quantum Electronics[JOURNAL]

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Precision-Microfabricated Fiber-Optic Probe for Intravascular Pressure and Temperature Sensing.

Poduval RK, Coote JM, Mosse CA … +3 more , Finlay MC, Desjardins AE, Papakonstantinou I

IEEE J Sel Top Quantum Electron · 2021 · PMID 33716587 · Full text

Small form-factor sensors are widely used in minimally invasive intravascular diagnostic procedures. Manufacturing complexities associated with miniaturizing current fiber-optic probes, particularly for multi-parameter s... Small form-factor sensors are widely used in minimally invasive intravascular diagnostic procedures. Manufacturing complexities associated with miniaturizing current fiber-optic probes, particularly for multi-parameter sensing, severely constrain their adoption outside of niche fields. It is especially challenging to rapidly prototype and iterate upon sensor designs to optimize performance for medical devices. In this work, a novel technique to construct a microscale extrinsic fiber-optic sensor with a confined air cavity and sub-micron geometric resolution is presented. The confined air cavity is enclosed between a 3 μm thick pressure-sensitive distal diaphragm and a proximal temperature-sensitive plano-convex microlens segment unresponsive to changes in external pressure. Simultaneous pressure and temperature measurements are possible through optical interrogation via phase-resolved low-coherence interferometry (LCI). Upon characterization in a simulated intravascular environment, we find these sensors capable of detecting pressure changes down to 0.11 mmHg (in the range of 760 to 1060 mmHg) and temperature changes of 0.036 °C (in the range 34 to 50 °C). By virtue of these sensitivity values suited to intravascular physiological monitoring, and the scope of design flexibility enabled by the precision-fabricated photoresist microstructure, it is envisaged that this technique will enable construction of a wide range of fiber-optic sensors for guiding minimally invasive medical procedures.

A hyperspectral imaging system for mapping haemoglobin and cytochrome-c-oxidase concentration changes in the exposed cerebral cortex.

Giannoni L, Lange F, Sajic M … +2 more , Smith KJ, Tachtsidis I

IEEE J Sel Top Quantum Electron · 2021 · PMID 33716586 · Full text

We present a novel hyperspectral imaging (HSI) system using visible and near-infrared (NIR) light on the exposed cerebral cortex of animals, to monitor and quantify changes in the oxygenation of haemoglobin and in cellu... We present a novel hyperspectral imaging (HSI) system using visible and near-infrared (NIR) light on the exposed cerebral cortex of animals, to monitor and quantify changes in the oxygenation of haemoglobin and in cellular metabolism via measurement of the redox states of cytochrome-c-oxidase (CCO). The system, named hNIR, is based on spectral scanning illumination at 11 bands (600, 630, 665, 784, 800, 818, 835, 851, 868, 881 and 894 nm), using a supercontinuum laser coupled with a rotating Pellin-Broca prism. Image reconstruction is performed with the aid of a Monte Carlo framework for photon pathlength estimation and post-processing correction of partial volume effects. The system is validated on liquid optical phantoms mimicking brain tissue haemodynamics and metabolism, and finally applied on the exposed cortex of mice undergoing alternating oxygenation challenges. The results of the study demonstrate the capacity of hNIR to map and quantify the haemodynamic and metabolic states of the exposed cortex at microvascular levels. This represents (to the best of our knowledge) the first example of simultaneous mapping and quantification of cerebral haemoglobin and CCO using visible and NIR HSI, which can potentially become a powerful tool for better understanding brain physiology.

Photodynamic Priming Modulates Endothelial Cell-Cell Junction Phenotype for Light-activated Remote Control of Drug Delivery.

Inglut CT, Gray KM, Vig S … +5 more , Jung JW, Stabile J, Zhang Y, Stroka KM, Huang HC

