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Potentials and limitations of miniaturized calorimeters for bioprocess monitoring

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Abstract

In theory, heat production rates are very well suited for analysing and controlling bioprocesses on different scales from a few nanolitres up to many cubic metres. Any bioconversion is accompanied by a production (exothermic) or consumption (endothermic) of heat. The heat is tightly connected with the stoichiometry of the bioprocess via the law of Hess, and its rate is connected to the kinetics of the process. Heat signals provide real-time information of bioprocesses. The combination of heat measurements with respirometry is theoretically suited for the quantification of the coupling between catabolic and anabolic reactions. Heat measurements have also practical advantages. Unlike most other biochemical sensors, thermal transducers can be mounted in a protected way that prevents fouling, thereby minimizing response drifts. Finally, calorimetry works in optically opaque solutions and does not require labelling or reactants. It is surprising to see that despite all these advantages, calorimetry has rarely been applied to monitor and control bioprocesses with intact cells in the laboratory, industrial bioreactors or ecosystems. This review article analyses the reasons for this omission, discusses the additional information calorimetry can provide in comparison with respirometry and presents miniaturization as a potential way to overcome some inherent weaknesses of conventional calorimetry. It will be discussed for which sample types and scientific question miniaturized calorimeter can be advantageously applied. A few examples from different fields of microbiological and biotechnological research will illustrate the potentials and limitations of chip calorimetry. Finally, the future of chip calorimetry is addressed in an outlook.

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References

  • Ahmad LM, Towe B, Wolf A, Mertens F, Lerchner J (2010) Binding event measurement using a chip calorimeter coupled to magnetic beads. Sens. Actuators, B 145:239–245

    CAS  Google Scholar 

  • Baier V, Foedisch R, Ihring A, Kessler E, Lerchner J, Wolf G (2005) Highly sensitive thermopile heat power sensor for micro-fluid calorimetry of biochemical processes. Sens Actuators, B 123–124:354–359

    Google Scholar 

  • Bataillard P (1993) Calorimetric sensing in bioanalytical chemistry: principles, applications and trends. Trends Anal Chem 12(10):387–394

    CAS  Google Scholar 

  • Bataillard P, Steffgen E, Haemmerli S, Manz A, Widmer HM (1993) An integrated silicon thermopile as biosensor for the thermal monitoring of glucose, urea and penicillin. Biosens Bioelectron 8(2):89–98

    CAS  PubMed  Google Scholar 

  • Beezer AE, Bettelheim KA, Newell RD, Stevens J (1974) The diagnosis of bacteriuria by flow microcalorimetry, a preliminary report. Sci Tools 21:13–16

    Google Scholar 

  • Biener R, Steinkämper A, Hofmann J (2010) Calorimetric control for high cell density cultivation of a recombinant Escherichia coli strain. J Biotechnol 146(1–2):45–53

    CAS  PubMed  Google Scholar 

  • Birou B, Marison IW, Stockar UV (1987) Calorimetric investigation of aerobic fermentations. Biotechnol Bioeng 30(5):650–660

    CAS  PubMed  Google Scholar 

  • Blomberg A, Larsson C, Gustafsson L (1988) Microcalorimetric monitoring of growth of Saccharomyces cerevisiae: osmotolerance in relation to physiological state. J Bacteriol 170(10):4562

    CAS  PubMed  PubMed Central  Google Scholar 

  • Braissant O, Daniels AU (2011) Closed ampoule isothermal microcalorimetry (IMC) for continuous real-time detection and evaluation of cultured mammalian cell activity and responses. In: Stoddard M (ed) Mammalian cell viability methods. Springer, Heidelberg, pp 191–208

    Google Scholar 

  • Braissant O, Wirz D, Goepfert B, Daniels AU (2010) Biomedical use of isothermal microcalorimeters. Sensor 10:9369–9383

