Liquid Flow Meter by Fiber-Optic Sensing of Heat Propagation.

Monitoring fluid flow rates is imperative for a variety of industries including biomedical engineering, chemical engineering, the food industry, and the oil and gas industries. We propose a flow meter that, unlike turbine or pressure-based sensors, is not flow intrusive, requires zero maintenance, has low risk of clogging, and is compatible with harsh conditions. Using optical fiber sensing, we monitor the temperature distribution along a fluid conduit. Pulsed heat injection locally elevates the fluid's temperature, and from the propagation velocity of the heat downstream, the fluid's velocity is determined. The method is experimentally validated for water and ethanol using optical frequency-domain reflectometry (OFDR) with millimetric spatial resolution over a 1.2 m-long conduit. Results demonstrate that such sensing yields accurate data with a linear response. By changing the optical fiber interrogation to time-domain distributed sensing approaches, the proposed technique can be scaled to cover sensing ranges of several tens of kilometers. On the other extreme, miniaturization for instance by using integrated optical waveguides could potentially bring this flow monitoring technique to microfluidic systems or open future avenues for novel "lab-in-a-fiber" technologies with biomedical applications.

Mass Flow Monitoring by Distributed Fiber Optical Temperature Sensing.

We developed a novel method to monitor mass flow based on distributed fiber optical temperature sensing. Examination of the temporal and spatial temperature distribution along the entire length of a locally heated fluidic conduit reveals heat flow under forced convection. Our experimental results are in good agreement with two-dimensional finite element analysis that couples fluid dynamic and heat transfer equations. Through analysis of the temperature distribution bidirectional flow rates can be measured over three orders of magnitude. The technique is not flow intrusive, works in harsh conditions, including high-temperatures, high pressures, corrosive media, and strong electromagnetic environments. We demonstrate a first experimental implementation on a short fluidic system with a length of one meter. This range covers many applications such as low volume drug delivery, diagnostics, as well as process and automation technology. Yet, the technique can, without restrictions, be applied to long range installations. Existing fiber optics infrastructures, for instance on oil pipelines or down hole installations, would only require the addition of a heat source to enable reliable flow monitoring capability.

A Novel Low-Power-Consumption All-Fiber-Optic Anemometer with Simple System Design.

A compact and low-power consuming fiber-optic anemometer based on single-walled carbon nanotubes (SWCNTs) coated tilted fiber Bragg grating (TFBG) is presented. TFBG as a near infrared in-fiber sensing element is able to excite a number of cladding modes and radiation modes in the fiber and effectively couple light in the core to interact with the fiber surrounding mediums. It is an ideal in-fiber device used in a fiber hot-wire anemometer (HWA) as both coupling and sensing elements to simplify the sensing head structure. The fabricated TFBG was immobilized with an SWCNT film on the fiber surface. SWCNTs, a kind of innovative nanomaterial, were utilized as light-heat conversion medium instead of traditional metallic materials, due to its excellent infrared light absorption ability and competitive thermal conductivity. When the SWCNT film strongly absorbs the light in the fiber, the sensor head can be heated and form a "hot wire". As the sensor is put into wind field, the wind will take away the heat on the sensor resulting in a temperature variation that is then accurately measured by the TFBG. Benefited from the high coupling and absorption efficiency, the heating and sensing light source was shared with only one broadband light source (BBS) without any extra pumping laser complicating the system. This not only significantly reduces power consumption, but also simplifies the whole sensing system with lower cost. In experiments, the key parameters of the sensor, such as the film thickness and the inherent angle of the TFBG, were fully investigated. It was demonstrated that, under a very low BBS input power of 9.87 mW, a 0.100 nm wavelength response can still be detected as the wind speed changed from 0 to 2 m/s. In addition, the sensitivity was found to be -0.0346 nm/(m/s) under the wind speed of 1 m/s. The proposed simple and low-power-consumption wind speed sensing system exhibits promising potential for future long-term remote monitoring and on-chip sensing in practical applications.

Simultaneous Temperature and Pressure Measurements in Compressible Flow Using Nanosecond O2 Coherent Anti-Stokes Raman Spectroscopy.

Simultaneous pure-rotational coherent anti-Stokes Raman spectroscopy (PRCARS) and vibrational O2 CARS spectroscopy (VCARS) were performed at elevated pressure and lowered temperature conditions in non-reacting compressible flow. We applied dual-pump CARS in a three-laser, three-color configuration to simultaneously acquire the PRCARS and VCARS spectra of O2. PRCARS spectra provide excellent sensitivity to temperature at relatively low temperatures. Pressure was extracted using the differential response of collisional effects in the PRCARS and the VCARS spectra. We used an under-expanded jet outside a choked converging nozzle as the compressible flow-field. We numerically analyze the pressure sensitivity of the combined CARS technique. Finally, we compare the collisional narrowing lineshape models of rotational diffusion narrowing and modified-exponential-gap model, for fitting the experimental spectrum.

