A brass-platinum electrochemical micro flow cell was developed to extract [18F]fluoride from an aqueous solution and release it into an organic based solution, suitable for subsequent radio-synthesis, in a fast and reliable manner. This cell does not suffer electrode erosion and is thus reusable while operating faster by enabling increased voltages. By optimizing temperature, trapping and release potentials, flow rates, and electrode materials, an overall [18F]fluoride trapping and release efficiency of 84±5% (n=7) was achieved. X-ray photoelectron spectroscopy (XPS) was used to analyze electrode surfaces of various metal-metal systems and the findings were correlated with the performance of the electrochemical cell. To demonstrate the reactivity of the released [18F]fluoride, the cell was coupled to a flow-through reactor and automated synthesis of [18F]FDG with a repeatable decay-corrected yield of 56±4% (n=4) was completed in <15 min. A multi-human dose of 5.92 GBq [18F]FDG was also demonstrated.

We report the high temperature reaction of iron acetylacetonate in phenyl ether in the presence of oleic acid and oleylamine that was used to synthesize monodisperse Fe3O4 nanoparticles. X-ray diffraction profile and high-angle annular dark-field images give evidence of self-assembled arrays with nanoparticle size of 4 nm. Magnetization versus temperature in the temperature range 2.5–160 K was measured in zero-field-cooled and field-cooled experiments and a blocking temperature Tb=20 K was obtained. Above Tb the nanoparticles show superparamagnetic behavior and the magnetization versus field for various temperature follows the Langevin function. M-H curves below Tb indicate the ferromagnetic behavior with Hc=60–400 Oe for temperature T=2.5–18.5 K.

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Miniaturized synthesis of positron emission tomography (PET) tracers is poised to offer numerous advantages including reduced tracer production costs and increased availability of diverse tracers. While many steps of the tracer production process have been miniaturized, there has been relatively little development of microscale systems for the quality control (QC) testing process that is required by regulatory agencies to ensure purity, identity, and biological safety of the radiotracer before use in human subjects. Every batch must be tested, and in contrast with ordinary pharmaceuticals, the whole set of tests of radiopharmaceuticals must be completed within a short-period of time to minimize losses due to radioactive decay. By replacing conventional techniques with microscale analytical ones, it may be possible to significantly reduce instrument cost, conserve lab space, shorten analysis times, and streamline this aspect of PET tracer production. We focus in this work on miniaturizing the subset of QC tests for chemical identity and purity. These tests generally require high-resolution chromatographic separation prior to detection to enable the approach to be applied to many different tracers (and their impurities), and have not yet, to the best of our knowledge, been tackled in microfluidic systems. Toward this end, we previously explored the feasibility of using the technique of capillary electrophoresis (CE) as a replacement for the "gold standard" approach of using high-performance liquid chromatography (HPLC) since CE offers similar separating power, flexibility, and sensitivity, but can readily be implemented in a microchip format. Using a conventional CE system, we previously demonstrated the successful separation of non-radioactive version of a clinical PET tracer, 3'-deoxy-3'-fluorothymidine (FLT), from its known by-products, and the separation of the PET tracer 1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-cytosine (D-FAC) from its α-isomer, with sensitivity nearly as good as HPLC. Building on this feasibility study, in this paper, we describe the first effort to miniaturize the chemical identity and purity tests by using microchip electrophoresis (MCE). The fully automated proof-of-concept system comprises a chip for sample injection, a separation capillary, and an optical detection chip. Using the same model compound (FLT and its known by-products), we demonstrate that samples can be injected, separated, and detected, and show the potential to match the performance of HPLC. Addition of a radiation detector in the future would enable analysis of radiochemical identity and purity in the same device. We envision that eventually this MCE method could be combined with other miniaturized QC tests into a compact integrated system for automated routine QC testing of radiopharmaceuticals in the future. Graphical abstract Miniaturized quality control (QC) testing of batches of radiopharmaceuticals via microfluidic analysis. The proof-of-concept hybrid microchip electrophoresis (MCE) device demonstrated the fea...

A novel injector for microchip electrophoresis (MCE) has been designed and evaluated that achieves very high repeatability of injection volume suitable for quantitative analysis. It eliminates the injection biases in electrokinetic injection and the dependence on pressure and sample properties in hydrodynamic injection. The microfluidic injector, made of poly(dimethylsiloxane) (PDMS), operates similarly to an HPLC injection valve. It contains a channel segment (chamber) with a well-defined volume that serves as an “injection loop”. Using on-chip microvalves, the chamber can be connected to the sample source during the “loading” step, and to the CE separation channel during the “injection” step. Once the valves are opened in the second state, electrophoretic potential is applied to separate the sample. For evaluation and demonstration purposes, the microinjector was connected to a 75 µm ID capillary and UV absorbance detector. For single compounds, a relative standard deviation (RSD) of peak area as low as 1.04% (n=11) was obtained, and for compound mixtures, RSD as low as 0.40% (n=4) was observed. Using the same microchip, the performance of this new injection technique was compared to hydrodynamic injection and found to have improved repeatability and less dependence on sample viscosity. Furthermore, a non-radioactive version of the positron-emission tomography (PET) imaging probe, FLT, was successfully separated from its known 3 structurally-similar byproducts with baseline resolution, demonstrating the potential for rapid, quantitative analysis of impurities to ensure the safety of batches of short-lived radiotracers. Both the separation efficiency and injection repeatability were found to be substantially higher when using the novel volumetric injection approach compared to electrokinetic injection (performed in the same chip). This novel microinjector provides a straightforward way to improve the performance of hydrodynamic injection and enables extremely repeatable sample volume injection in MCE. It could be used in any MCE application where volume repeatability is needed, including the quantitation of impurities in pharmaceutical or radiopharmaceutical samples.

Spinal cord injury (SCI) produces a significant loss of oligodendrocytes (OL) and demyelination. The oligodendrocyte precursor cells (OPCs) response includes a group of cellular changes in OPCs that are directed to replenish OL loss from the injury. However, this adaptive response is hampered and OPCs eventually die or fail to differentiate to mature and functional OL. In this study, we wanted to evaluate if overexpression of human superoxide dismutase 1 (hSOD1) in OPCs from the SOD1 transgenic rat could improve some of the features of the OPC response in vitro. We found that hSOD1 overexpression increases the proliferation of OPCs and accelerates their differentiation to mature OL in vitro. Furthermore, hSOD1 overexpression reduces oxidative stress-mediated death in OPCs. These results suggest hSOD1 as a therapeutic target to increase OPC response success and potentially, OL replacement and remyelination after SCI.

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Microscale systems that enable measurements of oncological phenomena at the single-cell level have a great capacity to improve therapeutic strategies and diagnostics. Such measurements can reveal unprecedented insights into cellular heterogeneity and its implications into the progression and treatment of complicated cellular disease processes such as those found in cancer. We describe a novel fluid-delivery platform to interface with low-cost microfluidic chips containing arrays of microchambers. Using multiple pairs of needles to aspirate and dispense reagents, the platform enables automated coating of chambers, loading of cells, and treatment with growth media or other agents (e.g., drugs, fixatives, membrane permeabilizers, washes, stains, etc.). The chips can be quantitatively assayed using standard fluorescence-based immunocytochemistry, microscopy, and image analysis tools, to determine, for example, drug response based on differences in protein expression and/or activation of cellular targets on an individual-cell level. In general, automation of fluid and cell handling increases repeatability, eliminates human error, and enables increased throughput, especially for sophisticated, multistep assays such as multiparameter quantitative immunocytochemistry. We report the design of the automated platform and compare several aspects of its performance to manually-loaded microfluidic chips.