Thesis

Optical tweezer and particle control of nucleation and growth at the microscale

Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2023
Thesis identifier
  • T16663
Person Identifier (Local)
  • 201978227
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Nucleation and growth of crystalline substances from solution is ubiquitous in the production of active pharmaceutical ingredients. However, a basic understanding of nucleation is still lacking after many years of study. One major problem in studies is due to the stochastic nature of nucleation, causing direct observation to be challenging. One possible solution to this is to use optical tweezers to promote nucleation localised to the tweezer focus. Although temporospatial influence and control over nucleation is achievable, some secondary considerations not usually part of the design of crystallisation processes must be considered, with a focus on optical properties with the aim of limiting laser induced heating. A preliminary study was conducted to allow crystal nucleation and growth experiments performed using the optical tweezer setup to be fully understood within context, examining nucleation and growth kinetics up to a scale of 3 mL on high throughput platforms. This study examined the effect of deuterated solvent and doping with spherical microparticles. The use of deuterated solvents resulted in the reduction of primary nucleation rates. Its impact on secondary nucleation and growth depended on the crystallising material. Doping with spherical microparticles was particle material dependent, with silica promoting nucleation and polystyrene’s effect being system and solvent isotopologue dependent. Optical tweezers allow direct control over localised growth of macroscopic crystals with the effect being dependent upon the solvent isotopologue, when using low laser power. Higher laser power allows the time and position of nucleation to be controlled within certain conditions of supersaturation, laser power and relative location of the tweezing focus within the solution. As well as allowing the growth rates of crystals nucleated from bulk undersaturated solutions to be measured, suggesting the enhancement of the local solute concentration in the region surrounding the optical tweezing focus.
Advisor / supervisor
  • Haw, Mark
  • Šefčik, Jan
Resource Type
DOI

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