With the rise of capillary HPLC systems, open tubular liquid chromatography (OTLC) has been garnering more attention due to the possible fundamental advantages of open tubular systems over conventional packed or monolithic systems. Performance has yet to reach its potential due in part to a variety of technical challenges, resulting in the need for very small injection volumes and sensitive detection. In this work, we have shown that with modern HPLC sample introduction and detection systems, along with careful fabrication of polymer stationary phases, that reverse phase open tubular liquid chromatography may be within reach. We have shown that, with small diameter (i.d. 30m) open tubular columns, complex multi-component mixtures (EPA 610, in-house drug mixture) can be separated. We have also shown that these columns are robust and can function over a wide range of flow rates (200-1000 nl/min), and may be useful for general reverse phase separation in the future. However, currently, more stationary phase development and procedure refinement is needed. Microstructured fibres (MSFs), a relatively new class of optical fibre which confine light within fibres through a refractive index change caused by the use of parallel air channels running throughout the length of the fibre, are explored as a new support material for open tubular liquid chromatography. The fine channel structures of MSFs enable reasonable sample volumes to be used compared to conventional open tubular systems, while offering a similar plug-like flow profile through the fibre. With current sample introduction and flow technologies, we have shown that the potential advantages of MSF columns is great even when simple C18 stationary phases are used; this was able to separate a four PAH mixture. However, a distribution in channel sizes caused by current manufacturing standards and a limited ability to evenly deposit polymer stationary phases in the fibres has kept MSF columns from reaching their full potential. / Thesis (Master, Chemistry) -- Queen's University, 2011-09-14 11:52:41.23