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At least 1,477 records · Page 82

An engineered lactate oxidase based electrochemical sensor for continuous detection of biomarker lactic acid in human sweat and serum

Lactate levels in humans reveal intensity and duration of exertion and provide a critical readout for the severity of life-threatening illnesses such as pediatric sepsis. Using the lactate oxidase enzyme (Lox) from Aerococcus viridians, we demonstrated its functionality for lactate electrochemical sensing in physiological fluids in a lab setting. The structure and dynamics of LOx were validated by crystallography, X-ray scattering, and hydroxyl radical protein footprinting. This provided a validated protein template for understanding and designing an enzyme-based electrochemical sensing elements. Using this template, LOx enzyme variants were generated and compared. Comparison of the variants demonstrates that one exhibits effective lactate sensing at significantly reduced operating voltages. Additionally, we demonstrate that the four hexahistidine-tags on each enzyme tetramer are sufficient for immobilization to create a durable, functional sensor, with no need for a covalent attachment, enabling self-immobilization and eliminating the need for additional immobilization steps. The functionality of the LOx enzyme variants was verified at physiological lactate concentrations in both human serum (0–4 mM) and artificial sweat (0–100 mM) using 3-electrode setups for analysis of the three variants in parallel. Accuracy of measurement in both artificial sweat and human serum were high. Employing a microfluidic flow cell, we successfully monitored varying lactate levels in physiological fluids continuously over a 2h period. Overall, this optimized LOx enzyme, which self-immobilizes onto gold sensing electrodes, facilitates efficient and reliable lactate detection and continuous monitoring at reduced operating voltages suitable for further development towards commercial use.

60 APPLIED LIFE SCIENCES↗

Radiosensitivity of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation

Purpose: To investigate the radiosensitivity of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation. Methods and Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line. Cell suspensions were generated by mechanical dissociation of GSC spheroids and embedded in a semi-solid 3D matrix before irradiation. Spheroid-like colonies were manually counted by microscopy. Cells were also recovered and quantified by fluorescence. CD133 expression and DNA damage were evaluated by flow cytometry. Results: The fraction of CD133{sup +} cells varied between 0.014% and 96% in the six GSC cultures and showed a nonsignificant correlation with plating efficiency and survival fractions. The 4 most photon-radioresistant GSC cultures were NCH644, NCH421k, NCH441, and NCH636. Clonogenic survival for proton irradiation revealed relative biologic effectiveness (RBE) in the range of 0.7-1.20. However, carbon irradiation rendered the photon-resistant GSC cultures sensitive, with average RBE of 1.87-3.44. This effect was partly attributed to impaired capability of GSC to repair carbon ion–induced DNA double-strand breaks as determined by residual DNA repair foci. Interestingly, radiosensitivity of U87 cells was comparable to GSC cultures using clonogenic survival as the standard readout. Conclusions: Carbon irradiation is effective in GSC eradication with similar RBE ranges approximately 2-3 as compared with non-stem GSC cultures (U87). Our data strongly suggest further exploration of GSC using classic radiobiology endpoints such as the here-used 3D clonogenic survival assay and integration of additional GSC-specific markers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Three-Dimensional Dosimetric Validation of a Magnetic Resonance Guided Intensity Modulated Radiation Therapy System

Purpose: To validate the dosimetric accuracy of a commercially available magnetic resonance guided intensity modulated radiation therapy (MRgIMRT) system using a hybrid approach: 3-dimensional (3D) measurements and Monte Carlo calculations. Methods and Materials: We used PRESAGE radiochromic plastic dosimeters with remote optical computed tomography readout to perform 3D high-resolution measurements, following a novel remote dosimetry protocol. We followed the intensity modulated radiation therapy commissioning recommendations of American Association of Physicists in Medicine Task Group 119, adapted to incorporate 3D data. Preliminary tests (“AP” and “3D-Bands”) were delivered to 9.5-cm usable diameter cylindrical PRESAGE dosimeters to validate the treatment planning system (TPS) for nonmodulated deliveries; assess the sensitivity, uniformity, and rotational symmetry of the PRESAGE dosimeters; and test the robustness of the remote dosimetry protocol. Following this, 4 clinical MRgIMRT plans (“MultiTarget,” “Prostate,” “Head/Neck,” and “C-Shape”) were measured using 13-cm usable diameter PRESAGE dosimeters. For all plans, 3D-γ (3% or 3 mm global, 10% threshold) passing rates were calculated and 3D-γ maps were examined. Point doses were measured with an IBA-CC01 ionization chamber for validation of absolute dose. Finally, by use of an in-house-developed, GPU-accelerated Monte Carlo algorithm (gPENELOPE), we independently calculated dose for all 6 Task Group 119 plans and compared against the TPS. Results: For PRESAGE measurements, 3D-γ analysis yielded passing rates of 98.7%, 99.2%, 98.5%, 98.0%, 99.2%, and 90.7% for AP, 3D-Bands, MultiTarget, Prostate, Head/Neck, and C-Shape, respectively. Ion chamber measurements were within an average of 0.5% (±1.1%) from the TPS dose. Monte Carlo calculations demonstrated good agreement with the TPS, with a mean 3D-γ passing rate of 98.5% ± 1.9% using a stricter 2%/2-mm criterion. Conclusions: We have validated the dosimetric accuracy of a commercial MRgIMRT system using high-resolution 3D techniques. We have demonstrated for the first time that hybrid 3D remote dosimetry is a comprehensive and feasible approach to commissioning MRgIMRT. This may provide better sensitivity in error detection compared with standard 2-dimensional measurements and could be used when implementing complex new magnetic resonance guided radiation therapy technologies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam

