Autonomous capillary systems for life science research and medical diagnostics

In autonomous capillary systems (CS) minute amounts of liquid are transported owing to capillary forces. Such CSs are appealing due to their portability, flexibility, and the exceptional physical behavior of liquids in micrometer sized microchannels, in particular, capillarity and short diffusion times. CSs have shown to be a promising technology for miniaturized immunoassays in life science research and diagnostics. Building on existing experimental demonstrations of immunoassays in CSs, a theoretical model of such immunoassays is implemented, tools and CSs for performing immunoassays are developed, key functional elements of CSs such as capillary pumps and valves are explored experimentally, and a proof-of-concept of the ultimate goal of one-step immunoassays are given in this work. For the theoretical modeling of immunoassays in CSs a finite difference algorithm is applied to delineate the role of the transport of analyte molecules in the microchannel (convection and diffusion), the kinetics of binding between the analyte and the capture antibodies, and the surface density of the capture antibody on the assay. The model shows that assays can be greatly optimized by varying the flow velocity of the solution of analyte in the microchannels. The model also shows how much the analyte-antibody binding constant and the surface density of the capture antibodies influence the performance of the assay. We derive strategies to optimize assays toward maximal sensitivity, minimal sample volume requirement or fast performance. A method using evaporation for controlling the flow rate in CSs was developed for maximum flexibility for developing assays. The method allows to use small CSs that initially are filled by capillary forces and then provide a well defined area of the liquid-air interface from which liquid can evaporate. Temperature and humidity are continuously measured and Peltier-elements are used to adjust the temperatures in multiple areas of the CSs relative to the dew-point. Thereby flow rates in the range from ~1.2 nL s−1 to ~30 pL s−1 could be achieved in the microchannels. This method was then used for screening cells for surface receptors. CSs, that do not need any peripherals for controlling flow rates become even more appealing. We explored the filling behavior of such CSs having microchannels of various length and large capillary pumps. The capillary pumps comprise microstructures of various sizes and shapes, which are spaced to encode certain capillary pressures. The spacing and shape of the microstructures is also used to orient the filling front to obtain a reliable filling behavior and to minimize the risk of entrapping air. We show how two capillary pumps having different hydrodynamic properties can be connected to program a sequence of slow and fast flow rates in CSs. Liquid filling CSs can hardly be stopped, but in some cases it might be beneficial to do so. In a separate chapter we explore how microstructures need to be designed to use capillary forces to stop, time, or trigger liquids. Besides well-defined flow rates in CSs accurately patterned capture antibodies (cAbs) are key for performing high-sensitive surface immunoassays in CSs. We present a method compatible with mass fabrication for patterning cAbs in dense lines of up to 8 lines per millimeter. These cAbs are used with CSs that are optimized for convenient handling, pipetting of solutions, pumping of liquids such as human serum, and visualization of signals for fluorescence immunoassays to detect c-reactive protein (CRP) with a sensitivity of 0.9 ng mL−1 (7.8 pM) from 1 uL of CRP-spiked human serum, within 11 minutes, with 4 pipetting steps, and a total volume of sample and reagents of <1.5 uL. CSs for diagnostic applications have different requirements than CSs that are used as a research tool in life sciences, where a high flexibility and performance primes over the ease of use and portability of the CSs. We give a proof-of-concept for one-step immunoassays based on CSs which we think can be the base for developing portable diagnostics for point-of-care applications. All reagents are preloaded in the CSs. A sample loaded in the CSs redissolves and reconstitutes the detection antibodies (dAbs), analyte-dAb-complexes are formed and detected downstream in the CSs. A user only needs to load a sample and measure the result using a fluorescence microscope or scanner. C-reactive protein was detected in human serum at clinical concentrations within 10 minutes and using only 2 uL of sample

The Beaming Pattern of Doppler Boosted Thermal Annihilation Radiation: Application to MeV Blazars

