Luminescence-Based Sensors for Bioprocess Applications

Part of the Springer Series on Fluorescence book series (SS FLUOR, volume 18)


Reliable robust sensor systems are essential to monitor in situ and allow controlling of the evolution of bioprocesses in order to maximize the product yields and guarantee their quality. The more chemical and biological information is collected, the better strategies can be applied to generate highly productive cell lines and successfully determine the target production profiles. While the most common sensors employed in cell cultivation processes are those that measure (in-line) physical parameters (temperature, liquid level, conductivity, redox potential, etc.), ruggedized chemical monitors such as pH and gas phase/dissolved O2 and pCO2 are essential to determine the status of the cultured microorganisms. Luminescent chemical sensors for these three parameters have demonstrated in the last few years their superiority over the traditional electrochemical sensors for in situ continuous real-time bioprocess monitoring, particularly those based on disposable analyte-sensitive patches attached to single-use bioreactors combined with emission lifetime measurements. This chapter reviews the progress achieved in luminescent sensing of O2, CO2, and pH for bioprocess applications that have led them to be the devices of choice for many manufacturers and customers in most situations.


Bioprocess monitoring Bioreactors Carbon dioxide CO2 Fluorescence Luminescence O2 Oxygen pH Probes Sensors 



The authors are indebted to the many public institutions, both national and European, and private companies that have funded our research on luminescent O2, CO2, and pH sensor technology and tailored indicator dyes over the last 20 years: the European Commission Framework Programs; EU Funds for Regional Development; the Spanish Ministries of Science, Technology, Industry, and Competitiveness; the Madrid Autonomous Region Government; Complutense University of Madrid; Santander Bank; Interlab Group; TGI; Agilent Technologies; CESA; TAP Biosystems (currently part of Sartorius Stedim); and Gas Natural Fenosa (now Naturgy). Our research in the 2016–2018 period was supported by the MINECO CTQ2015-69278-C2-2-R research grant and Naturgy SmartGreenGas project.


  1. 1.
    Classen J, Aupert F, Reardon KF, Solle D, Scheper T (2017) Spectroscopic sensors for in-line bioprocess monitoring in research and pharmaceutical industrial application. Anal Bioanal Chem 409:651–666PubMedGoogle Scholar
  2. 2.
    Roch P, Mandenius C-F (2016) On-line monitoring of downstream bioprocesses. Curr Opinion Chem Eng 14:112–120Google Scholar
  3. 3.
    Biechele P, Busse C, Solle D, Scheper T, Reardon K (2015) Sensor systems for bioprocess monitoring. Eng Life Sci 15:469–488Google Scholar
  4. 4.
    Rodríguez-Duran LV, Torres-Mancera MT, Trujillo-Roldán MA, Valdez-Cruz NA, Favela-Torres E, Saucedo-Castañeda G (2017) Standard instruments for bioprocess analysis and control. In: Larroche C, Sanroman M, Du G, Pandey A (eds) Current developments in biotechnology and bioengineering: bioprocesses, bioreactors and controls. Elsevier, Amsterdam, pp 593–626Google Scholar
  5. 5.
    Holzberg TR, Watson V, Brown S, Andar A, Ge X, Kostov Y, Tolosa L, Rao G (2018) Sensors for biomanufacturing process development: facilitating the shift from batch to continuous manufacturing. Curr Opinion Chem Eng 22:115–127Google Scholar
  6. 6.
    Busse C, Biechele P, de Vries I, Reardon KF, Solle D, Scheper T (2017) Sensors for disposable bioreactors. Eng Life Sci 17:940–952Google Scholar
  7. 7.
    O’Mara P, Farrell A, Bones J, Twomey K (2018) Staying alive! Sensors used for monitoring cell health in bioreactors. Talanta 176:130–139PubMedGoogle Scholar
  8. 8.
    Orellana G (2006) Fluorescence-based sensors. In: Baldini F, Chester AN, Homola J, Martellucci S (eds) Optical chemical sensors, NATO Sci Ser II, vol 224. Springer-Kluwer, Amsterdam, pp 99–116Google Scholar
  9. 9.
    Demchenko AP (2015) Introduction to fluorescence sensing, 2nd edn. Springer, ChamGoogle Scholar
  10. 10.
    Valeur B, Berberan-Santos MN (2012) Molecular fluorescence: principles and applications, 2nd edn. Wiley-VCH, WeinheimGoogle Scholar
  11. 11.
    Garcia-Ochoa F, Gomez E, Santos VE, Merchuk JC (2010) Oxygen uptake rate in microbial processes: an overview. Biochem Eng J 49:289–307Google Scholar
  12. 12.
    Anastasova S, Milanova M, Todorovsky D (2008) Photoluminescence response of Ru(II) complex immobilized in SiO2-based matrix to dissolved oxygen in beer. J Biochem Biophys Methods 70:1292–1296PubMedGoogle Scholar
  13. 13.
    Urriza-Arsuaga I, Bedoya M, Orellana G (2019) Luminescent sensor for O2 detection in biomethane streams. Sens Actuators B Chem 279:458–465Google Scholar
  14. 14.
    Wang X, Wolfbeis OS (2014) Optical methods for sensing and imaging oxygen: materials, spectroscopies and applications. Chem Soc Rev 43:3666–3761PubMedGoogle Scholar
  15. 15.
