Hardick, OJF; (2013) Fabrication of Nanofibres for High Productivity Downstream Processing. Doctoral thesis , UCL (University College London).

Abstract

As the bioprocessing industry advances in response to global pressure of driving down the cost of new and existing therapeutics the limitations of current chromatography systems are being ever more strained. From the cost of resins to the throughput volumes achievable, the development in downstream processing is not matching that of its upstream counterpart leading to chromatography accounting for over 50% of the total manufacturing costs in a typical process today. As a result the research and development of new systems is prominent and crucial to continuing advances in the industry. This study aims to offer one possible solution to the growing limitations of current purification techniques by exploring a novel chromatographic adsorbent from fabrication to optimised performance in a simulated moving bed system. Non-woven nanofibres offer a high surface area material that allows for convective flow operations. With regulatory demands of a commercial product in mind, we have demonstrated the reproducibility of fabrication of the adsorbents using controlled environment conditions. DEAE functionality was used to demonstrate proof of concept based on criteria including flow & mass transfer properties, binding capacity, reproducibility and life-cycle performance. Assembly into bespoke holders allowing for suitable flow distribution resulted in binding capacities of 20% and reproducible operation at flowrates of 50x those associated with beaded systems giving a potential 10-fold productivity increase. Lifetime studies showed that this adsorbent material operated reproducibly with the complex feed material of clarified yeast homogenate and harsh cleaning-in-place conditions over multiple cycles with reduced fouling when compared to membrane adsorbents. To exploit the properties of these novel adsorbents a simulated moving bed device was developed and optimised to demonstrate true productivities and the preferential operation of nanofibre adsorbents. Reproducible performance in this rapid re-use system was demonstrated using a two-component protein solution of BSA and cytochrome c.

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