Physics informed contour selection for rapid image segmentation.

Effective training of deep image segmentation models is challenging due to the need for abundant, high-quality annotations. To facilitate image annotation, we introduce Physics Informed Contour Selection (PICS)-an interpretable, physics-informed algorithm for rapid image segmentation without relying on labeled data. PICS draws inspiration from physics-informed neural networks (PINNs) and an active contour model called snake. It is fast and computationally lightweight because it employs cubic splines instead of a deep neural network as a basis function. Its training parameters are physically interpretable because they directly represent control knots of the segmentation curve. Traditional snakes involve minimization of the edge-based loss functionals by deriving the Euler-Lagrange equation followed by its numerical solution. However, PICS directly minimizes the loss functional, bypassing the Euler Lagrange equations. It is the first snake variant to minimize a region-based loss function instead of traditional edge-based loss functions. PICS uniquely models the three-dimensional (3D) segmentation process with an unsteady partial differential equation (PDE), which allows accelerated segmentation via transfer learning. To demonstrate its effectiveness, we apply PICS for 3D segmentation of the left ventricle on a publicly available cardiac dataset. We also demonstrate PICS's capacity to encode the prior shape information as a loss term by proposing a new convexity-preserving loss term for left ventricle. Overall, PICS presents several novelties in network architecture, transfer learning, and physics-inspired losses for image segmentation, thereby showing promising outcomes and potential for further refinement.

Instability of mixing layers: Momentum and thermal transport in the continuum breakdown regime.

We examine the momentum and thermal transport in the continuum breakdown regime of a mixing layer flow, which exhibits Kelvin-Helmholtz instability under ideal continuum conditions. The Grad 13 moment model is used as it provides an adequate description of the flow physics (second-order accurate in Knudsen number) in the transition regime. Analytical solutions are developed under breakdown conditions for two-dimensional, compressible, parallel shear flows. It is shown that the deviation of viscous stress and heat flux from the Navier-Stokes-Fourier system follows two different scaling regimes depending upon the Mach number. At low Mach numbers, the departure of all stress and heat-flux components depends only upon the Knudsen number. At high Mach number, the scaling of shear stress and transverse heat flux depends on the product of the Knudsen and Mach numbers. The normal stresses depend individually on the Knudsen and Mach number. The scaling results are verified against numerical simulations of compressible mixing layers performed using the unified gas kinetic scheme for various degrees of rarefaction.

Assessing an aflatoxin exposure biomarker: Exploring the interchangeability and correlation between venous and capillary blood samples.

Exposure to dietary aflatoxins has been recognized as a potential threat to child nutrition and growth, in addition to being a known carcinogen. The ability to accurately assess concentration of aflatoxin in the blood of at-risk individuals is therefore very important to inform public health policies and on-the-ground programs around the world. Venous blood is frequently used to quantify biomarkers of exposure such as AFB1-lysine adducts. However, venous blood collection methods are invasive, requiring highly trained staff, which makes this method challenging to implement, especially in resource-limited settings. In contrast, capillary blood collection by fingerprick is less invasive and has the potential for application in point-of-need monitoring. The aim of this exploratory study was to investigate the correlation and interchangeability of capillary and venous human blood samples in the quantification of AFB1-lysine adduct concentration. A total of 72 venous and capillary blood samples were collected from 36 women of reproductive age (16-49 years) in northern Uganda. All sample specimens were analyzed using high-performance liquid chromatography with fluorescence detection. Regression analysis and Bland-Altman analysis were performed to compare AFB1-lysine concentrations between venous and capillary sample pairs. Bland-Altman analysis of albumin-normalized AFB1-lysine data-bias was -0.023 pg/mg-albumin and the 95% limits of agreement were 0.51 to -0.56 pg/mg-albumin for log-transformed data. There was a positive correlation between albumin-normalized venous and capillary AFB1-lysine concentrations with r of 0.71 (p < .0001). A lack of any accepted clinical cutoff for aflatoxin exposure makes definition of an 'acceptable' limit for statistical analysis and comparison of methods challenging. Our data suggests a positive correlation between albumin-normalized AFB1-lysine concentrations in venous and capillary sample pairs, but relatively weak agreement and interchangeability based on Bland-Altman analysis.

Continuum breakdown in compressible mixing layers.

