Abstract
One of the major aims of bioprocess engineering is the real-time monitoring of important process variables. This is the basis of precise process control and is essential for high productivity as well as the exact documentation of the overall production process. Infrared spectroscopy is a powerful analytical technique to analyze a wide variety of organic compounds. Thus, infrared sensors are ideal instruments for bioprocess monitoring. The sensors are non-invasive, have no time delay due to sensor response times, and have no influence on the bioprocess itself. No sampling is necessary, and several components can be analyzed simultaneously. In general, the direct monitoring of substrates, products, metabolites, as well as the biomass itself is possible. In this review article, insights are provided into the different applications of infrared spectroscopy for bioprocess monitoring and the complex data interpretation. Different analytical techniques are presented as well as example applications in different areas.
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Acha V, Meurens M, Naveau H, Agathos S (2000) ATR-FTIR sensor development for continuous on-line monitoring of chlorinated aliphatic hydrocarbons in a fixed-bed bioreactor. Biotechnol Bioeng 68:473–487
American Society for Testing and Materials (1997) PA and note for guidance on the use of near infrared spectroscopy by the pharmaceutical industry and the date requirements for new submissions and variations, Method E 1655-97: Standard practices for infrared, multivariate, quantitative analysis, West Conshohocken, PMP/QWP/3309/01 and EMEA/CVMP/961/01
Arnold S, Gaensakoo R, Harvey L, McNeil B (2002) Use of at-line and in-situ near-infrared spectroscopy to monitor biomass in an industrial fed-batch Escherichia coli process. Biotechnol Bioeng 80:405–413
Arnold S, Crowley S, Woods N, Harvey L, McNeil B (2003) In-situ near infrared spectroscopy to monitor key analytes in mammalian cell cultivation. Biotechnol Bioeng 84:13–19
Bras L, Lopes M, Ferreira A, Menezes J (2008) A bootstrap-based strategy for spectral interval selection in PLS regression. J Chemom 22:695–700
Brown P (1992) Wavelength selection in multicomponent near-infrared calibration. J Chemometr 6:151–161
Cervera A, Petersen N, Lantz A, Larson A, Gernaey K (2009) Application of near-infrared spectroscopy for monitoring and control of cell culture and fermentation. Am Inst Chem Eng. doi:10.1002/btpr.280
Coen T, Saeys W, Ramon H, De Baerdemaeker J (2006) Optimizing the tuning parameters of least squares support vector machines regression for NIR spectra. J Chemom 20:184–192
Crowley J, Arnold S, Wood N, Harvey L, McNeil B (2005) Monitoring a high cell density recombinant Pichia pastoris fed-batch bioprocess using transmission and reflectance near infrared spectroscopy. Enzyme Microbiol Tech 36:621–628
Ferreira A, Menezes J (2006) Monitoring a complex medium fermentation with sample-sample two-dimensional FT-NIR correlation spectroscopy. Biotechnol Prog 22:866–872
Franco V, Perin J, Mantovani V, Goiceoechea H (2006) Monitoring substrate and products in a bioprocess with FTIR spectroscopy coupled to artificial neural networks enhanced with a genetic-algorithm-based method for wavelength selection. Talanta 68:1005–1012
Ge Z, Cavinato A, Callis J (1994) Non-invasive spectroscopy for monitoring cell density in a fermentation process. Anal Chem 66:1354–1362
Giavasis I, Robertson I, McNeill B, Harvey L (2003) Simultaneous and rapid monitoring of biomass and biopolymer production by Sphingomonas paucimobilis using Fourier transform-near infrared spectroscopy. Biotechnol Lett 25:975–979
Goicoechea H, Olivieri A (2003) A new family of genetic algorithms for wavelength interval selection in multivariate analytical spectroscopy. J Chemom 17:338–345
Gorry P (1990) General least-squares smoothing and differentiation by the convolution (Savitzky–Golay) method. Anal Chem 62:570–573
