Experimentally integrated dynamic modelling for intuitive optimisation of cell based processes and manufacture

作者: Adrian J. Stacey , Elizabeth A. Cheeseman , Katie E. Glen , Rebecca L.L. Moore , Robert J. Thomas

DOI: 10.1016/J.BEJ.2018.01.012

关键词:

摘要: Dynamic mechanistic modelling of cell culture is a key tool in bioprocess development to support optimisation and risk assessment. However, the approach underutilised industry due challenges including lack accessible tools structured approach, difficulty realising computationally tractable (low parameter) yet realistic models, specialised skill sets required. We have proposed that these issues could be partly addressed by developing parsimonious framework comprising set model building blocks, based on ordinary differential equation paradigm, representing common dynamics modulation thereof. The designed avoid obvious pathological behaviours. Further, specific instances within can simply visualised as directed graph with vertices system species, modulations, arcs interactions between them. extended describe timing nature experimental interventions. A visual intuitive route describing models an associated mathematical enables realisation software interface integration standard such those for sensitivity analysis parameter estimation. Such sufficient represent some simple mechanisms underpinning bioprocesses nonetheless lead highly non-linear counterintuitive outcomes. It also has relatively low learning burden users without formal training. concept include, example, partial equation-based approaches stochastic or spatially complex systems built up from small number parametrically well-behaved blocks.

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