Gas-kinetic simulations of rarefied and compressible mixing layers are performed to characterize continuum breakdown and the effect on the Kelvin-Helmholtz instability. The unified gas-kinetic scheme (UGKS) is used to perform the simulations at different Mach and Knudsen numbers. The UGKS stress tensor and heat-flux vector fields are compared against those given by the Navier-Stokes-Fourier constitutive equations. The most significant difference is seen in the shear stress and transverse heat flux. The study demonstrates the existence of two distinct continuum breakdown regimes, one at low and the other at high convective Mach numbers. Overall, at low convective Mach numbers, the deviation from continuum stress and heat flux appears to scale exclusively with the micro-macro length scale ratio given by the Knudsen number. On the other hand, at high convective Mach numbers, the deviation depends on the global micro-macro timescale ratio given by the product of Mach and Knudsen numbers. We further demonstrate that, unlike shear stresses and transverse heat flux, the deviations in normal stresses and the streamwise heat flux depend separately on Knudsen and Mach numbers. A local parameter called the gradient Knudsen number is proposed to characterize the rarefaction effects on the local momentum and thermal transport. Noncontinuum aspects of gas-kinetic stress-tensor and heat-flux behavior that Grad's 13-moment equation model reasonably captures are identified.

Portable Devices for Measurement of Vitamin A Concentrations in Edible Oil: Field Readiness of Available Options.

Vitamin A (VA) deficiency continues to be a major global health issue, despite measures to increase VA intake via consumption of staple foods such as edible oil. Portable quantitative and semiquantitative devices or test kits for internal quality control have the potential to overcome some of the limitations of traditional methods of testing, such as centralized laboratory, expensive equipment, and specially trained staff. This landscape analysis and comprehensive systematic mini-review catalogs and summarizes evidence on the analytical performance of portable quantitative and semiquantitative devices and test kits for the analysis of VA in edible oil. Studies or reports detailing the usability and validation of portable devices and/or test kits, as well as studies comparing device/test kit performance to a reference standard such as high-performance liquid chromatography (HPLC), were included. Identified devices and test kits were compared for performance versus the reference standard, usability, availability, and other characteristics. We identified four portable methods: two devices, the iCheck CHROMA and iCheck Chroma 3 from BioAnalyt; and two test kits, the QuickView from Bagco Enterprises and the Strategic Alliance for the Fortification of Vegetable Oils (SAFO) Test Kit by Badische Anilin and Soda Fabrik (BASF). Included studies reported the following: an internal validation of the portable method, a comparison of the portable method against a reference standard, a comparison of the portable method against another portable method, and several videos and company websites, which detailed device characteristics. iCheck CHROMA and QuickView quantified VA concentrations with high accuracy and precision compared to the reference standard for field-based quantification, were user-friendly, and provided results within 5 min. iCheck Chroma 3 requires more robust validation against a reference standard. We did not find data on internal validation or comparison against a reference standard for the current version of the SAFO test. Compared to QuickView and SAFO, the iCheck devices can transfer results to a hard drive or the Web, have an online order form for purchase, and meet a minimal set of criteria for point-of-need devices. iCheck, QuickView, and SAFO can quantify VA concentrations in the edible oils tested and determine whether a fortified oil meets country standards. Additional research is needed to validate these devices and test kits across additional oil types and document the ability to meet the minimal criteria for point-of-need devices suggested in this mini-review. Validation against a reference standard is required for SAFO. The limited number of portable methods available may be due to market saturation. Future market and use case analyses to inform the market size and utility of the different tests with publicly available data will allow new manufacturers, particularly those in lower-to-middle-income countries, to enter the market.

A diagnostic platform for rapid, simultaneous quantification of procalcitonin and C-reactive protein in human serum.

BACKGROUND: Early and accurate determination of bacterial infections as a potential cause for a patient's systemic inflammatory response is required for timely administration of appropriate treatment and antibiotic stewardship. Procalcitonin (PCT) and C-reactive protein (CRP) have both been used as biomarkers to infer bacterial infections, particularly in the context of sepsis. There is an urgent need to develop a platform for simultaneous quantification of PCT and CRP, to enable the potential use of these biomarkers at the point-of-care. METHODS: A multiplexed lateral flow assay (LFA) and a fluorescence optical reader were developed. Assay performance was validated by testing spiked antigens in the buffer, followed by a validation study comparing results with conventional assays (Roche Cobas e411 Elecsys PCT and Siemens ADVIA XPT CRP) in 25 archived remnant human serum samples. FINDINGS: A linear regression correlation of 0·97 (P < 0·01) was observed for PCT, and a correlation of 0·95 (P < 0·01) was observed for CRP using direct patient samples. We also validated our platform's ability to accurately quantify high-dose CRP in the hook effect range where excess unlabeled analytes occupy binding sites at test lines. INTERPRETATION: A fluorescence reader-based duplex LFA for simultaneous quantification of PCT and CRP was developed and successfully validated with clinical samples. The rapid, portable, and low-cost nature of the platform offers potential for differentiation of bacterial and viral infections in emergency and low-resource settings at the point-of-care. FUNDING: NIH/NIBIB Award 1R01EB021331, and Academic Venture Fund from the Atkinson Center for a Sustainable Future at Cornell University.

