Online analysis and process control in recombinant protein production (review).

Online analysis and control is essential for efficient and reproducible bioprocesses. A key factor in real-time control is the ability to measure critical variables rapidly. Online in situ measurements are the preferred option and minimize the potential loss of sterility. The challenge is to provide sensors with a good lifespan that withstand harsh bioprocess conditions, remain stable for the duration of a process without the need for recalibration, and offer a suitable working range. In recent decades, many new techniques that promise to extend the possibilities of analysis and control, not only by providing new parameters for analysis, but also through the improvement of accepted, well practiced, measurements have arisen.

[1]  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 .

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

[3]  W. Bentley,et al.  Green fluorescent protein in Saccharomyces cerevisiae: real-time studies of the GAL1 promoter. , 2000, Biotechnology and bioengineering.

[4]  Mario Jolicoeur,et al.  A multiwavelength fluorescence probe: is one probe capable for on-line monitoring of recombinant protein production and biomass activity? , 2005, Journal of Biotechnology.

[5]  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.

[6]  M Aizawa,et al.  Bioluminescent monitoring of intracellular ATP during fermentation. , 1999, Luminescence : the journal of biological and chemical luminescence.

[7]  R. Levesque,et al.  ASD-GFP vectors for in vivo expression technology in Pseudomonas aeruginosa and other gram-negative bacteria. , 1998, BioTechniques.

[8]  Thomas Maskow,et al.  On-line monitoring of lipid storage in yeasts using impedance spectroscopy. , 2008, Journal of biotechnology.

[9]  Dmitry Kirsanov,et al.  Fermentation monitoring using multisensor systems: feasibility study of the electronic tongue , 2004, Analytical and bioanalytical chemistry.

[10]  Beth Junker,et al.  On-line and in-situ monitoring technology for cell density measurement in microbial and animal cell cultures , 1994 .

[11]  A Lübbert,et al.  Bioreactor performance: a more scientific approach for practice. , 2001, Journal of biotechnology.

[12]  Ritzka,et al.  Fermentation monitoring and process control. , 1994, Current opinion in biotechnology.

[13]  Y. Duan,et al.  An improved optical pH sensor based on polyaniline , 2000 .

[14]  Gerald Striedner,et al.  Evaluation of the GFP signal and its aptitude for novel on-line monitoring strategies of recombinant fermentation processes. , 2004, Journal of biotechnology.

[15]  J. Shiloach,et al.  On‐line Monitoring of Bacterial Mass during Production of Recombinant Exotoxin A , 1994, Annals of the New York Academy of Sciences.

[16]  Chen Jianrong,et al.  Ion sensitive field effect transducer-based biosensors. , 2003, Biotechnology advances.

[17]  Sheng Yao,et al.  A long-term stable iridium oxide pH electrode , 2002 .

[18]  Franz Durst,et al.  Experimental investigation of local bubble size distributions in stirred vessels using Phase Doppler Anemometry , 2000 .

[19]  A. Pron,et al.  Polyaniline based optical pH sensor , 1997 .

[20]  David J. Clarke,et al.  Monitoring reactor biomass , 1986 .

[21]  C. P. Winlove,et al.  Metal-metal oxide pH sensors for physiological application. , 2006, Medical engineering & physics.

[22]  J. E. Dowd,et al.  On-line Measurements and Control of Viable Cell Density in Cell Culture Manufacturing Processes using Radio-frequency Impedance , 2006, Cytotechnology.

[23]  S. Ardizzone,et al.  Properties of thermally prepared iridium dioxide electrodes , 1981 .

[24]  Carmelo J. Felice,et al.  A pH Sensor Based on a Stainless Steel Electrode Electrodeposited With Iridium Oxide , 2009, IEEE Transactions on Education.

[25]  Ville Alopaeus,et al.  Modelling local bubble size distributions in agitated vessels , 2007 .

[26]  R. Carlson,et al.  Staining and quantification of poly‐3‐hydroxybutyrate in Saccharomyces cerevisiae and Cupriavidus necator cell populations using automated flow cytometry , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[27]  A Rudnitskaya,et al.  Multicomponent analysis of fermentation growth media using the electronic tongue (ET). , 2004, Talanta.

[28]  M. Barigou,et al.  Bubble-size distributions in a mechanically agitated gas—liquid contactor , 1992 .

[29]  Dong Liu,et al.  An optical pH sensor with a linear response over a broad range , 2000 .

