Tradespace as a decision making tool in bioprocess design

Abstract

The field of systems engineering upholds that fundamental engineering principles exist and are applicable across different domains and contexts. In this thesis, a state-of-the art decision and design evaluation method developed for aerospace systems, Multi-Attribute Tradespace Exploration (MATE) is complemented with Design of Experiments (DoE) and applied for the first time to a bioprocess design problem. The implementation of DoE was necessary due to the high complexity of bioprocess systems, where a design variable (or a reasonably small number of design variables) cannot be easily identified to explain a given attribute of the product or process. DoE not only allows the identification of design variables that most influence a given attribute, but also allows the development of Single-Utility-Functions facilitating the incorporation of the Multi- Utility component of the MATE method. The proposed new MATE-DoE method was implemented in two case studies to assess its applicability; namely bio-production of DHA and bio-production of a lipase enzyme. Based on published DoE experimental results, utility functions and cost estimations were carried out to develop a Tradespace. The resulting Tradespace demonstrates: (a) the possible implementation of the proposed method, (b) that the use of Tradespace complements the traditional bioprocess development practice by allowing decision makers to choose an architecture that optimizes for more than one objective (multi-objective), (c) that the proposed method takes into consideration the complex decision making process of customers (multi-attribute), and (d) that simultaneous comparison analysis to competitors and market standards are possible using the method. While the method was proven to be applicable, it is relatively complex and the number of experiments and market data required might prevent its broad implementation. Also, potential errors and misleading results might result from inaccurate input data. Special attention and effort need to be put in accurate Single-Utility Function (SUF) weight designation to avoid this problem. The importance of assessing the complete bioprocess, as opposed to individual unit operations, is highlighted. Finally, further studies to develop "rules of thumb" in order to simplify the proposed MATE-DoE method is suggested.