Point-of-Care Quantification of Serum Alpha-Fetoprotein for Screening Birth Defects in Resource-Limited Settings: Proof-of-Concept Study.

BACKGROUND: Maternal serum alpha-fetoprotein (MSAFP) concentration typically increases during pregnancy and is routinely measured during the second trimester as a part of screening for fetal neural tube defects and Down syndrome. However, most pregnancy screening tests are not available in the settings they are needed the most. A mobile device-enabled technology based on MSAFP for screening birth defects could enable the rapid screening and triage of high-risk pregnancies, especially where maternal serum screening and fetal ultrasound scan facilities are not easily accessible. Shifting the approach from clinic- and laboratory-dependent care to a mobile platform based on our point-of-care approach will enable translation to resource-limited settings and the global health care market. OBJECTIVE: The objective of this study is to develop and perform proof-of-concept testing of a lateral flow immunoassay on a mobile platform for rapid, point-of-care quantification of serum alpha-fetoprotein (AFP) levels, from a drop of human serum, within a few minutes. METHODS: The development of the immunoassay involved the selection of commercially available antibodies and optimization of their concentrations by an iterative method to achieve the required detection limits. We compared the performance of our method with that of commercially obtained human serum samples, with known AFP concentrations quantified by the Abbott ARCHITECT chemiluminescent magnetic microparticle immunoassay (CMIA). RESULTS: We tested commercially obtained serum samples (N=20) with concentrations ranging from 2.2 to 446 ng/mL to compare the results of our point-of-care assay with results from the Abbott ARCHITECT CMIA. A correlation of 0.98 (P<.001) was observed on preliminary testing and comparison with the CMIA. The detection range of our point-of-care assay covers the range of maternal serum AFP levels observed during pregnancy. CONCLUSIONS: The preliminary test results from the AFP test on the mobile platform performed in this study represent a proof of concept that will pave the way for our future work focused on developing a mobile device-enabled quad-screen point-of-care testing with the potential to enable the screening of high-risk pregnancies in various settings. The AFP test on the mobile platform can be applied to enable screening for high-risk pregnancies, within a few minutes, at the point of care even in remote areas where maternal serum tests and fetal ultrasound scans are not easily accessible; assessment of whether clinical follow-up and diagnostic testing may be needed after a positive initial screening evaluation; and development of surveillance tools for birth defects.

Measurement accuracy enhancement with multi-event detection using the deep learning approach in Raman distributed temperature sensors.

In this work, we present a novel deep learning framework for multi-event detection with enhanced measurement accuracy from the measured data of a Raman Optical Time Domain Reflectometer (Raman-OTDR). We demonstrate the utility of a deep learning-based approach by comparing the results from three popular neural networks, i.e. vanilla recurrent neural network (RNN), long short-term memory (LSTM), and gated recurrent unit (GRU). Before feeding the experimentally obtained data to the neural network, we sanitize our data through a correlation filtering operation to suppress outlier noise spikes. Based on experiments with Raman-OTDR traces consisting of single temperature event, we show that the GRU is able to provide better performance compared to RNN and LSTM models. Specifically, a bidirectional-GRU (bi-GRU) architecture is found to outperform other architectures owing to its use of data from both previous as well as later time steps. Although this feature is similar to that used recently in one dimension convolutional neural network (1D-CNN), the bi-GRU is found to be more effective in providing enhanced measurement accuracy while maintaining good spatial resolution. We also propose and demonstrate a threshold-based algorithm for accurate and fast estimation of multiple events. We demonstrate a 4x improvement in the spatial resolution compared to post-processing using conventional total variational denoising (TVD) filters, while the temperature accuracy is maintained within ± 0.5 oC of the set temperature.

Stimulated Brillouin scattering mitigation using optimized phase modulation waveforms in high power narrow linewidth Yb-doped fiber amplifiers.

