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Estimation of cancer risk based on the organ-absorbed dose is underway for the Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE). The reconstruction method for the organ-absorbed dose follows the approach adopted in the IARC 15-Country Collaborative Study, which examined the dosemeter response to photon exposure for the old film badge (FB) type, a multi-element FB and a thermoluminescence dosemeter. Until 2000, the dosemeters used in Japan were almost the same in the IARC study, so IARC study data could be used as they were. However, since 2000, the type of dosemeter has been replaced with active personal dosemeters (hereafter called electronic personal dosemeters), radio-photoluminescent glass dosemeters (Glass badge) and optically stimulated luminescence dosemeters (Luminess badge). Hence, it was necessary to collect these data again. A dosemeter response experiment was conducted using a device that irradiated an anthropomorphic phantom in the Japan Atomic Energy Agency calibration laboratories. The aim of the paper is to provide a conversion factor from reading in terms of Hp(10) to air kerma for realistic conditions for further conversion from air kerma to organ-absorbed dose. The obtained dosemeter responses for the dosemeter types currently used in Japan were consistent with those in the IARC study. These data will be utilized for J-EPISODE in reconstructing the organ-absorbed dose.

Objective. Dual energy computed tomography (DECT) has been shown to provide additional image information compared to conventional CT and has been used in clinical routine for several years. The objective of this work is to present a DECT implementation for a Small Animal Radiation Research Platform (SARRP) and to verify it with a quantitative analysis of a material phantom and a qualitative analysis with an ex-vivo mouse measurement. Approach. For dual energy imaging, two different spectra are required, but commercial small animal irradiators are usually not optimized for DECT. We present a method that enables dual energy imaging on a SARRP with sequential scanning and an Empirical Dual Energy Calibration (EDEC). EDEC does not require the exact knowledge of spectra and attenuation coefficients; instead, it is based on a calibration. Due to the SARRP geometry and reconstruction algorithm, the calibration is done using an artificial CT image based on measured values. The calibration yields coefficients to convert the measured images into material decomposed images. Main results. To analyze the method quantitatively, the electron density and the effective atomic number of a material phantom were calculated and compared with theoretical values. The electron density showed a maximum deviation from the theoretical values of less than 5% and the atomic number of slightly more than 6%. For use in mice, DECT is particularly useful in distinguishing iodine contrast agent from bone. A material decomposition of an ex-vivo mouse with iodine contrast agent was material decomposed to show that bone and iodine can be distinguished and iodine-corrected images can be calculated. Significance. DECT is capable of calculating electron density images and effective atomic number images, which are appropriate parameters for quantitative analysis. Furthermore, virtual monochromatic images can be obtained for a better differentiation of materials, especially bone and iodine contrast agent.

We describe a laser-plasma platform for photon-photon collision experiments to measure fundamental quantum electrodynamic processes such as the linear Breit-Wheeler process with real photons. The platform has been developed using the Gemini laser facility at the Rutherford Appleton Laboratory. A laser wakefield accelerator and a bremsstrahlung convertor are used to generate a collimated beam of photons with energies of hundreds of MeV, that collide with keV x-ray photons generated by a laser heated plasma target. To detect the pairs generated by the photon-photon collisions, a magnetic transport system has been developed which directs the pairs onto scintillation-based and hybrid silicon pixel single particle detectors. We present commissioning results from an experimental campaign using this laser-plasma platform for photon-photon physics, demonstrating successful generation of both photon sources, characterisation of the magnetic transport system and calibration of the single particle detectors, and discuss the feasibility of this platform for the observation of the Breit-Wheeler process. The design of the platform will also serve as the basis for the investigation of strong-field quantum electrodynamic processes such as the nonlinear Breit-Wheeler and the Trident process, or eventually, photon-photon scattering. We describe a laser–plasma platform for photon–photon collision experiments to measure fundamental quantum electrodynamic processes. As an example we describe using this platform to attempt to observe the linear Breit–Wheeler process. The platform has been developed using the Gemini laser facility at the Rutherford Appleton Laboratory. A laser Wakefield accelerator and a bremsstrahlung convertor are used to generate a collimated beam of photons with energies of hundreds of MeV, that collide with keV x-ray photons generated by a laser heated plasma target. To detect the pairs generated by the photon–photon collisions, a magnetic transport system has been developed which directs the pairs onto scintillation-based and hybrid silicon pixel single particle detectors (SPDs). We present commissioning results from an experimental campaign using this laser–plasma platform for photon–photon physics, demonstrating successful generation of both photon sources, characterisation of the magnetic transport system and calibration of the SPDs, and discuss the feasibility of this platform for the observation of the Breit–Wheeler process. The design of the platform will also serve as the basis for the investigation of strong-field quantum electrodynamic processes such as the nonlinear Breit–Wheeler and the Trident process, or eventually, photon–photon scattering.

Proteinuria is a condition in which an excessive amount of protein is excreted in urine. It is, among others, an indicator of kidney disease or risk of cardiovascular disease. Rapid and reliable diagnosis and monitoring of proteinuria is of great importance for both patients and their physicians. For that reason, a paper-based sensor for proteinuria diagnosis was designed, optimized, and validated utilizing smartphone-assisted signal acquisition. In the first step, a few commonly employed protein assays were optimized and compared in terms of analytical performance on paper matrix. The tetrabromophenol blue method was selected as the one providing a sufficiently low limit of detection (39 mg·L−1) on the one hand and appropriate long-term stability (up to 3 months) on the other hand. The optimized assay was employed for protein-to-creatinine ratio (PCR) determination on a single paper-based sensor. For both analytes the linear ranges were within the clinically relevant range. The analytical usefulness of the developed sensors was demonstrated by a PCR recovery study in artificial urine. The obtained PCR recoveries were from ca. 80 to 150%.

