Special Issue "Bioprocess Monitoring and Control"

A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Biological Systems".

Deadline for manuscript submissions: closed (30 April 2020).

Special Issue Editor

Prof. Dr. Bernd Hitzmann
Website
Guest Editor
Department of Process Analytics and Cereal Science, Institute of Food Science and Biotechnology, University of Hohenheim, Garbenstr. 23, 70599 Stuttgart, Germany
Interests: Process analytical technology (PAT); chemometrics; modelling; optimal design of experiments; optimization; automation; cultivation processes; food analytics; cereal technology
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Special Issue Information

Dear Colleagues,

Bioprocesses can be found in different areas such as the production of food, feed, energy, chemicals and pharmaceuticals. From biocatalysis to fermentation processes or mammalian cell cultures different reaction systems are applied. Due to the bioeconomy initiative in different countries the number of bioprocesses will grow further in the future. One characteristic feature of all these different bioprocesses is a complex reaction matrix where different substances play an important role. Frequently one has to deal with a three phase system, i. e. a liquid, a gas as well as a solid phase. For the optimal operation of these processes monitoring and supervision systems are required for all phases. And – although bioprocesses are applied since several thousand years, such as the fermentation of dough – on-line measurement systems for important process variables are still rare. Although the measurement of key variables is a challenge the control of them to guarantee optimal yield is even a higher challenge.

This Special Issue on “Bioprocess Monitoring and Control” intends to present novel examples of on-line monitoring and control techniques applied for any bioprocess. Topics include, but are not limited to:

  • Optical sensors, such as Raman, infrared and fluorescence spectroscopy,
  • Biosensors,
  • Electrochemical sensors
  • Gas-, liquid-, solid-phase sensors
  • Software sensors

Prof. Dr. Bernd Hitzmann
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Processes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Please note that for papers submitted after 31 December 2020 an APC of 2000 CHF applies. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Process analyzer
  • Sensor systems
  • On-line monitoring
  • Open and closed loop control
  • Bioprocess supervision

Published Papers (12 papers)