    Quaranta M, Borisov SM, Klimant I (2012) Indicators for optical oxygen sensors. Bioanal Rev 4:115–157PubMedPubMedCentralGoogle Scholar
  16. 16.
    Orellana G, García-Fresnadillo D (2004) Environmental and industrial optosensing with tailored luminescent Ru(II) Polypyridyl complexes. In: Narayanaswamy R, Wolfbeis OS (eds) Optical sensors. Springer, Berlin, pp 309–357Google Scholar
  17. 17.
    Demuth C, Varonier J, Jossen V, Eibl R, Eibl D (2016) Novel probes for pH and dissolved oxygen measurements in cultivations from milliliter to benchtop scale. Appl Microbiol Biotechnol 100:3853–3863PubMedGoogle Scholar
  18. 18.
    Schäpper D, Alam MN, Szita N, Lantz AE, Gernaey KV (2009) Application of microbioreactors in fermentation process development: a review. Anal Bioanal Chem 395:679–695PubMedGoogle Scholar
  19. 19.
    Grist SM, Chrostowski L, Cheung KC (2010) Optical oxygen sensors for applications in microfluidic cell culture. Sensors 10:9286–9316PubMedGoogle Scholar
  20. 20.
    Gruber P, Marques MPC, Szita N, Mayr T (2017) Integration and application of optical chemical sensors in microbioreactors. Lab Chip 17:2693–2712PubMedGoogle Scholar
  21. 21.
    Orellana G, López-Gejo J, Pedras B (2014) Silicone films for fiber-optic chemical sensing. In: Tiwari A, Soucek MD (eds) Concise encyclopedia of high-performance silicones. Scrivener-Wiley, Beverly, pp 339–354Google Scholar
  22. 22.
    Kroneis HW, Marsoner HJ (1983) A fluorescence-based sterilizable oxygen probe for use in bioreactors. Sens Actuators B Chem 4:587–592Google Scholar
  23. 23.
    Bambot SB, Holavanahali R, Lakowicz JR, Carter GM, Rao G (1993) Phase fluorometric sterilizable optical oxygen sensor. Biotechnol Bioeng 43:1139–1145Google Scholar
  24. 24.
    Kohls O, Scheper T (2000) Setup of a fiber optical oxygen multisensor-system and its applications in biotechnology. Sens Actuators B Chem 70:121–130Google Scholar
  25. 25.
    Navarro-Villoslada F, Orellana G, Moreno-Bondi MC, Vick T, Driver M, Hildebrand G, Liefeith K (2001) Fiberoptic luminescent sensors with composite oxygen-sensitive layers and anti-biofouling coatings. Anal Chem 73:5150–5156Google Scholar
  26. 26.
    Tolosa L, Kostov Y, Harms P, Rao G (2002) Noninvasive measurement of dissolved oxygen in shake flasks. Biotechnol Bioeng 80:594–597PubMedGoogle Scholar
  27. 27.
    John GT, Klimant I, Wittmann C, Heinzle E (2003) Integrated optical sensing of dissolved oxygen in microtiter plates: a novel tool for microbial cultivation. Biotechnol Bioeng 81:829–836PubMedGoogle Scholar
  28. 28.
    Jin P, Chu J, Miao Y, Tan J, Xhang S, Zhu W (2013) A NIR luminescent copolymer based on platinum porphyrin as high permeable dissolved oxygen sensor for microbioreactors. AICHE J 59:2743–2752Google Scholar
  29. 29.
    Guenther D, Mattley Y (2015) Monitoring oxygen and pH during E. coli fermentation. Ocean optics application notes. Accessed 10 Sept 2018
  30. 30.
    Ge X, Hanson M, Shen H, Kostov Y, Brorson KA, Frey DD, Moreira AR, Rao G (2006) Validation of an optical sensor-based high-throughput bioreactor system for mammalian cell culture. J Biotechnol 122:293–306PubMedGoogle Scholar
  31. 31.
    Schneider K, Schütz V, John GT, Heinzle E (2010) Optical device for parallel online measurement of dissolved oxygen and pH in shake flask cultures. Bioprocess Biosyst Eng 33:541–547PubMedGoogle Scholar
  32. 32.
    Naciri M, Kuystermans D, Al-Rubeai M (2008) Monitoring pH and dissolved oxygen in mammalian cell culture using optical sensors. Cytotechnology 57:245–250PubMedPubMedCentralGoogle Scholar
  33. 33.
    Cywinski PJ, Moro AJ, Stanca SE, Biskup C, Mohr GJ (2009) Ratiometric porphyrin-based layers and nanoparticles for measuring oxygen in biosamples. Sens Actuators B Chem 135:472–477Google Scholar
  34. 34.
    Cao J, Nagl S, Kothe E, Köhler JM (2014) Oxygen sensor nanoparticles for monitoring bacterial growth and characterization of dose-response functions in microfluidic screening. Microchim Acta 182:385–394Google Scholar
  35. 35.
    Horka M, Sun S, Ruszczak A, Garstecki P, Mayr T (2016) Lifetime of phosphorescence from nanoparticles yields accurate measurement of concentration of oxygen in microdoplets, allowing one to monitor the metabolism of bacteria. Anal Chem 88:12006–12012PubMedGoogle Scholar
  36. 36.