We demonstrate the mitigation of stimulated Brillouin scattering (SBS) in a double-clad single mode Yb-doped optical fiber amplifier through external phase modulation of narrow linewidth laser radiation using optimized periodic waveforms from an arbitrary waveform generator. Such optimized phase modulation waveforms are obtained through a multi-objective Pareto optimization based on a comprehensive model for SBS in high power narrow linewidth fiber amplifiers using Brillouin parameters determined from controlled measurements. The ability of our approach to mitigate SBS is tested experimentally as a function of RMS linewidth of the modulated optical radiation, and we measure an enhancement in SBS threshold with respect to optical linewidth of ∼ 10 GHz-1. Furthermore, we discuss the dependence of the SBS threshold enhancement on key parameters such as the amplifier length and the period of the optimized waveforms. Through simulations we find that waveforms of sufficiently long periods and optimized for a relatively long fiber (10 m) are effective for SBS suppression for shorter fibers as well. We also investigate the effect of increase in the bandwidth and amplitude of the modulation waveform on the SBS threshold enhancement observed at higher optical linewidth.

Influence of Knudsen and Mach numbers on Kelvin-Helmholtz instability.

The combined influence of rarefaction and compressibility on classical Kelvin-Helmholtz instability is investigated with numerical simulations employing the unified gas kinetic scheme. Five different regimes in the Reynolds-Mach-Knudsen number parameter space are identified. The flow features in various Mach and Knudsen number regimes are examined. Stabilizing action of compressibility leads to suppression of perturbation kinetic energy and vorticity and/or momentum thickness. The suppression due to rarefaction exhibits a different behavior. At high enough Knudsen numbers, even as the perturbation kinetic energy is suppressed, the vorticity and/or momentum thickness grows. The flow physics underlying the contrasting mechanisms of compressibility and rarefaction is highlighted.

A generalized deep learning framework for whole-slide image segmentation and analysis.

Histopathology tissue analysis is considered the gold standard in cancer diagnosis and prognosis. Whole-slide imaging (WSI), i.e., the scanning and digitization of entire histology slides, are now being adopted across the world in pathology labs. Trained histopathologists can provide an accurate diagnosis of biopsy specimens based on WSI data. Given the dimensionality of WSIs and the increase in the number of potential cancer cases, analyzing these images is a time-consuming process. Automated segmentation of tumorous tissue helps in elevating the precision, speed, and reproducibility of research. In the recent past, deep learning-based techniques have provided state-of-the-art results in a wide variety of image analysis tasks, including the analysis of digitized slides. However, deep learning-based solutions pose many technical challenges, including the large size of WSI data, heterogeneity in images, and complexity of features. In this study, we propose a generalized deep learning-based framework for histopathology tissue analysis to address these challenges. Our framework is, in essence, a sequence of individual techniques in the preprocessing-training-inference pipeline which, in conjunction, improve the efficiency and the generalizability of the analysis. The combination of techniques we have introduced includes an ensemble segmentation model, division of the WSI into smaller overlapping patches while addressing class imbalances, efficient techniques for inference, and an efficient, patch-based uncertainty estimation framework. Our ensemble consists of DenseNet-121, Inception-ResNet-V2, and DeeplabV3Plus, where all the networks were trained end to end for every task. We demonstrate the efficacy and improved generalizability of our framework by evaluating it on a variety of histopathology tasks including breast cancer metastases (CAMELYON), colon cancer (DigestPath), and liver cancer (PAIP). Our proposed framework has state-of-the-art performance across all these tasks and is ranked within the top 5 currently for the challenges based on these datasets. The entire framework along with the trained models and the related documentation are made freely available at GitHub and PyPi. Our framework is expected to aid histopathologists in accurate and efficient initial diagnosis. Moreover, the estimated uncertainty maps will help clinicians to make informed decisions and further treatment planning or analysis.

Highly portable quantitative screening test for prostate-specific antigen at point of care.

Prostate cancer (PCa) is the second most diagnosed cancer among men. Targeted PCa screening may decrease PCa-specific mortality. Prostate-specific antigen (PSA) is the most reliable and widely accepted tumor biomarker for screening and monitoring PCa status. However, in many settings, quantification of serum PSA requires access to centralized laboratories. In this study, we describe a proof-of-concept rapid test combined with a highly portable Cube™ reader for quantification of total PSA from a drop of serum within 20 min. We demonstrated the application of gold nanoshells as a label for lateral flow assay with significant increase in the measured colorimetric signal intensity to achieve five times lower detection limit when compared to the traditionally used 40 nm gold nanosphere labels, without a need for any additional signal amplification steps. We first optimized and evaluated the performance of the assay with commercially available total PSA calibrators. For initial validation with commercially available ACCESS Hybritech PSA calibrator, a detection range of 0.5-150 ng/mL was achieved. We compared the performance of our total PSA test with IMMULITE analyzer for quantification of total PSA in archived human serum samples. On preliminary testing with archived serums samples and comparison with IMMULITE total PSA assay, a correlation of 0.95 (p < .0001) was observed. The highly portable quantitative screening test for PSA described in this study has the potential to make PCa screening more accessible where diagnostic labs and automated immunoassay systems are not available, to reduce therapeutic turnaround time, to streamline clinical care, and to direct patient care for both initial screening and for post-treatment monitoring of patients.