    CAS  PubMed  PubMed Central  Google Scholar 

  • Buchholz F, Wolf A, Lerchner J, Mertens F, Harms H, Maskow T (2010) Chip calorimetry for fast and reliable evaluation of bactericidal and bacteriostatic treatments of biofilms. Antimicrob Agents Chemother 54(1):312–319

    CAS  PubMed  Google Scholar 

  • Cordier JL, Butsch BM, Birou B, Stockar U (1987) The relationship between elemental composition and heat of combustion of microbial biomass. Appl Microbiol Biotechnol 25(4):305–312

    CAS  Google Scholar 

  • Dejean L, Beauvoit B, Bunoust O, Fleury C, Guerin B, Rigoulet M (2001) The calorimetric–respirometric ratio is an on-line marker of enthalpy efficiency of yeast cells growing on a non-fermentable carbon source. Biochim Biophys Acta 1503(3):329–340

    CAS  PubMed  Google Scholar 

  • Deponte S, Steingroewer J, Löser C, Boschke L, Bley T (2004) Biomagnetic separation of Escherichia coli by use of anion-exchange beads: measurement and modeling of the kinetics of cell–bead interactions. Anal Bioanal Chem 379:419–426

    CAS  PubMed  Google Scholar 

  • Efremov MY, Schiettekatte F, Zhang M, Olson EA, Kwan AT, Berry RS, Allen LH (2000) Discrete periodic melting point observations for nanostructure ensembles. Phys Rev Lett 85(17):3560–3563

    CAS  PubMed  Google Scholar 

  • Garcia-Payo MC, Ampuero S, Liu JS, Marison IW, von Stockar U (2002) The development and characterization of a high resolution bio-reaction calorimeter for weakly exothermic cultures. Thermochim Acta 391(1–2):25–39

    CAS  Google Scholar 

  • Gnaiger E, Kemp RB (1990) Anaerobic metabolism in aerobic mammalian cells: information from the ratio of calorimetric heat flux and respirometric oxygen flux. Biochim Biophys Acta 1016:328–332

    CAS  PubMed  Google Scholar 

  • Groeneveld P, Stouthamer AH, Westerhoff HV (2009) Super life—how and why ‘cell selection’ leads to the fastest-growing eukaryote. FEBS J 276(1):254–270

    CAS  PubMed  Google Scholar 

  • Günther HH, Bergter F (1971) Bestimmung der Trockenmasse von Zellsuspensionen durch Extinktionsmessungen. Z Allg Mikrob 11(3):191–197

    Google Scholar 

  • Hansen LD, Macfarlane C, McKinnon N, Smith BN, Criddle RS (2004) Use of calorespirometric ratios, heat per CO2 and heat per O2, to quantify metabolic paths and energetics of growing cells. Thermochim Acta 422(1–2):55–61

    CAS  Google Scholar 

  • Higuera-Guisset J, Rodriguez-Viejo J, Chacon M, Munoz FJ, Vigues N, Mas J (2005) Calorimetry of microbial growth using a thermopile based microreactor. Thermochim Acta 427(1):187–191

    CAS  Google Scholar 

  • Johannessen EA, Weaver JMR, Bourova L, Svoboda P, Cobbold PH, Cooper JM (2002) Micromachined nanocalorimetric sensor for ultra-low-volume cell-based assays. Anal Chem 74(9):2190–2197

    CAS  PubMed  Google Scholar 

  • Köhler JM, Henkel T, Grodrian A, Kirner T, Roth M, Martin K, Metze J (2004) Digital reaction technology by micro segmented flow—components, concepts and applications. Chem Eng J 101(1–3):201–216

    Google Scholar 

  • Kwak BS, Kim BS, Cho HH, Park JS, Jung HI (2008) Dual thermopile integrated microfluidic calorimeter for biochemical thermodynamics. Microfluidics and Nanofluidics 5(2):255–262

    CAS  Google Scholar 

  • Kwan AT, Efremov MY, Olson EA, Schiettekatte F, Zhang M, Geil PH, Allen LH (2001) Nanoscale calorimetry of isolated polyethylene single crystals. J Polym Sci, Part B: Polym Phys 39(11):1237–1245

