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Hybrid Models Based on Machine Learning and an Increasing Degree of Process Knowledge: Application to Cell Culture Processes
(2022)Industrial & Engineering Chemistry ResearchIn this work, we aim to introduce the concept of the degree of hybridization for cell culture process modeling. We propose that a family of hybrid models can be created with varying fractions of process knowledge explicitly encoded in the model, defined as the degree of hybridization, with the two extremes being fully data-driven (0%) and fully mechanistic (100%) models. Subsequently, the aim is to compare the different models based on ...Journal Article -
Integration and digitalization in the manufacturing of therapeutic proteins
(2022)Chemical Engineering ScienceThe biopharmaceutical market has experienced a tremendous growth in the last years. However, this growth should be balanced considering the difficulty in bioproduct development and the associated high manufacturing costs. These limitations are pushing towards process intensification, stimulated by the Quality by Design (QbD) initiative. Integrated continuous biomanufacturing has emerged as a promising approach towards high throughputs and ...Journal Article -
Analysis and optimal design of batch and two-column continuous chromatographic frontal processes for monoclonal antibody purification
(2021)Biotechnology and BioengineeringThe increasing demand for efficient and robust processes in the purification of monoclonal antibodies (mAbs) has recently brought frontal chromatography to the forefront. Applied during the polishing step, it enables the removal of high molecular weight aggregates from the target product, achieving high purities. Typically, this process is operated in batch using a single column, which makes it intrinsically subjected to a purity-yield ...Journal Article -
Hybrid Models for the simulation and prediction of chromatographic processes for protein capture
(2021)Journal of Chromatography AThe biopharmaceutical industries are continuously faced with the pressure to reduce the development costs and accelerate development time scales. The traditional approach of heuristic-based or platform process-based optimization is soon getting obsolete, and more generalized tools for process development and optimization are required to keep pace with the emerging trends. Thus, advanced model-based methods that can reduce the can ensure ...Journal Article -
Hybrid Models Based on Machine Learning and an Increasing Degree of Process Knowledge: Application to Capture Chromatographic Step
(2021)Industrial & Engineering Chemistry ResearchIn process engineering, two paradigms of modeling approaches exist: the mechanistic and the data-driven approaches with the former being completely based on knowledge while the latter completely based on data. In our previous work, we highlighted the advantages of using hybrid models that explores the synergy between mechanistic and data-driven models. Here we introduce the concept of developing a series of hybrid models constituted by a ...Journal Article -
Readily Adsorbable Thermoresponsive Polymers for the Preparation of Smart Cell-Culturing Surfaces on Site
(2020)ACS Biomaterials Science & EngineeringThe efficacy of several cell therapy products is directly impacted by trypsinization, which can diminish the engrafting capacity of transplanted cells by cleaving cell surface receptors. Thermoresponsive surfaces can alleviate this drawback, enabling temperaturedriven and enzyme-free cell harvesting. However, the production of thermoresponsive surfaces relies on dedicated and complex equipment, often involving protocols dependent on high ...Journal Article -
Encapsulation of octenidine hydrochloride into bioresorbable polyesters for extended antimicrobial activity
(2020)European Polymer JournalNosocomial infections remain a serious threat even for patients of highly industrialized countries. These infections occur on surgical sites and wounds, on catheter entry sites, tubes and other indwelling devices. Medical devices providing local antiseptic action over an extended time period represent an opportunity to prevent such infections. One way to achieve this goal is the encapsulation of active molecules into bioresorbable polymer ...Journal Article -
Hybrid‐EKF: Hybrid model coupled with extended Kalman filter for real‐time monitoring and control of mammalian cell culture
(2020)Biotechnology and BioengineeringIn a decade when Industry 4.0 and quality by design are major technology drivers of biopharma, automated and adaptive process monitoring and control are inevitable requirements and model‐based solutions are key enablers in fulfilling these goals. Despite strong advancement in process digitalization, in most cases, the generated datasets are not sufficient for relying on purely data‐driven methods, whereas the underlying complex bioprocesses ...Journal Article -
Cell culture process metabolomics together with multivariate data analysis tools opens new routes for bioprocess development and glycosylation prediction
(2020)Biotechnology ProgressMultivariate latent variable methods have become a popular and versatile toolset to analyze bioprocess data in industry and academia. This work spans such applications from the evaluation of the role of the standard process variables and metabolites to the metabolomics level, that is, to the extensive number metabolic compounds detectable in the extracellular and intracellular domains. Given the substantial effort currently required for ...Journal Article -
Model based strategies towards protein A resin lifetime optimization and supervision
(2020)Journal of Chromatography AJournal Article