Current state of the art in rapid diagnostics for antimicrobial resistance.

Antimicrobial resistance (AMR) is a fundamental global concern analogous to climate change threatening both public health and global development progress. Infections caused by antimicrobial-resistant pathogens pose serious threats to healthcare and human capital. If the increasing rate of AMR is left uncontrolled, it is estimated that it will lead to 10 million deaths annually by 2050. This global epidemic of AMR necessitates radical interdisciplinary solutions to better detect antimicrobial susceptibility and manage infections. Rapid diagnostics that can identify antimicrobial-resistant pathogens to assist clinicians and health workers in initiating appropriate treatment are critical for antimicrobial stewardship. In this review, we summarize different technologies applied for the development of rapid diagnostics for AMR and antimicrobial susceptibility testing (AST). We briefly describe the single-cell technologies that were developed to hasten the AST of infectious pathogens. Then, the different types of genotypic and phenotypic techniques and the commercially available rapid diagnostics for AMR are discussed in detail. We conclude by addressing the potential of current rapid diagnostic systems being developed as point-of-care (POC) diagnostic tools and the challenges to adapt them at the POC level. Overall, this review provides an insight into the current status of rapid and POC diagnostic systems for AMR.

Hexosamine Pathway Activation Improves Protein Homeostasis through the Integrated Stress Response.

Activation of the hexosamine pathway (HP) through gain-of-function mutations in its rate-limiting enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) ameliorates proteotoxicity and increases lifespan in Caenorhabditis elegans. Here, we investigate the role of the HP in mammalian protein quality control. In mouse neuronal cells, elevation of HP activity led to phosphorylation of both PERK and eIF2α as well as downstream ATF4 activation, identifying the HP as a modulator of the integrated stress response (ISR). Increasing uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc) levels through GFAT1 gain-of-function mutations or supplementation with the precursor GlcNAc reduces aggregation of the polyglutamine (polyQ) protein Ataxin-3. Blocking PERK signaling or autophagy suppresses this effect. In C. elegans, overexpression of gfat-1 likewise activates the ISR. Consistently, co-overexpression of gfat-1 and proteotoxic polyQ peptides in muscles reveals a strong protective cell-autonomous role of the HP. Thus, the HP has a conserved role in improving protein quality control through modulation of the ISR.

A multiplexed in vitro assay system for evaluating human skeletal muscle functionality in response to drug treatment.

In vitro systems that mimic organ functionality have become increasingly important tools in drug development studies. Systems that measure the functional properties of skeletal muscle are beneficial to compound screening studies and also for integration into multiorgan devices. To date, no studies have investigated human skeletal muscle responses to drug treatments at the single myotube level in vitro. This report details a microscale cantilever chip-based assay system for culturing individual human myotubes. The cantilevers, along with a laser and photo-detector system, enable measurement of myotube contractions in response to broad-field electrical stimulation. This system was used to obtain baseline functional parameters for untreated human myotubes, including peak contractile force and time-to-fatigue data. The cultured myotubes were then treated with known myotoxic compounds and the resulting functional changes were compared to baseline measurements as well as known physiological responses in vivo. The collected data demonstrate the system's capacity for screening direct effects of compound action on individual human skeletal myotubes in a reliable, reproducible, and noninvasive manner. Furthermore, it has the potential to be utilized for high-content screening, disease modeling, and exercise studies of human skeletal muscle performance utilizing iPSCs derived from specific patient populations such as the muscular dystrophies.

Multi-point dynamic strain sensing using external modulation-based Brillouin optical correlation domain analysis.

