A disposable microfluidic cassette for DNA amplification and detection

A pneumatically driven, disposable, microfluidic cassette comprised of a polymerase chain reaction (PCR) thermal cycler, an incubation chamber to label PCR amplicons with upconverting phosphor (UPT) reporter particles, conduits, temperature-activated, normally closed hydrogel valves, and a lateral flow strip, was constructed and tested. The hydrogel valves, which were opened and closed with the aid of electrically controlled thermoelectric units, provided a simple means to seal the PCR reactor and suppress bubble formation. The hydrogel-based flow control was electronically addressable, leakage-free, and biocompatible. To test the device, a solution laden with genomic DNA isolated from B. cereus was introduced into the microfluidic cassette and a specific 305 bp fragment was amplified. The PCR amplicons were labelled with the phosphor (UPT) reporter particles, applied to the lateral flow strip, bound to pre-immobilized ligands, and detected with an IR laser that scanned the lateral flow strip and excited the phosphor (UPT) particles that, in turn, emitted light in the visible spectrum. The UPT particles do not bleach, they provide a permanent record, and they readily facilitate the filtering of background noise. The cassette described herein will be used for rapid testing at the point of care

Science Objectives and Rationale for the Radiation Belt Storm Probes Mission

The NASA Radiation Belt Storm Probes (RBSP) mission addresses how populationsof high energy charged particles are created, vary, and evolve in space environments,and specifically within Earths magnetically trapped radiation belts. RBSP, with a nominallaunch date of August 2012, comprises two spacecraft making in situ measurements for atleast 2 years in nearly the same highly elliptical, low inclination orbits (1.1 5.8 RE, 10).The orbits are slightly different so that 1 spacecraft laps the other spacecraft about every2.5 months, allowing separation of spatial from temporal effects over spatial scales rangingfrom 0.1 to 5 RE. The uniquely comprehensive suite of instruments, identical on the twospacecraft, measures all of the particle (electrons, ions, ion composition), fields (E and B),and wave distributions (dE and dB) that are needed to resolve the most critical science questions.Here we summarize the high level science objectives for the RBSP mission, providehistorical background on studies of Earth and planetary radiation belts, present examples ofthe most compelling scientific mysteries of the radiation belts, present the mission design ofthe RBSP mission that targets these mysteries and objectives, present the observation andmeasurement requirements for the mission, and introduce the instrumentation that will deliverthese measurements. This paper references and is followed by a number of companionpapers that describe the details of the RBSP mission, spacecraft, and instruments

Prompt energization of relativistic and highly relativistic electrons during a substorm interval: Van Allen Probes observations

Abstract On 17 March 2013, a large magnetic storm significantly depleted the multi-MeV radiation belt. We present multi-instrument observations from the Van Allen Probes spacecraft Radiation Belt Storm Probe A and Radiation Belt Storm Probe B at ~6 Re in the midnight sector magnetosphere and from ground-based ionospheric sensors during a substorm dipolarization followed by rapid reenergization of multi-MeV electrons. A 50% increase in magnetic field magnitude occurred simultaneously with dramatic increases in 100 keV electron fluxes and a 100 times increase in VLF wave intensity. The 100 keV electrons and intense VLF waves provide a seed population and energy source for subsequent radiation belt enhancements. Highly relativistic (\u3e2 MeV) electron fluxes increased immediately at L* ~ 4.5 and 4.5 MeV flux increased \u3e90 times at L* = 4 over 5 h. Although plasmasphere expansion brings the enhanced radiation belt multi-MeV fluxes inside the plasmasphere several hours postsubstorm, we localize their prompt reenergization during the event to regions outside the plasmasphere. Key Points Substorm dynamics are important for highly relativistic electron energization Cold plasma preconditioning is significant for rapid relativistic energization Relativistic / highly relativistic electron energization can occur in \u3c 5 hrs

Gradual diffusion and punctuated phase space density enhancements of highly relativistic electrons: Van Allen Probes observations