[30]  K. Yamuna Rani,et al.  Control of fermenters : a review , 1999 .

[31]  J B Callis,et al.  Noninvasive method for monitoring ethanol in fermentation processes using fiber-optic near-infrared spectroscopy. , 1990, Analytical chemistry.

[32]  Alvin W. Nienow,et al.  Bubble Sizes in Electrolyte and Alcohol Solutions in a Turbulent Stirred Vessel , 1997 .

[33]  J. Nielsen,et al.  On-line and in situ monitoring of biomass in submerged cultivations , 1997 .

[34]  Kazuyuki Shimizu,et al.  Application of artificial neural network and fuzzy control for fed-batch cultivation of recombinant Saccharomyces cerevisiae , 1996 .

[35]  R. Mutharasan,et al.  NADH and flavin fluorescence responses of starved yeast cultures to substrate additions , 1989, Biotechnology and bioengineering.

[36]  Dan Xiao,et al.  Dissolved oxygen sensor based on fluorescence quenching of oxygen-sensitive ruthenium complex immobilized on silica–Ni–P composite coating , 2006 .

[37]  Koji Asami,et al.  Monitoring cell cycle by impedance spectroscopy: experimental and theoretical aspects , 1998 .

[38]  F Gòdia,et al.  On-line monitoring of yeast cell growth by impedance spectroscopy. , 2005, Journal of biotechnology.

[39]  B. Weigl,et al.  New hydrophobic materials for optical carbon dioxide sensors based on ion pairing , 1995 .

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

[41]  A new pH-ISFET based dissolved oxygen sensor by employing electrolysis of oxygen , 1996 .

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

[43]  J. Zemel,et al.  pH-sensitive sputtered iridium oxide films , 1981 .

[44]  Rajeev J Ram,et al.  In situ bioprocess monitoring of Escherichia coli bioreactions using Raman spectroscopy , 2004 .

[45]  Govind Rao,et al.  Quantitative measurement of green fluorescent protein expression , 1996 .

[46]  J. Heijnen,et al.  Determination of in vivo oxygen uptake and carbon dioxide evolution rates from off-gas measurements under highly dynamic conditions. , 2003, Biotechnology and bioengineering.

[47]  Alisa Rudnitskaya,et al.  Monitoring batch fermentations with an electronic tongue. , 2003, Journal of biotechnology.

[48]  E. Magner,et al.  Trends in electrochemical biosensors. , 1998, The Analyst.

[49]  S Falkow,et al.  FACS-optimized mutants of the green fluorescent protein (GFP). , 1996, Gene.

[50]  Christopher L. Davey,et al.  The dielectric properties of biological cells at radiofrequencies : Applications in biotechnology , 1999 .

[51]  António Joaquim Serralheiro,et al.  Bubble size in aerated stirred tanks , 2002 .

[52]  Larry L. Hench,et al.  The sol-gel process , 1990 .

[53]  S. Sivakesava,et al.  Monitoring a bioprocess for ethanol production using FT-MIR and FT-Raman spectroscopy , 2001, Journal of Industrial Microbiology and Biotechnology.

[54]  T. P. Jones,et al.  Optical pH sensor based on the chemical modification of a porous polymer film , 1988 .

[55]  Brian McNeil,et al.  Near‐infrared spectroscopic monitoring of biomass, glucose, ethanol and protein content in a high cell density baker's yeast fed‐batch bioprocess , 2006, Yeast.

[56]  D. Kell,et al.  Noninvasive, On-Line Monitoring of the Biotransformation by Yeast of Glucose to Ethanol Using Dispersive Raman Spectroscopy and Chemometrics , 1999 .

[57]  Lisbeth Olsson,et al.  On-line cell mass monitoring of Saccharomyces cerevisiae cultivations by multi-wavelength fluorescence. , 2004, Journal of biotechnology.

[58]  Joaquim M. S. Cabral,et al.  Real-time bioprocess monitoring: Part I: In situ sensors , 2006 .

[59]  Joseph S. Alford,et al.  Bioprocess control: Advances and challenges , 2006, Comput. Chem. Eng..

[60]  Colette McDonagh,et al.  Development of an optical sensor probe for the detection of dissolved carbon dioxide , 2006 .

[61]  J. W. Hall,et al.  Determination of nutrient levels in a bioprocess using near-infrared spectroscopy , 1993 .