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Research

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Open AccessFeature PaperArticle
Control of Specific Growth Rate in Fed-Batch Bioprocesses: Novel Controller Design for Improved Noise Management
Processes 2020, 8(6), 679; https://doi.org/10.3390/pr8060679 - 09 Jun 2020
Abstract
Accurate control of the specific growth rate (µ) of microorganisms is dependent on the ability to quantify the evolution of biomass reliably in real time. Biomass concentration can be monitored online using various tools and methods, but the obtained signal is [...] Read more.
Accurate control of the specific growth rate (µ) of microorganisms is dependent on the ability to quantify the evolution of biomass reliably in real time. Biomass concentration can be monitored online using various tools and methods, but the obtained signal is often very noisy and unstable, leading to inaccuracies in the estimation of μ. Furthermore, controlling the growth rate is challenging as the process evolves nonlinearly and is subject to unpredictable disturbances originating from the culture’s metabolism. In this work, a novel feedforward-feedback controller logic is presented to counter the problem of noise and oscillations in the control variable and to address the exponential growth dynamics more effectively. The controller was tested on fed-batch cultures of Kluyveromyces marxianus, during which μ was estimated in real time from online biomass concentration measurements obtained with dielectric spectroscopy. It is shown that the specific growth rate can be maintained at different setpoint values with an average root mean square control error of 23 ± 6%. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessArticle
A Geometric Observer-Assisted Approach to Tailor State Estimation in a Bioreactor for Ethanol Production
Processes 2020, 8(4), 480; https://doi.org/10.3390/pr8040480 - 20 Apr 2020
Abstract
In this work, a systematic approach based on the geometric observer is proposed to design a model-based soft sensor, which allows the estimation of quality indexes in a bioreactor. The study is focused on the structure design problem where the set of innovated [...] Read more.
In this work, a systematic approach based on the geometric observer is proposed to design a model-based soft sensor, which allows the estimation of quality indexes in a bioreactor. The study is focused on the structure design problem where the set of innovated states has to be chosen. On the basis of robust exponential estimability arguments, it is found that it is possible to distinguish all the unmeasured states if temperature and dissolved oxygen concentration measurements are combined with substrate concentrations. The proposed estimator structure is then validated through numerical simulation considering two different measurement processor algorithms: the geometric observer and the extended Kalman filter. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessArticle
Maximization of Siderophores Production from Biocontrol Agents, Pseudomonas aeruginosa F2 and Pseudomonas fluorescens JY3 Using Batch and Exponential Fed-Batch Fermentation
Processes 2020, 8(4), 455; https://doi.org/10.3390/pr8040455 - 12 Apr 2020
Abstract
Twenty fluorescent Pseudomonas isolates were tested for their ability to produce siderophores on chrome azurol S (CAS) agar plates and their antagonistic activity against six plant pathogenic fungal isolates was assessed. Scaling-up production of siderophores from the promising isolates, P. aeruginosa F2 [...] Read more.
Twenty fluorescent Pseudomonas isolates were tested for their ability to produce siderophores on chrome azurol S (CAS) agar plates and their antagonistic activity against six plant pathogenic fungal isolates was assessed. Scaling-up production of siderophores from the promising isolates, P. aeruginosa F2 and P. fluorescens JY3 was performed using batch and exponential fed-batch fermentation. Finally, culture broth of the investigated bacterial isolates was used for the preparation of two economical bioformulations for controlling Fusarium oxysporum and Rhizoctonia solani. The results showed that both isolates yielded high siderophore production and they were more effective in inhibiting the mycelial growth of the tested fungi compared to the other bacterial isolates. Exponential fed-batch fermentation gave higher siderophore concentrations (estimated in 10 µL), which reached 67.05% at 46 h and 45.59% at 48 h for isolates F2 and JY3, respectively, than batch fermentation. Formulated P. aeruginosa F2 and P. fluorescens JY3 decreased the damping-off percentage caused by F. oxysporum with the same percentage (80%), while, the reduction in damping-off percentage caused by R. solani reached 87.49% and 62.5% for F2 and JY3, respectively. Furthermore, both formulations increased the fresh and dry weight of shoots and roots of wheat plants. In conclusion, bio-friendly formulations of siderophore-producing fluorescent Pseudomonas isolates can be used as biocontrol agents for controlling some plant fungal diseases. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessArticle
Effect of Nitrate and Perchlorate on Selenate Reduction in a Sequencing Batch Reactor
Processes 2020, 8(3), 344; https://doi.org/10.3390/pr8030344 - 16 Mar 2020
Abstract
Selenate removal from a water body is being vigorously debated owing to severe health impact, but inhibitions of coexisting anions have been reported. To suggest a viable treatment option, this study investigates the effect of nitrate and perchlorate on selenate reduction in a [...] Read more.
Selenate removal from a water body is being vigorously debated owing to severe health impact, but inhibitions of coexisting anions have been reported. To suggest a viable treatment option, this study investigates the effect of nitrate and perchlorate on selenate reduction in a laboratory-scale sequencing batch reactor. The experimental design tests how competing electron acceptors (NO3 and ClO4) and electron donor (acetate) limitations affect selenate reduction in the reactor. Results show that the reactor achieves almost complete selenate reduction within the initial concentration ranges of 0.1–1 mM by enriching selenate-reducing bacteria with appropriate temperature (30 °C) and acclimation period (50 days). We monitored simultaneous selenate and nitrate reduction in the reactor without specific inhibition due to a difference in microbial growth strategy related to electron donor status. Lack of perchlorate-reducing bacteria makes perchlorate addition (0.2 mM) not to be closely associated with dissimilative perchlorate reduction. These results provide information that can help us to understand the effect of competing electron acceptors on selenate reduction and the kinetics of potential parallel reactions in the reactor. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessArticle
Isolation, Identification and Antimicrobial Evaluation of Bactericides Secreting Bacillus subtilis Natto as a Biocontrol Agent
Processes 2020, 8(3), 259; https://doi.org/10.3390/pr8030259 - 25 Feb 2020
Cited by 1
Abstract
Herein, a bactericide-secreting Bacillus strain, potentially useful as a biocontrol agent, was isolated from the commercial Yanjing Natto food. Following the biochemical and physiological evaluation, the molecular identification was performed using 16S rDNA sequencing of polymerase chain reaction-amplified DNA that confirmed the natto [...] Read more.
Herein, a bactericide-secreting Bacillus strain, potentially useful as a biocontrol agent, was isolated from the commercial Yanjing Natto food. Following the biochemical and physiological evaluation, the molecular identification was performed using 16S rDNA sequencing of polymerase chain reaction-amplified DNA that confirmed the natto isolate as Bacillus subtilis natto (B. subtilis natto). The biocontrol (microbial inhibitory) capability of B. subtilis natto was investigated against Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and yeast (Yarrowia lipolytica) and recorded. The antimicrobial activity of B. subtilis natto was further enhanced by optimizing the growth medium for optimal bactericides secretion. Under optimized conditions, B. subtilis natto exhibited much higher inhibitory activity against S. aureus with a zone of inhibition diameter up to 27 mm. After 48 h incubation, the optimally yielded B. subtilis natto broth was used to extract and purify the responsible bactericides by silica gel column chromatography, gel column chromatography, and semi-preparative high-performance liquid chromatography. Structural identification of purified bactericides (designated as NT-5, NT-6, and NT-7) from B. subtilis natto was performed by 13C-nuclear magnetic resonance (NMR) and mass spectral analyses. The NMR comparison also revealed that NT-5, NT-6, and NT-7 had identical structures, except for the fatty chain. In summary, the present study suggests the improved biocontrol and/or microbial inhibitory potential of newly isolated bactericides secreting B. subtilis natto. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessArticle
Model-Based Monitoring of Occupant’s Thermal State for Adaptive HVAC Predictive Controlling
Processes 2019, 7(10), 720; https://doi.org/10.3390/pr7100720 - 10 Oct 2019
Cited by 1
Abstract
Conventional indoor climate design and control approaches are based on static thermal comfort/sensation models that view the building occupants as passive recipients of their thermal environment. Recent advances in wearable sensing technologies and their generated streaming data are providing a unique opportunity to [...] Read more.
Conventional indoor climate design and control approaches are based on static thermal comfort/sensation models that view the building occupants as passive recipients of their thermal environment. Recent advances in wearable sensing technologies and their generated streaming data are providing a unique opportunity to understand the user’s behaviour and to predict future needs. Estimation of thermal comfort is a challenging task given the subjectivity of human perception; this subjectivity is reflected in the statistical nature of comfort models, as well as the plethora of comfort models available. Additionally, such models are using not-easily or invasively measured variables (e.g., core temperatures and metabolic rate), which are often not practical and undesirable measurements. The main goal of this paper was to develop dynamic model-based monitoring system of the occupant’s thermal state and their thermoregulation responses under two different activity levels. In total, 25 participants were subjected to three different environmental temperatures at two different activity levels. The results have shown that a reduced-ordered (second-order) multi-inputs-single-output discrete-time transfer function (MISO-DTF), including three input variables (wearables), namely, aural temperature, heart rate, and average skin heat-flux, is best to estimate the individual’s metabolic rate (non-wearable) with a mean absolute percentage error of 8.7%. A general classification model based on a least squares support vector machine (LS-SVM) technique is developed to predict the individual’s thermal sensation. For a seven-class classification problem, the results have shown that the overall model accuracy of the developed classifier is 76% with an F1-score value of 84%. The developed LS-SVM classification model for prediction of occupant’s thermal sensation can be integrated in the heating, ventilation and air conditioning (HVAC) system to provide an occupant thermal state-based climate controller. In this paper, we introduced an adaptive occupant-based HVAC predictive controller using the developed LS-SVM predictive classification model. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessFeature PaperArticle