    Ungerböck B, Fellinger S, Sulzer P, Abel T, Mayr T (2014) Magnetic optical sensor particles: a flexible analytical tool for microfluidic devices. Analyst 139:2551–2559PubMedGoogle Scholar
  37. 37.
    Chojnacki P, Mistlberger G, Klimant I (2007) Separable magnetic sensors for the optical determination of oxygen. Angew Chem Int Ed 46:8850–8853Google Scholar
  38. 38.
    Flitsch D, Ladner T, Lukacs M, Büchs J (2016) Easy to use and reliable technique for online dissolved oxygen tension measurement in shake flasks using infrared fluorescent oxygen-sensitive nanoparticles. Microb Cell Factories 15:45Google Scholar
  39. 39.
    Ladner T, Flitsch D, Schlepütz T, Büchs J (2015) Online monitoring of dissolved oxygen tension in microtiter plates based on infrared fluorescent oxygen-sensitive nanoparticles. Microb Cell Factories 14:161Google Scholar
  40. 40.
    Mahler L, Tovar M, Weber T, Brandes S, Rudolph MM, Ehgartner J, Mayr T, Figge MT, Roth M, Zang E (2015) Enhanced and homogeneous oxygen availability during incubation of microfluidic droplets. RSC Adv 5:101871–101878Google Scholar
  41. 41.
    Scheucher E, Wilhelm S, Wolfbeis OS, Hirsch T, Mayr T (2015) Composite particles with magnetic properties, near-infrared excitation, and far-red emission for luminescence-based oxygen sensing. Microsys Nanoeng 1:15026Google Scholar
  42. 42.
    Gorris HH, Resch-Genger U (2017) Perspectives and challenges of photon-upconversion nanoparticles – part II bioanalytical applications. Anal Bioanal Chem 409:5875–5890PubMedGoogle Scholar
  43. 43.
    Mishra D, Tiwari R, Dwivedi AK (2016) Environmental impact assessment of thermal power plants- CO2 emission and control. Pollut Res 35:127–130Google Scholar
  44. 44.
    Ward KR, Yealy DM (1998) End-tidal carbon dioxide monitoring in emergency medicine, part 1: basic principles. Acad Emerg Med 5:628–636PubMedGoogle Scholar
  45. 45.
    Ward KR, Yealy DM (1998) End-tidal carbon dioxide monitoring in emergency medicine, part 2: clinical applications. Acad Emerg Med 5:637–646PubMedGoogle Scholar
  46. 46.
    Puligundla P, Jung J, Ko S (2012) Carbon dioxide sensors for intelligent food packaging applications. Food Control 25:328–333Google Scholar
  47. 47.
    Meng X, Kim S, Puligundla P, Ko S (2014) Carbon dioxide and oxygen gas sensors-possible application for monitoring quality, freshness, and safety of agricultural and food products with emphasis on importance of analytical signals and their transformation. J Korean Soc Appl Biol Chem 57:723–733Google Scholar
  48. 48.
    Emmerich S, Persily A (2001) State-of-the-art review of CO2 demand controlled ventilation technology and application. Technical report, National Institute of Standards and Technology, California Energy Commission, NISTIR 6729Google Scholar
  49. 49.
    Permentier K, Vercammen S, Soetaert S, Schellemans C (2017) Carbon dioxide poisoning: a literature review of an often forgotten cause of intoxication in the emergency department. Int J Emerg Med 10:14–17PubMedPubMedCentralGoogle Scholar
  50. 50.
    Purves WK, Sadava D, Orians GH (2004) Life, the science of biology, 7th edn. Sinauer Associates and W. H. Freeman, Sunderland, pp 139–140. ISBN 978-0-7167-9856-9Google Scholar
  51. 51.
    Dezengotita VM, Kimura R, Miller WM (1998) Effects of CO2 and osmolality on hybridoma cells: growth, metabolism and monoclonal antibody production. Cytotechnology 28:213–227PubMedPubMedCentralGoogle Scholar
  52. 52.
    Godoy-Silva R, Berdugo C, Chalmers JJ, Flickinger MC (2010) Aeration, mixing and hydrodynamics. Animal cell bioreactors. In: Flickinger MC (ed) Encyclopedia of industrial biotechnology: bioprocess, bioseparation, and cell technology. Wiley, New YorkGoogle Scholar
  53. 53.
    Nienow AW, Flickinger MC (2009) Impeller selection for animal cell culture. Encyclopedia of industrial biotechnology. Wiley, New YorkGoogle Scholar
  54. 54.
    Dixon NM, Kell DB (1989) The control and measurement of CO2 during fermentations. J Microbiol Methods 10:155–176Google Scholar
  55. 55.
    Zosel J, Oelssner W, Decker M, Gerlach G, Guth U (2011) The measurement of dissolved and gaseous carbon dioxide concentration. Meas Sci Technol 22:072001Google Scholar
  56. 56.
    Severinghaus JW, Bradley AF (1958) Electrodes for blood pO2 and pCO2 determination. J Appl Physiol 13:515–520PubMedGoogle Scholar
  57. 57.
    Lubbers DW, Opitz N (1975) The pCO2-/pO2-optode: a new probe for measurement of pCO2 or pO2 in fluids and gases. Z Naturforsch C 30:532–533PubMedGoogle Scholar
  58. 58.
    Zhujun Z, Seitz WR (1984) A carbon dioxide sensor based on fluorescence. Anal Chim Acta 160:305–309Google Scholar
  59. 59.