IEEE J Sel Top Quantum Electron · 2021 · PMID 33519171 · Full text

The blood-brain barrier (BBB) remains a major obstacle for drug delivery to the central nervous system. In particular, the tight and adherens junctions that join the brain capillary endothelial cells limit the diffusion... The blood-brain barrier (BBB) remains a major obstacle for drug delivery to the central nervous system. In particular, the tight and adherens junctions that join the brain capillary endothelial cells limit the diffusion of various molecules from the bloodstream into the brain. Photodynamic priming (PDP) is a non-cytotoxic modality that involves light activation of photosensitizers to photochemically modulate nearby molecules without killing the cells. Here we investigate the effects of sub-lethal photochemistry on junction phenotype (i.e., continuous, punctate, or perpendicular), as well as the BBB permeability in a transwell model of human brain microvascular endothelial cells (HBMECs). We showed that PDP decreases the continuous junction architecture by ~20%, increases the perpendicular junction architecture by ~40%, and has minimal impact on cell morphology in HBMECs. Furthermore, transwell permeability assay revealed that PDP improves the HBMEC permeability to dextran or nanoliposomes by up to 30-fold for 6-9 days. These results suggest that PDP could safely reverse the mature brain endothelial junctions without killing the HBMECs. This study not only emphasizes the critical roles of PDP in the modulation junction phenotype, but also highlights the opportunity to further develop PDP-based combinations that opens the cerebrum endothelium for enhanced drug transporter across the BBB.

Optofluidic Amplification-free Multiplex Detection of Viral Hemorrhagic Fevers.

Stambaugh A, Stott MA, Meena GG … +5 more , Tamhankar M, Carrion R, Patterson JL, Hawkins AR, Schmidt H

IEEE J Sel Top Quantum Electron · 2021 · PMID 33390686 · Full text

Infectious disease outbreaks such as Ebola and other Viral Hemorrhagic Fevers (VHF) require low-complexity, specific, and differentiated diagnostics as illustrated by the recent outbreak in the Democratic Republic of Con... Infectious disease outbreaks such as Ebola and other Viral Hemorrhagic Fevers (VHF) require low-complexity, specific, and differentiated diagnostics as illustrated by the recent outbreak in the Democratic Republic of Congo. Here, we describe amplification-free spectrally multiplex detection of four different VHF total RNA samples using multi-spot excitation on a multimode interference waveguide platform along with combinatorial fluorescence labeling of target nucleic acids. In these experiments, we observed an average of 8-fold greater fluorescence signal amplitudes for the Ebola total RNA sample compared to three other total RNA samples: Lake Victoria Marburg Virus, Ravn Marburg Virus, and Crimean-Congo Hemorrhagic Fever. We have attributed this amplitude amplification to an increased amount of RNA during synthesis of soluble glycoprotein in infection. This hypothesis is confirmed by single molecule detection of the total RNA sample after heat-activated release from the carrier microbeads. From these experiments, we observed at least a 5.3x higher RNA mass loading on the Ebola carrier microbeads compared to the Lake Victoria Marburg carrier microbeads, which is consistent with the known production of soluble glycoprotein during infection.

Analysis of Diffractive Optical Neural Networks and Their Integration with Electronic Neural Networks.

Mengu D, Luo Y, Rivenson Y … +1 more , Ozcan A

IEEE J Sel Top Quantum Electron · 2020 · PMID 33223801 · Full text

Optical machine learning offers advantages in terms of power efficiency, scalability and computation speed. Recently, an optical machine learning method based on Diffractive Deep Neural Networks (DNNs) has been introduce... Optical machine learning offers advantages in terms of power efficiency, scalability and computation speed. Recently, an optical machine learning method based on Diffractive Deep Neural Networks (DNNs) has been introduced to execute a function as the input light diffracts through passive layers, designed by deep learning using a computer. Here we introduce improvements to DNNs by changing the training loss function and reducing the impact of vanishing gradients in the error back-propagation step. Using five phase-only diffractive layers, we numerically achieved a classification accuracy of 97.18% and 89.13% for optical recognition of handwritten digits and fashion products, respectively; using both phase and amplitude modulation (complex-valued) at each layer, our inference performance improved to 97.81% and 89.32%, respectively. Furthermore, we report the integration of DNNs with electronic neural networks to create hybrid-classifiers that significantly reduce the number of input pixels into an electronic network using an ultra-compact front-end DNN with a layer-to-layer distance of a few wavelengths, also reducing the complexity of the successive electronic network. Using a 5-layer phase-only DNN jointly-optimized with a single fully-connected electronic layer, we achieved a classification accuracy of 98.71% and 90.04% for the recognition of handwritten digits and fashion products, respectively. Moreover, the input to the electronic network was compressed by >7.8 times down to 10×10 pixels. Beyond creating low-power and high-frame rate machine learning platforms, DNN-based hybrid neural networks will find applications in smart optical imager and sensor design.

Device architectures for low voltage and ultrafast graphene integrated phase modulators.