Laboratory Testing Methods for Novel Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2).

Following the first reports of coronavirus disease-19 (COVID-19) by China to the World Health Organization (WHO) on 31st December 2019, more than 4,302,774 novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cases have been reported by authorities in 212 countries and territories by 12th May 2020. The outbreak and spread of COVID-19 worldwide, highlights the critical need for developing rapid and accurate diagnostic testing methods for emerging human coronavirus (CoV) infections. Testing is crucial to track the spread of disease during a pandemic, and to swiftly permit public health interventions including isolation, quarantine, and appropriate clinical management of afflicted individuals. The key components of viral diagnostic tests are (1) collection of the appropriate sample (blood, nasal swab, and throat swab), (2) availability of the genetic and proteomic sequences of the novel virus for analysis, and (3) rapid and accurate laboratory testing methods. The current gold standard for the molecular diagnosis of SARS-CoV-2 infection is the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for the qualitative and quantitative detection of viral nucleic acids. Other relevant laboratory methods include enzyme-linked immunoassays (EIA) for viral antibody and antigen detection, and serum viral neutralization (SVN) assays for antibody neutralization determination. The challenges faced in developing a diagnostic test for a novel pathogen are the ability to measure low viral loads for early detection, to provide low or no cross-reactivity with other viral strains and to deliver results rapidly. Several point-of-care molecular devices are currently being integrated for fast and accurate diagnosis of SARS-CoV-2 infections. This review discusses the current laboratory methods available to test for coronaviruses by focusing on the present COVID-19 outbreak.

Complex differential variance angiography with noise-bias correction for optical coherence tomography of the retina.

Complex differential variance (CDV) provides phase-sensitive angiographic imaging for optical coherence tomography (OCT) with immunity to phase-instabilities of the imaging system and small-scale axial bulk motion. However, like all angiographic methods, measurement noise can result in erroneous indications of blood flow that confuse the interpretation of angiographic images. In this paper, a modified CDV algorithm that corrects for this noise-bias is presented. This is achieved by normalizing the CDV signal by analytically derived upper and lower limits. The noise-bias corrected CDV algorithm was implemented into an experimental 1 µm wavelength OCT system for retinal imaging that used an eye tracking scanner laser ophthalmoscope at 815 nm for compensation of lateral eye motions. The noise-bias correction improved the CDV imaging of the blood flow in tissue layers with a low signal-to-noise ratio and suppressed false indications of blood flow outside the tissue. In addition, the CDV signal normalization suppressed noise induced by galvanometer scanning errors and small-scale lateral motion. High quality cross-section and motion-corrected en face angiograms of the retina and choroid are presented.

Optofluidic chips with nanochannels for dynamic molecular detection using enhanced fluorescence.

The fabrication of a novel optofluidic chip using nanochannels optimized for DNA-stretched molecules and optical detection by enhanced fluorescence is reported. The chips are composed of a series of microchannels that allow the transport of molecules in the femto-liter per second inside a fluid or gas. The nanochannels are surrounded by a photonic crystal structure to enhance the emission of fluorescent light from the molecules, which can travel along the nanochannel, allowing for enhanced optical detection of the molecules in motion. The photonic crystal structure provides an enhancement up to 2.5 times in the light emitted from fluorescent molecules inside the nanochannels which increases to around 250 when normalized to the area of the nanochannels emitting fluorescence. The results may help to the detection of fluorescent molecules (like marked-DNA) in series by speeding it and allowing the use of less sophisticated equipment.

Velocity measurements in whole blood using acoustic resolution photoacoustic Doppler.

Acoustic resolution photoacoustic Doppler velocimetry promises to overcome the spatial resolution and depth penetration limitations of current blood flow measuring methods. Despite successful implementation using blood-mimicking fluids, measurements in blood have proved challenging, thus preventing in vivo application. A common explanation for this difficulty is that whole blood is insufficiently heterogeneous relative to detector frequencies of tens of MHz compatible with deep tissue photoacoustic measurements. Through rigorous experimental measurements we provide new insight that refutes this assertion. We show for the first time that, by careful choice of the detector frequency and field-of-view, and by employing novel signal processing methods, it is possible to make velocity measurements in whole blood using transducers with frequencies in the tens of MHz range. These findings have important implications for the prospects of making deep tissue measurements of blood flow relevant to the study of microcirculatory abnormalities associated with cancer, diabetes, atherosclerosis and other conditions.

Label-free fast 3D coherent imaging reveals pancreatic islet micro-vascularization and dynamic blood flow.