Hantelmann K, Kollecker M, Huell D, Hitzmann B, Scheper T (2005) Two-dimensional fluorescence spectroscopy: a novel approach for controlling fed-batch cultivations. J Biotechnol 121:410–417
Heise H, Müller U, Gärtner A, Hölscher N (2001) Improved chemometric strategies for quantitative FTIR spectral analysis and applications in atmospheric open-path monitoring. Field Anal Chem Technol 5:13–28
Henriques J, Buziol S, Stocker E, Voogd A, Menezes J (2009) Monitoring mammalian cell cultivations for monoclonal antibody production using near-infrared spectroscopy. Adv Biochem Engin/Biotechnol 116:73–97
Holm-Nielsen J, Lomborg C, Oleskowicz-Popiel P, Esbensen K (2008) On-line near infrared monitoring of glycerol-boosted anaerobic digestion processes: evaluation of process analytical technologies. Biotechnol Bioeng 99:302–313
Hongqiang L, Hongzhang C (2008) Near-infrared spectroscopy with a fiber-optic probe for state variables determination in solid-state fermentation. Process Biochem 43:511–516
Kiviharju K, Salonen K, Moilanen U, Meskanen E, Leisola M, Eerikäinen T (2007) On-line biomass measurements in bioreactor cultivations: comparison study of two on-line probes. J Ind Microbiol Biotechnol 34:561–566
Knuettel T, Meyer H, Scheper T (2006) The application of two-dimensional fluorescence spectroscopy for the on-line evaluation of modified enzymatic enantioselectivities in organic solvents by forming substrate salts. Enz Microb Technol 39:607–611
Kornmann H, Rhiel M, Cannizzaro C, Marison I, von Stockar U (2003) Methodology for real-time, multianalyte monitoring of fermentations using an in-situ mid-infrared sensor. Biotechnol Bioeng 82:702–709
Kornmann H, Valentinotti S, Duboc P, Marison I, von Stockar U (2004) Monitoring and control of Gluconacetobacter xylinus fed-batch cultures using in situ mid-IR spectroscopy. J Biotechnol 113:231–245
Lavine B (2000) Fundamental reviews: chemometrics. Anal Chem 72:91–98
Leardi R (1994) Application of a genetic algorithm to feature selection under full validation conditions and to outlier detection. J Chemometr 8:65–79
Marose S, Lindemann C, Ulber R, Scheper T (1999) Optical sensor systems for bioprocess monitoring. TIBTECH 17:30–34
Mazarevica G, Diewok J, Baena J, Lendl J (2004) On-line fermentation monitoring by mid-IR spectroscopy. Appl Spectrosc 58:804–810
Miller C (2000) Chemometrics for on-line spectroscopy applications—theory and practice. J Chemom 14:513–528
Navrátil M, Norberg A, Lembrén L, Mandenius C (2005) On-line multi-analyzer monitoring of biomass, glucose and acetate for growth rate control of a Vibrio cholerae fed-batch cultivation. J Biotechnol 115:67–79
Nordon A, Littlejohn D, Dann A, Jeffkins P, Richardson M, Simpson S (2008) In situ monitoring of a seed stage of a fermentation process using non-invasive NIR spectrometry. Analyst 133:660–666
Petersen N, Ödman P, Padrell A, Stocks S, Lantz A, Gernaey K (2009) In situ near infrared spectroscopy for analyte-specific monitoring of glucose and ammonium in Streptomyces coelicolor fermentations. Am Inst Chem Eng. doi:10.1002/btpr.288
Rhiel M, Ducommun P, Bolzonella I, Marison I, von Stockar U (2001) Real-time in situ monitoring of freely suspended and immobilized cell cultures based on mid-infrared spectroscopic measurements. Biotechnol Bioeng 77:174–185
Rhiel M, Amrhein M, Marison I, von Stockar U (2002) The influence of correlated calibration samples on the prediction performance of multivariate models based on mid-infrared spectra of animal cell cultures. Anal Chem 74:5227–5236
Rhiel M, Cohen M, Arnold M, Murhammer D (2004) On-line monitoring of human prostate cancer cells in a perfusion rotating wall vessel by near-infrared spectroscopy. Biotechnol Bioeng 86:852–861
Riley M, Rhiel M, Zhou X, Arnold M, Murhammer D (1997) Simultaneous monitoring of glucose and glutamine in insect cell cultures by NIR spectroscopy. Biotechnol Bioeng 55:11–15
