Sensors in disposable bioreactors status and trends.

For better control of productivity and product quality, detailed monitoring of various parameters is required. Since disposable bioreactors become more and more important for biotechnological applications, adequate sensors for this type of reactor are necessary. The required properties of sensors used in disposable reactors differ from those of sensors for multiuse reactors. For example, sensors which are in direct contact with the medium must be inexpensive, but do not need a long life-time, since they can be used only once.This chapter gives an overview on the state of the art and future trends in the field of sensors suited for use in disposable bioreactors. The main focus here is on in situ sensors, which can be based on optical, semiconductor and ultrasonic technologies, but current concepts for disposable sampling units are also reviewed.

[1]  A. Mohammad,et al.  Improved aeroponic culture of inocula of arbuscular mycorrhizal fungi , 2000, Mycorrhiza.

[2]  Karl Schügerl,et al.  Development and application of a new enzyme sensor type based on the EIS-capacitance structure for bioprocess control , 1994 .

[3]  Toyosaka Moriizumi,et al.  The Suitability of Ta2O5 as a Solid State Ion-Sensitive Membrane , 1987 .

[4]  K. Wise,et al.  An integrated-circuit approach to extracellular microelectrodes. , 1970, IEEE transactions on bio-medical engineering.

[5]  Josep Samitier,et al.  Integrated cell positioning and cell-based ISFET biosensors , 2007 .

[6]  Thomas Kullick,et al.  Application of enzyme-field effect transistor sensor arrays as detectors in a flow-injection analysis system for simultaneous monitoring of medium components. Part II. Monitoring of cultivation processes , 1995 .

[7]  Hiroshi Kawarada,et al.  Label-free DNA sensors using ultrasensitive diamond field-effect transistors in solution. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[8]  Piet Bergveld.  New Amplification Method for Depth Recording , 1968 .

[9]  Thomas Scheper,et al.  Application of 2D-fluorescence spectroscopy for on-line monitoring of pseudoenantiomeric transformations in supercritical carbon dioxide systems. , 2005, Analytical chemistry.

[10]  Thomas Becker,et al.  Future aspects of bioprocess monitoring. , 2007, Advances in biochemical engineering/biotechnology.

[11]  Roland Ulber,et al.  Optical sensor systems for bioprocess monitoring , 2003, Analytical and bioanalytical chemistry.

[12]  Daniel Schneditz,et al.  A sound‐speed sensor for the measurement of total protein concentration in disposable, blood‐perfused tubes , 1989 .

[13]  T. Scheper,et al.  Oxygen monitoring in supercritical carbon dioxide using a fibre optic sensor. , 2001, Enzyme and microbial technology.

[14]  Raoul Kopelman,et al.  Development of submicron chemical fiber optic sensors , 1992 .

[15]  Henry Y. Wang,et al.  Bioprocess monitoring and computer control: Key roots of the current PAT initiative , 2006, Biotechnology and bioengineering.

[16]  Kenneth F. Reardon,et al.  Novel applications of fluorescence sensors , 1990, Applied biochemistry and biotechnology.

[17]  Thomas Scheper,et al.  On-line monitoring of a quasi-enantiomeric reaction with two coumarin substrates via 2D-fluorescence spectroscopy , 2001 .

[18]  T. Scheper,et al.  Modelling of E.coli fermentations: comparison of multicompartment and variable structure models , 1997 .

[19]  Andrew Mills,et al.  Fluorescence plastic thin-film sensor for carbon dioxide , 1993 .

[20]  Thomas Scheper,et al.  In situ fluorescence monitoring of immobilizedClostridium acetobutylicum , 1986, Biotechnology Letters.

[21]  Bernd Hitzmann,et al.  The control of glucose concentration during yeast fed-batch cultivation using a fast measurement complemented by an extended Kalman filter , 2000 .

