Improvement in the design and operation of Bio-reactors and Bio-separators based on SMB Technology

Ph.DDOCTOR OF PHILOSOPH

Modeling and Optimization of Rare Earth Element Chromatography

The Rare Earth Elements are a group of metals, that are of growing technical and economical importance. Current separation techniques can be detrimental to the environment, and a clean technology for separation has been devised, based on analytical chromatography of the REEs. The thesis presents column preparation and impregnation to give desired properties of the separation system, experimental and model based optimization for operating points and design of a chromatography step for separating REEs

Advances in simulated moving bed : new operating modes : new design methodologies and product (FlexSMB-LSRE) development

Tese de doutoramento. Engenharia Química e Biológica. Faculdade de Engenharia. Universidade do Porto. 200

Optimisation of flow chemistry: tools and algorithms

The coupling of flow chemistry with automated laboratory equipment has become increasingly common and used to support the efficient manufacturing of chemicals. A variety of reactors and analytical techniques have been used in such configurations for investigating and optimising the processing conditions of different reactions. However, the integrated reactors used thus far have been constrained to single phase mixing, greatly limiting the scope of reactions for such studies. This thesis presents the development and integration of a millilitre-scale CSTR, the fReactor, that is able to process multiphase flows, thus broadening the range of reactions susceptible of being investigated in this way. Following a thorough review of the literature covering the uses of flow chemistry and lab-scale reactor technology, insights on the design of a temperature-controlled version of the fReactor with an accuracy of ±0.3 ºC capable of cutting waiting times 44% when compared to the previous reactor are given. A demonstration of its use is provided for which the product of a multiphasic reaction is analysed automatically under different reaction conditions according to a sampling plan. Metamodeling and cross-validation techniques are applied to these results, where single and multi-objective optimisations are carried out over the response surface models of different metrics to illustrate different trade-offs between them. The use of such techniques allowed reducing the error incurred by the common least squares polynomial fitting by over 12%. Additionally, a demonstration of the fReactor as a tool for synchrotron X-Ray Diffraction is also carried out by means of successfully assessing the change in polymorph caused by solvent switching, this being the first synchrotron experiment using this sort of device. The remainder of the thesis focuses on applying the same metamodeling and cross-validation techniques used previously, in the optimisation of the design of a miniaturised continuous oscillatory baffled reactor. However, rather than using these techniques with physical experimentation, they are used in conjunction with computational fluid dynamics. This reactor shows a better residence time distribution than its CSTR counterparts. Notably, the effect of the introduction of baffle offsetting in a plate design of the reactor is identified as a key parameter in giving a narrow residence time distribution and good mixing. Under this configuration it is possible to reduce the RTD variance by 45% and increase the mixing efficiency by 60% when compared to the best performing opposing baffles geometry

A multi-criteria design framework for the synthesis of complex pressure swing adsorption cycles for CO2 capture

Pressure Swing Adsorption (PSA) is the most efficient option for middle scale separation processes. PSA is a cyclic process whose main steps are adsorption, at high pressure, and regeneration of the adsorbent, at low pressure. The design of PSA cycles is still mainly approached experimentally due to the computational challenges posed by the complexity of the simulation and by the need to detect the performance at cyclic steady state (CSS). Automated tools for the design of PSA processes are desirable to allow a better understanding of the the complex relationship between the performance and the design variables. Furthermore, the operation is characterised by trade-o�ffs between conflicting criteria. A multi-objective flowsheet design framework for complex PSA cycles is presented. A suite of evolutionary procedures, for the generation of alternative PSA con�figurations has been developed, including simple evolution, simulated annealing as well as a population based procedure. Within this evolutionary procedure the evaluation of each cycle confi�guration generated requires the solution of a multi-objective optimisation problem which considers the conflicting objectives of recovery and purity. For this embedded optimisation problem a multi-objective genetic algorithm (MOGA), with a targeted fi�tness function, is used to generate the approximation to the Pareto front. The evaluation of each alternative design makes use of a number of techniques to reduce the computational burden. The case studies considered include the separation of air for N2 production, a fast cycle operation which requires a detailed di�ffusion model, and the separation of CO2 from flue gases, where complex cycles are needed to achieve a high purity product. The novel design framework is able to determine optimal configurations and operating conditions for PSA for these industrially relevant case studies. The results presented by the design framework can help an engineer to make informed design decisions

State Estimation, Covariance Estimation, and Economic Optimization of Semi-Batch Bioprocesses