Rodrigues L, Vieira L, Cardoso J, Menezes J (2008) The use of NIR as a multi-parametric in situ monitoring technique in filamentous fermentation systems. Talanta 75:1356–1361
Roggo Y, Chalus P, Maurer L, Lema-Martinez C, Edmond A, Jent N (2007) A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies. J Pharm Biomed Anal 44:683–700
Roychoudhury P, Harvey L, McNeil B (2006) At-line monitoring of ammonium, glucose, methyl oleate and biomass in a complex antibiotic fermentation process using attenuated total reflectance-mid-infrared (ATR-MIR) spectroscopy. Anal Chim Acta 561:218–224
Roychoudhury P, Harvey L, McNeil B (2007a) Simultaneous determination of glycerol and clavulanic acid in an antibiotic bioprocess using attenuated total reflectance mid infrared spectroscopy. Anal Chim Acta 585:246–252
Roychoudhury P, O’Kennedy R, McNeil B, Harvey L (2007b) Multiplexing fibre optic near infrared (NIR) spectroscopy as an emerging technology to monitor industrial bioprocesses. Anal Chim Acta 590:110–117
Schenk J, Marison I, von Stockar U (2006) A simple method to monitor and control methanol feeding of Pichia pastoris fermentations using mid-IR. J Biotechnol 128(344):353
Schenk J, Marison I, von Stockarl U (2008) pH prediction and control in bioprocesses using mid-infrared spectroscopy. Biotechnol Bioeng 100:82–93
Scheper T, Gebauer A, Sauerbrei A, Niehoff A, Schügerl K (1984) Measurement of biological parameters during fermentation processes. Anal Chim Acta 163:111–118
Scheper T, Hilmer J, Lammers F, Mueller C, Reinecke M (1996) Biosensors in bioprocess monitoring. J Chromat 725:3–12
Scheper T, Hitzmann B, Staerk E, Ulber R, Faurie R, Sosnitza P, Reardon K (1999) Bioanalytics: detailed insight into bioprocesses. Anal Chim Acta 400:121–143
Sellick C, Hansen R, Jarvis R, Maqsood A, Stephens G, Dickson A, Goodacre R (2010) Rapid monitoring of recombinant antibody production by mammalian cell cultures using Fourier transform infrared spectroscopy and chemometrics. Biotechnol Bioeng 106:432–442
Shamsipur M, Zare-Shahabadi V, Hemmateenejad B, Akhond M (2006) Ant colony optimisation: a powerful tool for wavelength selection. J Chemom 20:146–157
Sivakesava S, Irudayaraj J, Ali D (2001) Simultaneous determination of multiple components in lactic acid fermentation using FT-MIR, NIR, and FT-Raman spectroscopic techniques. Process Biochem 37:371–78
Soons Z, Streefland M, van Straten G, van Boxtel A (2008) Assessment of near infrared and “software sensor” for biomass monitoring and control. Chemometr Intell Lab Sys 94:166–174
Tosi S, Rossi M, Tamburini E, Vaccari G, Amaretti A, Matteuzzi D (2003) Assessment of in-line near-infrared spectroscopy for continuous monitoring of fermentation processes. Biotechnol Prog 19:1816–1821
Trevisan M, Poppi R (2008) Direct determination of ephedrine intermediate in a biotransformation reaction using infrared spectroscopy and PLS. Talanta 75:1021–1027
Udelhoven T, Schütt B (2000) Capability of feed-forward neural networks for a chemical evaluation of sediments with diffuse reflectance spectroscopy. Chemom Intell Lab Syst 51:9–22
Vaidyanathan S, White S, Harvey L, McNeil B (2003) Influence of morphology on the near-infrared spectra of mycelial biomass and its implications in bioprocess monitoring. Biotechnol Bioeng 82:715–724
Yamane Y, Mikami K, Higshida K, Kakizano T, Nishio N (1996) Estimation of the concentrations of cells, astaxanthin and glucose in a culture of Phaffia rhodozyma by near infrared reflectance spectroscopy. Biotechnol Tech 10:529–534
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Landgrebe, D., Haake, C., Höpfner, T. et al. On-line infrared spectroscopy for bioprocess monitoring. Appl Microbiol Biotechnol 88, 11–22 (2010). https://doi.org/10.1007/s00253-010-2743-8
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DOI: https://doi.org/10.1007/s00253-010-2743-8