Biocompatible low-cost CMOS electrodes for neuronal interfaces, cell impedance and other biosensors

The adaptation of standard integrated circuit (IC) technology for biosensors in drug discovery pharmacology, neural interface systems, environmental sensors and electrophysiology requires electrodes to be electrochemically stable, biocompatible and affordable. Unfortunately, the ubiquitous IC technology, complementary metal oxide semiconductor (CMOS), does not meet the first of these requirements. For devices intended only for research, modification of CMOS by post-processing using cleanroom facilities has been achieved by others. However, to enable adoption of CMOS as a basis for commercial biosensors, the economies of scale of CMOS fabrication must be maintained by using only low-cost post-processing techniques. The scope of this work was to develop post-processing methods that meet the electrochemical and biocompatibility requirements but within the low-cost constraint. Several approaches were appraised with the two most promising designs taken forward for further investigation. Firstly, a process was developed whereby the corrodible aluminium is anodised to form nanoporous alumina and further processed to optimise its impedance. A second design included a noble metal in the alumina pores to enhance further the electrical characteristics of the electrode. Experiments demonstrated for the first time the ability to anodise CMOS metallisation to form the desired electrodes. Tests showed the electrode addressed the problems of corrosion and presented a surface that was biocompatible with the NG108-15 neuronal cell line. Difficulties in assessing the influence of alumina porosity led to the development of a novel cell adhesion assay that showed for the first time neuronal cells adhere preferentially to large pores rather than small pores or planar aluminium. It was also demonstrated that porosity can be manipulated at room temperature by modifying the anodising electrolyte with polyethylene glycol. CMOS ICs were designed as multiple electrode arrays and optimised for neuronal recordings. This utilised the design incorporating a noble metal deposited into the porous alumina. Deposition of platinum was only partially successful, with better results using gold. This provided an electrode surface suitable for electric cell-substrate impedance sensors (ECIS) and many other sensor applications. Further processing deposited platinum black to improve signal-to-noise ratio for neuronal recordings. The developed processes require no specialised semiconductor fabrication equipment and can process CMOS ICs on laboratory or factory bench tops in less than one hour. During the course of electrode development, new methods for biosensor packaging were assessed: firstly, a biocompatible polyethylene glycol mould process was developed for improved prototype assembly. Secondly, a commercial ‘partial encapsulation’ process (Quik-Pak, U.S.) was assessed for biocompatibility. Cell vitality tests showed both methods were biocompatible and therefore suitable for use in cell-based biosensors. The post-processed CMOS electrode arrays were demonstrated by successfully recording neuronal cell electrical activity (action potentials) and by ECIS with a human epithelial cell line (Caco2). It is evident that these developments may provide a missing link that can enable commercialisation of CMOS biosensors. Further work is being planned to demonstrate the technology in context for specific markets.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Recovery-focused cognitive-behavioural therapy for recent-onset bipolar disorder:randomised controlled pilot trial

Background Despite evidence for the effectiveness of structured psychological therapies for bipolar disorder no psychological interventions have been specifically designed to enhance personal recovery for individuals with recent-onset bipolar disorder. Aims A pilot study to assess the feasibility and effectiveness of a new intervention, recovery-focused cognitive-behavioural therapy (CBT), designed in collaboration with individuals with recent-onset bipolar disorder intended to improve clinical and personal recovery outcomes. Method A single, blind randomised controlled trial compared treatment as usual (TAU) with recovery-focused CBT plus TAU (n = 67). Results Recruitment and follow-up rates within 10% of pre-planned targets to 12-month follow-up were achieved. An average of 14.15 h (s.d. = 4.21) of recovery-focused CBT were attended out of a potential maximum of 18 h. Compared with TAU, recovery-focused CBT significantly improved personal recovery up to 12-month follow-up (Bipolar Recovery Questionnaire mean score 310.87, 95% CI 75.00-546.74 (s.e. = 120.34), P = 0.010, d = 0.62) and increased time to any mood relapse during up to 15 months follow-up (χ(2) = 7.64, P<0.006, estimated hazard ratio (HR) = 0.38, 95% CI 0.18-0.78). Groups did not differ with respect to medication adherence. Conclusions Recovery-focused CBT seems promising with respect to feasibility and potential clinical effectiveness. Clinical- and cost-effectiveness now need to be reliably estimated in a definitive trial

Galaxy And Mass Assembly (GAMA)

The GAMA survey aims to deliver 250,000 optical spectra (3--7Ang resolution) over 250 sq. degrees to spectroscopic limits of r_{AB} <19.8 and K_{AB}<17.0 mag. Complementary imaging will be provided by GALEX, VST, UKIRT, VISTA, HERSCHEL and ASKAP to comparable flux levels leading to a definitive multi-wavelength galaxy database. The data will be used to study all aspects of cosmic structures on 1kpc to 1Mpc scales spanning all environments and out to a redshift limit of z ~ 0.4. Key science drivers include the measurement of: the halo mass function via group velocity dispersions; the stellar, HI, and baryonic mass functions; galaxy component mass-size relations; the recent merger and star-formation rates by mass, types and environment. Detailed modeling of the spectra, broad SEDs, and spatial distributions should provide individual star formation histories, ages, bulge-disc decompositions and stellar bulge, stellar disc, dust disc, neutral HI gas and total dynamical masses for a significant subset of the sample (~100k) spanning both the giant and dwarf galaxy populations. The survey commenced March 2008 with 50k spectra obtained in 21 clear nights using the Anglo Australian Observatory's new multi-fibre-fed bench-mounted dual-beam spectroscopic system (AAOmega).Comment: Invited talk at IAU 254 (The Galaxy Disk in Cosmological Context, Copenhagen), 6 pages, 5 figures, high quality PDF version available at http://www.eso.org/~jliske/gama