Significance: Fourier ptychography microscopy (FPM) is a computational optical imaging technology that employs angularly varying illuminations and a phase retrieval algorithm to achieve a wide field of view and high-resolution imaging simultaneously. In the FPM, LED position error will reduce the quality of the reconstructed high-resolution image. To correct the LED positions, current methods consider each of the LED positions as independent and use an optimization algorithm to get each of the positions. When the positional misalignment is large or the search position falls into a local optimal value, the current methods may lack stability and accuracy. Aim: We improve the model of the LED position and propose an accurate and stable two-step correction scheme (tcFPM) to calibrate the LED position error. Approach: The improved LED positions model combines the overall offset, which represents the relative deviation of the LED array and the optical axis, with the slight deviation of each LED’s independent position. In the tcFPM, the overall offset of the LED array is corrected at first, which obtains an approximate value of the overall offset of the LED array. Then the position of each LED is precisely adjusted, which obtains the slight offset of each LED. Results: This LED position error model is more in line with the actual situation. The simulation and experimental results show that the method has high accuracy in correcting the LED position. Furthermore, the reconstruction process of tcFPM is more stable and significantly improves the quality of the reconstruction results, which is compared with some LED position error correction methods. Conclusions: An LED position error correction technology is proposed, which has a stable iterative process and improves the reconstruction accuracy of complex amplitude.

Significance: As linear array transducers are widely used in clinical ultrasound imaging, photoacoustic tomography (PAT) with linear arrays is similarly suitable for clinical applications. However, due to the limited-view problem, a linear array has limited performance and leads to artifacts and blurring, which has hindered its broader application. There is a need to address the limited-view problem in PAT imaging with linear arrays. Aim: We investigate potential approaches for improving PAT reconstruction from linear array, by optimizing the detection geometry and implementing iterative reconstruction. Approach: PAT imaging with a single-array, dual-probe configurations in parallel-shape and L-shape, and square-shape configuration are compared in simulations and phantom experiments. An iterative model-based algorithm based on the variance-reduced stochastic gradient descent (VR-SGD) method is implemented. The optimum configuration found in simulation is validated on phantom experiments. Results: PAT imaging with dual-probe detection and VR-SGD algorithm is found to improve the limited-view problem compared to a single probe and provide comparable performance as full-view geometry in simulation. This configuration is validated in experiments where more complete structure is obtained with reduced artifacts compared with a single array. Conclusions: PAT with dual-probe detection and iterative reconstruction is a promising solution to the limited-view problem of linear arrays.

Proton imaging is a promising technology for proton radiotherapy as it can be used for: (1) direct sampling of the tissue stopping power, (2) input information for multi-modality RSP reconstruction, (3) gold-standard calibration against concurrent techniques, (4) tracking motion and (5) pre-treatment positioning. However, no end-to-end characterization of the image quality (signal-to-noise ratio and spatial resolution, blurring uncertainty) against the dose has been done. This work aims to establish a model relating these characteristics and to describe their relationship with proton energy and object size. The imaging noise originates from two processes: the Coulomb scattering with the nucleus, producing a path deviation, and the energy loss straggling with electrons. The noise is found to increases with thickness crossed and, independently, decreases with decreasing energy. The scattering noise is dominant around high-gradient edge whereas the straggling noise is maximal in homogeneous regions. Image quality metrics are found to behave oppositely against energy: lower energy minimizes both the noise and the spatial resolution, with the optimal energy choice depending on the application and location in the imaged object. In conclusion, the model presented will help define an optimal usage of proton imaging to reach the promised application of this technology and establish a fair comparison with other imaging techniques.

Heavy metals are highly toxic at trace levels and their pollution has shown great threat to the environment and public health worldwide where current detection methods require expensive instrumentation and laborious operation, which can only be accomplished in centralized laboratories. Herein, we report a low-cost, paper-based microfluidic analytical device (μPAD) for facile, portable, and disposable monitoring of mercury, lead, chromium, nickel, copper, and iron ions. Triple indicators or ligands that contain ions or molecules are preloaded on the μPADs and upon addition of a metal ion, the colorimetric indicators will elicit color changes observed by the naked eyes. The color features were quantitatively analyzed in a three-dimensional space of red, green, and blue or the RGB-space using digital imaging and color calibration techniques. The sensing platform offers higher accuracy for cross references, and is capable of simultaneous detection and discrimination of different metal ions in even real water samples. It demonstrates great potential for semiquantitative and even qualitative analysis with a sensitivity below the safe limit concentrations, and a controlled error range.

Significance Rehabilitation through facial prostheses' main goal is to aid individual's social reintegration as well as improving their quality of life. However, this treatment is not yet widely available in Brazil due to the lack of specialized clinics and the cost associated with the high number of necessary medical appointments until the final result. One of the steps in the process consists of measuring skin color, which is observer-dependent and may suffer from the effect of metamerism. Aim The methodology of our work aims to obtain a standard between different devices and greater fidelity to the color seen in person in order to reduce face-to-face iterations, reduce costs, and ensure better final results. Approach A physical device and a computer program were improved from previous projects. The changes included implementing the Thin-Plate Spline 3D algorithm for color calibration, in addition to an optional non-uniform illumination correction in the process. We also aim to improve the project's accessibility using a colorimeter. The methodology and the algorithms were both compared to readings from direct skin measurements as well as color references. Results After processing, the ΔEab* metric between images from the same segments is taken with different cameras and conditions of illumination decreased from 18.81 ± 4.85 to 4.85 ± 1.72. In addition, when the images were compared to colorimetric readings of the skin, the difference went from 14.93 ± 4.11 to 5.85 ± 1.61. It was also observed that using a less expensive device did not impact the readings. The project is open source and available at Github. Conclusions The results demonstrate the possibility of applying the methodology to assist in the manufacturing of facial prostheses to decrease the total number of consultations, in addition to providing greater reliability of the final result.