    Uttamlal M, Walt DR (1995) A fiber-optic carbon dioxide sensor for fermentation monitoring. Bio/Technology 13:597–601Google Scholar
  60. 60.
    Sipior J, Randers-Eichhorn L, Lakowicz JR, Carter GM, Rao G (1996) Phase fluorometric optical carbon dioxide gas sensor for fermentation off-gas monitoring. Biotechnol Prog 12:266–271Google Scholar
  61. 61.
    Ferguson JA, Healey BG, Bronk KS, Barnard SM, Walt DR (1997) Simultaneous monitoring of pH, CO2 and O2 using an optical imaging fiber. Anal Chim Acta 340:123–131Google Scholar
  62. 62.
    Chang Q, Randers-Eichhorn L, Lakowicz JR, Rao G (1998) Steam-sterilizable, fluorescence lifetime-based sensing film for dissolved carbon dioxide. Biotechnol Prog 14:326–331PubMedGoogle Scholar
  63. 63.
    Pattison RN, Swamy J, Mendenhall B, Hwang C, Frohlich BT (2000) Measurement and control of dissolved carbon dioxide in mammalian cell culture processes using an in situ fiber optic chemical sensor. Biotechnol Prog 16:769–774PubMedGoogle Scholar
  64. 64.
    Ge X, Rao G (2012) Real-time monitoring of shake flask fermentation and off gas using triple disposable noninvasive optical sensors. Biotechnol Prog 28:872–877PubMedGoogle Scholar
  65. 65.
    Ge X, Kostov Y, Rao G (2003) High-stability non-invasive autoclavable naked optical CO2 sensor. Biosens Bioelectron 18:857–865PubMedGoogle Scholar
  66. 66.
    Ge X, Kostov Y, Rao G (2005) Low-cost noninvasive optical CO2 sensing system for fermentation and cell culture. Biotechnol Bioeng 8:329–334Google Scholar
  67. 67.
    Haigh-Flórez D, Cano-Raya C, Bedoya M, Orellana G (2015) Rugged fibre-optic luminescent sensor for CO2 determination in microalgae photoreactors for biofuel production. Sens Actuators B Chem 221:978–984Google Scholar
  68. 68.
    Xavier MP, Orellana G, Moreno-Bondi MC, Diaz-Puente J (2000) Carbon dioxide monitoring in compost processes using fibre optic sensors based on a luminescent ruthenium(II) indicator. Quim Anal 19:118–126Google Scholar
  69. 69.
    Mills A, Chang Q, Mcmurray N (1992) Equilibrium studies on colorimetric plastic film sensors for carbon dioxide. Anal Chem 64:1383–1389Google Scholar
  70. 70.
    Mills A, Chang Q (1993) Fluorescence plastic thin-film sensor for carbon dioxide. Analyst 118:839–843Google Scholar
  71. 71.
    Mills A, Yusufu D (2016) Highly CO2 sensitive extruded fluorescent plastic indicator film based on HPTS. Analyst 141:999–1008PubMedGoogle Scholar
  72. 72.
    Ratterman M, Shen L, Klotzkin D, Papautsky I (2014) Carbon dioxide luminescent sensor based on a CMOS image array. Sens Actuators B Chem 198:1–6Google Scholar
  73. 73.
    Borisov SM, Seifner R, Klimant I (2011) A novel planar optical sensor for simultaneous monitoring of oxygen, carbon dioxide, pH and temperature. Anal Bioanal Chem 400:2463–2474PubMedPubMedCentralGoogle Scholar
  74. 74.
    Ertekin K, Klimant I, Neurauter G, Wolfbeis OS (2003) Characterization of a reservoir-type capillary optical microsensor for pCO2 measurements. Talanta 59:261–267PubMedGoogle Scholar
  75. 75.
    Wolfbeis OS, Kovács B, Goswami K, Klainer SM (1998) Fiber-optic fluorescence carbon dioxide sensor for environmental monitoring. Microchim Acta 129:181–188Google Scholar
  76. 76.
    Burke CS, Markey A, Nooney RI, Byrne P, McDonagh C (2006) Development of an optical sensor probe for the detection of dissolved carbon dioxide. Sens Actuators B Chem 119:288–294Google Scholar
  77. 77.
    Parker JW, Laksin O, Yu C, Lau M, Klima S, Fisher R, Scott I, Atwater BW (1993) Fiber-optic sensors for pH and carbon dioxide using a self-referencing dye. Anal Chem 65:2329–2334Google Scholar
  78. 78.
    Neurauter G, Klimant I, Wolfbeis OS (1999) Microsecond lifetime-based optical-carbon dioxide sensor using luminescence resonance energy transfer. Anal Chim Acta 382:67–75Google Scholar
  79. 79.
    He X, Rechnitz GA (1995) Linear response function for fluorescence-based fiber-optic CO2 sensors. Anal Chem 67:2264–2268Google Scholar
  80. 80.
    Wencel D, Moore JP, Stevenson N, McDonagh C (2010) Ratiometric fluorescence-based dissolved carbon dioxide sensor for use in environmental monitoring applications. Anal Bioanal Chem 398:1899–1907PubMedGoogle Scholar
  81. 81.