The beaming pattern of thermal annihilation radiation is broader than the beaming pattern produced by isotropic nonthermal electrons and positrons in the jets of radio-emitting active galactic nuclei which Compton scatter photons from an external isotropic radiation field. Thus blueshifted thermal annihilation radiation can provide the dominant contribution to the high-energy radiation spectrum at observing angles theta > 1/Gamma, where Gamma is the bulk Lorentz factor of the outflowing plasma. This effect may account for the spectral features of MeV blazars discovered with the Compton Telescope on the Compton Gamma Ray Observatory. Coordinated gamma-ray observations of annihilation line radiation to infer Doppler factors and VLBI radio observations to measure transverse angular speeds of outflowing plasma blobs can be used to determine the Hubble constant.Comment: 15 pages including 3 figures, requires AAS Latex macros, accepted for publication in The Astrophysical Journa

Acoustic scale from the angular power spectra of SDSS-III DR8 photometric luminous galaxies

We measure the acoustic scale from the angular power spectra of the Sloan Digital Sky Survey III (SDSS-III) Data Release 8 imaging catalog that includes 872,921 galaxies over ~ 10,000 deg^2 between 0.45<z<0.65. The extensive spectroscopic training set of the Baryon Oscillation Spectroscopic Survey (BOSS) luminous galaxies allows precise estimates of the true redshift distributions of galaxies in our imaging catalog. Utilizing the redshift distribution information, we build templates and fit to the power spectra of the data, which are measured in our companion paper, Ho et al. 2011, to derive the location of Baryon acoustic oscillations (BAO) while marginalizing over many free parameters to exclude nearly all of the non-BAO signal. We derive the ratio of the angular diameter distance to the sound horizon scale D_A/r_s= 9.212 + 0.416 -0.404 at z=0.54, and therefore, D_A= 1411+- 65 Mpc at z=0.54; the result is fairly independent of assumptions on the underlying cosmology. Our measurement of angular diameter distance D_A is 1.4 \sigma higher than what is expected for the concordance LCDM (Komatsu et al. 2011), in accordance to the trend of other spectroscopic BAO measurements for z >~ 0.35. We report constraints on cosmological parameters from our measurement in combination with the WMAP7 data and the previous spectroscopic BAO measurements of SDSS (Percival et al. 2010) and WiggleZ (Blake et al. 2011). We refer to our companion papers (Ho et al. 2011; de Putter et al. 2011) for investigations on information of the full power spectrum.Comment: 16 pages, 14 figures, 3 tables, submitted to Ap

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Charged Particle Production in Proton-, Deuteron-, Oxygen- and Sulphur-Nucleus Collisions at 200 GeV per Nucleon

The transverse momentum and rapidity distributions of net protons and negatively charged hadrons have been measured for minimum bias proton-nucleus and deuteron-gold interactions, as well as central oxygen-gold and sulphur-nucleus collisions at 200 GeV per nucleon. The rapidity density of net protons at midrapidity in central nucleus-nucleus collisions increases both with target mass for sulphur projectiles and with the projectile mass for a gold target. The shape of the rapidity distributions of net protons forward of midrapidity for d+Au and central S+Au collisions is similar. The average rapidity loss is larger than 2 units of rapidity for reactions with the gold target. The transverse momentum spectra of net protons for all reactions can be described by a thermal distribution with `temperatures' between 145 +- 11 MeV (p+S interactions) and 244 +- 43 MeV (central S+Au collisions). The multiplicity of negatively charged hadrons increases with the mass of the colliding system. The shape of the transverse momentum spectra of negatively charged hadrons changes from minimum bias p+p and p+S interactions to p+Au and central nucleus-nucleus collisions. The mean transverse momentum is almost constant in the vicinity of midrapidity and shows little variation with the target and projectile masses. The average number of produced negatively charged hadrons per participant baryon increases slightly from p+p, p+A to central S+S,Ag collisions.Comment: 47 pages, submitted to Z. Phys.

