Postgraduate research opportunities

Investigating secondary nucleation at the microscale using optical tweezing

Secondary nucleation of crystals using a ‘seed’ crystal is poorly understood phenomenon in pharmaceutical manufacturing. This project is a novel investigation of how microscopic mechanical disturbance of the seed promotes secondary nucleation, using a particle manipulated with an optical tweezer.

Number of places

One

Funding

Stipend, Home fee

Opens

29 January 2019

Duration

3 years

Eligibility

Students applying should have (or expect to achieve) a minimum 2.1 undergraduate degree in a relevant engineering/science discipline, and be highly motivated to undertake multidisciplinary research.

Project Details

In secondary nucleation, already formed ‘seed’ primary crystal nuclei generate new secondary nuclei in response to a varied range of stimuli such as mechanical disturbance, shear stress from flow and the presence of impurities. In manufacturing, uncontrolled secondary nucleation can lead to difficulties managing key process variables and outcome parameters including crystal solid form, growth rates and particle sizes. Secondary nucleation has been shown to be exquisitely sensitive to conditions including slight variations in mechanical disturbance and flow, presenting significant challenges for applications. The fundamental reasons for this sensitivity must lie in microscopic processes of detachment and addition of molecular material from and to existing nuclei, but there is little deep understanding of how these processes influence nucleation.

Most work on secondary nucleation has focussed on macroscopic bulk response eg to flow and agitation, as well as how the process then scales up to industry-relevant volumes, for example in secondary crystal generation from seed crystals in pharmaceutical manufacture. Much of the current industry knowhow and strategy is based on and limited by these empirical and trial-and-error approaches. This project will instead take a direct microscopic scale approach to improve our understanding of how microscale mechanical disturbance and shear flow influence secondary nucleation. We will develop a novel approach based on a particle trapped and manoeuvred by an optical tweezer to provide controlled micron-scale mechanical disturbance of a seed crystal. Direct optical observation then provides data on formation of secondary nuclei including nucleation and growth rates and spatial distribution of new crystals relative to seed and disturbance location. By controlling disturbance force, and rate and type (eg ‘direct’ or glancing impact on the seed crystal, or ‘scraping’ the disturber particle along the seed surface) we can then investigate how micron-scale events trigger secondary nucleation and how mechanical factors influence later crystal growth.

In addition to undertaking cutting edge research, students are also registered for the Postgraduate Certificate in Researcher Development (PGCert), which is a supplementary qualification that develops a student’s skills, networks and career prospects.

Funding Details

The studentship covers full UK/EU PhD tuition fees and a tax-free stipend of (approximately) £14, 500 per year.

Contact us

Ms Jacqueline Brown

+44(0) 141 574 5319

chemeng-pg-admissions@strath.ac.uk

James Weir Building, 75 Montrose Street, Glasgow, G1 1XJ

How to apply

Apply for this PhD project here.

Please quote the project title in your application.