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Development of a Spectroscopic, Monolithic, Label-Free Probe for Bioprocess Analysis

Platten, Robert H. G.; (2023) Development of a Spectroscopic, Monolithic, Label-Free Probe for Bioprocess Analysis. Doctoral thesis (Eng.D), UCL (University College London).

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Abstract

Cell therapies are a growing category of medicinal techniques that have shown great promise at effectively treating complex diseases such as cancers, particularly leukemia. One of the limiting factors in the manufacture of cell therapies is the ability to monitor and predict the growth behaviour of a cell culture of patient-derived primary cells. A novel bioreactor monitoring system has been developed based on Raman spectroscopy. In designing this system, great care and attention has been paid to gaining an understanding of the performance limiting factors, enabling this device to outperform existing state-of-the-art systems available today. The monitoring device also includes capabilities not present in existing systems, such as the ability to monitor multiple reactors simultaneously or to gain greater information of the system by using multiple monitoring channels simultaneously. Simulations were constructed to model the sub-components of the system. A simulation probe produces an estimation of the performance, and allows the prediction of performance in alternative geometries. Modelling of the passage of light through the spectrometer assembly allows rapid analysis of spectrometer parameters, and optimisation of spectral resolution and optical efficiency. The system was constructed and characterised to ensure performance, before being tested on the bench with samples of glucose, lactic acid and glutamine, determining a limit of detection of 5mM (0.6g/L) in a 200 second acquisition time. The system was also tested with samples at varying cell densities, and demonstrated an ability to measure cell counts to a sensitivity of 60 thousand cells/ml. Metabolite and cell count data was analysed with both a peak integration method and with a PLS algorithm to investigate the performance increase offered by the use of machine learning algorithms.

Type: Thesis (Doctoral)
Qualification: Eng.D
Title: Development of a Spectroscopic, Monolithic, Label-Free Probe for Bioprocess Analysis
Language: English
Additional information: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10175337
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