X-ray crystallography (the analysis of the diffraction pattern of a high-power X-ray) has become the preferred method for investigating complex molecular structures. Research has continued to improve both the hardware and software elements of this methodology; refining critical factors such as detectors, beam generation and post modelling computation to keep increasing performance. One overlooked, yet critical factor is increasingly impacting the developmental progress of this technology, sample loading. This is currently achieved via expensive, electromechanical and robotics systems, but technological advancement can increase measurement accuracy by improving positional accuracy, maintaining the crystal integrity by keeping them in their native solution and reduce experimentation times through faster loading; factors which are all currently limiting the minimum sample crystal size to >5 µm. A by product will be a reduction in investigation costs by reducing beamline set-up and testing time, potentially opening the technique to other research fields, e.g. biomedical, archaeological or engineering. This work focusses on a specific sub-section of the loading challenge, introducing a method which could achieve reliable sample loading of crystals below 5 µm, thus opening up the low micro and nano crystallography frontier. The solution proposed in this thesis implements a novel sample loading method, an optofluidic system which combines the advantages of both evanescent field optical tweezing and microfluidics. A low cost commercial Nanotweezer system and optofluidic chip technology were assessed via interferometry and SEM microscopy to determine the microfluidic and waveguide architecture. It was shown that across several chip batches the waveguide dimensions remained similar but with notable structural variations due to imperfect production and poor post manufacturing modifications, highlighting the need for an alternative chip design and manufacturing process. Factors affecting the sample generation and stabilization, crystallisation and microfluidic parameters were also investigated through a series of tweezing trials on latex nanospheres and lysosome crystals. Results indicated that an operational temperature of 2°C and a horizontal chip orientation (0° being optimal, but effective up to 60°) were the most critical factors. COMSOL modelling highlighted that both the evanescent field form and intensity could be tailored to the crystal size and shape via the addition of either “doughnut” or “bullseye” nano plasmonic antennas on the surface of the optofluidic chip waveguides. When combined with a 1-D PhC resonator array they formed a hybrid waveguide that increased the electric field intensity from 1.10 × 10⁷ V/m to 1.70 × 10⁷ V/m. A prototype manufacturing route for the refined architecture was evaluated. A first batch of upgraded optofluidics chips was upgraded using focused ion beam assisted gas deposition to generate the platinum plasmonic antennas. This method however, proved unsuccessful so the remaining batch was upgraded using e-beam lithography to generate gold plasmonic antennas. While satisfactory launching of the newly upgraded chips was not achieved due to technical limitations, characterisation testing of the default waveguide demonstrated microscale (2 µm) and sub-micron (0.8 µm) tweezing, and that such performance could theoretically be enhanced with the addition of the plasmonic antenna structures.