    CAS  Google Scholar 

  • Lahiji GR, Wise KD (1982) A batch-fabricated silicon thermopile infrared detector. IEEE Trans Electron Devices 29(1):14–22

    Google Scholar 

  • Lee W, Fon W, Axelrod BW, Roukes ML (2009) High-sensitivity microfluidic calorimeters for biological and chemical applications. Proc Natl Acad Sci USA 106(36):15225

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lerchner J, Wolf G, Auguet C, Torra V (2002) Accuracy in integrated circuit (IC) calorimeters. Thermochim Acta 382(1–2):65–76

    CAS  Google Scholar 

  • Lerchner J, Kirchner R, Seidel J, Wahlisch D, Wolf G, Konig WA (2006a) Determination of molar heats of absorption of enantiomers into thin chiral coatings by combined IC-calorimetric and microgravimetric (QMB) measurements. II. Thermodynamics of enantio selectivity in modified cyclodextrins. Thermochim Acta 445(2):98–103

    CAS  Google Scholar 

  • Lerchner J, Wolf A, Wolf G, Baier V, Kessler E, Nietzsch M, Krügel M (2006b) A new micro-fluid chip calorimeter for biochemical applications. Thermochim Acta 445(2):144–150

    CAS  Google Scholar 

  • Lerchner J, Maskow T, Wolf G (2008a) Chip calorimetry and its use for biochemical and cell biological investigations. Chem Eng Process 47(6):991–999

    CAS  Google Scholar 

  • Lerchner J, Wolf A, Buchholz F, Mertens F, Neu TR, Harms H, Maskow T (2008b) Miniaturized calorimetry—a new method for real-time biofilm activity analysis. J Microbiol Meth 74(2–3):74–81

    CAS  Google Scholar 

  • Lerchner J, Wolf A, Schneider HJ, Mertens F, Kessler E, Baier V, Funfak A, Nietzsch M, Krügel M (2008c) Nano-calorimetry of small-sized biological samples. Thermochim Acta 477(1–2):48–53

    CAS  Google Scholar 

  • Lewis G, Pardoe R, Bowen W, Lerchner J (2011) A low volume, flow-based approach to biocalorimetry. Paper presented at the 19. Ulm-Freiberger Kalorimetrietage, Freiberg, 16–18 March 2011

  • Mahadevan S, Dhandapani B, Sivaprakasam S, Mandal AB (2010) Batch kinetic studies on growth of salt tolerant Pseudomonas aeruginosa secreting protease in a biocalorimeter. Biotechnol Bioprocess Eng 15(4):670–675

    CAS  Google Scholar 

  • Mariana F, Buchholz F, Harms H, Yong Z, Yao J, Maskow T (2010) Isothermal titration calorimetry—a new method for the quantification of microbial degradation of trace pollutants. J Microbiol Methods 82(1):42–48

    CAS  PubMed  Google Scholar 

  • Maskow T, Lerchner J, Peitzsch M, Harms H, Wolf G (2006a) Chip calorimetry for the monitoring of whole cell biotransformation. J Biotechnol 122(4):431–442

    CAS  PubMed  Google Scholar 

  • Maskow T, Müller S, Losche A, Harms H, Kemp R (2006b) Control of continuous polyhydroxybutyrate synthesis using calorimetry and flow cytometry. Biotechnol Bioeng 93(3):541

    CAS  PubMed  Google Scholar 

  • Normant M, Dziekonskia M, Drzazgowskib J, Lamprecht I (2007) Metabolic investigations of aquatic organisms with a new twin heat conduction calorimeter. Thermochim Acta 458(1–2):101–106

    CAS  Google Scholar 

  • Novick A, Szilard L (1950) Experiments with the chemostat on spontaneous mutations of bacteria. Proc Natl Acad Sci USA 36(12):708