[22]  Kenneth F. Reardon,et al.  Metabolic Pathway Rates and Culture Fluorescence in Batch Fermentations of Clostridium Acetobutylicum , 1987 .

[23]  Karl Schügerl,et al.  Measurement of biological parameters during fermentation processes , 1984 .

[24]  Thomas Scheper,et al.  The application of two-dimensional fluorescence spectroscopy for the on-line evaluation of modified enzymatic enantioselectivities in organic solvents by forming substrate salts , 2006 .

[25]  Bernhard H. Weigl,et al.  Sensitivity studies on optical carbon dioxide sensors based on ion pairing , 1995 .

[26]  L. Brown,et al.  Disposable PVDF ultrasonic transducers for nondestructive testing applications , 1996, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[27]  Piet Bergveld,et al.  Thirty years of ISFETOLOGY ☆: What happened in the past 30 years and what may happen in the next 30 years , 2003 .

[28]  Bernd Hitzmann,et al.  In-situ- und On-line-Überwachung und Regelung biotechnologischer Prozesse , 1993 .

[29]  K Sato,et al.  On-line measurement of intracellular ATP of Saccharomyces cerevisiae and pyruvate during sake mashing. , 2000, Journal of bioscience and bioengineering.

[30]  H. Freitag,et al.  Biosensors in Analytical Biotechnology , 1996 .

[31]  Thomas Scheper,et al.  A bio-FET sensor for lactose based on co-immobilized β-galactosidase/glucose dehydrogenase , 1994 .

[32]  T. Scheper,et al.  A model system for a fluorometric biosensor using permeabilized Zymomonas mobilis or enzymes with protein confined dinucleotides , 1993, Biotechnology and bioengineering.

[33]  Ingo Klimant,et al.  Optical measurement of oxygen and temperature in microscale: strategies and biological applications , 1997 .

[34]  K. Schügerl,et al.  Progress in monitoring, modeling and control of bioprocesses during the last 20 years. , 2001, Journal of biotechnology.

[35]  K. Schügerl,et al.  Culture fluorescence studies on aerobic continuous cultures ofSaccharomyces cerevisiae , 1986, Applied Microbiology and Biotechnology.

[36]  Thomas Scheper,et al.  On-line monitoring and control of substrate concentrations in biological processes by flow injection analysis systems , 2004 .

[37]  Karl Schügerl,et al.  Monitoring of NADH-dependent culture fluorescence during the cultivation of Escherichia coli , 1987 .

[38]  B Hitzmann,et al.  Two-dimensional fluorescence spectroscopy: a novel approach for controlling fed-batch cultivations. , 2006, Journal of biotechnology.

[39]  Yordan Kostov,et al.  Rapid method for the preparation of a robust optical pH sensor. , 2003, The Analyst.

[40]  Karl Schügerl,et al.  Growth of E. coli in a stirred tank and in an air lift tower reactor with an outer loop , 1987 .

[41]  Thomas Scheper,et al.  Faseroptische Sauerstoffsensoren für Biotechnologie, Umwelt‐ und Lebensmitteltechnik , 1998 .

[42]  B Tartakovsky,et al.  Evaluation of Multiwavelength Culture Fluorescence for Monitoring the Aroma Compound 4‐Hydroxy‐2(or 5)‐ethyl‐5(or 2)‐methyl‐3(2H)‐furanone (HEMF) Production , 2008, Biotechnology progress.

[43]  Maurizio Valle,et al.  Bioelectrochemical signal monitoring of in-vitro cultured cells by means of an automated microsystem based on solid state sensor-array. , 2003, Biosensors & bioelectronics.

[44]  Tomoya Tanaka,et al.  Enzyme-based Field-Effect Transistor for Adenosine Triphosphate (ATP) Sensing , 2007, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[45]  Thomas-Helmut Scheper,et al.  Optical sensors for process monitoring in biotechnology , 1991, Other Conferences.

[46]  Dörte Solle,et al.  Chemometric Modelling based on 2D-Fluorescence Spectra without a Calibration Measurement , 2003, Bioinform..