Mao D, Cheng C, Wang F … +9 more , Xiao Y, Li T, Chang L, Soman A, Kananen T, Zhang X, Krainak M, Dong P, Gu T

IEEE J Sel Top Quantum Electron · 2021 · PMID 33154613 · Full text

The atomic layer thin geometry and semi-metallic band diagram of graphene can be utilized for significantly improving the performance matrix of integrated photonic devices. Its semiconductor-like behavior of Fermi-level... The atomic layer thin geometry and semi-metallic band diagram of graphene can be utilized for significantly improving the performance matrix of integrated photonic devices. Its semiconductor-like behavior of Fermi-level tunability allows graphene to serve as an active layer for electro-optic modulation. As a low loss metal layer, graphene can be placed much closer to active layer for low voltage operation. In this work, we investigate hybrid device architectures utilizing semiconductor and metallic properties of the graphene for ultrafast and energy efficient electro-optic phase modulators on semiconductor and dielectric platforms. (1) Directly contacted graphene-silicon heterojunctions. Without oxide layer, the carrier density of graphene can be modulated by the directly contact to silicon layer, while silicon intrinsic region stays mostly depleted. With doped silicon as electrodes, carrier can be quickly injected and depleted from the active region in graphene. The ultrafast carrier transit time and small RC constant promise ultrafast modulation speed (3dB bandwidth of 67 GHz) with an estimated V·L of 1.19 V·mm. (2) Graphene integrated lithium niobite modulator. As a transparent electrode, graphene can be placed close to integrated lithium niobate waveguide for improving coupling coefficient between optical mode profile and electric field with minimal additional loss (4.6 dB/cm). Numerical simulation indicates 2.5× improvement of electro-optic field overlap coefficient, with estimated V of 0.2 V.

Confocal Shear Wave Acoustic Radiation Force Optical Coherence Elastography for Imaging and Quantification of the In Vivo Posterior Eye.

He Y, Qu Y, Zhu J … +5 more , Zhang Y, Saidi A, Ma T, Zhou Q, Chen Z

IEEE J Sel Top Quantum Electron · 2019 · PMID 32042240 · Full text

Retinal diseases, such as age-related macular degeneration (AMD), are the leading cause of blindness in the elderly population. Since no known cures are currently present, it is crucial to diagnose the condition in its e... Retinal diseases, such as age-related macular degeneration (AMD), are the leading cause of blindness in the elderly population. Since no known cures are currently present, it is crucial to diagnose the condition in its early stages so that disease progression is monitored. Recent advances show that the mechanical elasticity of the posterior eye changes with the onset of AMD. In this work, we present a quantitative method of mapping the mechanical elasticity of the posterior eye using confocal shear wave acoustic radiation force optical coherence elastography (SW-ARF-OCE). This technique has been developed and validated with both an ex-vivo porcine tissue model and a customized in-vivo rabbit model, which both showed the quantified elasticity variations between different layers. This study verifies the feasibility of using this technology for the quantification and diagnosis of retinal diseases from the in-vivo posterior eye.

Viscosity monitoring during hemodiluted blood coagulation using optical coherence elastography.

Xu X, Zhu J, Yu J … +1 more , Chen Z

IEEE J Sel Top Quantum Electron · 2019 · PMID 31857783 · Full text

Rapid and accurate clot diagnostic systems are needed for the assessment of hemodiluted blood coagulation. We develop a real-time optical coherence elastography (OCE) system, which measures the attenuation coefficient of... Rapid and accurate clot diagnostic systems are needed for the assessment of hemodiluted blood coagulation. We develop a real-time optical coherence elastography (OCE) system, which measures the attenuation coefficient of a compressional wave induced by a piezoelectric transducer (PZT) in a drop of blood using optical coherence tomography (OCT), for the determination of viscous properties during the dynamic whole blood coagulation process. Changes in the viscous properties increase the attenuation coefficient of the sample. Consequently, dynamic blood coagulation status can be monitored by relating changes of the attenuation coefficient to clinically relevant coagulation metrics, including the initial coagulation time and the clot formation rate. This system was used to characterize the influence of activator kaolin and the influence of hemodilution with either NaCl 0.9% or hydroxyethyl starch (HES) 6% on blood coagulation. The results show that PZT-OCE is sensitive to coagulation abnormalities and is able to characterize blood coagulation status based on viscosity-related attenuation coefficient measurements. PZT-OCE can be used for point-of-care testing for diagnosis of coagulation disorders and monitoring of therapies.

