Bioprocess control and monitoring

Biotechnological processes share with most biological systems the need to operate under specific conditions of pH, temperature, concentration of substrate and/or products. Maintaining the desired conditions over time despite the intervention of disturbances is the aim of bioprocess control in industry, which has its counterpart in biological systems in homeostasis. In this subject, the dynamics of industrial bioprocesses and examples in microbiology and biomedicine are discussed in parallel with an eminently practical perspective. The process simulator will be used to facilitate computer experiments and promote inductive learning, thus allowing a large part of the mathematical content that characterizes process control manuals to be dispensed with. Specifically, this subject aims for students to be able to:
- Solve basic problems related to modeling and process dynamics
- Identify and modify various control strategies based on the considered process.
- Identify and list the different control elements necessary to monitor the basic variables in industrial biotechnological processes.
- Distinguish the basic elements of instrumentation
- Know the state-of-the-art techniques for monitoring bioprocesses

The contents of this course are: Dynamics of bioprocesses; Control techniques in bioprocesses. feedback Examples of control in bioprocesses and biomedicine; Instrumentation: sensors and biosensors, transmitters and controllers; Monitoring of bioprocesses

These contents are articulated as follows:

1 - Introduction
Lectures: The need for control in biotechnological processes and biological systems. The monitoring difficulties inherent in biological processes.
Computer class: Introduction to Matlab/Simulink for dynamic simulation
1h Lec + 1h Comp

2 - Dynamic behavior of bioprocesses
Lectures: Representation of dynamic models of biological processes. Simple steady state and transient systems. Analysis of the dynamic response to external changes. delay Stability and oscillations.
Seminar: Mathematical study of dynamic responses
Computer classroom: Dynamic simulation in Matlab/Simulink of various biotechnological processes (PHA production, S. cerevisiae cultivation, water treatment bioreactor, anaerobic systems...) and biological systems (predator/prey in bioreactor...)
5h Lec + 2h Sem + 4h Comp

3 - Bioprocess control techniques
Lectures: Open loop and closed loop control. Feedback and feedforward control. Control strategies: on/off, proportional and integral. Cascade control. The problem of delay in the control of bioprocesses. Controller tuning.
Control in biological processes: homeostasis. Mathematical analysis of simple cases of gene regulation: the lac operon. The Goodwin Oscillator. Quorum sensing.
Seminar: Controller tuning methods.
Computer class: Application of control strategies to systems studied in unit 2.
6h Lec + 2h Sem + 4h Comp

Unit 4 - General instrumentation and bioprocesses
Lectures: Main components of the control system: sensors and actuators (pumps and valves). Monitoring of biological activity using online, in-line, at-line and offline methods. Relationship with process control.
Seminar: Discussion and interpretation of monitoring strategies in P&ID diagrams; selection of instrumentation elements
2h Lec + 2h Sem + 1h Comp

Unit 5 - Monitoring of bioprocesses
Lectures: The need to monitor bioprocesses; interpretation of operation data; soft sensors, supervised and unsupervised learning techniques
Seminar: Comparison of monitoring techniques for different case studies
Computer class: In silico monitoring of a bioprocess using machine learning techniques
4h Lec + 1h Sem + 2h Comp

Given the multidisciplinary approach to this course, there is no specific book followed as main text. The following sources will be used, reading and putting in common during lectures some selected chapters.

Dochain, D. (ed.) 2008. Bioprocess control [on line ]. 1st ed. Hoboken: Wiley. Available at: https://onlinelibrary-wiley-com.ezbusc.usc.gal/doi/pdf/10.1002/97804706…


Gòdia, F. López, J. 2010. Ingeniería bioquímica [on line ]. Madrid: Síntesis. Available at: https://prelo.usc.eres/Record/Xebook1-478

Ingalls, B. 2012. Mathematical modeling in systems biology: an introduction. Cambridge: The MIT Press

Huusom, J.K. 2016. Control of bioprocesses. In J. Villadsen, ed. Fundamental bioengineering [on line ]. Ch. 15. Available at:
https://onlinelibrary-wiley-com.ezbusc.usc.gal/doi/book/10.1002/9783527…

Larroche, C., Sanromán, M.A La., Du, G. Pandey, La. (ed.) 2016. Current developments in biotechnology and bioengineering. Bioprocesses, bioreactors and controls [on line ]. 1st ed. Amsterdam: Elsevier. Ch. 16-26. Available at:
https://www-sciencedirect-com.ezbusc.usc.gal/book/9780444636638/current…