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oroszi S, Jakob T, Wilhelm C, Harms H, Maskow T (2011) Photosynthetic energy conversion in the diatom Phaeodactylum tricornutum. J Therm Anal Calorim 104:223–231

    CAS  Google Scholar 

  • Peitzsch M, Kiesel B, Harms H, Maskow T (2008) Real time analysis of Escherichia coli biofilms using calorimetry. Chem Eng Process 47(6):1000–1006

    CAS  Google Scholar 

  • Qureshi N, Annous BA, Ezeji TC, Karcher P, Maddox IS (2005) Biofilm reactors for industrial bioconversion processes: employing potential of enhanced reaction rates. Microb Cell Fact 4(1):24

    PubMed  PubMed Central  Google Scholar 

  • Recht MI, Bruyker DD, Bell AG, Wolkin MV, Peeters E, Anderson GB, Kolatkar AR, Bern MW, Kuhn P, Bruce RH (2008) Enthalpy array analysis of enzymatic and binding reactions. Anal Biochem 377(1):33–39

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ripa KT, Mardh PA, Hovelius B, Ljungholm K (1977) Microcalorimetry as a tool for evaluation of blood culture media. J Clin Microbiol 5(4):393–396

    CAS  PubMed  PubMed Central  Google Scholar 

  • Salemme FR (2004) High-throughput biochemistry heats up. Nat Biotechnol 22(9):1100–1101

    CAS  PubMed  Google Scholar 

  • Schön A, Wadsö I (1988) The use of microcalorimetry in studies of mammalian cells. J Therm Anal Calorim 33(1):47–54

    Google Scholar 

  • Schubert T, Breuer U, Harms H, Maskow T (2007) Calorimetric bioprocess monitoring by small modifications to a standard bench-scale bioreactor. J Biotechnol 130(1):24–31

    CAS  PubMed  Google Scholar 

  • Stephanopoulos GN, Aristidou AA, Nielsen J (1998) Metabolic engineering: principles and methodologies. Academic, San Diego

    Google Scholar 

  • Thornton W (1917) The relation of oxygen to the heat of combustion of organic compounds. Philos Mag 33:196–203

    CAS  Google Scholar 

  • Torra V, Auguet C, Lerchner J, Marinelli P, Tachoire H (2001) Identification of micro-scale calorimetric devices. I. Establishing the experimental rules for accurate measurements. J Therm Anal Calorim 66(1):255–264

    CAS  Google Scholar 

  • Torres FE, Kuhn P, De Bruyker D, Bell AG, Wolkin MV, Peeters E, Williamson JR, Anderson GB, Schmitz GP, Recht MI, Schweizer S, Scott LG, Ho JH, Elrod SA, Schultz PG, Lerner RA, Bruce RH (2004) Enthalpy arrays. Proc Natl Acad Sci USA 101(26):9517–9522

    CAS  PubMed  PubMed Central  Google Scholar 

  • Trampuz A, Salzmann S, Antheaume J, Daniels AU (2007) Microcalorimetry: a novel method for detection of microbial contamination in platelet products. Transfusion 47(9):1643–1650

    PubMed  Google Scholar 

  • Türker M (2003) Measurement of metabolic heat in a production-scale bioreactor by continuous and dynamic calorimetry. Chem Eng Commun 190:573–598

    Google Scholar 

  • van Gulik WM, Heijnen JJ (1995) A metabolic network stoichiometry analysis of microbial growth and product formation. Biotechnol Bioeng 48(6):681–698

    PubMed  Google Scholar 

  • van Herwaarden AW (2005) Overview of calorimeter chips for various applications. Thermochim Acta 432(2):192–201

    Google Scholar 

  • van Kleeff BHA, Kuenen JG, Heijnen JJ (1996) Heat flux measurements for the fast monitoring of dynamic responses to glucose additions by yeasts that were subjected to different feeding regimes in continuous culture. Biotechnol Prog 12(4):510–518

