Laser-induced nucleation for crystallisation of high-value materials in continuous manufacturing processes

Batch processing in tanks is the favoured method in industry for manufacture of high-value solid chemicals, such as agrochemicals, dyes and pharmaceuticals. There are a number of disadvantages to batch processing: large amounts of material are committed to each stage; failure can cause loss of the entire batch; there can be large variations in batch repeatability; and it is difficult to scale-up to larger volumes due to limitations on heat flow. Continuous flow manufacture in pipelines offers significant improvements over batch processing: continual processing of small volumes reduces risks in process failures; it is greener technology because it produces less waste; throughput can be increased; capital and running costs are lower; higher surface areas make it easier to heat and cool processes. A grand challenge in implementing continuous flow manufacture is handling of solids, in particular nucleation of fine crystals. Properties of the solid, such as size, shape and internal structure of crystals have enormous effects on their suitability, e.g., as drugs, pesticides, fertilizers. These properties can be difficult to control. Mixing and shear changes the fluid's readiness to grow crystals.

Our research programme aims to improve on current methods for crystallisation in continuous flow by using short, intense pulses of laser light to induce nucleation at specific points and times in the tubes of a continuous flow reactor. So far our laser-induced crystallisation method has been studied in the laboratory using only static sample vials and droplets. We therefore need to study our technique under mixing and flow conditions. Our objective is to demonstrate that our method can grow crystals at different locations where the fluid conditions favour certain crystal shapes, sizes and structures. Such techniques are not already available to industry. Even fractional improvements through this method could yield substantial improvements in the quality of solids, and could encourage industry to switch to continuous flow for more processes. Of course we do not claim that this will be a magic bullet to solve all challenges for continuous manufacture of high-value solids. However, we believe that the technique could stand to make significant savings and improvements in some processes, e.g., in the pharmaceutical industry.

To make our programme relevant to the needs of industry, our project will embark on collaboration with a recently formed consortium for Continuous Manufacture and Crystallisation (CMAC). This group have secured significant investment through government (EPSRC), seven universities, three top-tier global-scale manufacturers (GlaxoSmithKline, AstraZeneca, Novartis), and another 28 industrial partners. CMAC aims to accelerate the adoption of continuous manufacturing processes, systems and plants for the production of pharmaceuticals and fine-chemicals to higher levels of quality, with lower costs, more quickly, and in a more sustainable manner. Our collaboration will ensure that industry leaders have fast and direct access to the outcomes of our research programme.

The direct academic impacts of the proposed research include a deeper knowledge of the fundamental chemistry and physics of nucleation under flow conditions. Understanding gained from this work may be extended to diverse branches of science where nucleation is important, e.g., atmospheric condensation, biocrystallisation, ice formation.

Direct economic impacts include making available a new technique for solid particle formation under flow conditions for continuous manufacture. The research outcomes will enable manufacturers to implement new continuous flow processes, or to improve existing processes. Such improvements will lead to reduced capital and running costs, reduced process risks, enhanced sustainability, and enhanced product quality. These improvements will be beneficial to manufacture industries such as the pharmaceuticals (e.g., drug production), agrochemicals (such as pesticide), and food industry (e.g., ice formation).

The academic and economic impacts extend to wider societal issues, e.g., predicting cloud condensation and aerosol formation in the atmosphere for weather prediction, and enhanced manufacturing output leading to greater employment and wealth-creation.