    Lochman L, Zimcik P, Klimant I, Novakova V, Borisov SM (2017) Red-emitting CO2 sensors with tunable dynamic range based on pH-sensitive azaphthalocyanine indicators. Sens Actuators B Chem 246:1100–1107Google Scholar
  82. 82.
    Amao Y, Nakamura N (2004) Optical CO2 sensor with the combination of colorimetric change of α-naphtholphthalein and internal reference fluorescent porphyrin dye. Sens Actuators B Chem 100:347–351Google Scholar
  83. 83.
    Pérez de Vargas-Sansalvador IM, Carvajal MA, Roldán-Muñoz OM, Banqueri J, Fernández-Ramos MD, Capitán-Vallvey LF (2009) Phosphorescent sensing of carbon dioxide based on secondary inner-filter quenching. Anal Chim Acta 655:66–74PubMedGoogle Scholar
  84. 84.
    Fritzsche E, Gruber P, Schutting S, Fischer JP, Strobl M, Muller JD, Borisov SM, Klimant I (2017) Highly sensitive poisoning-resistant optical carbon dioxide sensors for environmental monitoring. Anal Methods 9:55–65Google Scholar
  85. 85.
    Sipior J, Bambot S, Romauld M, Carter GM, Lakowicz JR, Rao G (1995) A lifetime-based optical CO2 gas sensor with blue or red excitation and stokes or anti-stokes detection. Anal Biochem 227:309–318PubMedGoogle Scholar
  86. 86.
    von Bültzingslöwen C, McEvoy AK, McDonagh C, MacCraith BD (2003) Lifetime-based optical sensor for high-level pCO2 detection employing fluorescence resonance energy transfer. Anal Chim Acta 480:275–283Google Scholar
  87. 87.
    Szmacinski H, Lakowicz JR (1993) Optical measurements of pH using fluorescence lifetimes and phase-modulation fluorometry. Anal Chem 65:1668–1674PubMedGoogle Scholar
  88. 88.
    Thompson RB, Frisoli JK, Lakowicz JR (1992) Phase fluorometry using a continuously modulated laser diode. Anal Chem 64:2075–2078Google Scholar
  89. 89.
    Orellana G, Moreno-Bondi MC, Segovia E, Marazuela MD (1992) Fiber-optic sensing of carbon dioxide based on excited-state proton transfer to a luminescent ruthenium(II) complex. Anal Chem 64:2210–2215Google Scholar
  90. 90.
    Marazuela MD, Moreno Bondi MC, Orellana G (1998) Luminescence lifetime quenching of a ruthenium(II) polypyridyl dye for optical sensing of carbon dioxide. Appl Spectrosc 52:1314–1320Google Scholar
  91. 91.
    Marazuela MD, Moreno Bondi MC, Orellana G (1995) Enhanced performance of a fibre-optic luminescence CO2 sensor using carbonic anhydrase. Sens Actuators B Chem 29:126–131Google Scholar
  92. 92.
    Lakowicz JR, Castellano FN, Dattelbaum JD, Tolosa L, Rao G, Gryczynski I (1998) Low-frequency modulation sensors using nanosecond fluorophores. Anal Chem 70:5115–5121PubMedGoogle Scholar
  93. 93.
    von Bültzingslöwen C, McEvoy AK, McDonagh C, MacCraith BD, Klimant I, Krausec C, Wolfbeis OS (2002) Sol-gel based optical carbon dioxide sensor employing dual luminophore referencing for application in food packaging technology. Analyst 127:1478–1483Google Scholar
  94. 94.
    Yafuso M, Suzuki JK (1989) Gas sensors. US patent 4,824,789Google Scholar
  95. 95.
    Alderete JE, Olstein AD, Furlong SC (1998) Optical carbon dioxide sensor and associated methods of manufacture. US Patent 5,714,121Google Scholar
  96. 96.
    Adrian W, Mark BS (2002) Optical carbon dioxide sensors. US Patent 6,338,822Google Scholar
  97. 97.
    Furlong SC (1997) Simultaneous dual excitation/single emission fluorescent sensing method for pH and pCO2. US Patent 5,672,515Google Scholar
  98. 98.
    Bretscher KR, Baker JA, Wood KB, Nguyen MT, Hamer MA, Rueb CJ (1997) Novel emulsion for robust sensing of glass. WO Patent 9,719,348Google Scholar
  99. 99.
    Bentsen JG, Wood KB (1995) Sensor with improved drift stability. US Patent 5,403,746Google Scholar
  100. 100.
    Klainer SM, Goswami K, Herron NR, Simon SJ, Eccles LA (1990) Reservoir fiber optic chemical sensors. US Patent 4,892,383Google Scholar
  101. 101.
    Orellana G, Moreno-Bondi, MC (1992) Sensor óptico. ES Patent 2,023,593Google Scholar
  102. 102.
    Mills A, Hodgen S (2005) Fluorescent carbon dioxide indicators. In: Geddes CD, Lakowicz JR (eds) Topics in fluorescence spectroscopy. Advanced concepts in fluorescence sensing part a: small molecule sensing, vol 9. Springer, New York, pp 119–161Google Scholar
  103. 103.
    Ho QT, Verboven P, Verlinden BE, Herremans E, Wevers M, Carmeliet J, Nicolaï BM (2011) A three-dimensional multiscale model for gas exchange in fruit. Plant Physiol 155:1158–1168, and references thereinPubMedPubMedCentralGoogle Scholar
  104. 104.
