About the Project
Manufacturing nano- and microstructured products often involves nucleation of solids from solution, to form crystals, gels or disordered aggregates. A major example is the production of pharmaceutical crystals, but other applications include nanoporous materials (eg for energy/gas storage), microstructured materials (eg for photonics, ceramics and foods) and nanoparticle-based materials (eg quantum dots for medical and electronics technology).
Control of nucleation in these manufacturing processes remains a major challenge. In pharmaceuticals, nucleation of the wrong ‘polymorph’ crystal structure can lead to complete product failure costing billions of dollars[1]. This lack of control is partly because the fundamental science of nucleation, beyond very simple and usually inapplicable models, is unclear[2]. Additionally most manufacturing processes involve flow, whether stirring a vessel in a ‘batch’ process or in continuous manufacturing, and flow has been shown to have significant effects on nucleation and growth. In pharmaceuticals, again, even though crystals are assembled from molecules, nucleation has been shown to involve larger micron-scale liquid ‘clusters’, so that the energy input even by relatively weak flows (those typical in manufacture and transport) can have major structural consequences [3]. Furthermore because in such materials length scales (10nm to microns) and kinetic timescales (10-3 to 100 s) are larger and longer than the purely ‘molecular’, shear/extension rates in weak and slow flows also have significant interplay with phase transitions and structure. Essentially, the energy input by flow plays a significant role in determining how the system explores its kinetic phase diagram as the product is formed.
The aim of this project is both to improve our understanding of this interplay of flow with nucleation, and to explore use of flow, localised to the micron-scale, to control nucleation. The ultimate goal is to provide the capability to ‘dial up’ any desired nucleation rate and crystal or aggregate structure using flow.
Localising the use of flow is the key advance. Typically, nucleation is a highly localised event, while flow is applied, in typical manufacturing processes, to the bulk of the entire system: so such ‘process flow’ is too blunt a tool with which to try to control small-scale local nucleation. Therefore the project’s objective is to design and demonstrate a non-invasive optically-driven method to generate a localised, micron-scale flow in the crystallizing system. An optical tweezer—a laser used to manipulate objects at the micron-scale—will be used to create a localised shear flow in the nucleating fluid by rotating a micron-scale obstacle [4]. The obstacle’s position, shape and size control the flow field, while rate of rotation (set by laser intensity) controls flow rates. The method thus produces a well-defined ‘nucleation zone’ where parameters such as nucleation rate density (the number of nuclei formed per unit time per unit volume) and crystal structure can, in principle, be directly ‘selected’ via the precisely-controlled flow rate and flow field geometry.
Having developed the method, the further objective is to develop a prototype device which can be straightforwardly implemented in real industrial processes such as pharmaceutical production.
Funding Notes
This PhD project is offered on a self-funding basis; it is open to applicants with their own funding or those applying to funding sources.
Tuition fees for 2016 for postgraduate research students at the University of Strathclyde are £4,121 for home/EU students and £17,500 for international students; this does not include bench fees.
References
[1] D. Erdemir et al, Curr. Opin. Drug Discovery Development 10 (2007), 746.
[2] R.J. Davey et al, Angewandte Rev 52 (2013), 2166
[3] eg P. Vekilov, Nanoscale 2(2010) 2346.
[4] A.I. Bishop et al Phys. Rev. Lett. 92(2004) 198104