One of the most critical aspects of any chemical process engineer is the ability to gather, analyze, and trust incoming process data as it is often required in control and process monitoring applications. In real processes, online data can be unreliable due to factors such as poor tuning, calibration drift, or mechanical drift. Outside of these sources of noise, it may not be economically viable to directly measure all process states of interest (e.g., component concentrations). While process models can help validate incoming process data, models are often subject to plant-model mismatches, unmodeled disturbances, or lack enough detail to track all process states (e.g., dissolved oxygen in a bioprocess). As a result, directly utilizing the process data or the process model exclusively in these applications is often not possible or simply results in suboptimal performance. To address these challenges and achieve a higher level of confidence in the process states, estimation theory is used to blend online measurements and process models together to derive a series of state estimates. By utilizing both sources, it is possible to filter out the noise and derive a state estimate close to the true process conditions. This work deviates from the traditional state estimation field that mostly addresses continuous processes and examines how techniques such as extended Kalman Filter (EKF) and moving horizon estimation (MHE) can be applied to semi-batch processes. Additionally, this work considers how plant-model mismatches can be overcome through parameter-based estimation algorithms such as Dual EKF and a novel parameter-MHE (P-MHE) algorithm. A galacto-oligosaccharide (GOS) process is selected as the motivating example as some process states are unable to be independently measured online and require state estimation to be implemented. Moreover, this process is representative of the broader bioprocess field as it is subject to high amounts of noise, less rigorous models, and is traditionally operated using batch/semi-batch reactors. In conjunction with employing estimation approaches, this work also explores how to effectively tune these algorithms. The estimation algorithms selected in this work require careful tuning of the model and measurement covariance matrices to balance the uncertainties between the process models and the incoming measurements. Traditionally, this is done via ad-hoc manual tuning from process control engineers. This work modifies and employs techniques such as direct optimization (DO) and autocovariance least-squares (ALS) to accurately estimate the covariance values. Poor approximation of the covariances often results in poor estimation of the states or drives the estimation algorithm to failure. Finally, this work develops a semi-batch specific dynamic real-time optimization (DRTO) algorithm and poses a novel costing methodology for this specific type of problem. As part of this costing methodology, an enzyme specific cost scaling correlation is proposed to provide a realistic approximation of these costs in industrial contexts. This semi-batch DRTO is combined with the GOS process to provide an economic analysis using Kluyveromyces lactis (K. lactis) β-galactosidase enzyme. An extensive literature review is carried out to support the conclusions of the economic analysis and motivate application to other bioprocesses

Chemometric tools for automated method-development and data interpretation in liquid chromatography

The thesis explores the challenges and advancements in the field of liquid chromatography (LC), particularly focusing on complex sample analysis using high-resolution mass spectrometry (MS) and two-dimensional (2D) LC techniques. The research addresses the need for efficient optimization and data-handling strategies in modern LC practice. The thesis is divided into several chapters, each addressing specific aspects of LC and polymer analysis. Chapter 2 provides an overview of the need for chemometric tools in LC practice, discussing methods for processing and analyzing data from 1D and 2D-LC systems and how chemometrics can be utilized for method development and optimization. Chapter 3 introduces a novel approach for interpreting the molecular-weight distribution and intrinsic viscosity of polymers, allowing quantitative analysis of polymer properties without prior knowledge of their interactions. This method correlates the curvature parameter of the Mark-Houwink plot with the polymer's structural and chemical properties. Chapters 4 and 5 focus on the analysis of cellulose ethers (CEs), essential in various industrial applications. A new method is presented for mapping the substitution degree and composition of CE samples, providing detailed compositional distributions. Another method involves a comprehensive 2D LC-MS/MS approach for analyzing hydroxypropyl methyl cellulose (HPMC) monomers, revealing subtle differences in composition between industrial HPMC samples. Chapter 6 introduces AutoLC, an algorithm for automated and interpretive development of 1D-LC separations. It uses retention modeling and Bayesian optimization to achieve optimal separation within a few iterations, significantly improving the efficiency of gradient LC separations. Chapter 7 focuses on the development of an open-source algorithm for automated method development in 2D-LC-MS systems. This algorithm improves separation performance by refining gradient profiles and accurately predicting peak widths, enhancing the reliability of complex gradient LC separations. Chapter 8 addresses the challenge of gradient deformation in LC instruments. An algorithm based on the stable function corrects instrument-specific gradient deformations, enabling accurate determination of analyte retention parameters and improving data comparability between different sources. Chapter 9 introduces a novel approach using capacitively-coupled-contactless-conductivity detection (C4D) to measure gradient profiles without adding tracer components. This method enhances inter-system transferability of retention models for polymers, overcoming the limitations of UV-absorbance detectable tracer components. Chapter 10 discusses practical choices and challenges faced in the thesis chapters, highlighting the need for well-defined standard samples in industrial polymer analysis and emphasizing the importance of generalized problem-solving approaches. The thesis identifies future research directions, emphasizing the importance of computational-assisted methods for polymer analysis, the utilization of online reaction modulation techniques, and exploring continuous distributions obtained through size-exclusion chromatography (SEC) in conjunction with triple detection. Chemometric tools are recognized as essential for gaining deeper insights into polymer chemistry and improving data interpretation in the field of LC