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

Spectral Cube Visualisation and Explorer Tool from the Herschel Interactive Processing Environment (HIPE)

We present the interactive tool for visualizing and exploring spectral cubes of the Herschel Interactive Processing Environment (HIPE). With this GUI tool, one can easily plot the spectra within the cube, compare several cubes from the same region of the sky, and run a number of analysis tasks on them (such as computing velocity/dispersion maps or position-velocity diagrams). The tool is integrated within the Spectral Explorer from HIPE, which offers additional functionality such as an interface to the spectral fitter tool. All the actions with HIPE tools produce Python code, which can later be reused in scripts for automation. Various results can be saved as FITS files and loaded into other astronomical analysis tools

Effects of iron-ore mining and processing on metal bioavailability in a tropical coastal lagoon

In water systems, water quality and geochemical properties of sediments determine the speciation of trace metals, metal transport, and sediment-water exchange, influencing metal availability and its potential effects on biota. Studies from temperate climates have shown that iron-ore mining and tailing wastewaters, besides being a source of trace metals, usually show high levels of dissolved ions and particulate suspended matter, thus having the potential of indirectly changing metal bioavailability. For the first time in the tropics, we identified the effects of iron-ore mining and processing on metal bioavailability in a coastal lagoon. With an extensive sampling scheme, we investigated the potential sources of metals; the links among metal levels in water, sediments, and invertebrates; and the contrasting effects on metal speciation and bioavailability. The metals Fe, Mn, Al, Cr, Zn, Cu, Ni, Pb, Cd, Hg, and As were measured in water, sediments (surface and profiles), and invertebrates from Mãe-Bá Lagoon and in the sites directly influenced by the mining operations (tailing dams and nearby rivers). In addition, samples from two other lagoons, considered pristine, were analyzed. The study area is located in the southeast of Brazil (Iron Quadrangle Region and a coastal area of Espírito Santo State). General water characteristics included pH, dissolved organic carbon, alkalinity, and anion composition. Water metal speciation was assessed by a speciation model (Chemical Equilibria in Aquatic Systems). Grain-size distribution, organic carbon, carbonate, and acid volatile sulfide (AVS) were determined in sediments. Statistical methods included comparison of means by Mann-Whitney test, ordination and correlation analyses, and analysis of regression for geochemical normalization of metals with grain size. The dissolved metal concentrations, the total metal levels in sediments, and the normalization based on the fine sediment fraction showed that the mining operations constitute potential sources of Fe, Mn, Cr, Cu, Ni, Pb, As, and Hg to Mãe-Bá Lagoon. However, trace metal availability was reduced because of increased pH, hardness, and sulfide content (356 μmol/g) in the sites influenced by the mining. The lagoon showed similar water chemistry as in the mining sites, with metal bioavailability further decreased by the presence of dissolved organic carbon and chloride. Although AVS levels in the lagoon were low (0.48-56 μmol/g), metal bioavailability was reduced because of the presence of organic matter. Metal levels in invertebrates confirmed the predicted low metal bioavailability in Mãe-Bá Lagoon. The lagoon was considered moderately contaminated only by Hg and As. The iron-ore mining and processing studied here constitute potential sources of metal pollution into the tropical lagoon. Contrary to expectations, however, it also contributes to reducing the overall metal bioavailability in the lagoon. These findings are believed to be useful for evaluating metal exposure in a more integrated way, identifying not only the sources of pollution but also how they can affect the components involved in metal speciation and bioavailability in water systems, leading to new insights

Sediments and the "system" : from site-specific to regional-scale research : a story of joy in researching dirt

For both of us, it has been a struggle on how to write a kind of official “Farewell address” to our colleagues. After all, we do it only once in our lifetime. The result is twofold; we will have one editorial with a broad and short (admittedly very biased) history and outlook of our experience, and a second, more scientific editorial, which covers the first 10 years of our Journal of Soils and Sediments

Mr. C. Asser’s handleiding tot de beoefening van het Nederlands burgerlijk recht: Bijzondere overeenkomsten: Verzekering

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