Development of an integrated modeling, estimation and control framework for bioprocesses towards modularity

• Grant number: 18/04933-5
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2018
• End date: September 30, 2021
• Field of knowledge: Engineering - Chemical Engineering - Chemical Process Industries
• Agreement: West Virginia University
• Principal Investigator: Marcelo Perencin de Arruda Ribeiro
• Grantee: Marcelo Perencin de Arruda Ribeiro
• Principal researcher abroad: Fernando Vines Faria De Lima
• Institution abroad: West Virginia University (WVU), United States
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

This project focuses on research in bioprocess applications from joint Brazil-U.S collaboration between UFSCar and WVU that addresses the modern challenges of bioprocess modular manufacturing. This collaboration has been ongoing since 2015 and thus has already created research and educational opportunities for both countries. The outcomes of this project are expected to lead to a framework for modeling, estimation and control of bioprocess operations.Batch and fed-batch are very common modes of bioprocess operations, as the continuous mode may present biocatalysts (cells or purified enzymes) deactivation (cells die and enzymes denature), which requires their replacement in a matter of hours or days. Biocatalysts are also often inhibited by the substrate (reactant) and hence the latter must be added in a controlled way so that maximum process selectivity/productivity is achieved. There are also other aspects that favor discontinuous bioprocess operations, such as process scale and quality control. However, several challenges arise during the operation of discontinuous reactors. For example, for such operation, the state variables vary with time and the process must be monitored, optimized and controlled online in order to obtain the optimal state/input profiles. To accomplish this goal, an integrated framework for bioprocesses is proposed in this project. The two principal investigators (PIs) from Brazil (UFSCar) and USA (WVU) are particularly well-positioned to carry out the proposed research considering their credentials in their research area and successful collaborations between the two groups. Moreover, the PIs have jointly developed modeling, state estimation and control approaches for airlift bioreactors. This collaboration resulted in a peer-review journal paper (Campani et al., 2018). In this proposal, such approaches are extended to produce an improved framework for modular bioprocesses. This framework is implemented to address the enzymatic synthesis of galacto-oligosaccharide from whey permeate/lactose. The enzymatic synthesis of galacto-oligosaccharide (GOS) using ²-galactosidase, associated with the production of the whey protein concentrate (WPC), can be an alternative way to utilize the often discarded whey permeate by small-scale producers of dairy products. GOS is an added-value prebiotic used in infant and senior formulas. ²-galactosidase is a GRAS (Generally Recognized as Safe) enzyme and its removal from the product is not required. However, the high cost of the enzyme and the control of many parameters that impact the reaction yield of the formation of Lactose into GOS may make the investment in this process risky. This bioprocess application perfectly fits the concept of modular manufacturing and smart plants (Christofides et al., 2007), in which small-scale units could be designed and distributed around farms.To carry out this research, the following aims detailed below are proposed: (i) build mathematical models of the process and define optimal substrate and enzyme feeding profiles; (ii) formulate computational state estimation and control approaches for bioprocesses; (iii) apply the integrated state estimation and control framework to the bioprocess. All steps in this research will occur in tandem and will explore the synergy between the experimental and simulation tasks performed by both research teams. Experimental validation will be carried out to evaluate proposed approaches and models. At the end of this two-year research, we expect to have a validated optimized process with a proper control system that will be ready for a preliminary economic evaluation. This evaluation will aim the assessment of a modular scale process for the treatment of whey in small-scale dairy industries based on the WPC and GOS production. This work will thus have an impact on industry and higher education in Brazil and USA. (AU)