    Long C, Anderson W, Finch C, Hickman J (2012) CO2 measurement in microfluidic devices. Facilitating biological applications using a flow-through cell. In: Genetic engineering & biotechnology news. Accessed 15 Dec 2018
  105. 105.
    Sørensen SPL (1909) Etudes enzymatiques; II. Sur la mesure et l’importance de la concentration des ions hydrogene dans les reactions enzymatiques. Compt Rend Lab Carlsberg 8:1Google Scholar
  106. 106.
    Buck RP, Rondinini S, Covington AK, Baucke FGK, Brett CMA, Camoes MF, Milton MJT, Mussini T, Naumann R, Pratt KW, Spitzer P, Wilson GS (2002) Measurement of pH. Definition, standards, and procedures. Pure Appl Chem 74:2169–2200Google Scholar
  107. 107.
    McMillan GK, Cameron RA (2005) Advanced pH measurement and control, 3rd edn. ISA, Research Triangle ParkGoogle Scholar
  108. 108.
    Orellana G, Cano-Raya C, López-Gejo J, Santos AR (2011) Online monitoring sensors. In: Wilderer P (ed) Treatise on water science, vol 3. Academic Press, Oxford, p 221Google Scholar
  109. 109.
    Harms P, Kostov Y, Rao G (2002). Curr Opin Biotechnol 13:124PubMedGoogle Scholar
  110. 110.
    Lam H, Kostov Y (2009) Optical instrumentation for bioprocess monitoring. In: Rao G (ed) Optical sensor systems in biotechnology, vol 116. Springer, Berlin, pp 1–4Google Scholar
  111. 111.
    Glindkamp A, Riechers D, Rehbock C, Hitzmann B, Scheper T, Reardon KF (2009) Sensors in disposable bioreactors status and trends. Adv Biochem Eng Biotechnol 115:145–169PubMedGoogle Scholar
  112. 112.
    Scholz F (2011) From the Leiden jar to the discovery of the glass electrode by Max Cremer. J Solid State Electrochem 15:5–14Google Scholar
  113. 113.
    Wencel D, Abel T, McDonagh C (2014) Optical chemical pH sensors. Anal Chem 86:15–29PubMedGoogle Scholar
  114. 114.
    Demuth C (2014) Chemische Sensoren in der Bioprozessanalytik. Chem Unserer Zeit 48:60–67Google Scholar
  115. 115.
    Riley M (2005) Instrumentation and process control. In: Ozturk S, Hu WS (eds) Cell culture technology for pharmaceutical and cell-based therapies. CRC Press, Boca Raton, pp 249–298Google Scholar
  116. 116.
    Richter A, Paschew G, Klatt S, Lienig J, Arndt KF, Adler HJ (2008) Review on hydrogel-based pH sensors and microsensors. Sensors 8:561–581PubMedGoogle Scholar
  117. 117.
    Wang XD, Wolfbeis OS (2016) Fiber-optic chemical sensors and biosensors (2013–2015). Anal Chem 88:203–227PubMedGoogle Scholar
  118. 118.
    Mohamad F, Tanner MG, Choudhury D, Choudhary TR, Wood HAC, Harringtone K, Bradley M (2017) Controlled core-to-core photo-polymerisation – fabrication of an optical fibre-based pH sensor. Analyst 142:3569–3572PubMedGoogle Scholar
  119. 119.
    Kocincova AS, Borisov SM, Krause C, Wolfbeis OS (2007) Fiber-optic microsensors for simultaneous sensing of oxygen and pH, and of oxygen and temperature. Anal Chem 79:8486–8493PubMedGoogle Scholar
  120. 120.
    Kahlert H, Scholz F (2013) Acid-base diagrams. Springer, BerlinGoogle Scholar
  121. 121.
    Murtaza A, Chang Q, Rao G, Lin H, Lakowicz JR (1997) Long-lifetime metal-ligand pH probe. Anal Biochem 247:216–222PubMedGoogle Scholar
  122. 122.
    Clarke Y, Xu W, Demas JN, DeGraff BA (2000) Lifetime-based pH sensor system based on a polymer-supported ruthenium(II) complex. Anal Chem 72:3468–3475PubMedGoogle Scholar
  123. 123.
    Vasylevska GS, Borisov SM, Krause C, Wolfbeis OS (2016) Indicator-loaded permeation-selective microbeads for use in fiber optic simultaneous sensing of pH and dissolved oxygen. Chem Mater 18:4609–4616Google Scholar
  124. 124.
    Borisov SM, Mayr T, Klimant I (2008) Poly(styrene-block-vinylpyrrolidone) beads as a versatile material for simple fabrication of optical nanosensors. Anal Chem 80:573–582PubMedGoogle Scholar
  125. 125.
    Bowyer WJ, Xu W, Demas JN (2009) Determining proton diffusion in polymer films by lifetimes of luminescent complexes measured in the frequency domain. Anal Chem 81:378–384PubMedGoogle Scholar
  126. 126.
    Tormo L, Bustamante N, Colmenarejo G, Orellana G (2010) Can luminescent Ru(II) polypyridyl dyes measure pH directly? Anal Chem 82:5195–5204PubMedGoogle Scholar
  127. 127.
    Mistlberger G, Koren K, Borisov SM, Klimant I (2010) Magnetically remote-controlled optical sensor spheres for monitoring oxygen or pH. Anal Chem 82:2124–2128PubMedPubMedCentralGoogle Scholar
  128. 128.