    PubMed  Google Scholar 

  • Vanderzee CE, Mansson M, Wadsö I, Sunner S (1972) Enthalpies of formation of mono- and diammonium succinates and of aqueous ammonia and ammonium ion. J Chem Thermodyn 4(4):541–550

    CAS  Google Scholar 

  • Verhaegen K, Baert K, Simaels J, Van Driessche W (2000) A high-throughput silicon microphysiometer. Sensors and Actuators, A 82(1–3):186–190

    CAS  Google Scholar 

  • Voisard D, Pugeaud P, Kumar AR, Jenny K, Jayaraman K, Marison IW, von Stockar U (2002) Development of a large-scale biocalorimeter to monitor and control bioprocesses. Biotechnol Bioeng 80(2):125–138

    CAS  PubMed  Google Scholar 

  • von Rège H, Sand W (1998) Evaluation of biocide efficacy by microcalorimetric determination of microbial activity in biofilms. J Microbiol Methods 33(3):227

    Google Scholar 

  • von Stockar U, Marison IW (1991) Large-scale calorimetry and biotechnology. Thermochim Acta 193:215–242

    Google Scholar 

  • von Stockar U, Gustafsson L, Larsson C, Marison I, Tissot P, Gnaiger E (1993) Thermodynamic considerations in constructing energy balances for cellular growth. Biochim Biophys Acta 1183(2):221–240

    Google Scholar 

  • Weikert C, Sauer U, Bailey JE (1997) Use of a glycerol-limited, long-term chemostat for isolation of Escherichia coli mutants with improved physiological properties. Microbiology 143(5):1567

    CAS  PubMed  Google Scholar 

  • Wentzien S, Sand W, Albertsen A, Steudel R (1994) Thiosulfate and tetrathionate degradation as well as biofilm generation by Thiobacillus intermedius and Thiobacillus versutus studied by microcalorimetry, HPLC, and ion-pair chromatography. Arch Microbiol 161(2):116–125

    CAS  Google Scholar 

  • Winter W, Höhne GWH (2003) Chip-calorimeter for small samples. Thermochim Acta 403(1):43–53

    CAS  Google Scholar 

  • Xu J, Reiserer R, Tellinghuisen J, Wikswo JP, Baudenbacher FJ (2008) A microfabricated nanocalorimeter: design, characterization, and chemical calibration. Anal Chem 80(8):2728–2733

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Tadigadapa S (2004) Calorimetric biosensors with integrated microfluidic channels. Biosens Bioelectron 19(12):1733–1743

    CAS  PubMed  Google Scholar 

  • Zhou Y, Yao J, He M, Choi MMF, Feng L, Chen H, Wang F, Chen K, Zhuang R, Maskow T (2010) Reduction in toxicity of arsenic(III) to Halobacillus sp. Y35 by kaolin and their related adsorption studies. J Hazard Mater 176(1–3):487–494

    CAS  PubMed  Google Scholar 

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Acknowledgement

Financial support of the German Research Council (Deutsche Forschungsgemeinschaft, Le1128/1-1, Ma3746/2-1, Ma3746/2-3) and German Federation of Industrial Research Associations (AiF BMWi, AiF-Nr. 244 ZBG) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Environmental Microbiology, UFZ, Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318, Leipzig, Germany

    Thomas Maskow, Torsten Schubert, Friederike Buchholz & Hauke Harms

  2. AVT-Aachener Verfahrenstechnik, Biochemical Engineering, Sammelbau Biologie, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany

    Lars Regestein & Jochen Buechs

  3. TU Bergakademie Freiberg, Institute of Physical Chemistry, Leipziger Strasse 29, 09596, Freiberg, Germany

    Antje Wolf, Florian Mertens & Johannes Lerchner

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  1. Thomas Maskow
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Correspondence to Thomas Maskow.

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Maskow, T., Schubert, T., Wolf, A. et al. Potentials and limitations of miniaturized calorimeters for bioprocess monitoring. Appl Microbiol Biotechnol 92, 55–66 (2011). https://doi.org/10.1007/s00253-011-3497-7

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