Purpose: We investigated the performance of a neural network (NN) material decomposition method under varying pileup conditions. Approach: Experiments were performed at tube current settings that provided count rates incident on the detector through air equal to 9%, 14%, 27%, 40%, and 54% of the maximum detector count rate. An NN was trained for each count-rate level using transmission measurements through known thicknesses of basis materials (PMMA and aluminum). The NN trained for each count-rate level was applied to x-ray transmission measurements through test materials and to CT data of a rod phantom. Material decomposition error was evaluated as the distance in basis material space between the estimated thicknesses and ground truth. Results: There was no clear trend between count-rate level and material decomposition error for all test materials except neoprene. As an example result, Teflon error was 0.33 cm at the 9% count-rate level and 0.12 cm at the 54% count-rate level for the x-ray transmission experiments. Decomposition error increased with count-rate level for the neoprene test case, with 0.65-cm error at 9% count-rate level and 1.14-cm error at the 54% count-rate level. In the CT study, material decomposition error decreased with increasing incident count rate. For example, the material decomposition error for Teflon was 0.089, 0.066, 0.054 at count-rate levels of 14%, 27%, and 40%, respectively. Conclusions: Results demonstrate over a range of incident count-rate levels that an NN trained at a specific count-rate level can learn the relationship between photon-counting spectral measurements and basis material thicknesses.

Significance: Oxygenation is one of the skin tissue physiological properties to follow for patient care management. Furthermore, long-term monitoring of such parameters is needed at the patient bed as well as outside the hospital. Diffuse reflectance spectroscopy has been widely used for this purpose. Aim: The aim of the study is to propose a low-cost system for the long-term measurement of skin physiological parameters in contact. Approach: We have developed a low-cost, wearable, CMOS-based device. We propose an original method for processing diffuse reflectance data to calculate the tissue oxygen saturation (StO2). Results: We tested the device for the assessment of tissue oxygenation during a first-in-human clinical trial that took place at the Grenoble University Hospital France. Conclusions: The results of this clinical trial show a good accordance between our sensor and commercial devices used a reference.

Contains fulltext : 224762.pdf (Publisher’s version ) (Open Access) Forensic firearm examination provides the court of law with information about the source of fired cartridge cases. We assessed the validity of source decisions of a computer-based method and of 73 firearm examiners who compared breechface and firing pin impressions of 48 comparison sets. We also compared the computer-based method's comparison scores with the examiners' degree-of-support judgments and assessed the validity of the latter. The true-positive rate (sensitivity) and true-negative rate (specificity) of the computer-based method (for the comparison of both the breechface and firing pin impressions) were 94.4% and at least 91.7%, respectively. For the examiners, the true-positive rate was at least 95.3% and the true-negative rate was at least 86.2%. The validity of the source decisions improved when the evaluations of breechface and firing pin impressions were combined and for the examiners also when the perceived difficulty of the comparison decreased. The examiners were reluctant to provide source decisions for 'difficult' comparisons even though their source decisions were mostly correct. The correlation between the computer-based method's comparison scores and the examiners' degree-of-support judgments was low for the same-source comparisons to negligible for the different-source comparisons. Combining the outcomes of computer-based methods with the judgments of examiners could increase the validity of firearm examinations. The examiners' numerical degree-of-support judgments for their source decisions were not well-calibrated and showed clear signs of overconfidence. We suggest studying the merits of performance feedback to calibrate these judgments. 16 p.

While current trends in Green Analytical Chemistry aim at reducing or simplifying sample treatment, food usually comprises complex matrices where direct analysis is not possible in most cases. In this context, sample treatment plays a pivotal role. Biogenic amines are naturally formed in many foodstuffs due to the action of microorganisms, while their presence has been associated with adverse health effects. In this work, the extraction of seven biogenic amines (cadaverine, histamine, phenylethylamine, putrescine, spermidine, spermine, and tyramine) from beer samples has been simplified using laboratory filter paper as sorbent without any further modification. The analysis of the eluates by direct infusion mass spectrometry reduces the time of analysis, increasing the sample throughput. This simple but effective method enabled the determination of the analytes with limits of detection as low as 0.06 mg•L−1 and relative standard deviations better than 11.9 %. The suitability of the method has been assessed by analyzing eight different types of beers by the standard addition method.

Purpose: Hyperspectral imaging (HSI) is a non-contact optical imaging technique with the potential to serve as an intraoperative computer-aided diagnostic tool. Our work analyzes the optical properties of visible structures in the surgical field for automatic tissue categorization. Approach: Building an HSI-based computer-aided tissue analysis system requires accurate ground truth and validation of optical soft tissue properties as these show large variability. We introduce and validate two different hyperspectral intraoperative imaging setups and their use for the analysis of optical tissue properties. First, we present an improved multispectral filter-wheel setup integrated into a fully digital microscope. Second, we present a novel setup of two hyperspectral snapshot cameras for intraoperative usage. Both setups are operating in the spectral range of 400 up to 975 nm. They are calibrated and validated using the same database and calibration set. Results: For validation, a color chart with 18 well-defined color spectra in the visual range is analyzed. Thus the results acquired with both settings become transferable and comparable to each other as well as between different interventions. On patient data of two different otorhinolaryngology procedures, we analyze the optical behaviors of different soft tissues and show a visualization of such different spectral information. Conclusion: The introduced calibration pipeline for different HSI setups allows comparison between all acquired spectral information. Clinical in vivo data underline the potential of HSI as an intraoperative diagnostic tool and the clinical usability of both introduced setups. Thereby, we demonstrate their feasibility for the in vivo analysis and categorization of different human soft tissues.