    Schröder CR, Weidgans BM, Klimant I (2005) pH fluorosensors for use in marine systems. Analyst 130:907–916PubMedGoogle Scholar
  129. 129.
    Borisov SM, Gatterer K, Klimant I (2010) Red light-excitable dual lifetime referenced optical pH sensors with intrinsic temperature compensation. Analyst 135:1711–1717PubMedGoogle Scholar
  130. 130.
    Xia T, Zhu F, Jiang K, Cui Y, Yang Y, Qian G (2017) A luminescent ratiometric pH sensor based on a nanoscale and biocompatible Eu/Tb-mixed MOF. Dalton Trans 46:7549–7555PubMedGoogle Scholar
  131. 131.
    Acquah I, Roh J, Ahn DJ (2017) Dual-fluorophore silica microspheres for ratiometric acidic pH sensing. Macromol Res 25:950955Google Scholar
  132. 132.
    Shen L, Lu X, Tian H, Zhu W (2011) A long wavelength fluorescent hydrophilic copolymer based on naphthalenediimide as pH sensor with broad linear response range. Macromolecules 44:5612–5618Google Scholar
  133. 133.
    Wencel D, Higgins C, Klukowska A, MacCraith BD, McDonagh C (2007) Novel sol-gel derived films for luminescence-based oxygen and pH sensing. Mater Sci Poland 25:767–779Google Scholar
  134. 134.
    Vuppu S, Kostov Y, Rao G (2009) Economical wireless optical ratiometric pH sensor. Meas Sci Technol 20:045202Google Scholar
  135. 135.
    Aigner D, Borisov SM, Orriach-Fernández FJ, Fernández-Sánchez JF, Saf R, Klimant I (2012) New fluorescent pH sensors based on covalently linkable PET rhodamines. Talanta 99:194–201PubMedPubMedCentralGoogle Scholar
  136. 136.
    Turel M, Cajlakovic M, Austin E, Dakin JP, Uray G, Lobnik A (2008) Direct UV-LED lifetime pH sensor based on a semi-permeable sol-gel membrane immobilized luminescent Eu3+ chelate complex. Sens Actuators B Chem 131:247–253Google Scholar
  137. 137.
    Kateklum R, Gauthier-Manuel B, Pieralli C, Mankhetkorn S, Wacogne B (2017) Improving the sensitivity of amino-silanized sensors using self-structured silane layers: application to fluorescence pH measurement. Sens Actuators B Chem 248:605–612Google Scholar
  138. 138.
    Kolthoff JM (1927) Ueber die Anwendung von Mischindicatoren in der Acidimetrie und Alkalimetrie. Biochem Z 189:26–32Google Scholar
  139. 139.
    Chauhan VM, Burnett GR, Aylott JW (2011) Dual-fluorophore ratiometric pH nanosensor with tuneable pKa and extended dynamic range. Analyst 136:1799–1801PubMedGoogle Scholar
  140. 140.
    Hashemi P, Zarjani RA (2008) A wide range pH optical sensor with mixture of Neutral Red and Thionin immobilized on an agarose film coated glass slide. Sens Actuators B Chem 135:112–115Google Scholar
  141. 141.
    Martinez-Olmos A, Capel-Cuevas S, López-Ruiz N, Palma AJ, de Orbe I, Capitán-Vallvey LF (2011) Sensor array-based optical portable instrument for determination of pH. Sens Actuators B Chem 156:840–848Google Scholar
  142. 142.
    Devadhasan JP, Kim S (2015) An ultrasensitive method of real time pH monitoring with complementary metal oxide semiconductor image sensor. Anal Chim Acta 858:55–59PubMedGoogle Scholar
  143. 143.
    Gotor T, Ashokkumar P, Hecht M, Keil K, Rurack K (2017) Optical pH sensor covering the range from pH 0−14 compatible with mobile-device readout and based on a set of rationally designed indicator dyes. Anal Chem 89:8437–8444PubMedGoogle Scholar
  144. 144.
    Shamsipur M, Abbasitabar F, Zare-Shahabadi V, Shahabadi, Akhond M (2008) Broad-range optical pH sensor based on binary mixed-indicator doped sol-gel film and application of artificial neural network. Anal Lett 41:3113–3123Google Scholar
  145. 145.
    Capel-Cuevas S, Cuéllar MP, de Orbe-Payá I, Pegalajar MC, Capitán-Vallvey LF (2011) Full-range optical pH sensor array based on neural networks. Microchem J 97:225–233Google Scholar
  146. 146.
    Safavi A, Bagheri M (2003) Novel optical pH sensor for high and low pH values. Sens Actuators B Chem 90:143–150Google Scholar
  147. 147.
    Ma X, Cheng J, Liu J, Zhou X, Xiang H (2015) Ratiometric fluorescent pH probes based on aggregation-induced emission-active salicylaldehyde azines. New J Chem 39:492–500Google Scholar
  148. 148.
    Malins C, Glever HG, Keyes TE, Vos JG, Dressick WJ, MacCraith BD (2000) Sol-gel immobilised ruthenium(II) polypyridyl complexes as chemical transducers for optical pH sensing. Sens Actuators B Chem 67:89–95Google Scholar
  149. 149.
