Physical and chemical property characterisation in HTT by in-situ analysis and smart data processing

Modern fine chemical research and production (for example in pharmaceuticals or in health-care product formulation) is moving away from processes in large volumes in batch vessels to flowing systems that offer advantages in manufacturing efficiencies. Continuous flow systems can be useful in high throughput experimentation as well as in production, as changes in conditions can be implemented quickly to assess their effect on a reaction or formulation, leading to faster optimization. However, in order to control the processes and investigate quickly the outcome of parameter changes, one needs to be able to make in situ or non-invasive measurements of the chemical and physical properties. This project had three strands of research that supported the acquisition and use of data from high throughput and flow systems.
In the case of the optical research, two laser-cavity routes were followed to produce a) an optical system capable of detecting 1 molecule in a trillion by building a laser cavity around the reaction vessel and b) real-time Raman analysis of the chemistry taking place with a spatial resolution of around 10 microns. The first approach involved intra-cavity absorption measurements, which although successful were found to be limited in their applicability. The second approach was more fruitful, although the full development did not take place until a follow-on research project. Part of the optical research featured developments in probe technology for mid-infrared spectroscopic analysis that could be done in situ to allow chemical changes to be monitored in real time. This work led to further research with a Scottish-based SME and resulted in an optimized MIR optical fibre probe based on novel MIR transmitting fibres.
The main outcome of the acoustic part of the research was a better understanding of the instrumental and transducer developments required for active acoustic analysis of viscous multi-component media. In particular, the limitations of current systems for analysis of ultrasonic wave propagation across e.g. detergents or shampoo liquids were identified and partially rectified. The intention of this part of the project was to devise measurement systems based on acoustic spectrometry to study changes in formulations and their physical properties. As a result of the findings from this project other acoustic investigations were pursued with separate funding resulting in improved transducer design, signal processing algorithms and modeling methodologies.
The multivariate mathematical aspects of the project were focused on novel algorithms for quantitative analysis by Raman spectrometry and other optical techniques, especially where corrections were required to account for changes in process parameters on measured spectra. As with the other parts of the project, the outcomes led to follow-on research that produced additional algorithms that could be used to account for scattering effect by particles and permitted easy calibration transfer between instrumental systems such as when different optical probes were to be used in e.g. scaled-up operations.
So, in addition to producing direct outcomes, the project nurtured research in several additional directions that resulted in new funding being realized from industry and the research funders.