Nanoparticles for the control of nucleation and crystallisation

Despite the increasing successes in discovering protein-based medicines, their manufacture in a cost effective and reliable fashion remains a major industrial challenge, which currently limits the ability of the biopharmaceutical industry to deliver solutions to patients. Crystallisation can potentially offer a paradigm-changing breakthrough for purification in biopharmaceuticals. It is well known that nucleation is a conception stage and governs the entire crystallisation process. The influence of nanoparticle porosity and surface chemistry on heterogeneous nucleation and crystallisation of macromolecules will be presented - for batch and continuous crystallisation (oscillatory flow crystallisers) platforms for small molecule pharmaceutical solids and large complex biopharmaceuticals. The impact of nanoparticle seed properties on the induction times for batch crystallisation and development of a continuous bioseparation platform will be presented. A Template Induced Polymorphic Occurrence Domain (TiPOD) concept on the nucleation of different polymorphic forms, and approaches based on Quartz Crystal Microbalance for surface heterogeneous nucleation will be discussed. For the continuous platform, the impact of amplitude and frequency on crystallisation of a model protein (lysozyme), and a scale-up workflow will be presented. Here, we demonstrate the potential of a continuous protein crystallisation platform for downstream separation. Here, we show how nanoparticles can be designed to control nucleation and develop seeding strategies to realise a continuous biocrystallisation platform.

Dr Jerry YY Heng heads the Surfaces and Particle Engineering Laboratory at the Department of Chemical Engineering, Imperial College London. He holds a B.Eng (Chem. Eng, 1st Class) from Universiti Teknologi Malaysia and a Ph.D. in Chemical Engineering from Imperial College London (2006). His research interest is in crystallisation and surface properties of crystalline solids (processing, manufacturability and formulation). He currently has over 90 journal publications (Scopus ID 12799561600), and currently supervises 3 postdocs and 6 PhD students. He currently holds an EPSRC Manufacturing the Futures Fellow (2016-2021), a Fellow of the Academy of Pharmaceutical Sciences Great Britain and the Higher Education Academy, Deputy Editor in Chief for Chemical Engineering Research & Design, thematic editor of Particuology and serves on the Editorial Board of the Proceedings of the Royal Society of London A.