Searches For High-Frequency Variations In The B-8 Solar Neutrino Flux At The Sudbury Neutrino Observatory

We have performed three searches for high-frequency signals in the solar neutrino flux measured by the Sudbury Neutrino Observatory, motivated by the possibility that solar g-mode oscillations could affect the production or propagation of solar B-8 neutrinos. The first search looked for any significant peak in the frequency range 1-144 day(-1), with a sensitivity to sinusoidal signals with amplitudes of 12% or greater. The second search focused on regions in which g-mode signals have been claimed by experiments aboard the Solar and Heliospheric Observatory satellite, and was sensitive to signals with amplitudes of 10% or greater. The third search looked for extra power across the entire frequency band. No statistically significant signal was detected in any of the three searches.Natural Sciences and Engineering Research Council, CanadaIndustry Canada, CanadaNational Research Council, CanadaNorthern Ontario Heritage Fund, CanadaAtomic Energy of Canada, Ltd., CanadaOntario Power Generation, CanadaHigh Performance Computing Virtual Laboratory, CanadaCanada Foundation for InnovationDept. of Energy, USNational Energy Research Scientific Computing Center, USScience and Technologies Facilities Council, UKAstronom

Low-Multiplicity Burst Search At The Sudbury Neutrino Observatory

Results are reported from a search for low-multiplicity neutrino bursts in the Sudbury Neutrino Observatory. Such bursts could indicate the detection of a nearby core-collapse supernova explosion. The data were taken from Phase I (1999 November-2001 May), when the detector was filled with heavy water, and Phase II (2001 July-2003 August), when NaCl was added to the target. The search was a blind analysis in which the potential backgrounds were estimated and analysis cuts were developed to eliminate such backgrounds with 90% confidence before the data were examined. The search maintained a greater than 50% detection probability for standard supernovae occurring at a distance of up to 60 kpc for Phase I and up to 70 kpc for Phase II. No low-multiplicity bursts were observed during the data-taking period.Natural Sciences and Engineering Research Council, CanadaIndustry Canada, CanadaNational Research Council, CanadaNorthern Ontario Heritage Fund, CanadaAtomic Energy of Canada, Ltd., CanadaOntario Power Generation, CanadaHigh Performance Computing Virtual Laboratory, CanadaCanada Foundation for Innovation, CanadaCanada Research Chairs, CanadaDepartment of Energy, USNational Energy Research Scientific Computing Center, USAlfred P. Sloan Foundation, USScience and Technology Facilities Council, UKFundacao para a Ciencia e a Technologia, PortugalAstronom

Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection

Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains. IMPORTANCE Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans

Low Multiplicity Burst Search at the Sudbury Neutrino Observatory

Results are reported from a search for low-multiplicity neutrino bursts in the Sudbury Neutrino Observatory (SNO). Such bursts could indicate detection of a nearby core-collapse supernova explosion. The data were taken from Phase I (November 1999 - May 2001), when the detector was filled with heavy water, and Phase II (July 2001 - August 2003), when NaCl was added to the target. The search was a blind analysis in which the potential backgrounds were estimated and analysis cuts were developed to eliminate such backgrounds with 90% confidence before the data were examined. The search maintained a greater than 50% detection probability for standard supernovae occurring at a distance of up to 60 kpc for Phase I and up to 70 kpc for Phase II. No low-multiplicity bursts were observed during the data-taking period.Comment: 11 pages, 4 figures, submitted to Ap

A Search for Neutrinos from the Solar hep Reaction and the Diffuse Supernova Neutrino Background with the Sudbury Neutrino Observatory

A search has been made for neutrinos from the hep reaction in the Sun and from the diffus

Combined Analysis of all Three Phases of Solar Neutrino Data from the Sudbury Neutrino Observatory

We report results from a combined analysis of solar neutrino data from all phases of the Sudbury Neutrino Observatory. By exploiting particle identification information obtained from the proportional counters installed during the third phase, this analysis improved background rejection in that phase of the experiment. The combined analysis resulted in a total flux of active neutrino flavors from 8B decays in the Sun of (5.25 \pm 0.16(stat.)+0.11-0.13(syst.))\times10^6 cm^{-2}s^{-1}. A two-flavor neutrino oscillation analysis yielded \Deltam^2_{21} = (5.6^{+1.9}_{-1.4})\times10^{-5} eV^2 and tan^2{\theta}_{12}= 0.427^{+0.033}_{-0.029}. A three-flavor neutrino oscillation analysis combining this result with results of all other solar neutrino experiments and the KamLAND experiment yielded \Deltam^2_{21} = (7.41^{+0.21}_{-0.19})\times10^{-5} eV^2, tan^2{\theta}_{12} = 0.446^{+0.030}_{-0.029}, and sin^2{\theta}_{13} = (2.5^{+1.8}_{-1.5})\times10^{-2}. This implied an upper bound of sin^2{\theta}_{13} < 0.053 at the 95% confidence level (C.L.)