Single-cell metabolite analysis provides valuable information on cellular function and response to external stimuli. While recent advances in mass spectrometry reached the sensitivity required to investigate metabolites in single cells, current methods commonly isolate and sacrifice cells, inflicting a perturbed state and preventing complementary analyses. Here, we propose a two-step approach that combines nondestructive and quantitative withdrawal of intracellular fluid with subpicoliter resolution using fluidic force microscopy, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The developed method enabled the detection and identification of 20 metabolites recovered from the cytoplasm of individual HeLa cells. The approach was further validated in C-glucose feeding experiments, which showed incorporation of labeled carbon atoms into different metabolites. Metabolite sampling, followed by mass spectrometry measurements, enabled the preservation of the physiological context and the viability of the analyzed cell, providing opportunities for complementary analyses of the cell before, during, and after metabolite analysis.

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The ion conductivity of two series of porous ceramic diaphragms impregnated with caustic potash was investigated by electrochemical impedance spectroscopy. To understand the impact of the pore structure on ion conductivity, the threedimensional (3-D) pore geometry of the diaphragms was characterized with synchrotron x-ray absorption tomography. Ion migration was calculated based on an extended pore structure model, which includes the electrolyte conductivity and geometric pore parameters, for example, tortuosity (s) and constriction factor (b), but no fitting parameters. The calculated ion conductivities are in agreement with the data obtained from electrochemical measurements on the Correspondence concerning this article should be addressed to D. Wiedenmann at daniel.wiedenmann@gmail.com.Published in " " which should be cited to refer to this work.http://doc.rero.ch diaphragms. The geometric tortuosity was found to be nearly independent of porosity. Pore path constrictions diminish with increasing porosity. The lower constrictivity provides more pore space that can effectively be used for mass transport. Direct measurements from tomographs of tortuosity and constrictivity opens new possibilities to study pore structures and transport properties of porous materials.

Intermittent scanning for continuous-wave quantum cascade lasers is proposed along with a custom-built laser driver optimized for such operation. This approach lowers the overall heat dissipation of the laser by dropping its drive current to zero between individual scans and holding a longer pause between scans. This allows packaging cw-QCLs in TO–3 housings with built-in collimating optics, thus reducing cost and footprint of the device. The fully integrated, largely analog, yet flexible laser driver eliminates the need for any external electronics for current modulation, lowers the demands on power supply performance, and allows shaping of the tuning current in a wide range. Optimized ramp shape selection leads to large and nearly linear frequency tuning (>1.5 cm−1). Experimental characterization of the proposed scheme with a QCL emitting at 7.7 μm gave a frequency stability of 3.2×10−5 cm−1 for the laser emission, while a temperature dependence of 2.3×10−4 cm−1/K was observed when the driver electronics was exposed to sudden temperature changes. We show that these characteristics make the driver suitable for high precision trace gas measurements by analyzing methane absorption lines in the respective spectral region.

Small angle x-ray scattering has been proven to be a valuable method for accessing structural information below the spatial resolution limit implied by direct imaging. Here, we theoretically derive the relation that links the subpixel differential phase signal provided by the sample to the moments of scattering distributions accessible by refraction sensitive x-ray imaging techniques. As an important special case we explain the scatter or dark-field contrast in terms of the sample's phase signal. Further, we establish that, for binary phase objects, the nth moment scales with the difference of the refractive index decrement to the power of n. Finally, we experimentally demonstrate the utility of the moments by quantitatively determining the particle sizes of a range of powders with a laboratory-based setup.

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