A colorimetric paper-based enzyme-coupled antimony tin oxide nanoparticle (ATONP) nanobiosensor for selective detection of Cd

Significance: Diffuse reflectance spectroscopy (DRS) is frequently used to assess oxygen saturation and hemoglobin concentration in living tissue. Methods solving the inverse problem may include time-consuming nonlinear optimization or artificial neural networks (ANN) determining the absorption coefficient one wavelength at a time. Aim: To present an ANN-based method that directly outputs the oxygen saturation and the hemoglobin concentration using the shape of the measured spectra as input. Approach: A probe-based DRS setup with dual source-detector separations in the visible wavelength range was used. ANNs were trained on spectra generated from a three-layer tissue model with oxygen saturation and hemoglobin concentration as target. Results: Modeled evaluation data with realistic measurement noise showed an absolute root-mean-square (RMS) deviation of 5.1% units for oxygen saturation estimation. The relative RMS deviation for hemoglobin concentration was 13%. This accuracy is at least twice as good as our previous nonlinear optimization method. On blood-intralipid phantoms, the RMS deviation from the oxygen saturation derived from partial oxygen pressure measurements was 5.3% and 1.6% in two separate measurement series. Results during brachial occlusion showed expected patterns. Conclusions: The presented method, directly assessing oxygen saturation and hemoglobin concentration, is fast, accurate, and robust to noise. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Funding Agencies|Swedish Research CouncilSwedish Research Council [2014-6141]; Swedens innovation agency VINNOVA via the program MedTech4Health [2016-02211]; Swedens innovation agency VINNOVA via the program Swelife and MedTech4Health [2017-01435]

Significance: Spatial frequency domain imaging (SFDI) is a quantitative imaging method to measure absorption and scattering of tissue, from which several chromophore concentrations (e.g., oxy-/deoxy-/meth-hemoglobin, melanin, and carotenoids) can be calculated. Employing a method to extract additional spectral bands from RGB components (that we named cross-channels), we designed a handheld SFDI device to account for these pigments, using low-cost, consumer-grade components for its implementation and characterization. Aim: With only three broad spectral bands (red, green, blue, or RGB), consumer-grade devices are often too limited. We present a methodology to increase the number of spectral bands in SFDI devices that use RGB components without hardware modification. Approach: We developed a compact low-cost RGB spectral imager using a color CMOS camera and LED-based mini projector. The components’ spectral properties were characterized and additional cross-channel bands were calculated. An alternative characterization procedure was also developed that makes use of low-cost equipment, and its results were compared. The device performance was evaluated by measurements on tissue-simulating optical phantoms and in-vivo tissue. The measurements were compared with another quantitative spectroscopy method: spatial frequency domain spectroscopy (SFDS). Results: Out of six possible cross-channel bands, two were evaluated to be suitable for our application and were fully characterized (520 ± 20 nm; 556 ± 18 nm). The other four cross-channels presented a too low signal-to-noise ratio for this implementation. In estimating the optical properties of optical phantoms, the SFDI data have a strong linear correlation with the SFDS data (R2 = 0.987, RMSE = 0.006 for μa, R2 = 0.994, RMSE = 0.078 for μs′). Conclusions: We extracted two additional spectral bands from a commercial RGB system at no cost. There was good agreement between our device and the research-grade SFDS system. The alternative characterization procedure we have presented allowed us to measure the spectral features of the system with an accuracy comparable to standard laboratory equipment. Funding agencies: Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation

Significance: Spatial frequency domain imaging (SFDI) is a diffuse optical measurement technique that can quantify tissue optical absorption (μa) and reduced scattering (μ0 s) on a pixelby-pixel basis. Measurements of μa at different wavelengths enable the extraction of molar concentrations of tissue chromophores over a wide field, providing a noncontact and label-free means to assess tissue viability, oxygenation, microarchitecture, and molecular content. We present here openSFDI: an open-source guide for building a low-cost, small-footprint, threewavelength SFDI system capable of quantifying μa and μ0 s as well as oxyhemoglobin and deoxyhemoglobin concentrations in biological tissue. The companion website provides a complete parts list along with detailed instructions for assembling the openSFDI system. Aim: We describe the design of openSFDI and report on the accuracy and precision of optical property extractions for three different systems fabricated according to the instructions on the openSFDI website. Approach: Accuracy was assessed by measuring nine tissue-simulating optical phantoms with a physiologically relevant range of μa and μ0 s with the openSFDI systems and a commercial SFDI device. Precision was assessed by repeatedly measuring the same phantom over 1 h. Results: The openSFDI systems had an error of 0 6% in μa and −2 3% in μ0 s, compared to a commercial SFDI system. Bland–Altman analysis revealed the limits of agreement between the two systems to be 0.004 mm−1 for μa and −0.06 to 0.1 mm−1 for μ0 s. The openSFDI system had low drift with an average standard deviation of 0.0007 mm−1 and 0.05 mm−1 in μa and μ0 s, respectively. Conclusion: The openSFDI provides a customizable hardware platform for research groups seeking to utilize SFDI for quantitative diffuse optical imaging. Funding agencies: U.S. Department of Defense (DoD)United States Department of Defense [W81XWH-15-1-0070]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; European Research Council under the European UnionEuropean Research Council (ERC) [715737]; Fre

A thermal calorimetric apparatus was designed, built and calibrated for measuring the activity of the artificial 144 Ce —144 Pr antineutrino source. This measurement will be performed at the Laboratori Nazionali del Gran Sasso in Italy, just before the source insertion in the tunnel under the Borexino detector and a precision better than 1% is required for a disappearance technique measurement in the SOX (Short distance neutrino Oscillation with BoreXino) project. In this work the apparatus is described and the most important results from the calibration measurements are shown, where the final precision of few per thousand is demonstrated.

Dialkyl diketene dimers are used as sizing agents in the manufacture of paper and board for food contact applications to increase wetting stability. Unbound residues can hydrolyze and decarboxylate into dialkylketones. These non-intentionally added substances (NIAS) have potential to migrate to fatty foods in contact with those packaging materials. In Germany, the Federal Institute for Risk Assessment (BfR) established a specific migration limit (SML) of 5 mg/kg for the transfer of these dialkylketones into foodstuffs. In order to investigate the differences between simulants and real foods, an analytical method was optimized for extraction and quantification of dialkylketones in edible oils and fatty foods by gas chromatography coupled with flame ionization detection (GC-FID), and additionally by gas chromatography with mass spectrometry (GC-MS), to confirm their identification and to quantify them in case of interferences. Dialkylketones are separated from the extracted fat by alkaline saponification of the triglycerides. Dialkylketones migration from paper-based food contact articles into organic solvents isooctane and dichloromethane, in olive and sunflower oils, and in fatty foods (croissants, Gouda, cheddar cheese, and salami was studied). As a result, it was found that the simulating tests, including the edible oil extraction tests, gave migration values that exceeded the SML largely, while the migration with the food samples were largely below the SML. Antía Lestido Cardama is grateful for her predoctoral grant “Programa de axudas á etapa predoutoral” da Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) SI

