Optical instrumentation for bioprocess monitoring.

In this chapter the optical sensors for oxygen, pH, carbondioxide and optical density (OD) which are essential for bioprocess monitoring are introduced, their measurement principles are explained and their realization and applications are shown. In addition sensors for ethanol and GFP are presented. With the exception of the optical density sensor all others employ certain fluorophores that are sensitive to the designated parameter. These fluorophores along with their optical properties, the sensing mechanisms and their mathematical formulations are described. An important part of this chapter covers the development of the optoelectronic hardware for low cost systems that are able to measure the fluorescence lifetime and fluorescence intensity ratio. The employment of these probes in the bioprocess monitoring is demonstrated in different fermentation examples.

[1]  M. Zinbo Determination of one-carbon to three-carbon alcohols and water in gasoline alcohol blends by liquid chromatography , 1984 .

[2]  B. MacCraith,et al.  Ruthenium-doped sol-gel derived silica films: Oxygen sensitivity of optical decay times , 1994 .

[3]  L. Allain,et al.  Doped Thin-Film Sensors via a Sol-Gel Process for High-Acidity Determination. , 1997, Analytical chemistry.

[4]  I. Raimundo,et al.  Evaluation of fibre optical chemical sensors for flow analysis systems , 1998 .

[5]  W. Bentley,et al.  Ex vivo monitoring of protein production in baculovirus-infected Trichoplusia ni larvae with a GFP-specific optical probe. , 2003, Biotechnology and bioengineering.

[6]  G. Rao,et al.  Low-cost gated system for monitoring phosphorescence lifetimes , 2003 .

[7]  K. Timmis,et al.  Green fluorescent protein-based reporter systems for genetic analysis of bacteria including monocopy applications. , 1997, Gene.

[8]  J J Valdes,et al.  Observations of green fluorescent protein as a fusion partner in genetically engineered Escherichia coli: monitoring protein expression and solubility. , 2000, Biotechnology and bioengineering.

[9]  Tianlu Chen,et al.  Phenol red immobilized PVA membrane for an optical pH sensor with two determination ranges and long-term stability , 2005 .

[10]  Tuan Leng Tay,et al.  Development of transgenic fish for ornamental and bioreactor by strong expression of fluorescent proteins in the skeletal muscle. , 2003, Biochemical and biophysical research communications.

[11]  Ingo Klimant,et al.  Microsecond lifetime-based optical carbon dioxide sensor using luminescence resonance energy transfer , 1999 .

[12]  W. Stemmer,et al.  Improved Green Fluorescent Protein by Molecular Evolution Using DNA Shuffling , 1996, Nature Biotechnology.

[13]  Yordan Kostov,et al.  Optical Ratiometric Sensor for Alcohol Measurements , 2007 .

[14]  S R Goldstein,et al.  A miniature fiber optic pH sensor for physiological use. , 1980, Journal of biomechanical engineering.

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

[16]  György Marko-Varga,et al.  On-line fermentation process monitoring of carbohydrates and ethanol using tangential-flow filtration and column liquid chromatography , 1993 .

[17]  I. Karube,et al.  Gas-Phase Biosensor for Ethanol , 1994 .

[18]  A. Mills,et al.  COLORIMETRIC POLYMER FILM SENSORS FOR DISSOLVED CARBON-DIOXIDE , 1994 .

[19]  W. Rudolf Seitz,et al.  pH sensor based on immobilized fluoresceinamine , 1982 .

[20]  C. Albano,et al.  On-line green fluorescent protein sensor with LED excitation. , 1997, Biotechnology and bioengineering.

[21]  C. Albano,et al.  All solid-state GFP sensor. , 2000, Biotechnology and bioengineering.

[22]  Hermann Marsoner,et al.  Fluorimetric analysis , 1983 .

[23]  R. Haugland,et al.  Spectral and photophysical studies of benzo[c]xanthene dyes: dual emission pH sensors. , 1991, Analytical biochemistry.

[24]  Gary M. Carter,et al.  Low cost phase-modulation measurements of nanosecond fluorescence lifetimes using a lock-in amplifier , 1999 .

[25]  L. Gorton,et al.  A reagentless amperometric biosensor for alcohol detection in column liquid chromatography based on co-immobilized peroxidase and alcohol oxidase in carbon paste. , 1993, Journal of biotechnology.

[26]  M. Ueda,et al.  Quantitative evaluation of the enhanced green fluorescent protein displayed on the cell surface of Saccharomyces cerevisiae by fluorometric and confocal laser scanning microscopic analyses , 2001, Applied Microbiology and Biotechnology.

[27]  A. Rollins,et al.  A novel fiber-optic pH sensor incorporating carboxy SNAFL-2 and fluorescent wavelength-ratiometric detection. , 1998, Journal of biomedical materials research.

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

[29]  Helmut Offenbacher,et al.  Fluorescence optical sensors for continuous determination of near-neutral pH values , 1986 .

[30]  G. Lutty The acute intravenous toxicity of biological stains, dyes, and other fluorescent substances. , 1978, Toxicology and applied pharmacology.

[31]  J. Severinghaus,et al.  Electrodes for blood pO2 and pCO2 determination. , 1958, Journal of applied physiology.