Ultrahigh dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control; however, mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, High Intensity Gamma Ray Source (HIGS), paired with an organotypic ex vivo brain metastasis model. We varied interpulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma coculture model of brain metastasis to assess effects on normal and neoplastic tissues. Live-cell and bioluminescence imaging demonstrated cancer cell growth effects, whereas normal tissue responses and immune activation were assessed using live-cell imaging, cytokine profiles, and confocal microscopy. Here, we performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates. The highest IDR of the FLASH beam to date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in 1 pulse of 1 µs duration. Beam targeting was accurate to <1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased tumor necrosis factor α and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation. Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

Kay, Tyler V. [Duke University, Durham, NC (United↗

The impact of 2 H 9/2 → 4 I 13/2 emission from Er 3+ ions on ratiometric optical temperature sensing with Yb 3+ /Er 3+ co-doped upconversion materials

Yb 3+ /Er 3+ co-doped upconversion materials are widely used for luminescence intensity ratio (LIR) thermometry, where the relative intensity ratio of the green luminescence transitions ( 2 H 11/2 4 I 15/2 and 4 S 3/2 4 I 15/2 ) of Er 3+ dopant ions changes with temperature. In this work we report on the impact of an additional transition from the 2 H 9/2 level to the intermediate 4 I 13/2 level, which overlaps with the green luminescence normally used for LIR thermometry. The 2 H 9/2 4 I 13/2 emission overlaps extensively with the 4 S 3/2 4 I 15/2 emission and is more sensitive to pump power. The wavelength intervals used to integrate both 2 H 11/2 4 I 15/2 and 4 S 3/2 4 I 15/2 luminescence need be selected carefully in order to achieve accurate temperature readouts.

36 MATERIALS SCIENCE↗

Radiation-induced changes in the optical properties of NaMgF3(Sm): Observation of resettable Sm radio-photoluminescence

Highlights: • NaMgF{sub 3}(Sm) shows photoluminescence from Sm{sup 3+} and Sm{sup 2+}. • Optically stimulated luminescence occurs via Sm{sup 3+}. • Stable valence conversion from Sm{sup 3+} to Sm{sup 2+} is induced by X-ray irradiation. • The Sm valence ratio can be used to non-destructively measure doses up to ∼500 Gy. • The Sm valence conversion can be reversed by deep UV stimulation. - Abstract: Stable radio-photoluminescence (RPL) is observed in NaMgF{sub 3}(Sm) after X-ray irradiation due to valence conversion of Sm{sup 3+} to Sm{sup 2+}. This valence conversion can be reversed by deep UV (254 nm) illumination. It is likely that this reversible process occurs via defects near some of the Sm{sup 3+} sites that act as hole traps. The ratio of the Sm{sup 2+}/Sm{sup 3+} RPL emissions follows an exponential-type curve dependence on X-ray dose where the ratio saturates above ∼500 Gy. Optically stimulated luminescence (OSL) is also observed but only from Sm{sup 3+} and primarily from electrons trapped at F-centers. The OSL response is demonstrated to be linear up to 100 Gy. Thus, NaMgF{sub 3}(Sm) has potential as a dosimeter where individual irradiations can be monitored via OSL and the total cumulative dose via non-destructive RPL readout. The RPL can be optically reset when required.