In diabetes, pancreatic ß-cells play a key role. These cells are clustered within structures called islets of Langerhans inside the pancreas and produce insulin, which is directly secreted into the blood stream. The dense vascularization of islets of Langerhans is critical for maintaining a proper regulation of blood glucose homeostasis and is known to be affected from the early stage of diabetes. The deep localization of these islets inside the pancreas in the abdominal cavity renders their in vivo visualization a challenging task. A fast label-free imaging method with high spatial resolution is required to study the vascular network of islets of Langerhans. Based on these requirements, we developed a label-free and three-dimensional imaging method for observing islets of Langerhans using extended-focus Fourier domain Optical Coherence Microscopy (xfOCM). In addition to structural imaging, this system provides three-dimensional vascular network imaging and dynamic blood flow information within islets of Langerhans. We propose our method to deepen the understanding of the interconnection between diabetes and the evolution of the islet vascular network.

Comparison of amplitude-decorrelation, speckle-variance and phase-variance OCT angiography methods for imaging the human retina and choroid.

We compared the performance of three OCT angiography (OCTA) methods: speckle variance, amplitude decorrelation and phase variance for imaging of the human retina and choroid. Two averaging methods, split spectrum and volume averaging, were compared to assess the quality of the OCTA vascular images. All data were acquired using a swept-source OCT system at 1040 nm central wavelength, operating at 100,000 A-scans/s. We performed a quantitative comparison using a contrast-to-noise (CNR) metric to assess the capability of the three methods to visualize the choriocapillaris layer. For evaluation of the static tissue noise suppression in OCTA images we proposed to calculate CNR between the photoreceptor/RPE complex and the choriocapillaris layer. Finally, we demonstrated that implementation of intensity-based OCT imaging and OCT angiography methods allows for visualization of retinal and choroidal vascular layers known from anatomic studies in retinal preparations. OCT projection imaging of data flattened to selected retinal layers was implemented to visualize retinal and choroidal vasculature. User guided vessel tracing was applied to segment the retinal vasculature. The results were visualized in a form of a skeletonized 3D model.

Particle streak velocimetry-optical coherence tomography: a novel method for multidimensional imaging of microscale fluid flows.

We present a new OCT method for flow speed quantification and directional velocimetry: particle streak velocimetry-OCT (PSV-OCT). PSV-OCT generates two-dimensional, 2.5-vector component (vx ,|vy |,vz ) maps of microscale flow velocity fields. Knowledge of 2.5-vector components also enables the estimation of total flow speed. The enabling insight behind PSV-OCT is that tracer particles in sparsely-seeded fluid flow trace out streaks in (x,z,t)-space. The streak orientations in x-t and z-t yield vx and vz , respectively. The in-plane (x-z plane) residence time yields the out-of-plane speed |vy |. Vector component values are generated by fitting streaks to a model of image formation that incorporates equations of motion in 3D space. We demonstrate cross-sectional estimation of (vx ,|vy |,vz ) in two important animal models in ciliary biology: Xenopus embryos (tadpoles) and mouse trachea.

Erratum: Particle streak velocimetry-optical coherence tomography: a novel method for multidimensional imaging of microscale fluid flows: erratum.

[This corrects the article on p. 1590 in vol. 7.].

Blood flow velocity vector field reconstruction from dual-beam bidirectional Doppler OCT measurements in retinal veins.

In this paper, we demonstrate the possibility to reconstruct the actual blood flow velocity vector field in retinal microvessels from dual-beam bidirectional Doppler optical coherence tomography measurements. First, for a better understanding of measured phase patterns, several flow situations were simulated on the basis of the known dual beam measurement geometry. We were able to extract the vector field parameters that determine the measured phase pattern, allowing for the development of an algorithm to reconstruct the velocity vector field from measured phase data. In a next step, measurements were performed at a straight vessel section and at a venous convergence; the obtained phase data were evaluated by means of the new approach. For the straight vessel section, the reconstructed flow velocity vector field yielded a parabolic flow. For the venous convergence, however, the reconstructed vector field deviated from a parabolic profile, but was in very good accordance with the simulated vector field for the given vessel geometry. The proposed algorithm allows predictions of the velocity vector field. Moreover, the algorithm is also sensitive to directional changes of the flow velocity as small as <1°, thereby offering insight in the flow characteristics of the non-Newtonian fluid blood in microvessels.

OCT angiography by absolute intensity difference applied to normal and diseased human retinas.

We compare four optical coherence tomography techniques for noninvasive visualization of microcapillary network in the human retina and murine cortex. We perform phantom studies to investigate contrast-to-noise ratio for angiographic images obtained with each of the algorithm. We show that the computationally simplest absolute intensity difference angiographic OCT algorithm that bases only on two cross-sectional intensity images may be successfully used in clinical study of healthy eyes and eyes with diabetic maculopathy and branch retinal vein occlusion.

