Understanding the fundamental properties of macromolecules has enhanced the development of emerging technologies used to improve biomedical research. Currently, there is a critical need for innovative platforms that can illuminate the function of biomedical reagents in a native environment. To address this need, we have developed an in situ approach to visualize the dynamic behavior of biomedically relevant macromolecules at the nanoscale. Newly designed silicon nitride devices containing integrated "microwells" were used to enclose active macromolecular specimens in liquid for transmission electron microscopy imaging purposes.We were able to successfully examine novel magnetic resonance imaging contrast reagents, micelle suspensions, liposome carrier vehicles, and transcribing viral assemblies. With each specimen tested, the integrated microwells adequately maintained macromolecules in discrete local environments while enabling thin liquid layers to be produced.
BACKGROUND: LC-MS/MS with multiple reaction monitoring (MRM) is a powerful tool for quantifying target analytes in complex matrices. However, the technique lacks selectivity when plasma free metanephrines are measured. We propose the use of multistage fragmentation (MRM 3 ) to improve the analytical selectivity of plasma free metanephrine measurement.
In situ transmission electron microscopy (TEM) imaging through liquids has gained significant interest for a broad range of biological and material science applications [1, 2]. Liquid samples can be confined in a closed cell created by stacking two silicon nitride (SiN) microchips together, creating an isolated liquid chamber within the vacuum system of the microscope. However, creating and maintaining thin, uniform liquid specimens is challenging due to the pressure differential between the liquid-filled cell and the column vacuum. This issue causes significant bulging to occur across the thin membranes [3, 4]. We have shown that reinforcing the SiN membrane reduces membrane bulging while maintaining a suitably large imaging area [1]. Here we describe two types of patent-pending microchip designs with reinforced membranes that further improve the uniformity and area available for sample observation.
A spin wave Doppler technique is used to measure the spin transfer velocity and the current polarization in current-carrying (Ni 0.80 Fe 0.20) 1-x Gd x alloy wires. Reduced magnetization values with Gd doping suggest possible increases in the spin transfer velocity. Contrary to these expectations, we measured a decrease in the spin transfer velocity upon introducing Gd dopants. For a current density of 10 11 A/m 2 , the measured velocities range from 6.0 m/s ± 0.6 m/s for pure Permalloy (Ni 0.80 Fe 0.20) to 2.6 m/s ± 0.3 m/s for (Ni 0.80 Fe 0.20) 0.945 Gd 0.055. Interpretation of these values yields a current polarization ranging from 0.71 ± 0.02 to 0.30 ± 0.01 for the same compositions. These results reveal that Gd dopants in Permalloy have a more significant impact on the current polarization than on the material's magnetization for these alloy compositions.
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