In order to assess the moisture content of wood chips on an industrial scale, readily applicable techniques are required. Thus, near infrared (NIR) spectroscopy was used to estimate moisture in wood chips by means of partial least squares regressions. NIR spectra were obtained in spectrometer with an integrating sphere and optical fiber probe, on the longitudinal and transverse surface of Eucalyptus wood chips. The specimens had their masses and NIR spectra measured in 10 steps during drying from saturated to anhydrous condition. Principal Component Analysis was performed to explore the effect of moisture of wood chip on NIR signatures. The values of moisture content of chips were associated with the respective NIR spectra by Partial Least Squares Regression (PLS-R) and Partial Least Squares Discriminant Analysis (PLS-DA) to estimate the moisture content of wood chips and its moisture classes, respectively. Model developed from spectra recorded on the longitudinal face by the integrating sphere method presented statistics slightly better (R²cv = 0,96; RMSEcv = 7,15 %) than model based on optical fiber probe (R²cv = 0,90; RMSEcv = 11,86 %). This study suggests that for calibration of robust predictive model for estimating moisture content in chips the spectra should be recorded on the longitudinal surface of wood using the integrating sphere acquisition method.

A novel strategy for fabricating the paper-based valves on microfluidic paper-based analytical devices (μPADs) was described to control fluid in a user-friendly way. Initial prototypes of 3D μPADs manipulate the spatial distribution of fluid within the device. The movable paper channel in a different layer could be achieved using the channel's connection or disconnection to realize the valve function using plastic comb binding spines (PCBS). The entire valve manipulation process was similar to a desk calendar that can be flipped over and turned back. It is notable that this kind of PCBS valve can control a fluid in a simple and easy way without the timing setting or any trigger, and this advantage makes it user-friendly for untrained users to carry out the complex and high throughput operations. The reusable plastic comb binding spines greatly reduce the cost of fabricating paper-based valves. To evaluate the performance, the actual samples of Fe (II) and nitrite were successfully analyzed. We hope this method will introduce a new approach to fabrication of paper-based valves on μPADs in the future.

Near-infrared spectroscopy (NIRS) to monitor muscle oxygen saturation (SmO2) is rapidly expanding into applied sports settings. However, the technology is limited due to its inability to convey quantifiable values. A test battery to assess reliability and validity of a 0% to 100% scale modeled by a commercially available NIRS device was established. This test battery applies a commonly used technique, the arterial occlusion method (AOM) to assess repeatability, reproducibility, and face validity. A total of 22 participants completed the test battery to scrutinize the 0% to 100% scale provided by the device. All participants underwent repeated AOM tests in passive and active conditions. The SmO2 minimum and SmO2 maximum values were obtained from the AOM and were used in the subsequent analysis. Repeatability and reproducibility were tested for equivalency and Bland–Altman plots were generated. Face validity was assessed by testing SmO2 values against an a priori defined threshold for mixed venous blood during AOM response. The device exhibits an appropriately functional 0% to 100% scale that is reliable in terms of repeatability and reproducibility. Under the conditions applied in the test battery design, the device is considered valid for application in sports.

The capabilities of electret ion chambers (EICs) to measure mean ambient dose equivalent rates were investigated by performing both laboratory and field studies of their properties. First, EICs were ‘calibrated’ to measure ambient gamma dose equivalent in the Ionizing Calibration Laboratory of the Greek Atomic Energy Commission. The EICs were irradiated with different gamma photon energies and from different angles. Calibration factors were deduced (electret’s voltage drop due to irradiation in terms of ambient dose equivalent). In the field studies, EICs were installed at eight locations belonging to the Greek Early Warning System Network (which is based on Reuter-Stokes ionization chambers) for three periods, averaging 5 months each. In the same locations, in situ gamma spectrometry measurements were performed with portable germanium detectors. Gamma ambient dose equivalent rates were deduced by the in situ gamma spectrometry measurements and by soil sample analysis. The mean daily electret potential drop (in Volts) was compared with the mean daily ambient dose equivalent, measured with a portable HPGe detector and Reuter-Stokes high-pressure ionization chambers. From these measurements, ‘field’ calibration factors (electret’s voltage drop due to gamma radiation in terms of ambient dose equivalent) were deduced and found in very good agreement with the values deduced in Laboratory. The influence of cosmic radiation and the intrinsic voltage loss when performing long-term environmental gamma measurements with EICs, was estimated.

Immunoassays and high-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) are both widely used methods for drug screening in toxicology. We investigated an alternative approach for rapid drug screening: paper spray MS (PS-MS). In paper spray, the biofluid sample is spotted onto a paper substrate. Upon application of a spray solvent and an electric potential, extraction and ionization occur directly from the paper without any need for additional sample preparation. We developed two paper spray high-resolution MS/MS targeted drug screening assays using a quadrupole-orbitrap mass spectrometer, one the positive ion mode and one in the negative ion mode. In the positive ion mode, over 130 drugs and drug metabolites were semi-quantitatively screened at sub-toxic concentrations in a single 2.5 min analysis. Limits of detection and calibration performances for each target compound are reported. The PS-MS/MS assay was tested on authentic postmortem specimens, and its screening ability and semi-quantitative performance were evaluated against independent LC-MS-MS screening and confirmation assays with good agreement. The paper spray MS/MS showed good qualitative agreement with LC-MS-MS; the true positive rate of paper spray MS/MS was 92%, and the true negative rate was over 98%. The quantitative results between the two methods were also acceptable for a screening application; Passing-Bablok regression yielded a slope of 1.17 and a Pearson's correlation coefficient of 0.996. A separate PS-MS/MS negative ion screening method was also developed for a small panel of barbiturates and structural analogs, demonstrating its potential for acidic drug detection and screening.