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: Baryon Acoustic Oscillations in the Data Release 9 Spectroscopic Galaxy Sample

We present measurements of galaxy clustering from the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III (SDSS-III). These use the Data Release 9 (DR9) CMASS sample, which contains 264,283 massive galaxies covering 3275 square degrees with an effective redshift z=0.57 and redshift range 0.43 < z < 0.7. Assuming a concordance Lambda-CDM cosmological model, this sample covers an effective volume of 2.2 Gpc^3, and represents the largest sample of the Universe ever surveyed at this density, n = 3 x 10^-4 h^-3 Mpc^3. We measure the angle-averaged galaxy correlation function and power spectrum, including density-field reconstruction of the baryon acoustic oscillation (BAO) feature. The acoustic features are detected at a significance of 5\sigma in both the correlation function and power spectrum. Combining with the SDSS-II Luminous Red Galaxy Sample, the detection significance increases to 6.7\sigma. Fitting for the position of the acoustic features measures the distance to z=0.57 relative to the sound horizon DV /rs = 13.67 +/- 0.22 at z=0.57. Assuming a fiducial sound horizon of 153.19 Mpc, which matches cosmic microwave background constraints, this corresponds to a distance DV(z=0.57) = 2094 +/- 34 Mpc. At 1.7 per cent, this is the most precise distance constraint ever obtained from a galaxy survey. We place this result alongside previous BAO measurements in a cosmological distance ladder and find excellent agreement with the current supernova measurements. We use these distance measurements to constrain various cosmological models, finding continuing support for a flat Universe with a cosmological constant.Comment: 33 page

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: measurements of the growth of structure and expansion rate at z=0.57 from anisotropic clustering

We analyze the anisotropic clustering of massive galaxies from the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey (BOSS) Data Release 9 (DR9) sample, which consists of 264,283 galaxies in the redshift range 0.43 < z < 0.7 spanning 3,275 square degrees. Both peculiar velocities and errors in the assumed redshift-distance relation ("Alcock-Paczynski effect") generate correlations between clustering amplitude and orientation with respect to the line-of-sight. Together with the sharp baryon acoustic oscillation (BAO) standard ruler, our measurements of the broadband shape of the monopole and quadrupole correlation functions simultaneously constrain the comoving angular diameter distance (2190 +/- 61 Mpc) to z=0.57, the Hubble expansion rate at z=0.57 (92.4 +/- 4.5 km/s/Mpc), and the growth rate of structure at that same redshift (d sigma8/d ln a = 0.43 +/- 0.069). Our analysis provides the best current direct determination of both DA and H in galaxy clustering data using this technique. If we further assume a LCDM expansion history, our growth constraint tightens to d sigma8/d ln a = 0.415 +/- 0.034. In combination with the cosmic microwave background, our measurements of DA, H, and growth all separately require dark energy at z > 0.57, and when combined imply \Omega_{\Lambda} = 0.74 +/- 0.016, independent of the Universe's evolution at z<0.57. In our companion paper (Samushia et al. prep), we explore further cosmological implications of these observations.Comment: 19 pages, 11 figures, submitted to MNRAS, comments welcom

The Baryon Oscillation Spectroscopic Survey of SDSS-III

The Baryon Oscillation Spectroscopic Survey (BOSS) is designed to measure the scale of baryon acoustic oscillations (BAO) in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large scale structure. BOSS uses 1.5 million luminous galaxies as faint as i=19.9 over 10,000 square degrees to measure BAO to redshifts z<0.7. Observations of neutral hydrogen in the Lyman alpha forest in more than 150,000 quasar spectra (g<22) will constrain BAO over the redshift range 2.15<z<3.5. Early results from BOSS include the first detection of the large-scale three-dimensional clustering of the Lyman alpha forest and a strong detection from the Data Release 9 data set of the BAO in the clustering of massive galaxies at an effective redshift z = 0.57. We project that BOSS will yield measurements of the angular diameter distance D_A to an accuracy of 1.0% at redshifts z=0.3 and z=0.57 and measurements of H(z) to 1.8% and 1.7% at the same redshifts. Forecasts for Lyman alpha forest constraints predict a measurement of an overall dilation factor that scales the highly degenerate D_A(z) and H^{-1}(z) parameters to an accuracy of 1.9% at z~2.5 when the survey is complete. Here, we provide an overview of the selection of spectroscopic targets, planning of observations, and analysis of data and data quality of BOSS.Comment: 49 pages, 16 figures, accepted by A

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr