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Special Issue "Sensors for Bioprocess Monitoring and Control"

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A special issue of Sensors (ISSN 1424-8220). This special issue belongs to the section "Biosensors".

Deadline for manuscript submissions: closed (30 August 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Bernd Hitzmann

Department of Process Analysis and Cereal Technology, Institute of Food Science and Biotechnology, University of Hohenheim, Garbenstr. 23, 70599 Stuttgart, Germany
Website | E-Mail
Phone: 0049 711 459 23286
Fax: +49 711 459 23259
Interests: process analytical technologies, spectroscopic sensors, image analysis, biosensors, chemometrics, software sensors, observers, process modeling, process control algorithms, cereal technology

Special Issue Information

Dear Colleagues,

The monitoring of bioprocesses is still a challenging task. Without real time information of the actual state, an optimal process operation cannot be guaranteed. If cultivation processes are considered, one has to deal with a complex, non-linear, multi-parameter and time variant system. Therefore, to meet the requirements for bioprocesses supervision, advanced sensor techniques are necessary. Due to the increasing use of disposable bioreactors, the sensors for these applications must also be disposable or easy to connect to the reactor. If process variables cannot be measured directly, or are too costly or time-consuming to measure, then soft-sensors can be applied. Typically several raw measurements are used in combination with an empirical or theoretical model for the prediction of process variables.

For an optimal operation of a bioreactor, not only measurements are important but also the utilization of the information in a close loop control system. In recent years, many contributions have been published dealing with closed loop control of bioprocesses, but only a minority have actually been applied in real bioprocesses; mostly simulations are used. However, for these control systems, requirements such as stability and reliability for the measurement sensors are even more of a challenge.

Review articles as well as original research papers relating to the monitoring and control of bioprocesses are solicited with particular interest in papers concerning applications where the sensor information is directly used for bioprocess automation.

Prof. Dr. Bernd Hitzmann
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Sensors 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 1800 CHF (Swiss Francs).


Keywords

  • soft-sensors
  • cultivation process
  • process supervision
  • closed loop control
  • actuator

Published Papers (11 papers)

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Research

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Open AccessArticle Universal Capacitance Model for Real-Time Biomass in Cell Culture
Sensors 2015, 15(9), 22128-22150; doi:10.3390/s150922128
Received: 17 April 2015 / Revised: 18 July 2015 / Accepted: 25 August 2015 / Published: 2 September 2015
Cited by 2 | PDF Full-text (4383 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Capacitance probes have the potential to revolutionize bioprocess control due to their safe and robust use and ability to detect even the smallest capacitors in the form of biological cells. Several techniques have evolved to model biomass statistically, however, there are problems with
[...] Read more.
Capacitance probes have the potential to revolutionize bioprocess control due to their safe and robust use and ability to detect even the smallest capacitors in the form of biological cells. Several techniques have evolved to model biomass statistically, however, there are problems with model transfer between cell lines and process conditions. Errors of transferred models in the declining phase of the culture range for linear models around +100% or worse, causing unnecessary delays with test runs during bioprocess development. The goal of this work was to develop one single universal model which can be adapted by considering a potentially mechanistic factor to estimate biomass in yet untested clones and scales. The novelty of this work is a methodology to select sensitive frequencies to build a statistical model which can be shared among fermentations with an error between 9% and 38% (mean error around 20%) for the whole process, including the declining phase. A simple linear factor was found to be responsible for the transferability of biomass models between cell lines, indicating a link to their phenotype or physiology. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Figures

Open AccessArticle Design and Test of a Low-Cost RGB Sensor for Online Measurement of Microalgae Concentration within a Photo-Bioreactor
Sensors 2015, 15(3), 4766-4780; doi:10.3390/s150304766
Received: 10 November 2014 / Revised: 16 December 2014 / Accepted: 15 January 2015 / Published: 26 February 2015
Cited by 5 | PDF Full-text (1147 KB) | HTML Full-text | XML Full-text
Abstract
In this study, a low-cost RGB sensor is developed to measure online the microalgae concentration within a photo-bioreactor. Two commercially available devices, i.e., a spectrophotometer for offline measurements and an immersed probe for online measurements, are used for calibration and comparison purposes.
[...] Read more.
In this study, a low-cost RGB sensor is developed to measure online the microalgae concentration within a photo-bioreactor. Two commercially available devices, i.e., a spectrophotometer for offline measurements and an immersed probe for online measurements, are used for calibration and comparison purposes. Furthermore, the potential of such a sensor for estimating other variables is illustrated with the design of an extended Luenberger observer. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Figures

Open AccessArticle Monitoring Lipase/Esterase Activity by Stopped Flow in a Sequential Injection Analysis System Using p-Nitrophenyl Butyrate
Sensors 2015, 15(2), 2798-2811; doi:10.3390/s150202798
Received: 1 November 2014 / Revised: 24 December 2014 / Accepted: 13 January 2015 / Published: 27 January 2015
PDF Full-text (3761 KB) | HTML Full-text | XML Full-text
Abstract
Lipases and esterases are biocatalysts used at the laboratory and industrial level. To obtain the maximum yield in a bioprocess, it is important to measure key variables, such as enzymatic activity. The conventional method for monitoring hydrolytic activity is to take out a
[...] Read more.
Lipases and esterases are biocatalysts used at the laboratory and industrial level. To obtain the maximum yield in a bioprocess, it is important to measure key variables, such as enzymatic activity. The conventional method for monitoring hydrolytic activity is to take out a sample from the bioreactor to be analyzed off-line at the laboratory. The disadvantage of this approach is the long time required to recover the information from the process, hindering the possibility to develop control systems. New strategies to monitor lipase/esterase activity are necessary. In this context and in the first approach, we proposed a lab-made sequential injection analysis system to analyze off-line samples from shake flasks. Lipase/esterase activity was determined using p-nitrophenyl butyrate as the substrate. The sequential injection analysis allowed us to measure the hydrolytic activity from a sample without dilution in a linear range from 0.05–1.60 U/mL, with the capability to reach sample dilutions up to 1000 times, a sampling frequency of five samples/h, with a kinetic reaction of 5 min and a relative standard deviation of 8.75%. The results are promising to monitor lipase/esterase activity in real time, in which optimization and control strategies can be designed. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Open AccessArticle Study of a Liquid Plug-Flow Thermal Cycling Technique Using a Temperature Gradient-Based Actuator
Sensors 2014, 14(11), 20235-20244; doi:10.3390/s141120235
Received: 3 September 2014 / Revised: 8 October 2014 / Accepted: 21 October 2014 / Published: 27 October 2014
Cited by 2 | PDF Full-text (1124 KB) | HTML Full-text | XML Full-text
Abstract
Easy-to-use thermal cycling for performing rapid and small-volume DNA amplification on a single chip has attracted great interest in the area of rapid field detection of biological agents. For this purpose, as a more practical alternative to conventional continuous flow thermal cycling, liquid
[...] Read more.
Easy-to-use thermal cycling for performing rapid and small-volume DNA amplification on a single chip has attracted great interest in the area of rapid field detection of biological agents. For this purpose, as a more practical alternative to conventional continuous flow thermal cycling, liquid plug-flow thermal cycling utilizes a thermal gradient generated in a serpentine rectangular flow microchannel as an actuator. The transit time and flow speed of the plug flow varied drastically in each temperature zone due to the difference in the tension at the interface between temperature gradients. According to thermal distribution analyses in microfluidics, the plug flow allowed for a slow heating process, but a fast cooling process. The thermal cycle of the microfluid was consistent with the recommended temperature gradient for PCR. Indeed, amplification efficiency of the plug flow was superior to continuous flow PCR, and provided an impressive improvement over previously-reported flow microchannel thermal cycling techniques. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Open AccessArticle Development of Electronic Nose and Near Infrared Spectroscopy Analysis Techniques to Monitor the Critical Time in SSF Process of Feed Protein
Sensors 2014, 14(10), 19441-19456; doi:10.3390/s141019441
Received: 11 August 2014 / Revised: 25 September 2014 / Accepted: 29 September 2014 / Published: 17 October 2014
Cited by 2 | PDF Full-text (1156 KB) | HTML Full-text | XML Full-text
Abstract
In order to assure the consistency of the final product quality, a fast and effective process monitoring is a growing need in solid state fermentation (SSF) industry. This work investigated the potential of non-invasive techniques combined with the chemometrics method, to monitor time-related
[...] Read more.
In order to assure the consistency of the final product quality, a fast and effective process monitoring is a growing need in solid state fermentation (SSF) industry. This work investigated the potential of non-invasive techniques combined with the chemometrics method, to monitor time-related changes that occur during SSF process of feed protein. Four fermentation trials conducted were monitored by an electronic nose device and a near infrared spectroscopy (NIRS) spectrometer. Firstly, principal component analysis (PCA) and independent component analysis (ICA) were respectively applied to the feature extraction and information fusion. Then, the BP_AdaBoost algorithm was used to develop the fused model for monitoring of the critical time in SSF process of feed protein. Experimental results showed that the identified results of the fusion model are much better than those of the single technique model both in the training and validation sets, and the complexity of the fusion model was also less than that of the single technique model. The overall results demonstrate that it has a high potential in online monitoring of the critical moment in SSF process by use of integrating electronic nose and NIRS techniques, and data fusion from multi-technique could significantly improve the monitoring performance of SSF process. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Open AccessArticle Monitoring Key Parameters in Bioprocesses Using Near-Infrared Technology
Sensors 2014, 14(10), 18941-18959; doi:10.3390/s141018941
Received: 1 September 2014 / Revised: 19 September 2014 / Accepted: 25 September 2014 / Published: 13 October 2014
Cited by 7 | PDF Full-text (2944 KB) | HTML Full-text | XML Full-text
Abstract
Near-infrared spectroscopy (NIRS) is known to be a rapid and non-destructive technique for process monitoring. Bioprocesses are usually complex, from both the chemical (ill-defined medium composition) and physical (multiphase matrix) aspects, which poses an additional challenge to the development of robust calibrations. We
[...] Read more.
Near-infrared spectroscopy (NIRS) is known to be a rapid and non-destructive technique for process monitoring. Bioprocesses are usually complex, from both the chemical (ill-defined medium composition) and physical (multiphase matrix) aspects, which poses an additional challenge to the development of robust calibrations. We investigated the use of NIRS for on-line and in-line monitoring of cell, substrate and product concentrations, during aerobic and anaerobic bacterial fermentations, in different fermentation strategies. Calibration models were built up, then validated and used for the automated control of fermentation processes. The capability of NIR in-line to discriminate among differently shaped bacteria was tested. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Open AccessArticle A Soft Sensor for Bioprocess Control Based on Sequential Filtering of Metabolic Heat Signals
Sensors 2014, 14(10), 17864-17882; doi:10.3390/s141017864
Received: 29 June 2014 / Revised: 12 September 2014 / Accepted: 17 September 2014 / Published: 26 September 2014
Cited by 6 | PDF Full-text (1586 KB) | HTML Full-text | XML Full-text
Abstract
Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling
[...] Read more.
Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Open AccessArticle Application of an Online-Biomass Sensor in an Optical Multisensory Platform Prototype for Growth Monitoring of Biotechnical Relevant Microorganism and Cell Lines in Single-Use Shake Flasks
Sensors 2014, 14(9), 17390-17405; doi:10.3390/s140917390
Received: 24 July 2014 / Revised: 2 September 2014 / Accepted: 3 September 2014 / Published: 17 September 2014
Cited by 7 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the context of this work we evaluated a multisensory, noninvasive prototype platform for shake flask cultivations by monitoring three basic parameters (pH, pO2 and biomass). The focus lies on the evaluation of the biomass sensor based on backward light scattering. The
[...] Read more.
In the context of this work we evaluated a multisensory, noninvasive prototype platform for shake flask cultivations by monitoring three basic parameters (pH, pO2 and biomass). The focus lies on the evaluation of the biomass sensor based on backward light scattering. The application spectrum was expanded to four new organisms in addition to E. coli K12 and S. cerevisiae [1]. It could be shown that the sensor is appropriate for a wide range of standard microorganisms, e.g., L. zeae, K. pastoris, A. niger and CHO-K1. The biomass sensor signal could successfully be correlated and calibrated with well-known measurement methods like OD600, cell dry weight (CDW) and cell concentration. Logarithmic and Bleasdale-Nelder derived functions were adequate for data fitting. Measurements at low cell concentrations proved to be critical in terms of a high signal to noise ratio, but the integration of a custom made light shade in the shake flask improved these measurements significantly. This sensor based measurement method has a high potential to initiate a new generation of online bioprocess monitoring. Metabolic studies will particularly benefit from the multisensory data acquisition. The sensor is already used in labscale experiments for shake flask cultivations. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Figures

Open AccessArticle Rapid Determination of the Chemical Oxygen Demand of Water Using a Thermal Biosensor
Sensors 2014, 14(6), 9949-9960; doi:10.3390/s140609949
Received: 23 April 2014 / Revised: 12 May 2014 / Accepted: 28 May 2014 / Published: 6 June 2014
Cited by 2 | PDF Full-text (806 KB) | HTML Full-text | XML Full-text
Abstract
In this paper we describe a thermal biosensor with a flow injection analysis system for the determination of the chemical oxygen demand (COD) of water samples. Glucose solutions of different concentrations and actual water samples were tested, and their COD values were determined
[...] Read more.
In this paper we describe a thermal biosensor with a flow injection analysis system for the determination of the chemical oxygen demand (COD) of water samples. Glucose solutions of different concentrations and actual water samples were tested, and their COD values were determined by measuring the heat generated when the samples passed through a column containing periodic acid. The biosensor exhibited a large linear range (5 to 3000 mg/L) and a low detection limit (1.84 mg/L). It could tolerate the presence of chloride ions in concentrations of 0.015 M without requiring a masking agent. The sensor was successfully used for detecting the COD values of actual samples. The COD values of water samples from various sources were correlated with those obtained by the standard dichromate method; the linear regression coefficient was found to be 0.996. The sensor is environmentally friendly, economical, and highly stable, and exhibits good reproducibility and accuracy. In addition, its response time is short, and there is no danger of hazardous emissions or external contamination. Finally, the samples to be tested do not have to be pretreated. These results suggest that the biosensor is suitable for the continuous monitoring of the COD values of actual wastewater samples. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)

Review

Jump to: Research

Open AccessReview Fluorescence Spectroscopy and Chemometric Modeling for Bioprocess Monitoring
Sensors 2015, 15(5), 10271-10291; doi:10.3390/s150510271
Received: 27 February 2015 / Revised: 22 April 2015 / Accepted: 27 April 2015 / Published: 30 April 2015
Cited by 12 | PDF Full-text (1021 KB) | HTML Full-text | XML Full-text
Abstract
On-line sensors for the detection of crucial process parameters are desirable for the monitoring, control and automation of processes in the biotechnology, food and pharma industry. Fluorescence spectroscopy as a highly developed and non-invasive technique that enables the on-line measurements of substrate and
[...] Read more.
On-line sensors for the detection of crucial process parameters are desirable for the monitoring, control and automation of processes in the biotechnology, food and pharma industry. Fluorescence spectroscopy as a highly developed and non-invasive technique that enables the on-line measurements of substrate and product concentrations or the identification of characteristic process states. During a cultivation process significant changes occur in the fluorescence spectra. By means of chemometric modeling, prediction models can be calculated and applied for process supervision and control to provide increased quality and the productivity of bioprocesses. A range of applications for different microorganisms and analytes has been proposed during the last years. This contribution provides an overview of different analysis methods for the measured fluorescence spectra and the model-building chemometric methods used for various microbial cultivations. Most of these processes are observed using the BioView® Sensor, thanks to its robustness and insensitivity to adverse process conditions. Beyond that, the PLS-method is the most frequently used chemometric method for the calculation of process models and prediction of process variables. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
Open AccessReview Mechanomyographic Parameter Extraction Methods: An Appraisal for Clinical Applications
Sensors 2014, 14(12), 22940-22970; doi:10.3390/s141222940
Received: 20 August 2014 / Revised: 28 October 2014 / Accepted: 4 November 2014 / Published: 3 December 2014
Cited by 4 | PDF Full-text (1087 KB) | HTML Full-text | XML Full-text
Abstract
The research conducted in the last three decades has collectively demonstrated that the skeletal muscle performance can be alternatively assessed by mechanomyographic signal (MMG) parameters. Indices of muscle performance, not limited to force, power, work, endurance and the related physiological processes underlying muscle
[...] Read more.
The research conducted in the last three decades has collectively demonstrated that the skeletal muscle performance can be alternatively assessed by mechanomyographic signal (MMG) parameters. Indices of muscle performance, not limited to force, power, work, endurance and the related physiological processes underlying muscle activities during contraction have been evaluated in the light of the signal features. As a non-stationary signal that reflects several distinctive patterns of muscle actions, the illustrations obtained from the literature support the reliability of MMG in the analysis of muscles under voluntary and stimulus evoked contractions. An appraisal of the standard practice including the measurement theories of the methods used to extract parameters of the signal is vital to the application of the signal during experimental and clinical practices, especially in areas where electromyograms are contraindicated or have limited application. As we highlight the underpinning technical guidelines and domains where each method is well-suited, the limitations of the methods are also presented to position the state of the art in MMG parameters extraction, thus providing the theoretical framework for improvement on the current practices to widen the opportunity for new insights and discoveries. Since the signal modality has not been widely deployed due partly to the limited information extractable from the signals when compared with other classical techniques used to assess muscle performance, this survey is particularly relevant to the projected future of MMG applications in the realm of musculoskeletal assessments and in the real time detection of muscle activity. Full article
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)

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