Abstract The dual-spacecraft Van Allen Probes mission has provided a new window into mega electron volt (MeV) particle dynamics in the Earth\u27s radiation belts. Observations (up to E ~10 MeV) show clearly the behavior of the outer electron radiation belt at different timescales: months-long periods of gradual inward radial diffusive transport and weak loss being punctuated by dramatic flux changes driven by strong solar wind transient events. We present analysis of multi-MeV electron flux and phase space density (PSD) changes during March 2013 in the context of the first year of Van Allen Probes operation. This March period demonstrates the classic signatures both of inward radial diffusive energization and abrupt localized acceleration deep within the outer Van Allen zone (L ~4.0 ± 0.5). This reveals graphically that both competing mechanisms of multi-MeV electron energization are at play in the radiation belts, often acting almost concurrently or at least in rapid succession. Key Points Clear observations to higher energy than ever before Precise detection of where and how acceleration takes place Provides new eyes on megaelectron Volt

Energetic charged particle fluxes relevant to Ganymede's polar region

The JEDI instrument made measurements of energetic charged particles near Ganymede during a close encounter with that moon. Here we find ion flux levels are similar close to Ganymede itself but outside its magnetosphere and on near wake and open field lines. But energetic electron flux levels are more than a factor of 2 lower on polar and near-wake field lines than on nearby Jovian field lines at all energies reported here. Flux levels are relevant to the weathering of the surface, particularly processes that affect the distribution of ice, since surface brightness has been linked to the open-closed field line boundary. For this reason, we estimate the sputtering rates expected in the polar regions due to energetic heavy ions. Other rates, such as those related to radiolysis by plasma and particles that can reach the surface, need to be added to complete the picture of charged particle weathering

Quantifying hiss-driven energetic electron precipitation: A detailed conjunction event analysis

Abstract We analyze a conjunction event between the Van Allen Probes and the low-altitude Polar Orbiting Environmental Satellite (POES) to quantify hiss-driven energetic electron precipitation. A physics-based technique based on quasi-linear diffusion theory is used to estimate the ratio of precipitated and trapped electron fluxes (R), which could be measured by the two-directional POES particle detectors, using wave and plasma parameters observed by the Van Allen Probes. The remarkable agreement between modeling and observations suggests that this technique is applicable for quantifying hiss-driven electron scattering near the bounce loss cone. More importantly, R in the 100-300 keV energy channel measured by multiple POES satellites over a broad L magnetic local time region can potentially provide the spatiotemporal evolution of global hiss wave intensity, which is essential in evaluating radiation belt electron dynamics, but cannot be obtained by in situ equatorial satellites alone. Key Points Measured and calculated hiss Bw from POES electron measurements agree well Electron ratio measured by POES is able to estimate hiss wave intensity This technique can be used to provide global hiss wave distributio

Chorus acceleration of radiation belt relativistic electrons during March 2013 geomagnetic storm

Abstract The recent launching of Van Allen probes provides an unprecedent opportunity to investigate variations of the radiation belt relativistic electrons. During the 17-19 March 2013 storm, the Van Allen probes simultaneously detected strong chorus waves and substantial increases in fluxes of relativistic (2 - 4.5 MeV) electrons around L = 4.5. Chorus waves occurred within the lower band 0.1-0.5fce (theelectron equatorial gyrofrequency), with a peak spectral density ∼10-4 nT 2/Hz. Correspondingly, relativistic electron fluxes increased by a factor of 102-103 during the recovery phase compared to the main phase levels. By means of a Gaussian fit to the observed chorus spectra, the drift and bounce-averaged diffusion coefficients are calculated and then used to solve a 2-D Fokker-Planck diffusion equation. Numerical simulations demonstrate that the lower-band chorus waves indeed produce such huge enhancements in relativistic electron fluxes within 15 h, fitting well with the observation. Key Points Initial RBSP correlated data of chorus waves and relativistic electron fluxes A realistic simulation to examine effect of chorus on relativistic electron flux Chorus yields huge increases inelectron flux rapidly, consistent with data

The Energetic Particle Detector (EPD) Investigation and the Energetic Ion Spectrometer (EIS) for the Magnetospheric Multiscale (MMS) Mission