We report a novel technique to detect dynamic strain variations simultaneously at multiple locations. Our technique is based on Brillouin optical correlation domain analysis implemented through external modulation to generate multiple independently-accessible correlation peaks within the sensing fiber. Experiments are carried out to demonstrate the precise determination of Brillouin frequency shift (BFS) from multiple locations independently. As a proof of principle, two correlation peaks are generated within a 1 km long fiber and their independent tunability is verified experimentally by mapping the spatial profile of the two correlations. We also experimentally demonstrate the detection of dynamic strain variations at two locations simultaneously, each with a spatial resolution of 60 cm over 100 m long fiber.

Raman amplification of optical beam carrying orbital angular momentum in a multimode step-index fiber.

We experimentally demonstrate 15 dB of Raman amplification of 1115 nm pulses in an orbital angular momentum mode (OAMM) with charge l=+2, S=+1 in 5 m of step-index 25 µm-diameter-core fiber. The total output reaches 4.5 kW of peak power and 68.5 µJ of energy in ∼15 ns pulses at 4 kHz repetition rate. An Yb-doped fiber source pumps the Raman amplifier at 1060 nm with 60 ns pulses. Using a spatial light modulator for modal decomposition, we measure 83% purity for the amplified target OAMM of selected polarization. To the best of our knowledge, this is the first time high energy, peak power, gain, and purity are achieved in a fiber Raman amplifier for a single OAMM.

Rapid diagnostics for point-of-care quantification of soluble transferrin receptor.

BACKGROUND: Iron deficiency (ID) and anaemia are major health concerns, particularly in young children. Screening for ID based on haemoglobin (Hb) concentration alone has been shown to lack sensitivity and specificity. The American Academy of Pediatrics (AAP) recommends soluble transferrin receptor (sTfR) as a promising approach to screen for iron deficiency. However, in most settings, assessment of iron status requires access to centralized laboratories. There is an urgent need for rapid, sensitive, and affordable diagnostics for sTfR at the point-of-care. METHODS: An immunochromatographic assay-based point-of-care screening device was developed for rapid quantification of sTfR from a drop of serum within a few minutes. Performance optimization of the assay was done in sTfR-spiked buffer and commercially available sTfR calibrator, followed by a small-scale proof-of-concept validation with archived serum samples. FINDINGS: On preliminary testing with archived serum samples and comparison with Ramco ELISA, a correlation of 0.93 (P < 0.0001) was observed, demonstrating its potential for point-of-care assessment of iron status. INTERPRETATION: The analytical performance of the point-of-care sTfR screening device indicates the potential for application in home-use test kits and field settings, especially in low- and middle-income settings. An added advantage of sTfR quantification in combination with our previously reported serum ferritin diagnostics is in integration of Cook's equation as a quantitative and minimally-invasive indicator of total body iron stores. FUND: Thrasher Research Fund (Early Career Award #13379), NIH R03 EB 023190, NSF grant #1343058, and Nutrition International (project #10-8007-CORNE-01).

High-yield paper-based quantitative blood separation system.

Interest in developing paper-based devices for point-of-care diagnostics in resource-limited settings has risen remarkably in recent decades. In this paper, we demonstrate what we refer to as "high yield passive rrythrocyte removal" (HYPER) technology, which utilizes capillary forces in a unique cross-flow filtration for the separation of whole blood with performance comparable to centrifuges. As we will demonstrate, state-of-the-art passive blood separation methods implemented in paper-based systems exhibit rapid blood cell clogging on the filtration media or serum outlet and yield only about 10-30% of the total serum present in the sample. Our innovation results from the inclusion of a differentiation pad, which exploits hydrodynamic effects to reduce the formation of a fouling layer on the blood filtration membrane resulting in more than 60% serum yield with undiluted whole blood as direct input. To demonstrate the effectiveness of the HYPER technology we implement it in a lateral flow system and demonstrate the accurate quantification of vitamin A and iron levels in whole blood samples in 15 minutes.

Multimode-pumped Raman amplification of a higher order mode in a large mode area fiber.

We report the first demonstration of Raman amplification in a fiber of a single Bessel-like higher order mode using a multimode pump source. We amplify the LP08-mode with a 559-µm2 effective mode area at a signal wavelength of 1115 nm in a pure-silica-core step-index fiber. A maximum of 18 dB average power gain is achieved in a 9-m long gain fiber, with output pulse energy of 115 µJ. The Raman pump source comprises a pulsed 1060 nm ytterbium-doped fiber amplifier with V-value ~30, which is matched to the Raman gain fiber. The pump depletion as averaged over the signal pulses reaches 36.7%. The conversion of power from the multimode pump into the signal mode demonstrates the potential for efficient brightness enhancement with low amplification-induced signal mode purity degradation.