Browsing by Subject "miniatyrisointi"
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(2013)It is well known that the central nervous system is a highly isolated tissue. Because of this the physico-chemical criteria to be met by an orally administered central nervous system drug are very strict. This work describes methods that can be used to select drug candidates and screening collections that have a higher possibility of being relevant to central nervous system drug development projects. This work also argues that small molecular space is so vast that it is difficult to imagine any progress without focusing screening collections in some way or another. Given that most available commercial compounds are very similar in some respects, it is very much possible that this presents a bottle-neck for the progress of drug development as a whole. Therefore, research on novel methods for compound production are also evaluated. In addition, this work describes the miniaturization and automation of a previously published ELISA-based assay. This assay measures the activation of a tyrosine kinase receptor (TrkB), expressed in a fibroblast cell line. The receptor, and it's endogenous ligand, Brain-derived neurotrophic factor, have been linked to the mechanism of action of previously discovered medical interventions used in the treatment of depression. Such an assay can be used to discover either small molecule agonists or antagonists acting upon the receptor. These molecules could possibly be clinically relevant in the treatment of depressive disorders and anxiety. It is demonstrated that it is indeed possible to miniaturize and automate the method, making it significantly more suitable for high-throughput screening. The original method was carried out in 24-well plates, transferring the samples to another plate for measurement. The new design uses 96-well plates and performs the entire process on the same plate.
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(2014)Miniaturizing of analytical techniques in mass spectrometry has received a lot of attention amongst scientists. The gains of miniaturization of analytical systems are rapid analyses, lower solvent consumption, the option for automatization and lower costs. A glass-made microchip heated nebulizer and a newer version, steel-made nebulizer, have been recently developed. The aim of this study was to evaluate and compare performances of the nebulizers. Changes in test conditions and effects of different dopants to intensiveness of the analytes' signals were analyzed. Speed of nebulizer gas, speed of analyte flow and magnitude of heating were the parameters of the changes in test conditions. The temperature of the flow from the nebulizers was also measured and analyzed. The intensiveness profiles of the analytes between the nebulizers were unequal, when changes in the speed of nebulizer gas and magnitude of heating were measured. The nebulizers reacted the same way to changes of the speed of analyte flow. The faster the analyte flow was, the more intensive the analytes' signals were. The steel tube nebulizer generated on average more intensive signals of the analytes than glass-made microchip. Temperature of the glass-made nebulizer was considerably higher than that of steel tube nebulizer. The most intensive signals of the analytes were achieved when toluene was used as a dopant. Steel tube nebulizer was more efficient in ionizing analytes than glass-made microchip. However, with steel tube nebulizer it could be difficult to analyze compounds with high boiling point. One goal of this study was to combine the steel tube nebulizer with capLC, but due to technical failures of the capLC equipment this was not possible. In the future, it would be beneficial to improve the steel tube nebulizer's heating mechanism. Also it could be combined with other ionization techniques as has been done with glass-made nebulizer.
Now showing items 1-2 of 2