[47]  Pierre Temple-Boyer,et al.  Development of chemical field effect transistors for the detection of urea , 2003 .

[48]  Jens Zosel,et al.  Encapsulation of ISFET sensor chips , 2005 .

[49]  Thomas Scheper,et al.  Fluorescence monitoring of immobilzed microorganisms in cultures , 1988 .

[50]  T. Scheper,et al.  In situ microscopy for on-line determination of biomass. , 1998, Biotechnology and bioengineering.

[51]  Xudong Ge,et al.  High-stability non-invasive autoclavable naked optical CO2 sensor. , 2003, Biosensors & bioelectronics.

[52]  T. Matsuo,et al.  Characteristics of reference electrodes using a polymer gate ISFET , 1984 .

[53]  Michael J. Schöning,et al.  CIP (cleaning-in-place) suitable “non-glass” pH sensor based on a Ta2O5-gate EIS structure , 2005 .

[54]  G. Shi,et al.  A water-soluble cationic oligopyrene derivative : Spectroscopic studies and sensing applications , 2009 .

[55]  G. Wehnert,et al.  Biotechnological applications of fiber-optic sensing: multiple uses of a fiber-optic fluorimeter☆ , 1993 .

[56]  M. Esashi,et al.  Methods of isfet fabrication , 1981 .

[57]  F. Plötz,et al.  Applications of biosensor systems for bioprocess monitoring , 1991 .

[58]  Dörte Solle,et al.  A New Evaluation Method for 2‐D Fluorescence Spectra Based on Theoretical Modeling , 2003 .

[59]  Pavel Neuzil,et al.  An ISFET-based immunosensor for the detection of β-Bungarotoxin , 2002 .

[60]  K. Schügerl,et al.  Characterization of bioreactors by in-situ fluorometry , 1986 .

[61]  N. Jaffrezic‐Renault,et al.  Sensitization of dielectric surfaces by chemical grafting: application to pH ISFETs and REFETs , 1992 .

[62]  B Tartakovsky,et al.  Application of Scanning Fluorometry for Monitoring of a Fermentation Process , 1996, Biotechnology progress.

[63]  Thomas Scheper,et al.  Pbs‐field‐effect‐transistor for heavy metal concentration monitoring , 1995 .

[64]  Bernd Henning,et al.  Process monitoring using ultrasonic sensor systems. , 2006, Ultrasonics.

[65]  Thomas Scheper,et al.  Optische Inline-Messverfahren zur Zellzahl- und Zellgrößenbestimmung in der Bioprozesstechnik , 2007 .

[66]  S. Arnold,et al.  Use of at‐line and in‐situ near‐infrared spectroscopy to monitor biomass in an industrial fed‐batch Escherichia coli process , 2002, Biotechnology and bioengineering.

[67]  Y. Maa,et al.  Performance of sonication and microfluidization for liquid-liquid emulsification. , 1999, Pharmaceutical development and technology.

[68]  Otto S. Wolfbeis,et al.  Materials for fluorescence-based optical chemical sensors , 2005 .

[69]  R Millner,et al.  Theoretical and experimental studies on the influence of ultrasound on immobilized enzymes , 1987, Biotechnology and bioengineering.

[70]  Thomas Scheper,et al.  Biosensors in bioprocess monitoring , 1996 .

[71]  G. Wehnert,et al.  Ein kombinierter Fluoreszenz‐/Streulicht‐Sensor und dessen Einsatz zur Prozeßbeobachtung in der Biotechnologie , 1990 .

[72]  Yong-Sik Yim,et al.  Classification of two-dimensional fluorescence spectra using self-organizing maps , 2005 .

[73]  Karl Schügerl,et al.  Bio-field-effect transistors for process control in biotechnology , 1991 .

[74]  Shimshon Belkin,et al.  Fluorescence and bioluminescence reporter functions in genetically modified bacterial sensor strains , 2003 .