    Sánchez-Barragán I, Costa-Fernández JM, Sanz-Medel A (2005) Tailoring the pH response range of fluorescent-based pH sensing phases by sol-gel surfactants co-immobilization. Sens Actuators B Chem 107:69–77Google Scholar
  150. 150.
    Cui H, Chen Y, Li L, Wu Y, Tang Z, Fu H, Tian Z (2014) Hybrid fluorescent nanoparticles fabricated from pyridine-functionalized polyfluorene-based conjugated polymer as reversible pH probes over a broad range of acidity-alkalinity. Microchim Acta 181:1529–1539Google Scholar
  151. 151.
    Gonçalves HMR, Maule CD, Jorge PAS, Esteves da Silva JCG (2008) Fiber optic lifetime pH sensing based on ruthenium(II) complexes with dicarboxybipyridine. Anal Chim Acta 626:62–70PubMedGoogle Scholar
  152. 152.
    Kasik I, Mrazek J, Martan T, Pospisilova M, Podrazky O, Matejec V, Hoyerova K, Kaminek M (2010) Fiber-optic pH detection in small volumes of biosamples. Anal Bioanal Chem 398:1883–1889PubMedGoogle Scholar
  153. 153.
    Liebsch G, Klimant I, Krause C, Wolfbeis OS (2001) Fluorescent imaging of pH with optical sensors using time domain dual lifetime referencing. Anal Chem 73:4354–4363PubMedGoogle Scholar
  154. 154.
    Hiruta Y, Yoshizawa N, Citterio D, Suzuki K (2012) Highly durable double sol-gel layer ratiometric fluorescent pH optode based on the combination of two types of quantum dots and absorbing pH indicators. Anal Chem 84:10650–10656PubMedGoogle Scholar
  155. 155.
    Higgins B, DeGraff BA, Demas JN (2005) Luminescent transition metal complexes as sensors: structural effects on pH response. Inorg Chem 44:6662–6669PubMedGoogle Scholar
  156. 156.
    Kumar R, Yadav R, Kolhe MA, Bhosale RS, Narayan R (2018) 8-Hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) based high fluorescent, pH stimuli waterborne polyurethane coatings. Polymer 136:157–165Google Scholar
  157. 157.
    Barnadas-Rodríguez R, Estelrich J (2008) Effect of salts on the excited state of pyranine as determined by steady-state fluorescence. J Photochem Photobiol A Chem 198:262–267Google Scholar
  158. 158.
    Medintz I, Hildebrandt N (2014) FRET – förster resonance energy transfer: from theory to applications. Wiley-VCH, WeinheimGoogle Scholar
  159. 159.
    Bambot SB, Sipior J, Lakowicz JR, Rao G (1994) Lifetime-based optical sensing of pH using resonance energy transfer in sol-gel films. Sens Actuators B Chem 22:181–188Google Scholar
  160. 160.
    Poehler E, Pfeiffer SA, Herm M, Gaebler M, Busse B, Nagl S (2016) Microchamber arrays with an integrated long luminescence lifetime pH sensor. Anal Bioanal Chem 408:2927–2935PubMedGoogle Scholar
  161. 161.
    Borisov SM, Klimant I (2013) A versatile approach for ratiometric time-resolved read-out of colorimetric chemosensors using broadband phosphors as secondary emitters. Anal Chim Acta 787:219–225PubMedGoogle Scholar
  162. 162.
    Marose S, Lindemann C, Ulber R, Scheper T (1999) Optical sensor systems for bioprocess monitoring. Trends Biotechnol 17:30–34Google Scholar
  163. 163.
    Janzen NH, Schmidt M, Krause C, Weuster-Botz D (2015) Evaluation of fluorimetric pH sensors for bioprocess monitoring at low pH. Bioprocess Biosyst Eng 38:1685–1692PubMedGoogle Scholar
  164. 164.
    Kocincova AS, Nagl S, Arain S, Krause C, Borisov SM, Arnold M, Wolfbeis OS (2008) Multiplex bacterial growth monitoring in 24-well microplates using a dual optical sensor for dissolved oxygen and pH. Biotechnol Bioeng 100:430–438PubMedGoogle Scholar
  165. 165.
    Kusterer A, Krause C, Kaufmann K, Arnold M, Weuster-Botz D (2008) Fully automated single-use stirred-tank bioreactors for parallel microbial cultivations. Bioprocess Biosyst Eng 31:207–215PubMedGoogle Scholar
  166. 166.
    Vallejos JR, Micheletti M, Brorson KA, Moreira AR, Rao G (2012) Optical sensor enabled rocking T-flasks as novel upstream bioprocessing tools. Biotechnol Bioeng 109:2295–2305PubMedGoogle Scholar
  167. 167.
    Badugu R, Kostov Y, Rao G, Tolosa L (2008) Development and application of an excitation ratiometric optical pH sensor for bioprocess monitoring. Biotechnol Prog 24:1393–1401PubMedGoogle Scholar
  168. 168.
    Kermis HR, Kostov Y, Harms P, Rao G (2002) Dual excitation ratiometric fluorescent pH sensor for noninvasive bioprocess monitoring: development and application. Biotechnol Prog 18:1047–1053PubMedGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Chemical Optosensors & Applied Photochemistry Group (GSOLFA), Department of Organic Chemistry, Faculty of ChemistryComplutense University of MadridMadridSpain

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