Measurement of ultraviolet (UV) radiation is important for human health, especially with the expanded usage of short wavelength UV for sterilization purposes. This work examines unlaminated Gafchromic EBT3 film for UV radiation monitoring. The authors exposed the film to select wavelengths in the UV spectrum, ranging from 207 to 328 nm, and measured the change in optical density. The response of the film is wavelength dependent, and of the wavelengths tested, the film was most sensitive to 254 nm light, with measurable values as low as 10 µJ/cm2. The film shows a dose-dependent response that extends over more than four orders of magnitude. The response of the film to short wavelength UV is comparable to the daily safe exposure limits for humans, thus making it valuable as a tool for passive UV radiation monitoring.

We demonstrate the possibility of measuring FRET efficiency with a low-cost frequency-domain fluorescence lifetime imaging microscope (FD-FLIM). The system utilizes single-frequency-modulated excitation, which enables the use of cost-effective laser sources and electronics, simplification of data acquisition and analysis, and a dual-channel detection capability. Following calibration with coumarin 6, we measured the apparent donor lifetime in mTFP1-mVenus FRET standards expressed in living cells. We evaluated the system's sensitivity by differentiating the short and long lifetimes of mTFP1 corresponding to the known standards' high and low FRET efficiency, respectively. Furthermore, we show that the lifetime of the vinculin tension sensor, VinTS, at focal adhesions (2.30 ± 0.16 ns) is significantly (p l 10 - 6) longer than the lifetime of the unloaded TSMod probe (2.02 ± 0.16 ns). The pixel dwell time was 6.8 μs for samples expressing the FRET standards, with signal typically an order of magnitude higher than VinTS. The apparent FRET efficiency ( E FRET app ) of the standards, calculated from the measured apparent lifetime, was linearly related to their known FRET efficiency by a factor of 0.92 to 0.99 (R2 = 0.98). This relationship serves as a calibration curve to convert apparent FRET to true FRET and circumvent the need to measure multiexponential lifetime decays. This approach yielded a FRET efficiency of 18% to 19.5%, for VinTS, in agreement with published values. Taken together, our results demonstrate a cost-effective, fast, and sensitive FD-FLIM approach with the potential to facilitate applications of FLIM in mechanobiology and FRET-based biosensing.

Accurate assessment of burn severity is critical for wound care and the course of treatment. Delays in classification translate to delays in burn management, increasing the risk of scarring and infection. To this end, numerous imaging techniques have been used to examine tissue properties to infer burn severity. Spatial frequency-domain imaging (SFDI) has also been used to characterize burns based on the relationships between histologic observations and changes in tissue properties. Recently, machine learning has been used to classify burns by combining optical features from multispectral or hyperspectral imaging. Rather than employ models of light propagation to deduce tissue optical properties, we investigated the feasibility of using SFDI reflectance data at multiple spatial frequencies, with a support vector machine (SVM) classifier, to predict severity in a porcine model of graded burns. Calibrated reflectance images were collected using SFDI at eight wavelengths (471 to 851 nm) and five spatial frequencies (0 to 0.2 mm−1). Three models were built from subsets of this initial dataset. The first subset included data taken at all wavelengths with the planar (0 mm−1) spatial frequency, the second comprised data at all wavelengths and spatial frequencies, and the third used all collected data at values relative to unburned tissue. These data subsets were used to train and test cubic SVM models, and compared against burn status 28 days after injury. Model accuracy was established through leave-one-out cross-validation testing. The model based on images obtained at all wavelengths and spatial frequencies predicted burn severity at 24 h with 92.5% accuracy. The model composed of all values relative to unburned skin was 94.4% accurate. By comparison, the model that employed only planar illumination was 88.8% accurate. This investigation suggests that the combination of SFDI with machine learning has potential for accurately predicting burn severity.

Ultrasound (US) guided diffuse optical tomography has demonstrated great potential for breast cancer diagnosis, treatment monitoring, and chemotherapy response prediction. Optical measurements of four different wavelengths are used to reconstruct unknown optical absorption maps, which are then used to calculate the hemoglobin concentration distribution of the US visible lesion. Reconstructed absorption maps are prone to image artifacts from outliers in measurement data from tissue heterogeneity, bad coupling between tissue and light guides, and motion by patient or operator. We propose an automated iterative perturbation correction algorithm to reduce image artifacts based on the structural similarity index (SSIM) of absorption maps of four optical wavelengths. The initial image is estimated from the truncated pseudoinverse solution. The SSIM was calculated for each wavelength to assess its similarity with other wavelengths. An absorption map is repeatedly reconstructed and projected back into measurement space to quantify projection error. Outlier measurements with highest projection errors are iteratively removed until all wavelength images are structurally similar with SSIM values greater than a threshold. Clinical data demonstrate statistically significant improvement in image artifact reduction.

Calcium imaging is emerging as a popular technique in neuroscience. A major reason is that intracellular calcium transients are reflections of electrical events in neurons. For example, calcium influx in the soma and axonal boutons accompanies spiking activity, whereas elevations in dendrites and dendritic spines are associated with synaptic inputs and local regenerative events. However, calcium transients have complex spatiotemporal dynamics, and since most optical methods visualize only one of the somatic, axonal, and dendritic compartments, a straightforward inference of the underlying electrical event is typically challenging. We highlight experiments that have directly calibrated in vivo calcium signals recorded using fluorescent indicators against electrophysiological events. We address commonly asked questions such as: Can calcium imaging be used to characterize neurons with high firing rates? Can the fluorescent signal report a decrease in spiking activity? What is the evidence that calcium transients in subcellular compartments correspond to distinct presynaptic axonal and postsynaptic dendritic events? By reviewing the empirical evidence and limitations, we suggest that, despite some caveats, calcium imaging is a versatile method to characterize a variety of neuronal events in vivo.