[75]  David R. Walt,et al.  A fiber-optic sensor for CO2 measurement , 1988 .

[76]  T. Scheper,et al.  A new version of an in situ sampling system for bioprocess analysis , 1996 .

[77]  J. Eijkel,et al.  A novel description of ISFET sensitivity with the buffer capacity and double-layer capacitance as key parameters , 1995 .

[78]  K Schügerl,et al.  On‐Line Measurement of Culture Fluorescence for Process Monitoring and Control of Biotechnological Processes , 1987, Annals of the New York Academy of Sciences.

[79]  Bernd Hitzmann,et al.  Optical pH sensing using spectral analysis , 2007 .

[80]  Oliver Kohls,et al.  Setup of a fiber optical oxygen multisensor-system and its applications in biotechnology , 2000 .

[81]  N J Titchener-Hooker,et al.  Economic comparison between conventional and disposables-based technology for the production of biopharmaceuticals. , 2001, Biotechnology and bioengineering.

[82]  M. Dawgul,et al.  Miniaturised reference electrodes for field-effect sensors compatible to silicon chip technology , 2005 .

[83]  M. RAMA RAO.  Temperature Dependence of Adiabatic Compressibility , 1941, Nature.

[84]  P Bergveld,et al.  Development, operation, and application of the ion-sensitive field-effect transistor as a tool for electrophysiology. , 1972, IEEE transactions on bio-medical engineering.

[85]  Thomas Scheper,et al.  Two‐Dimensional Fluorescence Spectroscopy: A New Tool for On‐Line Bioprocess Monitoring , 1998, Biotechnology progress.

[86]  Roland Ulber,et al.  Enzym‐Feldeffekttransistoren als enantioselektive Detektoren in der Fließinjektionsanalyse , 1994 .

[87]  Bernd Hitzmann,et al.  Application of enzyme field-effect transistor sensor arrays as detectors in a flow-injection system for simultaneous monitoring of medium components. Part I. Preparation and calibration. , 1994 .

[88]  Chi K. Chang,et al.  Electronic spectroscopy, photophysical properties, and emission quenching studies of an oxidatively robust perfluorinated platinum porphyrin. , 2004, Inorganic chemistry.

[89]  T. Scheper,et al.  Fluorescence monitoring during cultivation of Enterobacter aerogenes at different oxygen levels , 1999, Applied Microbiology and Biotechnology.

[90]  Michael J. Schöning,et al.  New concepts of miniaturised reference electrodes in silicon technology for potentiometric sensor systems , 2004 .

[91]  Michael C. Flickinger,et al.  Encyclopedia of bioprocess technology : fermentation, biocatalysis, and bioseparation , 1999 .

[92]  Peter Hauptmann,et al.  REVIEW ARTICLE: Application of ultrasonic sensors in the process industry , 2002 .

[93]  Byoung-Ho Kang,et al.  Enhancement of physical and chemical properties of thin film Ag/AgCl reference electrode using a Ni buffer layer , 2004 .

[94]  Thomas Scheper,et al.  Biosensors for enantioselective analysis , 1994 .

[95]  Segyeong Joo,et al.  Chemical sensors with integrated electronics. , 2008, Chemical reviews.

[96]  Thomas Scheper,et al.  Biosensors for process monitoring , 2005, Journal of Industrial Microbiology.

[97]  Dörte Solle,et al.  Chemometric modelling with two-dimensional fluorescence data for Claviceps purpurea bioprocess characterization. , 2003, Journal of biotechnology.

[98]  T. Scheper,et al.  A fiber optic biosensor based on fluorometric detection using confined macromolecular nicotinamide adenine dinucleotide derivatives , 1990 .

[99]  Antonio Delgado,et al.  Hybrid data model for the improvement of an ultrasonic-based gravity measurement system , 2002 .