Abstract The Energetic Particle Detector (EPD) Investigation is one of 5 fields-and-particles investigations on the Magnetospheric Multiscale (MMS) mission. MMS comprises 4 spacecraft flying in close formation in highly elliptical, near-Earth-equatorial orbits targeting understanding of the fundamental physics of the important physical process called magnetic reconnection using Earth’s magnetosphere as a plasma laboratory. EPD comprises two sensor types, the Energetic Ion Spectrometer (EIS) with one instrument on each of the 4 spacecraft, and the Fly’s Eye Energetic Particle Spectrometer (FEEPS) with 2 instruments on each of the 4 spacecraft. EIS measures energetic ion energy, angle and elemental compositional distributions from a required low energy limit of 20 keV for protons and 45 keV for oxygen ions, up to \u3e0.5 MeV (with capabilities to measure up to \u3e1 MeV). FEEPS measures instantaneous all sky images of energetic electrons from 25 keV to \u3e0.5 MeV, and also measures total ion energy distributions from 45 keV to \u3e0.5 MeV to be used in conjunction with EIS to measure all sky ion distributions. In this report we describe the EPD investigation and the details of the EIS sensor. Specifically we describe EPD-level science objectives, the science and measurement requirements, and the challenges that the EPD team had in meeting these requirements. Here we also describe the design and operation of the EIS instruments, their calibrated performances, and the EIS in-flight and ground operations. Blake et al. (The Flys Eye Energetic Particle Spectrometer (FEEPS) contribution to the Energetic Particle Detector (EPD) investigation of the Magnetospheric Magnetoscale (MMS) Mission, this issue) describe the design and operation of the FEEPS instruments, their calibrated performances, and the FEEPS in-flight and ground operations. The MMS spacecraft will launch in early 2015, and over its 2-year mission will provide comprehensive measurements of magnetic reconnection at Earth’s magnetopause during the 18 months that comprise orbital phase 1, and magnetic reconnection within Earth’s magnetotail during the about 6 months that comprise orbital phase 2

Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices

Objective The aim of this study was to investigate how head and neck squamous cell carcinoma (HNSCC) tissue biopsies maintained in a pseudo in vivo environment within a bespoke microfluidic device respond to radiation treatment. Study Design Feasibility study. Setting Tertiary referral center. Subjects and Methods Thirty-five patients with HNSCC were recruited, and liver tissue from 5 Wistar rats was obtained. A microfluidic device was used to maintain the tissue biopsy samples in a viable state. Rat liver was used to optimize the methodology. HNSCC was obtained from patients with T1-T3 laryngeal or oropharyngeal SCC; N1-N2 metastatic cervical lymph nodes were also obtained. Irradiation consisted of single doses of between 2 Gy and 40 Gy and a fractionated course of 5×2 Gy. Cell death was assessed in the tissue effluent using the soluble markers lactate dehydrogenase (LDH) and cytochrome c and in the tissue by immunohistochemical detection of cleaved cytokeratin18 (M30 antibody). Results A significant surge in LDH release was demonstrated in the rat liver after a single dose of 20 Gy; in HNSCC, it was seen after 40 Gy compared with the control. There was no significant difference in cytochrome c release after 5 Gy or 10 Gy. M30 demonstrated a dose-dependent increase in apoptotic index for a given increase in single-dose radiotherapy. There was a significant increase in apoptotic index between 1×2 Gy and 5×2 Gy. Conclusion M30 is a superior method compared with soluble markers in detecting low-dose radiation-induced cell death. This microfluidic technique can be used to assess radiation-induced cell death in HNSCC and therefore has the potential to be used to predict radiation response

Plasmatrough exohiss waves observed by Van Allen Probes: Evidence for leakage from plasmasphere and resonant scattering of radiation belt electrons

Abstract Exohiss waves are whistler mode hiss observed in the plasmatrough region. We present a case study of exohiss waves and the corresponding background plasma distributions observed by the Van Allen Probes in the dayside low-latitude region. The analysis of wave Poynting fluxes, suprathermal electron fluxes, and cold electron densities supports the scenario that exohiss leaks from the plasmasphere into the plasmatrough. Quasilinear calculations further reveal that exohiss can potentially cause the resonant scattering loss of radiation belt electrons