[62]  Friedrich Srienc,et al.  Single-cell variability in growing Saccharomyces cerevisiae cell populations measured with automated flow cytometry. , 2004, Journal of biotechnology.

[63]  H Voigt,et al.  Diamond-like carbon-gate pH-ISFET , 1997 .

[64]  Francisco Valero,et al.  A simple model‐based control for Pichia pastoris allows a more efficient heterologous protein production bioprocess , 2006, Biotechnology and bioengineering.

[65]  J J Horvath,et al.  In Situ Fluorescence Cell Mass Measurements of Saccharomyces cerevisiae Using Cellular Tryptophan , 1993, Biotechnology progress.

[66]  Jorge M. T. Vasconcelos,et al.  Experimental and modelling study of gas dispersion in a double turbine stirred tank , 2002 .

[67]  E. Tamburini,et al.  Near-Infrared Spectroscopy: A Tool for Monitoring Submerged Fermentation Processes Using an Immersion Optical-Fiber Probe , 2003, Applied spectroscopy.

[68]  PREPARATION OF AN OXIDIZED IRIDIUM ELECTRODE AND THE VARIATION OF ITS POTENTIAL WITH PH , 1984 .

[69]  Yordan Kostov,et al.  Bioprocess monitoring. , 2002, Current opinion in biotechnology.

[70]  K. Kiviharju,et al.  Biomass measurement online: the performance of in situ measurements and software sensors , 2008, Journal of Industrial Microbiology & Biotechnology.

[71]  Marvin J. Johnson,et al.  Steam sterilizable probes for dissolved oxygen measurement , 1964 .

[72]  D B Kell,et al.  On-Line, Real-Time Measurements of Cellular Biomass using Dielectric Spectroscopy , 2000, Biotechnology & genetic engineering reviews.

[73]  M. Chidambaram,et al.  Fuzzy logic control of a fed-batch fermentor , 1993 .

[74]  In-Situ Microscopy for On-Line and In-Line Monitoring of Cell Populations in Bioreactors , 2001 .

[75]  S S Ozturk,et al.  Evaluation and applications of optical cell density probes in mammalian cell bioreactors , 1995, Biotechnology and bioengineering.

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

[77]  Chen Jianrong,et al.  New technology for the detection of pH. , 2005, Journal of biochemical and biophysical methods.

[78]  Marcin Majda,et al.  Effects of Electrodeposition Conditions and Protocol on the Properties of Iridium Oxide pH Sensor Electrodes , 2009 .

[79]  A. Bannari,et al.  CFD MODELING OF GAS DISPERSION AND BUBBLE SIZE IN A DOUBLE TURBINE STIRRED TANK , 2006 .

[80]  S Shioya,et al.  Knowledge-based design and operation of bioprocess systems. , 1999, Journal of bioscience and bioengineering.

[81]  R. C. Kuhad,et al.  Evaluation of biomass. , 1994, Advances in biochemical engineering/biotechnology.

[82]  A. Fiechter,et al.  Biomass determination. , 1992, Journal of biotechnology.

[83]  Ana P Ferreira,et al.  Monitoring complex media fermentations with near-infrared spectroscopy: comparison of different variable selection methods. , 2005, Biotechnology and bioengineering.

[84]  J. S. Guez,et al.  The viability of animal cell cultures in bioreactors: Can it be estimated online by using in situ microscopy? , 2010 .

[85]  Marc Madou,et al.  A pH Electrode Based on Melt-Oxidized Iridium Oxide , 2001 .

[86]  M. F. Mallette Chapter XV Evaluation of Growth by Physical and Chemical Means , 1969 .

[87]  H. Schwan Electrical properties of tissue and cell suspensions. , 1957, Advances in biological and medical physics.

[88]  Pauline M. Doran,et al.  Bioprocess Engineering Principles , 1995 .

[89]  K. Shirahige,et al.  Progression of cell cycle monitored by dielectric spectroscopy and flow‐cytometric analysis of DNA content , 2000, Yeast.

[90]  Douglas B. Kell,et al.  Dielectric permittivity of microbial suspensions at radio frequencies: a novel method for the real-time estimation of microbial biomass , 1987 .

[91]  Hisbullah,et al.  Design of a Fuzzy Logic Controller for Regulating Substrate Feed to Fed-Batch Fermentation , 2003 .

[92]  Steven E. J. Bell,et al.  Analysis of luminescent samples using subtracted shifted Raman spectroscopy , 1998 .