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We review the key building blocks of a design framework for modeling and optimizing biomedical systems under development in the Biological Systems Engineering Laboratory and the Centre for Process Systems Engineering at Imperial College. The framework features the following components: (i) in vitro environment, where model parameters can be obtained and new setups can be tested; (ii) in silico environment, including a simulation module for representing relevant physical or biological processes, and an optimization module, for calculating improved in vitro or in vivo outcomes; (iii) in vivo environment, from which organ and patient-specific parameters are collected and which can also implement personalized suggestions for improved outcomes. Two applications in the area of healthy and diseased blood are thoroughly discussed to exemplify the framework's characteristics. We discuss progress in the different areas and the way in which they are connected and finally propose a hybrid in vitro/in silico/in vivo platform.

Recent work developed a novel, biomimetic, cost-effective three-dimensional hollow fibre bioreactor for growing healthy red blood cells ex vivo ( Panoskaltsis et al., 2012 ). This bioreactor recapitulates architectural and functional properties of erythrocyte formation and thereby reduces the need for expensive growth factors by more than an order of magnitude. Individual experiments to empirically improve the bioreactor are intensive, so we propose global superstructure optimisation for bioreactor design. Our approach integrates topological design choices with operating conditions. Design choices include: number of parallelised bioreactors; number and type of hollow fibres; size and aspect ratio. Operating conditions are: feed concentrations; flowrate through the reactor. This manuscript quantitatively demonstrates, for the first time, the potential for ex vivo red blood cell production to compete openly against the transfusion market for rare blood. We discuss the potential of superstructure design not only on this individual bioreactor but also more generally on bioprocess optimisation.