36 MATERIALS SCIENCE↗

Iodine detection in Ag-mordenite based sensors: Charge conduction pathway determinations

Detection of radiological iodine gas after nuclear accidents or in nuclear fuel reprocessing is necessary for the safety of human life and the environment. The development of sensors for the detection of iodine benefits from the incorporation of nanoporous materials with high selectivity for I 2 from common competing gases in air. Silver mordenite zeolite (Ag-MOR) is widely-used material for capture of gaseous iodine (I 2 ). In this paper, thin film zeolite coatings were applied to Pt interdigitated electrodes (IEDs) to fabricate iodine gas sensors with direct electrical readout responses. Correlations between occluded ion, exposure to iodine gas, resultant AgI nanoparticle polymorphs and location in zeolite with resultant impedance spectroscopy (IS) properties are described. Furthermore, IS is leveraged to elucidate the changes in charge conduction pathways as determined by the cation-zeolite film incorporated in the sensor. Silver mordenite reveals a significant change in impedance upon exposure to gaseous I 2 at 70 °C, and the magnitude and direction of the response is dependent on whether the Ag + -mordenite is reduced (Ag 0 ) before I 2 exposure. An equivalent circuit model is developed to describe the movement of charge along the surface and through the pores of the mordenite grains. Relative changes in the impedance of these conduction pathways are related to the chemical changes from Ag + or Ag 0 to resultant AgI polymorph phase. Lastly, together, these results inform design of a compact Ag-mordenite sensor for direct electrical detection of gaseous I 2 .

36 MATERIALS SCIENCE↗

The Prompt Fission Neutron Spectrum of 235 U(n,f) below 2.5 MeV for Incident Neutrons from 0.7 to 20 MeV

New prompt fission neutron spectrum measurements are reported for 235 U(n,f) reactions induced by neutrons with energies from 0.7 to 20 MeV. These measurements cover outgoing neutron energies from 2.5 MeV down to 10 keV, using an array of 6 Li-glass scintillators for neutron detection and a double time-of-flight technique. The neutrons were produced at the Weapons Neutron Research facility of the Los Alamos Neutron Science Center. A detailed MCNP ® model of the experimental equipment and the surrounding room was used to interpret the experimental results. Backgrounds were measured in situ, making use of the time-dependent singles rates of the various detectors with asynchronous readout from waveform digitizers. The results presented here have been included in a re-evaluation of the fission neutron spectra for this fissioning system, a description of which is presented elsewhere in this issue.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Micromegas detectors for CLAS12

The electron accelerator of the Thomas Jefferson Laboratory (VI, USA) will soon be upgraded to deliver 12 GeV high intensity beams. This increase in the performance will give the opportunity to study the nucleon structure with an unprecedented accuracy. To meet this end, new equipments will be installed in the experimental areas, particularly in the Hall B/CLAS spectrometer. One of the most challenging aspects is the installation of a Central Tracker surrounding the target, dedicated to the detection of particles emitted at large angles. Micromegas detectors have been chosen to be a major element of this new equipment, due to their high rate capability as well as their robustness and light material. Using the recent bulk technology, part of these gaseous detectors are planned to be assembled in thin cylinders to maximize the acceptance. On the other hand, the presence of a strong magnetic field either perpendicular or parallel to the readout strips has important consequences which need to be carefully investigated. Finally, resistive Micromegas have been studied to further improve the rate capability.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

A measurement of the energy and timing resolution of GlueX Forward Calorimeter using an electron beam

The performance of the GlueX Forward Calorimeter was studied using a small version of the detector and a variable energy electron beam derived from the Hall B tagger at Jefferson Lab. For electron energies from 110 MeV to 260 MeV, which are near the lower-limits of the design sensitivity, the fractional energy resolution was measured to range from 20% to 14%, which meets the design goals. The use of custom 250 MHz flash ADCs for readout allowed precise measurements of signal arrival times. The detector achieved timing resolutions of 0.38 ns for a single 100 mV pulse, which will allow timing discrimination of photon beam bunches and out-of-time background during the operation of the GlueX detector.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Focal-plane detector system for the KATRIN experiment

Here, the local plane detector system for the KArlsiuhe TRItium Neutrino (KATRIN) experiment consists of a multi-pixel silicon p-i-n-diode array, custom readout electronics, two superconducting solenoid magnets, an ultra high vacuum system, a high vacuum system, calibration and monitoring devices, a scintillating veto, and a custom data-acquisition system, It is designed to detect the low-energy electrons selected by the KATRIN main spectrometer. We describe the system and summarize its performance after its final installation.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Absolute position measurement in a gas time projection chamber via transverse diffusion of drift charge

Time Projection Chambers (TPCs) with charge readout via micro pattern gaseous detectors can provide detailed measurements of charge density distributions. We here report on measurements of alpha particle tracks, using a TPC where the drift charge is amplified with Gas Electron Multipliers and detected with a pixel ASIC. We find that by measuring the 3-D topology of drift charge and fitting for its transverse diffusion, we obtain the absolute position of tracks in the drift direction. For example, we obtain a precision of 1~cm for 1~cm-long alpha track segments. To our knowledge this is the first demonstration of such a measurement in a gas TPC. This technique has several attractive features: it does not require knowledge of the initial specific ionization, is robust against bias from diffuse charge below detection threshold, and is also robust against high charge densities that saturate the detector response.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Use of high-granularity CdZnTe pixelated detectors to correct response non-uniformities caused by defects in crystals

