Biosensors with high sensitivity and short time-to-result that are capable of detecting biomarkers in body fluids such as serum are an important prerequisite for early diagnostics in modern healthcare provision. Here, we report the development of an electrochemical impedance-based sensor for the detection in serum of human interleukin-8 (IL-8), a pro-angiogenic chemokine implicated in a wide range of inflammatory diseases. The sensor employs a small and robust synthetic non-antibody capture protein based on a cystatin scaffold that displays high affinity for human IL-8 with a KD of 35±10 nM and excellent ligand specificity. The change in the phase of the electrochemical impedance from the serum baseline, ∆θ(ƒ), measured at 0.1 Hz, was used as the measure for quantifying IL-8 concentration in the fluid. Optimal sensor signal was observed after 15 min incubation, and the sensor exhibited a linear response versus logarithm of IL-8 concentration from 900 fg/ml to 900 ng/ml. A detection limit of around 90 fg/ml, which is significantly lower than the basal clinical levels of 5–10 pg/ml, was observed. Our results are significant for the development of point-of-care and early diagnostics where high sensitivity and short time-to-results are essential.
Cyclohexane allowed to capillary condense from vapor in an annular wedge pore of mica in a surface force apparatus (SFA) remains liquid down to at least 14 K below the bulk melting-point T(m). This is an example of supercooling of a liquid due to confinement, like melting-point depression in porous media. In the wedge pore, however, the supercooled liquid is in equilibrium with vapor, and the amount of liquid (and thereby the radius of curvature r of the liquid-vapor interface) depends on the surface tension gamma(LV) of the liquid, not the interfacial tension between the solid and liquid. At coexistence r is inversely proportional to the temperature depression DeltaT below T(m), in accordance with a recently proposed model [P. Barber, T. Asakawa, and H. K. Christenson, J. Phys. Chem. C 111, 2141 (2007)]. We have now extended this model to include effects due to the temperature dependence of both the surface tension and the enthalpy of melting. The predictions of the improved model have been quantitatively verified in experiments using both a Mark IV SFA and an extended surface force apparatus (eSFA). The three-layer interferometer formed by the two opposing, backsilvered mica surfaces in a SFA was analyzed by conventional means (Mark IV) and by fast spectral correlation of up to 40 fringes (eSFA). We discuss the absence of freezing in the outermost region of the wedge pore down to 14 K below T(m) and attribute it to nonequilibrium (kinetic) supercooling, whereas the inner region of the condensate is thermodynamically supercooled.
We have studied the capillary condensation of water from saturated vapor below 0 degrees C in the annular wedge-pore formed around two mica surfaces in contact in a surface force apparatus. The condensed water remains liquid down to at least -9 degrees C, and the measured condensate size is close to the predictions of a recent model for the dependence of the interfacial curvature of supercooled capillary condensates on temperature and surface tension. The small deviation observed may be accounted for by assuming that solute as K(2)CO(3) from the mica-condensate interface dissolves in the condensates and gives rise to an additional depression of the freezing point apart from that caused by the interface curvature. By contrast, measurements of the interface curvature at relative vapor pressures of 0.95-0.99 at 20 degrees C confirm a significantly larger deviation from the Kelvin equation. The magnitude of the deviation is in remarkable agreement with that calculated from the results of an earlier study of capillary condensation of water from a nonpolar liquid, also at T = 20 degrees C. Evidently, additional solute from the surrounding mica surface migrates into the condensates at room temperature. We conclude that the surface diffusion of ions on mica is much slower at subzero temperatures than at room temperature.
Legislative restrictions and the needs of consumers have created a demand for sustainable materials. Polylactide (PLA) is a biodegradable polyester with advantageous mechanical properties, however, due to its low crystallization rate, it also has low thermomechanical stability. Its range of application temperatures can be widened using nucleating agents and fillers including basalt powder (BP), a waste product from the mining industry. This study analyzed the possibility of enhancing the properties of a PLA-BP composite by chemically treating the filler. Basalt powder was subjected to silanization with 3-aminopropyltriethoxysilane or γ-glycidoxypropyltrimethoxysilane and mixed with PLA at 5–20 wt%. The nucleating effect of a potassium salt of 3,5-bis(methoxycarbonyl) (LAK-301) in the silanized composite was also evaluated. The properties of the materials with silanized BP were compared with the unmodified basalt powder. The miscibility of the filler and the polymer was assessed by oscillatory rheometry. The structure of the composites was studied using scanning electron microscopy and their thermomechanical properties were analyzed using dynamic mechanical thermal analysis. Mechanical properties such as tensile strength, hardness and impact strength, and heat deflection temperature of the materials were also determined. It was concluded that BP-filled nucleated PLA composites presented satisfactory thermomechanical stability without silanization, but chemical treatment could improve the matrix–filler interactions.
Identification of novel genes involved in sexual development is crucial for understanding disorders of sex development (DSD). Here, we propose a member of the START domain family, the X chromosome STARD8, as a DSD candidate gene. We have identified a missense mutation of this gene in 2 sisters with 46,XY gonadal dysgenesis, inherited from their heterozygous mother. Gonadal tissue of one of the sisters contained Leydig cells overloaded with cholesterol droplets, i.e., structures previously identified in 46,XY DSD patients carrying mutations in the STAR gene encoding another START domain family member, which is crucial for steroidogenesis. Based on the phenotypes of our patients, we propose a dual role of STARD8 in sexual development, namely in testes determination and testosterone synthesis. However, further studies are needed to confirm the involvement of STARD8 in sexual development.
We present an efficient solid phase synthesis methodology that provides easy access to a range of functionalised long-chain alkanethiol-oligoethyleneglycols that form well-defined self-assembled monolayers on gold and are compatible with pre- or post-assembly conjugation of (bio)molecules. We demonstrate the versatility of our synthetic route by synthesising LCAT-OEGs with a range of functional moieties, including peptides, electro-active redox groups, chemical handles for post-assembly conjugation of (bio)molecules, and demonstrate the application of our LCAT-OEG monolayers in immunosensing, where they show good biocompatibility with minimal biofouling.
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