Combining Mechanistic Modeling and Raman Spectroscopy for Monitoring Antibody Chromatographic Purification
Processes 2019, 7(10), 683; https://doi.org/10.3390/pr7100683 - 01 Oct 2019
Cited by 1
Abstract
Chromatography is widely used in biotherapeutics manufacturing, and the corresponding underlying mechanisms are well understood. To enable process control and automation, spectroscopic techniques are very convenient as on-line sensors, but their application is often limited by their sensitivity. In this work, we investigate [...] Read more.
Chromatography is widely used in biotherapeutics manufacturing, and the corresponding underlying mechanisms are well understood. To enable process control and automation, spectroscopic techniques are very convenient as on-line sensors, but their application is often limited by their sensitivity. In this work, we investigate the implementation of Raman spectroscopy to monitor monoclonal antibody (mAb) breakthrough (BT) curves in chromatographic operations with a low titer harvest. A state estimation procedure is developed by combining information coming from a lumped kinetic model (LKM) and a Raman analyzer in the frame of an extended Kalman filter approach (EKF). A comparison with suitable experimental data shows that this approach allows for the obtainment of reliable estimates of antibody concentrations with reduced noise and increased robustness. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessFeature PaperArticle
Effects of Conventional Flotation Frothers on the Population of Mesophilic Microorganisms in Different Cultures
Processes 2019, 7(10), 653; https://doi.org/10.3390/pr7100653 - 25 Sep 2019
Abstract
Bioleaching is an environment-friendly and low-investment process for the extraction of metals from flotation concentrate. Surfactants such as collectors and frothers are widely used in the flotation process. These chemical reagents may have inhibitory effects on the activity of microorganisms through a bioleaching [...] Read more.
Bioleaching is an environment-friendly and low-investment process for the extraction of metals from flotation concentrate. Surfactants such as collectors and frothers are widely used in the flotation process. These chemical reagents may have inhibitory effects on the activity of microorganisms through a bioleaching process; however, there is no report indicating influences of reagents on the activity of microorganisms in the mixed culture which is mostly used in the industry. In this investigation, influences of typical flotation frothers (methyl isobutyl carbinol and pine oil) in different concentrations (0.01, 0.10, and 1.00 g/L) were examined on activates of bacteria in the mesophilic mixed culture (Acidithiobacillus ferrooxidans, Leptospirillum ferrooxidans, and Acidithiobacillus thiooxidans). For comparison purposes, experiments were repeated by pure cultures of Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans in the same conditions. Results indicated that increasing the dosage of frothers has a negative correlation with bacteria activities while the mixed culture showed a lower sensitivity to the toxicity of these frothers in comparison with examined pure cultures. Outcomes showed the toxicity of Pine oil is lower than methyl isobutyl carbinol (MIBC). These results can be used for designing flotation separation procedures and to produce cleaner products for bio extraction of metals. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessArticle
Bioenvironmental Zonal Controlling of Incubated Avian Embryo Using Localised Infrared Heating
Processes 2019, 7(10), 651; https://doi.org/10.3390/pr7100651 - 23 Sep 2019
Abstract
The main objective of any bioenvironmental controller is to create favourable bioenvironmental conditions around the living-system. In industrial incubation practice of chicken embryo, it is sometimes difficult to fill large incubators with uniform eggs, which leads to suboptimal results. The ideal incubation solution [...] Read more.
The main objective of any bioenvironmental controller is to create favourable bioenvironmental conditions around the living-system. In industrial incubation practice of chicken embryo, it is sometimes difficult to fill large incubators with uniform eggs, which leads to suboptimal results. The ideal incubation solution is a machine that is capable of coping with all sorts of variabilities in eggs. This can be realised in practice by creating different zones of different environmental conditions within the same machine. In the present study, a two-levels controller was designed and implemented to combine both convective and radiative heating to incubate eggs. On the higher level, three model-predictive-control (MPC) constrained controllers were developed to regulate the power applied to nine IR-radiators divided into three zones based on continuous feedback of the eggshell temperatures in each zone. On the lower level, a PID controller was used to maintain the air temperature within an experimental incubator at a fixed level (34 °C) lower than the standard incubation temperature. Four full incubation trials were carried out to test and implement the developed zonal controllers. The implementation results showed that the developed controllers were able to follow the reference trajectory defined for each zone. It was possible to keep the eggshell temperatures within the middle region (zone) different from the sidelong regions (zones) while the air temperature kept constant at 34 °C. The average hatching result (HOF) of the four full incubation trial was 84.0% (±0.5). The developed two-levels control system is a promising technique for demand-based climate controller and to optimizing energy use by using multi-objectives MPCs with constraint on total energy consumption. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Review