Mapping flows in vivo is essential for the investigation of cardiovascular pathologies in animal models. The limitation of optical-based methods, such as space-time cross correlation, is the scattering of light by the connective and fat components and the direct wave front distortion by large inhomogeneities in the tissue. Nonlinear excitation of the sample fluorescence helps us by reducing light scattering in excitation. However, there is still a limitation on the signal-background due to the wave front distortion. We develop a diffractive optical microscope based on a single spatial light modulator (SLM) with no movable parts. We combine the correction of wave front distortions to the cross-correlation analysis of the flow dynamics. We use the SLM to shine arbitrary patterns of spots on the sample, to correct their optical aberrations, to shift the aberration corrected spot array on the sample for the collection of fluorescence images, and to measure flow velocities from the cross-correlation functions computed between couples of spots. The setup and the algorithms are tested on various microfluidic devices. By applying the adaptive optics correction algorithm, it is possible to increase up to 5 times the signal-to-background ratio and to reduce approximately of the same ratio the uncertainty of the flow speed measurement. By working on grids of spots, we can correct different aberrations in different portions of the field of view, a feature that allows for anisoplanatic aberrations correction. Finally, being more efficient in the excitation, we increase the accuracy of the speed measurement by employing a larger number of spots in the grid despite the fact that the two-photon excitation efficiency scales as the fourth power of this number: we achieve a twofold decrease of the uncertainty and a threefold increase of the accuracy in the evaluation of the flow speed.

In Fourier-domain optical coherence tomography (FD-OCT), proper signal sampling and dispersion compensation are essential steps to achieve optimal axial resolution. These calibration steps can be performed through numerical signal processing, but require calibration information about the system that may require lengthy and complex measurement protocols. We report a highly robust calibration procedure that can simultaneously determine correction vectors for nonlinear wavenumber sampling and dispersion compensation. The proposed method requires only two simple mirror measurements and no prior knowledge about the system’s illumination source or detection scheme. This method applies to both spectral domain and swept-source OCT systems. Furthermore, it may be implemented as a low-cost fail-safe to validate the proper function of calibration hardware such as k-clocks. We demonstrate the method’s simple implementation, effectiveness, and robustness on both types of OCT systems.

Background: Development of cost-effective platforms for identification of biomarkers is of paramount importance in low-income settings. The present work focuses on the development of a microfluidic paper-based analytical device (μPADs) for the diagnosis of osteoporosis by measuring three important bone biomarkers – calcium, alkaline phosphatase and vitamin D. Methods: Antibody-based detection is realized in μPAD reservoirs based on principle of colorimetric sensing, where μPAD images are captured using a smartphone. The results are compared with the calibration curves to give proper quantification of analytes. Conclusion: This device can be potentially developed into a point-of-care diagnostic device for low-income settings. To the best of our understanding, a μPAD platform for simultaneous diagnosis of multiple osteoporosis markers is not reported yet.

© The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License 2017. We investigate a scheme for noninvasive continuous monitoring of absolute cerebral blood flow (CBF) in adult human patients based on a combination of time-resolved dynamic contrast-enhanced near-infrared spectroscopy (DCE-NIRS) and diffuse correlation spectroscopy (DCS) with semi-infinite head model of photon propogation. Continuous CBF is obtained via calibration of the DCS blood flow index (BFI) with absolute CBF obtained by intermittent intravenous injections of the optical contrast agent indocyanine green. A calibration coefficient (?) for the CBF is thus determined, permitting conversion of DCS BFI to absolute blood flow units at all other times. A study of patients with acute brain injury (N 7) is carried out to ascertain the stability of ?. The patientaveraged DCS calibration coefficient across multiple monitoring days and multiple patients was determined, and good agreement between the two calibration coefficients measured at different times during single monitoring days was found. The patient-averaged calibration coefficient of 1.24 × 109 omL/100 g/ min/ocm2/sp was applied to previously measured DCS BFI from similar brain-injured patients; in this case, absolute CBF was underestimated compared with XeCT, an effect we show is primarily due to use of semi-infinite homogeneous models of the head.

Laser speckle contrast imaging (LSCI) enables video rate imaging of blood flow. However, its relation to tissue blood perfusion is nonlinear and depends strongly on exposure time. By contrast, the perfusion estimate from the slower laser Doppler flowmetry (LDF) technique has a relationship to blood perfusion that is better understood. Multiexposure LSCI (MELSCI) enables a perfusion estimate closer to the actual perfusion than that using a single exposure time. We present and evaluate a method that utilizes contrasts from seven exposure times between 1 and 64 ms to calculate a perfusion estimate that resembles the perfusion estimate from LDF. The method is based on artificial neural networks (ANN) for fast and accurate processing of MELSCI contrasts to perfusion. The networks are trained using modeling of Doppler histograms and speckle contrasts from tissue models. The importance of accounting for noise is demonstrated. Results show that by using ANN, MELSCI data can be processed to LDF perfusion with high accuracy, with a correlation coefficient R = 1.000 for noise-free data, R = 0.993 when a moderate degree of noise is present, and R = 0.995 for in vivo data from an occlusion-release experiment.

The purpose of this study was to perform an initial investigation of the possibility to determine breast cancer growth rate with (14)C bomb-pulse dating. Tissues from 11 breast cancers, diagnosed in 1983, were retrieved from a regional biobank. The estimated average age of the majority of the samples overlapped the year of collection (1983) within 3σ Thus, this first study of tumour tissue has not yet demonstrated that (14)C bomb-pulse dating can obtain information on the growth of breast cancer. However, with further refinement, involving extraction of cell types and components, there is a possibility that fundamental knowledge of tumour biology might still be gained by the bomb-pulse technique. Additionally, δ (13)C and δ (15)N analyses were performed to obtain dietary and metabolic information, and to serve as a base for improvement of the age determination.