Mandenius, C.-F. (2016). Multivariate Modeling for Bioreactor Monitoring and Control. In Bioreactors (pp. 1–1). John Wiley & Sons. https://doi.org/10.1002/9783527683369.ch13

Mandenius, C.-F. (2016). Soft Sensor Design for Bioreactor Monitoring and Control. In Bioreactors (pp. 1–1). John Wiley & Sons. https://doi.org/10.1002/9783527683369.ch14


Simpson, R. and Sastry, S.K. (2013) Chemical and Bioprocess Engineering. Springer

Sonnleitner, B. 2016. Real-time measurement and monitoring of bioprocesses. In J. Villadsen, ed. Fundamental bioengineering [on line ]. Ch. 14. Available at:
https://onlinelibrary-wiley-com.ezbusc.usc.gal/doi/book/10.1002/9783527…

Knowledge: Con01
Abilities/skills: H/D01, H/D02, H/D05, H/D14
Competencies: Comp02, Comp03

The methodology of this subject attempts to dispense with most of the mathematical content that characterizes the teaching of process control and dynamic systems. Rather, it attempts to convey in an intuitive and practical way how biological systems and industrial bioprocesses behave dynamically and how to design control and monitoring strategies based on these dynamic responses. In addition, emphasis is placed on the relevance of feedback in biological systems, establishing parallels with content studied in other subjects of the degree.

The expository classes will consist of master lessons combined with short tests to encourage active participation.

The interactive seminar sessions will focus on students performing exercises to delve deeper into the concepts seen in the expository sessions.

Matlab/Simulink software will be used for the dynamic simulation of selected bioprocesses and biological systems in the computer classroom sessions. The simulation models, implemented in Simulink, will be provided by the teacher to be used in carrying out virtual experiments, in the design and testing of controllers and in the application of monitoring strategies. Matlab/Simulink software can be freely installed on personal computers connected to the USC network through access to the campus license.

The group tutorial will be dedicated to the visit to a monitoring and control system of a facility in the field of biotechnology.
Attendance at the computer room and the technical visit is mandatory.

The Moodle application will be used as a communication tool with the students, offering information about the teaching program throughout the course in the classroom and complementary materials for the study of the subject (teacher notes as well as scientific-technical articles ) and thus encourage the student's autonomous study and the management of bibliographic sources in English.

The skills to achieve with each activity are:
Expository - Con01, H/D01, H/D02, H/D14, Comp03, Comp02
Interactive seminar - Con01, H/D01, H/D14
Computer class: Con01, H/D01, H/D02, H/D05, Comp02
Group tutoring - Con01, Comp03

The student's grade is the weighted average of the performance obtained in a) the exam 50%, b) teamwork 25%, c) the delivery of exercises/work in the computer room (20%) and d) the referring report to the group tutoring visit (5%). The final exam is complementary to the continuous evaluation, composed of sections b), c) and d).
To take into account the scores obtained in sections b), c) and d) in the final grade, it will be necessary to achieve a minimum grade of 35% in the exam (theory).

A student who did not take the exam or the teamwork will be considered No Show. In the event that the subject is not passed on the first opportunity, the student will be evaluated again in section a) on the second opportunity and the grades from the other sections will be retained. The student who takes the exam on the second opportunity and does not submit the team work may submit an individual work on a similar topic indicated by the teaching team.

The continuous evaluation notes (sections b, c and d) will not be saved from one course to another, so the repeating student will have to redo the group tutoring sessions, team work and computer classes.

In the event of fraudulent performance of any evaluable activity, the provisions of the “Regulations for the evaluation of the academic performance of two students and review of grades” will be applied.

The skills are evaluated in the following sections:
• Final exam: Con01, H/D01, H/D02, H/D14, Comp03, Comp02
• Teamwork: Con01, H/D01, H/D02, H/D05, Comp02
• Computer class exercises and seminars: Con01, H/D01, H/D14
• Group tutoring report: Con01, Comp03

The course has a workload equivalent to 4.5 ECTS that are distributed as indicated in the table. The total workload is 112.5 hours.

Distribution of training activity during work hours
Expository classes - 18
Seminars - 7
Computer room - 12
Group tutorials - 1
Personal work -72
Exam – 2.5
TOTAL 120

Attendance and active participation in the classroom and use of the Moodle environment is recommended to follow the content of the subject and to facilitate communication between teacher and students.

The course language will be Galician, but English bibliography will be used for assignments.

If there is any discrepancy between the versions of this guide in different languages, the version in Galician will prevail.