Towards continuous biomanufacturing a computational approach for the intensification of monoclonal antibody production

Current industrial trends encourage the development of sustainable, environmentally friendly processes with reduced energy and raw material consumption. Meanwhile, the increasing market demand as well as the tight regulations in product quality, necessitate efficient operating procedures that guarantee products of high purity. In this direction, process intensification via continuous operation paves the way for the development of novel, eco-friendly processes, characterized by higher productivity compared to batch (Nicoud, 2014). The shift towards continuous operation could advance the market of high value biologics, such as monoclonal antibodies (mAbs), as it would lead to shorter production times, decreased costs, as well as significantly less energy consumption (Konstantinov and Cooney, 2015, Xenopoulos, 2015). In particular, mAb production comprises two main steps: the culturing of the cells (upstream) and the purification of the targeted product (downstream). Both processes are highly complex and their performance depends on various parameters. In particular, the efficiency of the upstream depends highly on cell growth and the longevity of the culture, while product quality can be jeopardized in case the culture is not terminated timely. Similarly, downstream processing, whose main step is the chromatographic separation, relies highly on the setup configuration, as well as on the composition of the upstream mixture. Therefore, it is necessary to understand and optimize both processes prior to their integration. In this direction, the design of intelligent computational tools becomes eminent. Such tools can form a solid basis for the: (i) execution of cost-free comparisons of various operating strategies, (ii) design of optimal operation profiles and (iii) development of advanced, intelligent control systems that can maintain the process under optimal operation, rejecting disturbances. In this context, this work focuses on the development of advanced computational tools for the improvement of the performance of: (a) chromatographic separation processes and (b) cell culture systems, following the systematic PAROC framework and software platform (Pistikopoulos et al., 2015). In particular we develop model-based controllers for single- and multi-column chromatographic setups based on the operating principles of an industrially relevant separation process. The presented strategies are immunized against variations in the feed stream and can successfully compensate for time delays caused due to the column residence time. Issues regarding the points of integration in multi-column systems are also discussed. Moreover, we design and test in silico model-based control strategies for a cell culture system, aiming to increase the culture productivity and drive the system towards continuous operation. Challenges and potential solutions for the seamless integration of the examined bioprocess are also investigated at the end of this thesis.Open Acces

Predictive control using an FPGA with application to aircraft control

Alternative and more efficient computational methods can extend the applicability of MPC to systems with tight real-time requirements. This paper presents a ``system-on-a-chip'' MPC system, implemented on a field programmable gate array (FPGA), consisting of a sparse structure-exploiting primal dual interior point (PDIP) QP solver for MPC reference tracking and a fast gradient QP solver for steady-state target calculation. A parallel reduced precision iterative solver is used to accelerate the solution of the set of linear equations forming the computational bottleneck of the PDIP algorithm. A numerical study of the effect of reducing the number of iterations highlights the effectiveness of the approach. The system is demonstrated with an FPGA-in-the-loop testbench controlling a nonlinear simulation of a large airliner. This study considers many more manipulated inputs than any previous FPGA-based MPC implementation to date, yet the implementation comfortably fits into a mid-range FPGA, and the controller compares well in terms of solution quality and latency to state-of-the-art QP solvers running on a standard PC.This work was supported by EPSRC (Grants EP/G030308/1, EP/G031576/1 and EP/I012036/1) and the EU FP7 Project EMBOCON grant agreement number FP7-ICT-2009-4 248940, as well as industrial support from Xilinx, the Mathworks, and the European Space Agency.This is the author's version of an article that has been published in this journal. Changes were made to this version by the publisher prior to publication. The final version of record is available at: http://dx.doi.org/10.1109/TCST.2013.2271791. Copyright (c) 2014 IEEE. Personal use is permitted. For any other purposes, permission must be obtained from the IEEE by emailing [email protected]

1-Bit processing based model predictive control for fractionated satellite missions

In this thesis, a 1-bit processing based Model Predictive Control (OBMPC) structure is proposed for a fractionated satellite attitude control mission. Despite the appealing advantages of the MPC algorithm towards constrained MIMO control applications, implementing the MPC algorithm onboard a small satellite is certainly challenging due to the limited onboard resources. The proposed design is based on the 1-bit processing concept, which takes advantage of the affine relation between the 1-bit state feedback and multi-bit parameters to implement a multiplier free MPC controller. As multipliers are the major power consumer in online optimization, the OBMPC structure is proven to be more efficient in comparison to the conventional MPC implementation in term of power and circuit complexity. The system is in digital control nature, affected by quantization noise introduced by Δ∑ modulators. The stability issues and practical design criteria are also discussed in this work. Some other aspects are considered in this work to complete the control system. Firstly, the implementation of the OBMPC system relies on the 1-bit state feedbacks. Hence, 1-bit sensing components are needed to implement the OBMPC system. While the ∆∑ modulator based Microelectromechanical systems (MEMS) gyroscope is considered in this work, it is possible to implement this concept into other sensing components. Secondly, as the proposed attitude mission is based on the wireless inter-satellite link (ISL), a state estimator is required. However, conventional state estimators will once again introduce multi-bit signals, and compromise the simple, direct implementation of the OBMPC controller. Therefore, the 1-bit state estimator is also designed in this work to satisfy the requirements of the proposed fractionated attitude control mission. The simulation for the OBMPC is based on a 2U CubeSat model in a fractionated satellite structure, in which the payload and actuators are separated from the controller and controlled via the ISL. Matlab simulations and FPGA implementation based performance analysis shows that the OBMPC is feasible for fractionated satellite missions and is advantageous over the conventional MPC controllers