A Wearable Fiberless Optical Sensor for Continuous Monitoring of Cerebral Blood Flow in Mice.

Huang C, Gu Y, Chen J … +6 more , Bahrani AA, Abu Jawdeh EG, Bada HS, Saatman K, Yu G, Chen L

IEEE J Sel Top Quantum Electron · 2019 · PMID 31666792 · Full text

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 hemo... 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. The movement of red blood cells in brain cortex (i.e., CBF) produces spatial fluctuations of laser speckles, which are captured by the camera. The DSCF system was calibrated using tissue phantoms and validated in a human forearm and mouse brains for continuous monitoring of blood flow increases and decreases against the established technologies. Significant correlations were observed among these measurements (R ≥ 0.80, p < 10). This small fiberless probe has the potential to be worn by a freely moving conscious mouse. Moreover, the flexible source-detector configuration allows for varied probing depths up to ~8 mm, which is sufficient for transcranially detecting CBF in the cortices of rodents and newborn infants.

High dynamic range fluorescence imaging.

Vinegoni C, Feruglio PF, Weissleder R

IEEE J Sel Top Quantum Electron · 2019 · PMID 31598059 · Full text

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... 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. In this manuscript we summarize recent work from our group and others, to extended conventional to high dynamic range fluorescence imaging. These strategies have many biological applications, such as mapping of neural connections, vascular imaging, bio-distribution studies or pharmacologic imaging at the single cell and organ level.

High-Speed Integrated Endoscopic Photoacoustic and Ultrasound Imaging System.

Li Y, Zhu Z, Jing JC … +8 more , Chen JJ, Heidari E, He Y, Zhu J, Ma T, Yu M, Zhou Q, Chen Z

IEEE J Sel Top Quantum Electron · 2019 · PMID 31447542 · Full text

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 translati... 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 .

Multispectral Endoscopy with Light Gating for Early Cancer Detection.

Qiu L, Zhang L, Turzhitsky V … +10 more , Khan U, Zakharov Y, Kantekure K, Vitkin E, Itzkan I, Pleskow DK, Sawhney M, Berzin TM, Goldsmith JD, Perelman LT

IEEE J Sel Top Quantum Electron · 2019 · PMID 31244520 · Full text

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 di... 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. However multiple scattering randomizes the signal from the underlying connective tissue which obscures the desired signal. In order to extract diagnostic information from the reflected signal the multiple scattering component related to connective tissue scattering and absorption must be removed. This is accomplished using described here spatial or polarization gating implemented with endoscopically compatible fiber optic probes.

A 512×512 SPAD Image Sensor with Integrated Gating for Widefield FLIM.

Ulku AC, Bruschini C, Antolovic IM … +5 more , Charbon E, Kuo Y, Ankri R, Weiss S, Michalet X

IEEE J Sel Top Quantum Electron · 2019 · PMID 31156324 · Full text

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... 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. Thanks to the sensor's number of pixels (the largest to date) and the fully integrated gated operation, SwissSPAD2 enables widefield FLIM with an all-solid-state solution and at relatively high frame rates. This was demonstrated with preliminary results on organic dyes and semiconductor quantum dots using both decay fitting and phasor analysis. Furthermore, pixels with an exceptionally low dark count rate and high photon detection probability enable uniform and high quality imaging of biologically relevant fluorescent samples stained with multiple dyes. While future versions will feature the addition of microlenses and optimize firmware speed, our results open the way to low-cost alternatives to commercially available scientific time-resolved imagers.

Plasmonic Interferometer Array Biochip as a New Mobile Medical Device for Cancer Detection.

Zeng X, Yang Y, Zhang N … +5 more , Ji D, Gu X, Jornet J, Wu Y, Gan Q

IEEE J Sel Top Quantum Electron · 2019 · PMID 30983848 · Full text

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. Specifi... 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. By recording the intensity changes in real-time, one can effectively screen biomolecular binding events and analyze the binding kinetics. By integrating signals from multiple sensor pairs to enhance the signal-to-noise ratio, superior sensing resolutions of 1.63×10 refractive index unit (RIU) in refractive index change and 3.86×10 exosomes/mL in exosome detection were realized, respectively. Importantly, this PIA sensor can be imaged by a miniaturized microscope system coupled with a smart phone to realize a portable and highly sensitive healthcare device. The sensing resolution of 9.72×10 exosomes/mL in exosome detection was realized using the portable sensing system building upon a commercial smartphone.