Following our successful demonstration of the position-sensitive virtual Frisch-grid detectors, we investigated the feasibility of using high-granularity position sensing to correct response non-uniformities caused by the crystal defects in CdZnTe (CZT) pixelated detectors. The development of high-granularity detectors able to correct response non-uniformities on a scale comparable to the size of electron clouds opens the opportunity of using unselected off-the-shelf CZT material, whilst still assuring high spectral resolution for the majority of the detectors fabricated from an ingot. Here, we present the results from testing 3D position-sensitive 15×15×10 mm 3 pixelated detectors, fabricated with conventional pixel patterns with progressively smaller pixel sizes: 1.4, 0.8, and 0.5 mm. We employed the readout system based on the H3D front-end multi-channel ASIC developed by BNL's Instrumentation Division in collaboration with the University of Michigan. We use the sharing of electron clouds among several adjacent pixels to measure locations of interaction points with sub-pixel resolution. By using the detectors with small-pixel sizes and a high probability of the charge-sharing events, we were able to improve their spectral resolutions in comparison to the baseline levels, measured for the 1.4-mm pixel size detectors with small fractions of charge-sharing events. These results demonstrate that further enhancement of the performance of CZT pixelated detectors and reduction of costs are possible by using high spatial-resolution position information of interaction points to correct the small-scale response non-uniformities caused by crystal defects present in most devices.

36 MATERIALS SCIENCE↗

Digital pulse processing for NaI(Tl) detectors

We apply two different post-processing techniques to digital pulses induced by photons in a NaI(Tl) detector and compare the obtained energy resolution to the standard analog approach. Our digital acquisition approach is performed using a single-stage acquisition with a fast digitizer. Both the post-processing techniques we propose rely on signal integration. In the first, the pulse integral is calculated by directly numerically integrating the pulse digital samples, while in the second the pulse integral is estimated by a model-based fitting of the pulse. Our study used a 7.62 cm×7.62 cm cylindrical NaI(Tl) detector that gave a 7.60% energy resolution (at 662 keV), using the standard analog acquisition approach, based on a pulse shaping amplifier. The new direct numerical integration yielded a 6.52% energy resolution. The fitting approach yielded a 6.55% energy resolution, and, although computationally heavier than numerical integration, is preferable when only the early samples of the pulse are available. We also evaluated the timing performance of a fast–slow detection system, encompassing an EJ-309 and a NaI(Tl) scintillator. Here, we use two techniques to determine the pulse start time: constant fraction discrimination (CFD) and adaptive noise threshold timing (ANT), for both the analog and digital acquisition approach. With the analog acquisition approach, we found a system time resolution of 5.8 ns and 7.3 ns, using the constant fraction discrimination and adaptive noise threshold timing, respectively. With the digital acquisition approach, a time resolution of 1.2 ns was achieved using the ANT method and 3.3 ns using CFD at 50% of the maximum, to select the pulse start time. Finally, the proposed direct digital readout and post-processing techniques can improve the application of NaI(Tl) detectors, traditionally considered ‘slow’, for fast counting and correlation measurements, while maintaining a good measurement of the energy resolution.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Time and position resolution of the scintillator strips for a muon system at future colliders

In this study, prototype scintilator+WLS strips with SiPM readout for a muon system at future colliders were tested for light yield, time resolution and position resolution. Depending on the configuration, light yield of up to 36 photoelectrons per muon per SiPM has been observed, as well as time resolution of 0.45 ns and position resolution along the strip of 7.7 cm.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Studies with cathode drift chambers for the GlueX experiment at Jefferson Lab

A drift chamber system consisting of 24 1 m-diameter chambers with both cathode and wire readout (total of 12,672 channels) is operational in Hall D at Jefferson Lab (Virginia). Two cathode strip planes and one wire plane in each chamber register the same avalanche allowing the study of avalanche development, charge induction process, and strip resolution. We demonstrate a method for reconstructing the two-dimensional distribution of the avalanche “center-of-gravity” position around the wire from an 55 Fe source with resolutions down to 30 μm. We estimate the azimuthal extent of the avalanche around the wire as a function of the total charge for an Ar/CO 2 gas mixture. By means of cluster counting using a modified 3 cm-gap chamber, we observe significant space charge effects within the same track, resulting in an extent of the avalanche along the wire.

42 ENGINEERING↗

Pixel sensors with slim edges and small pitches for the CMS upgrades for HL-LHC

Here, planar n-in-n silicon detectors with small pitches and slim edges are being investigated for the innermost layers of tracking devices for the foreseen upgrades of the LHC experiments. Sensor prototypes compatible with the CMS readout, fabricated by Sintef, were tested in the laboratory and with a 120 GeV/c proton beam at the Fermilab test beam facility before and after irradiation with up to 2 × 10 15 neq/cm 2 fluence. Preliminary results of the data analysis are presented.

43 PARTICLE ACCELERATORS↗