Depth selective acousto-optic flow measurement.

Optical based methods for non-invasive measurement of regional blood flow tend to incorrectly assess cerebral blood flow, due to contribution of extra-cerebral tissues to the obtained signal. We demonstrate that spectral analysis of phase-coded light signals, tagged by specific ultrasound patterns, enables differentiation of flow patterns at different depths. Validation of the model is conducted by Monte Carlo simulation. In-vitro experiments demonstrate good agreement with the simulations' results and provide a solid validation to depth discrimination ability. These results suggest that signal contamination originating from extra-cerebral tissue may be eliminated using spectral analysis of ultrasonically tagged light.

Optical coherence Doppler tomography for quantitative cerebral blood flow imaging.

Optical coherence Doppler tomography (ODT) is a promising neurotechnique that permits 3D imaging of the cerebral blood flow (CBF) network; however, quantitative CBF velocity (CBFv) imaging remains challenging. Here we present a simple phase summation method to enhance slow capillary flow detection sensitivity without sacrificing dynamic range for fast flow and vessel tracking to improve angle correction for absolute CBFv quantification. Flow phantom validation indicated that the CBFv quantification accuracy increased from 15% to 91% and the coefficient of variation (CV) decreased 9.3-fold; in vivo mouse brain validation showed that CV decreased 4.4-/10.8- fold for venular/arteriolar flows. ODT was able to identify cocaine-elicited microischemia and quantify CBFv disruption in branch vessels and capillaries that otherwise would have not been possible.

Measurement of the total retinal blood flow using dual beam Fourier-domain Doppler optical coherence tomography with orthogonal detection planes.

We present a system capable of measuring the total retinal blood flow using a combination of dual beam Fourier-domain Doppler optical coherence tomography with orthogonal detection planes and a fundus camera-based retinal vessel analyzer. Our results show a high degree of conformity of venous and arterial flows, which corroborates the validity of the measurements. In accordance with Murray's law, the log-log regression coefficient between vessel diameter and blood flow was found to be ~3. The blood's velocity scaled linearly with the vessel diameter at higher diameters (> 60 µm), but showed a clear divergence from the linear dependence at lower diameters. Good agreement with literature data and the large range and high measurement sensitivity point to a high potential for further investigations.

Bone tissue phantoms for optical flowmeters at large interoptode spacing generated by 3D-stereolithography.

A bone tissue phantom prototype allowing to test, in general, optical flowmeters at large interoptode spacings, such as laser-Doppler flowmetry or diffuse correlation spectroscopy, has been developed by 3D-stereolithography technique. It has been demonstrated that complex tissue vascular systems of any geometrical shape can be conceived. Absorption coefficient, reduced scattering coefficient and refractive index of the optical phantom have been measured to ensure that the optical parameters reasonably reproduce real human bone tissue in vivo. An experimental demonstration of a possible use of the optical phantom, utilizing a laser-Doppler flowmeter, is also presented.

Dove prism based rotating dual beam bidirectional Doppler OCT.

Traditional Doppler OCT is highly sensitive to motion artifacts due to the dependence on the Doppler angle. This limits its accuracy in clinical practice. To overcome this limitation, we use a bidirectional dual beam technique equipped with a novel rotating scanning scheme employing a Dove prism. The volume is probed from two distinct illumination directions with variable controlled incidence plane, allowing for reconstruction of the true flow velocity at arbitrary vessel orientations. The principle is implemented with Swept Source OCT at 1060nm with 100,000 A-Scans/s. We apply the system to resolve pulsatile retinal absolute blood velocity by performing segment scans around the optic nerve head and circumpapillary scan time series.

Real-time eye motion correction in phase-resolved OCT angiography with tracking SLO.

In phase-resolved OCT angiography blood flow is detected from phase changes in between A-scans that are obtained from the same location. In ophthalmology, this technique is vulnerable to eye motion. We address this problem by combining inter-B-scan phase-resolved OCT angiography with real-time eye tracking. A tracking scanning laser ophthalmoscope (TSLO) at 840 nm provided eye tracking functionality and was combined with a phase-stabilized optical frequency domain imaging (OFDI) system at 1040 nm. Real-time eye tracking corrected eye drift and prevented discontinuity artifacts from (micro)saccadic eye motion in OCT angiograms. This improved the OCT spot stability on the retina and consequently reduced the phase-noise, thereby enabling the detection of slower blood flows by extending the inter-B-scan time interval. In addition, eye tracking enabled the easy compounding of multiple data sets from the fovea of a healthy volunteer to create high-quality eye motion artifact-free angiograms. High-quality images are presented of two distinct layers of vasculature in the retina and the dense vasculature of the choroid. Additionally we present, for the first time, a phase-resolved OCT angiogram of the mesh-like network of the choriocapillaris containing typical pore openings.