Characterization of Magnetic Nanoparticle-Seeded Microspheres for Magnetomotive and Multimodal Imaging.

Marjanovic M, Nguyen FT, Ahmad A … +3 more , Huang PC, Suslick KS, Boppart SA

IEEE J Sel Top Quantum Electron · 2019 · PMID 30880897 · Full text

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 e... 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. By leveraging the benefits of these various imaging modalities with the use of only a single agent, a magnetic microsphere, it becomes possible to use a widefield imaging method (such as MRI or small animal fluorescence imaging) to initially locate the agent, and then use MM-OCT to obtain dynamic contrast images with cellular level morphological resolution. In addition to multimodal contrast-enhanced imaging, these microspheres could serve as drug carriers for targeted delivery under image guidance. Although the preparation and surface modifications of protein microspheres containing iron oxide nanoparticles has been previously described and feasibility studies conducted, many questions regarding their production and properties remain. Since the use of multifunctional microspheres could have high clinical relevance, here we report a detailed characterization of their properties and behavior in different environments to highlight their versatility. The work presented here is an effort for the development and optimization of nanoparticle-based microspheres as multi-modal contrast agents that can bridge imaging modalities on different size scales, especially for their use in MM-OCT and MRI imaging.

Dual-axis confocal microscopy for point-of-care pathology.

Wei L, Yin C, Liu JTC

IEEE J Sel Top Quantum Electron · 2019 · PMID 30872909 · Full text

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 un... 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 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.

Enhanced Detection of Single Viruses On-Chip via Hydrodynamic Focusing.

Black JA, Hamilton E, Hueros RAR … +3 more , Parks JW, Hawkins AR, Schmidt H

IEEE J Sel Top Quantum Electron · 2019 · PMID 30686911 · Full text

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 biop... 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. Chip-plane focusing is provided by a system of microfluidic channels to force the particles towards a region of high optical collection efficiency. Focusing is demonstrated and enhanced detection is quantified using fluorescent polystyrene beads where the coefficient of variation is found to decrease by a factor of 4 with the addition of hydrodynamic focusing. The mean signal amplitude of fluorescently tagged single H1N1 viruses is found to increase with the addition of focusing by a factor of 1.64.

MAESTROS: A Multiwavelength Time-Domain NIRS System to Monitor Changes in Oxygenation and Oxidation State of Cytochrome-C-Oxidase.

Lange F, Dunne L, Hale L … +1 more , Tachtsidis I

IEEE J Sel Top Quantum Electron · 2019 · PMID 30450021 · Full text

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... 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 ([HbO], [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. The interface between the system and the tissue is based on optical fibres. This arrangement allows us to resolve up to 16 wavelengths, within the range of 650-900 nm, at a sampling rate compatible with the physiology (from 0.5 to 2 Hz). In this paper, we describe the system and assess its performance based on two specifically designed protocols for photon migration instruments, the basic instrument protocol and nEUROPt protocols, and on a well characterized liquid phantom based on Intralipid and water. Then, the ability to resolve [HbO ], [HHb], and [oxCCO] is demonstrated on a homogeneous liquid phantom, based on blood for [HbO], [HHb], and yeast for [oxCCO]. In the future, the system could be used to monitor brain tissue physiology.

Indium Phosphide Photonic Integrated Circuits for Free Space Optical Links.

Zhao H, Pinna S, Song B … +4 more , Megalini L, Brunelli STŠ, Coldren LA, Klamkin J

IEEE J Sel Top Quantum Electron · 2018 Nov · PMID 30416332 · Full text

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) lase... 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. Error-free operation was achieved at 3 Gbps for an equivalent link length of 180 m (up to 300 m with forward error correction).

Robust Visualization and Discrimination of Nanoparticles by Interferometric Imaging.

Trueb J, Avci O, Sevenler D … +2 more , Connor JH, Ünlü MS

IEEE J Sel Top Quantum Electron · 2017 · PMID 28989270 · Full text

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 ac... 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. Specifically, we describe a image acquisition processing method for the discrimination and accurate counting of nanoparticles that greatly reduces both the number of false positives and false negatives. These engineering improvements are critical steps in the translation of SP-IRIS towards applications in medical diagnostics.
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