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Open AccessReview
Well-Defined Conjugated Macromolecules Based on Oligo(Arylene Ethynylene)s in Sensing
Processes 2020, 8(5), 539; https://doi.org/10.3390/pr8050539 - 03 May 2020
Abstract
Macromolecules with well-defined structures in terms of molar mass and monomer sequence became interesting building blocks for modern materials. The precision of the macromolecular structure makes fine-tuning of the properties of resulting materials possible. Conjugated macromolecules exhibit excellent optoelectronic properties that make them [...] Read more.
Macromolecules with well-defined structures in terms of molar mass and monomer sequence became interesting building blocks for modern materials. The precision of the macromolecular structure makes fine-tuning of the properties of resulting materials possible. Conjugated macromolecules exhibit excellent optoelectronic properties that make them exceptional candidates for sensor construction. The importance of chain length and monomer sequence is particularly important in conjugated systems. The oligomer length, monomer sequence, and structural modification often influence the energy bang gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the molecules that reflect in their properties. Moreover, the supramolecular aggregation that is often observed in oligo-conjugated systems is usually strongly affected by even minor structural changes that are used for sensor designs. This review discusses the examples of well-defined conjugated macromolecules based on oligo(arylene ethynylene) skeleton used for sensor applications. Here, exclusively examples of uniform macromolecules are summarized. The sensing mechanisms and importance of uniformity of structure are deliberated. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessFeature PaperReview
Modeling and Exploiting Microbial Temperature Response
Processes 2020, 8(1), 121; https://doi.org/10.3390/pr8010121 - 17 Jan 2020
Cited by 1
Abstract
Temperature is an important parameter in bioprocesses, influencing the structure and functionality of almost every biomolecule, as well as affecting metabolic reaction rates. In industrial biotechnology, the temperature is usually tightly controlled at an optimum value. Smart variation of the temperature to optimize [...] Read more.
Temperature is an important parameter in bioprocesses, influencing the structure and functionality of almost every biomolecule, as well as affecting metabolic reaction rates. In industrial biotechnology, the temperature is usually tightly controlled at an optimum value. Smart variation of the temperature to optimize the performance of a bioprocess brings about multiple complex and interconnected metabolic changes and is so far only rarely applied. Mathematical descriptions and models facilitate a reduction in complexity, as well as an understanding, of these interconnections. Starting in the 19th century with the “primal” temperature model of Svante Arrhenius, a variety of models have evolved over time to describe growth and enzymatic reaction rates as functions of temperature. Data-driven empirical approaches, as well as complex mechanistic models based on thermodynamic knowledge of biomolecular behavior at different temperatures, have been developed. Even though underlying biological mechanisms and mathematical models have been well-described, temperature as a control variable is only scarcely applied in bioprocess engineering, and as a conclusion, an exploitation strategy merging both in context has not yet been established. In this review, the most important models for physiological, biochemical, and physical properties governed by temperature are presented and discussed, along with application perspectives. As such, this review provides a toolset for future exploitation perspectives of temperature in bioprocess engineering. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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Open AccessFeature PaperReview
Practical Solutions for Specific Growth Rate Control Systems in Industrial Bioreactors
Processes 2019, 7(10), 693; https://doi.org/10.3390/pr7100693 - 02 Oct 2019
Cited by 1
Abstract
This contribution discusses the main challenges related to successful application of automatic control systems used to control specific growth rate in industrial biotechnological processes. It is emphasized that, after the implementation of basic automatic control systems, primary attention shall be paid to the [...] Read more.
This contribution discusses the main challenges related to successful application of automatic control systems used to control specific growth rate in industrial biotechnological processes. It is emphasized that, after the implementation of basic automatic control systems, primary attention shall be paid to the specific growth rate control systems because this process variable critically affects the physiological state of microbial cultures and the formation of the desired product. Therefore, control of the specific growth rate enables improvement of the quality and reproducibility of the biotechnological processes. The main requirements have been formulated that shall be met to successfully implement the specific growth rate control systems in industrial bioreactors. The relatively easy-to-implement schemes of specific growth rate control systems have been reviewed and discussed. The recommendations for selection of particular control systems for specific biotechnological processes have been provided. Full article
(This article belongs to the Special Issue Bioprocess Monitoring and Control)
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