An efficient and robust method to measure vitamin D (25-hydroxy vitamin D3(25(OH)D3) and 25-hydroxy vitamin D2in dried blood spots (DBS) has been developed and applied in the pan-European multi-centre, internet-based, personalised nutrition intervention study Food4Me. The method includes calibration with blood containing endogenous 25(OH)D3, spotted as DBS and corrected for haematocrit content. The methodology was validated following international standards. The performance characteristics did not reach those of the current gold standard liquid chromatography-MS/MS in plasma for all parameters, but were found to be very suitable for status-level determination under field conditions. DBS sample quality was very high, and 3778 measurements of 25(OH)D3were obtained from 1465 participants. The study centre and the season within the study centre were very good predictors of 25(OH)D3levels (P3level on 20 January and a maximum on 21 July. The seasonal amplitude varied from centre to centre. The largest difference between winter and summer levels was found in Germany and the smallest in Poland. The model was cross-validated to determine the consistency of the predictions and the performance of the DBS method. The Pearson’s correlation between the measured values and the predicted values wasr0·65, and thesdof their differences was 21·2 nmol/l. This includes the analytical variation and the biological variation within subjects. Overall, DBS obtained by unsupervised sampling of the participants at home was a viable methodology for obtaining vitamin D status information in a large nutritional study.

Microfluidic paper-based analytical devices (μPADs) were used to detect the iron ion content in the water of a natural hot spring in order to assess the applicability of this process to the environmental analysis of natural water. The μPADs were fabricated using a wax printer after the addition of hydroxylamine into the detection reservoirs to reduce Fe(3+) to Fe(2+), 1,10-phenanthroline for the forming of a complex, and poly(acrylic acid) for ion-pair formation with an acetate buffer (pH 4.7). The calibration curve of Fe(3+) showed a linearity that ranged from 100 to 1000 ppm in the semi-log plot whereas the color intensity was proportional to the concentration of Fe(3+) and ranged from 40 to 350 ppm. The calibration curve represented the daily fluctuation in successive experiments during four days, which indicated that a calibration curve must be constructed for each day. When freshly prepared μPADs were compared with stored ones, no significant difference was found. The μPADs were applied to the determination of Fe(3+) in a sample of water from a natural hot spring. Both the accuracy and the precision of the μPAD method were evaluated by comparisons with the results obtained via conventional spectrophotometry. The results of the μPADs were in good agreement with, but less precise than, those obtained via conventional spectrophotometry. Consequently, the μPADs offer advantages that include rapid and miniaturized operation, although the precision was poorer than that of conventional spectrophotometry.

In this paper, a pen-on-paper electrochemiluminescence (PoP-ECL) device was entirely hand drawn and written in commercially available crayon and pencil in turn for the first time, and a constant potential-triggered sandwich-type immunosensor was introduced into the PoP-ECL device to form a low-cost ECL immunodevice proof. Each PoP-ECL device contained a hydrophilic paper channel and two PoP electrodes, and the PoP-ECL device was produced as follows: crayon was firstly used to draw hydrophobic regions on pure cellulose paper to create the hydrophilic paper channels followed with a baking treatment, and then a 6B-type black pencil with low resistivity was applied for precision writing, as the PoP electrodes, across the hydrophilic paper channel. For further point-of-care testing, a portable, low-cost rechargeable battery was employed as the power source to provide constant potential to the PoP electrodes to trigger the ECL. Using Carbohydrate antigen 199 as model analyte, this PoP-ECL immunodevice showed a good linear response range from 0.01–200 U mL−1 with a detection limit of 0.0055 U mL−1, a high sensitivity and stability. The proposed PoP-ECL immunodevice could be used in point-of-care testing of other tumor markers for remote regions and developing countries.

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Angularly resolved elastic light scattering is an established technique for probing the average size of organelles in biological tissue and cellular ensembles. Focusing of the incident light to illuminate no more than one cell at a time restricts the minimum forward-scattering angle θmin that can be detected. Series of simulated single-cell angular-scattering patterns have been generated to explore how size estimates vary as a function of θmin. At a setting of θmin=20 deg, the size estimates hop unstably between multiple minima in the solution space as simulated noise (mimicking experimentally observed levels) is varied. As θmin is reduced from 20 deg to 10 deg, the instability vanishes, and the variance of estimates near the correct answer also decreases. The simulations thus suggest that robust Mie theory fits to single-cell scattering at 785 nm excitation require measurements down to at least 15 deg. Notably, no such instability was observed at θmin=20 deg for narrow bead distributions. Accurate sizing of traditional calibration beads is, therefore, insufficient proof that an angular-scattering system is capable of robust analysis of single cells. Experimental support for the simulation results is also presented using measurements on cells fixed with formaldehyde.

Sugar-rich diets and poor dental hygiene promote the formation of a biofilm (plaque) that strongly adheres to the dental enamel surface and fosters the evolution of aciduric bacteria. The acid contributes to demineralization of the exterior tooth enamel, which accelerates after the pH drops below a critical value (∼5.5) for extended time periods resulting in the need for restorative procedures. Preventative techniques to alert the dentist and caries-susceptible patients regarding vulnerability to dental decay require a clinical measure of plaque activity. Therefore, there is a need to evaluate the acid production capability of plaque deposits in the pits and fissures of occlusal and interproximal regions. A ratiometric fluorescence pH-sensing device has been developed using an FDA-approved dye and LED excitation. Fluorescein spectral profiles were collected using a spectrometer and analyzed with a spectral unmixing algorithm for calibration over the pH range of 4.5 to 7. An in vivo pilot study on human subjects was performed using a sucrose rinse to accelerate bacterial metabolism and to measure the time-dependent drop in pH. The optical system is relatively immune to confounding factors such as photobleaching, dye concentration, and variation in excitation intensity associated with earlier dye-based pH measurement techniques.

A simple and low-cost fabrication method for paper-based diagnostic devices (PBDDs) is described in this study. Street-available polymer solutions were screen printed onto filter papers to create hydrophobic patterns for fluidic channels. In order to obtain fully functional hydrophobic patterns for fluids, the original polymer solutions were diluted with butyl acetate to yield a suitable viscosity range between 30-200 cP for complete patterning on paper. Typical pH and glucose tests with color indicators were performed on the screen printed PBDDs. Images of the PBDDs were analyzed by computers to obtain calibration curves for pH between 2 and 12 and glucose concentration ranging from 10-1000 mmol dm(-3). Detection of formaldehyde in acetone was also carried out to show the possibility of using this PBBD for analytical detection with organic solvents. An exemplar PBDD with simultaneous pH and glucose detection was also used to demonstrate the feasibility of applying this technique for realistic diagnostic applications.