[100]  Andrew Mills,et al.  Equilibrium studies on colorimetric plastic film sensors for carbon dioxide , 1992 .

[101]  Xin Lu,et al.  In situ multi-wavelength fluorescence spectroscopy as effective tool to simultaneously monitor spore germination, metabolic activity and quantitative protein production in recombinant Aspergillus niger fed-batch cultures. , 2007, Journal of biotechnology.

[102]  R. Faurie,et al.  Use of Bioanalytical Systems for the Improvement of Industrial Tryptophan Production , 2001 .

[103]  T. Scheper,et al.  Two FIA-based biosensor systems studied for bioprocess monitoring. , 1993, Journal of biotechnology.

[104]  N. D. Rooij,et al.  Multi-ion Sensing System Based on Glass-encapsulated pH-ISFETs and a Pseudo-REFET , 1990 .

[105]  Jay D Keasling,et al.  Microbioreactor arrays with parametric control for high‐throughput experimentation , 2004, Biotechnology and bioengineering.

[106]  Thomas Scheper,et al.  In-situ microscopy: Online process monitoring of mammalian cell cultures , 2004, Cytotechnology.

[107]  David R. Walt,et al.  A Fiber-Optic Carbon Dioxide Sensor for Fermentation Monitoring , 1995, Bio/Technology.

[108]  P Bergveld,et al.  Development of an ion-sensitive solid-state device for neurophysiological measurements. , 1970, IEEE transactions on bio-medical engineering.

[109]  Thomas Lorenz,et al.  Pros and cons: on-line versus off-line analysis of fermentations , 1986 .

[110]  Samir Kumar Khanal,et al.  Ultrasound Applications in Wastewater Sludge Pretreatment: A Review , 2007 .

[111]  Bernd Hitzmann,et al.  Optical chemo- and biosensors for use in clinical applications , 1997 .

[112]  Bernd Hitzmann,et al.  State variables monitoring by in situ multi-wavelength fluorescence spectroscopy in heterologous protein production by Pichia pastoris. , 2006, Journal of biotechnology.

[113]  T. Scheper,et al.  Visualizing transport processes at liquid-liquid interfaces--the application of laser-induced fluorescence. , 2003, Journal of colloid and interface science.

[114]  Shimshon Belkin,et al.  Genotoxicity monitoring using a 2D-spectroscopic GFP whole cell biosensing system , 2003 .

[115]  Raoul Kopelman,et al.  Ratiometric fiber optic sensors for the detection of inter- and intra-cellular dissolved oxygen , 2005 .

[116]  B. Jähne,et al.  In situ microscopy for on‐line characterization of cell‐populations in bioreactors, including cell‐concentration measurements by depth from focus , 1995, Biotechnology and bioengineering.

[117]  Thomas Scheper,et al.  Optical sensor systems for bioprocess monitoring , 1999 .

[118]  T. Scheper,et al.  Preliminary Study towards the Use of In‐situ Microscopy for the Online Analysis of Microcarrier Cultivations , 2007 .

[119]  Peter Hauptmann,et al.  Ultrasonic density sensor—analysis of errors due to thin layers of deposits on the sensor surface , 1999 .

[120]  J. Eijkel,et al.  A general model to describe the electrostatic potential at electrolyte oxide interfaces , 1996 .

[121]  Bernd Hitzmann,et al.  Bioanalytics: detailed insight into bioprocesses , 1999 .

[122]  Jan C.T. Eijkel,et al.  The remarkable similarity between the acid-base properties of ISFETs and proteins and the consequences for the design of ISFET biosensors , 1995 .

[123]  K. Schügerl,et al.  Development of biosensors based on an electrolyte isolator semiconductor (EIS) -capacitor structure and their application for process monitoring. Part I. Development of the biosensors and their characterization , 1995 .

[124]  B. Lendl,et al.  On-Line Fermentation Monitoring by Mid-Infrared Spectroscopy , 2004, Applied spectroscopy.