[32]  Aleksandra Lobnik,et al.  Optical pH sensor based on the absorption of antenna generated europium luminescence by bromothymolblue in a sol–gel membrane , 2001 .

[33]  M. Moreno-Bondi,et al.  Reversible fiber-optic fluorosensing of lower alcohols , 1995 .

[34]  J. Trevors,et al.  Applications of the green fluorescent protein as a molecular marker in environmental microorganisms. , 1999, Journal of microbiological methods.

[35]  Yi Liu,et al.  Monitoring of DsRed protein concentration in frozen insect larvae , 2003, SPIE BiOS.

[36]  G. Rao,et al.  Ratiometric Alcohol Sensor based on a Polymeric Nile Blue , 2008 .

[37]  Max E. Lippitsch,et al.  Luminescence Quenching Behavior of an Oxygen Sensor Based on a Ru(II) Complex Dissolved in Polystyrene , 1995 .

[38]  Ana M Azevedo,et al.  Ethanol biosensors based on alcohol oxidase. , 2005, Biosensors & bioelectronics.

[39]  Joseph R. Lakowicz,et al.  Phase Fluorometric Optical Carbon Dioxide Gas Sensor for Fermentation Off‐Gas Monitoring , 1996, Biotechnology progress.

[40]  J. Hegemann,et al.  Green fluorescent protein as a marker for gene expression and subcellular localization in budding yeast , 1996, Yeast.

[41]  J. Hart,et al.  Development of a disposable ethanol biosensor based on a chemically modified screen-printed electrode coated with alcohol oxidase for the analysis of beer. , 2000, Biosensors & bioelectronics.

[42]  Yordan Kostov,et al.  Dual Excitation Ratiometric Fluorescent pH Sensor for Noninvasive Bioprocess Monitoring: Development and Application , 2002, Biotechnology progress.

[43]  H. Belghith,et al.  An enzyme electrode for on‐line determination of ethanol and methanol , 1987, Biotechnology and bioengineering.

[44]  W. Bentley,et al.  Rapid non-invasive monitoring of baculovirus infection for insect larvae using green fluorescent protein reporter under early-to-late promoter and a GFP-specific optical probe , 2006 .

[45]  Ursula E. Spichiger-Keller,et al.  Optical alcohol sensor using lipophilic Reichardt’s dyes in polymer membranes , 2001 .

[46]  W A Weigand,et al.  Monitoring GFP-operon fusion protein expression during high cell density cultivation of Escherichia coli using an on-line optical sensor. , 1999, Biotechnology and bioengineering.

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

[48]  J. Lakowicz Principles of fluorescence spectroscopy , 1983 .

[49]  Gelii V. Ponomarev,et al.  Phosphorescent Complexes of Porphyrin Ketones: Optical Properties and Application to Oxygen Sensing , 1995 .

[50]  O. Wolfbeis,et al.  Fluorescence sensor for monitoring ionic strength and physiological pH values , 1986 .

[51]  Kwok-Yin Wong,et al.  Optical characteristics of a ruthenium(II) complex immobilized in a silicone rubber film for oxygen measurement , 1993 .

[52]  G. Rao,et al.  Fluorescence Lifetime-based Sensing of Methanol , 1997 .

[53]  David R. Walt,et al.  Physiological pH fiber-optic chemical sensor based on energy transfer , 1987 .

[54]  U. Spichiger-Keller,et al.  Fluorescent ligands for optical sensing of alcohols: synthesis and characterisation of p-N,N-dialkylamino-trifluoroacetylstilbenes , 1997 .

[55]  G. Rao,et al.  Ratiometric oxygen sensing: detection of dual-emission ratio through a single emission filter. , 2000, The Analyst.

[56]  New Fluorescent Optical PH Sensors with Minimal Effects of Ionic Strength , 2008 .

[57]  J. Pines,et al.  GFP in mammalian cells. , 1995, Trends in genetics : TIG.

[58]  S. Kain,et al.  An enhanced green fluorescent protein allows sensitive detection of gene transfer in mammalian cells. , 1996, Biochemical and biophysical research communications.

[59]  Leah Tolosa,et al.  Noninvasive measurement of dissolved oxygen in shake flasks. , 2002, Biotechnology and bioengineering.

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

[61]  Z. Rosenzweig,et al.  Fiber-optic oxygen sensor based on the fluorescence quenching of tris (5-acrylamido, 1,10 phenanthroline) ruthenium chloride , 1998 .

[62]  W. Rudolf Seitz,et al.  A fluorescence sensor for quantifying pH in the range from 6.5 to 8.5 , 1984 .

[63]  U. Spichiger-Keller,et al.  Novel fluorescent sensor membranes for alcohols based on p-N, N-dioctylamino-4′-trifluoroacetylstilbene , 1997 .

[64]  R. Tsien Fluorescent indicators of ion concentrations. , 1989, Methods in cell biology.

[65]  W. Bentley,et al.  Insect larval expression process is optimized by generating fusions with green fluorescent protein. , 1999, Biotechnology and bioengineering.

[66]  Tomoko Nakanishi,et al.  ‘Green mice’ as a source of ubiquitous green cells , 1997, FEBS letters.