1932

Abstract

Oxygen plays a fundamental role in respiration and metabolism, and quantifying oxygen levels is essential in many environmental, industrial, and research settings. Microdevices facilitate the study of dynamic, oxygen-dependent effects in real time. This review is organized around the key needs for oxygen measurement in microdevices, including integrability into microfabricated systems; sensor dynamic range and sensitivity; spatially resolved measurements to map oxygen over two- or three-dimensional regions of interest; and compatibility with multimodal and multianalyte measurements. After a brief overview of biological readouts of oxygen, followed by oxygen sensor types that have been implemented in microscale devices and sensing mechanisms, this review presents select recent applications in organs-on-chip in vitro models and new sensor capabilities enabling oxygen microscopy, bioprocess manufacturing, and pharmaceutical industries. With the advancement of multiplexed, interconnected sensors and instruments and integration with industry workflows, intelligent microdevice-sensor systems including oxygen sensors will have further impact in environmental science, manufacturing, and medicine.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-anchem-061020-111458
2022-06-13
2024-06-23
Loading full text...

Full text loading...

/deliver/fulltext/anchem/15/1/annurev-anchem-061020-111458.html?itemId=/content/journals/10.1146/annurev-anchem-061020-111458&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Carreau A, El Hafny-Rahbi B, Matejuk A, Grillon C, Kieda C 2011. Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J. Cell. Mol. Med. 15:61239–53
    [Google Scholar]
  2. 2.
    Bristow RG, Hill RP. 2008. Hypoxia and metabolism: hypoxia, DNA repair and genetic instability. Nat. Rev. Cancer 8:3180–92
    [Google Scholar]
  3. 3.
    Lee P, Chandel NS, Simon MC. 2020. Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat. Rev. Mol. Cell Biol. 21:5268–83
    [Google Scholar]
  4. 4.
    Dunwoodie SL. 2009. The role of hypoxia in development of the mammalian embryo. Dev. Cell 17:6755–73
    [Google Scholar]
  5. 5.
    Haase VH. 2013. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev 27:141–53
    [Google Scholar]
  6. 6.
    Suda T, Takubo K, Semenza GL. 2011. Metabolic regulation of hematopoietic stem cells in the hypoxic niche. Cell Stem Cell 9:4298–310
    [Google Scholar]
  7. 7.
    Hong WX, Hu MS, Esquivel M, Liang GY, Rennert RC et al. 2014. The role of hypoxia-inducible factor in wound healing. Adv. Wound Care 3:5390–99
    [Google Scholar]
  8. 8.
    Wang GL, Jiang BH, Rue EA, Semenza GL. 1995. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. PNAS 92:125510–14
    [Google Scholar]
  9. 9.
    Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC et al. 1999. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:6733271–75
    [Google Scholar]
  10. 10.
    Ivan M, Kondo K, Yang H, Kim W, Valiando J et al. 2001. HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:5516464–68
    [Google Scholar]
  11. 11.
    Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J et al. 2001. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:5516468–72
    [Google Scholar]
  12. 12.
    Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY et al. 2000. Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel-Lindau protein. Nat. Cell Biol. 2:7423–27
    [Google Scholar]
  13. 13.
    Kamura T, Sato S, Iwai K, Czyzyk-Krzeska M, Conaway RC, Conaway JW. 2000. Activation of HIFα ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. PNAS 97:1910430–35
    [Google Scholar]
  14. 14.
    Cockman ME, Masson N, Mole DR, Jaakkola P, Chang GW et al. 2000. Hypoxia inducible factor-α binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. 275:3325733–41
    [Google Scholar]
  15. 15.
    Jiang BH, Semenza GL, Bauer C, Marti HH. 1996. Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am. J. Physiol. Cell Physiol. 271:4 Part 1C1172–80
    [Google Scholar]
  16. 16.
    Krieg M, Haas R, Brauch H, Acker T, Flamme I, Plate KH. 2000. Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene 19:485435–43
    [Google Scholar]
  17. 17.
    Kondo K, Klco J, Nakamura E, Lechpammer M, Kaelin WG. 2002. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 1:3237–46
    [Google Scholar]
  18. 18.
    Blancher C, Moore JW, Robertson N, Harris AL. 2001. Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor HIF-1α, HIF-2α, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3′-kinase/Akt signaling pathway. Cancer Res 61:197349–55
    [Google Scholar]
  19. 19.
    Agani F, Jiang B-H. 2013. Oxygen-independent regulation of HIF-1: novel involvement of PI3K/Akt/mTor pathway in cancer. Curr. Cancer Drug Targets 13:3245–51
    [Google Scholar]
  20. 20.
    Iommarini L, Porcelli AM, Gasparre G, Kurelac I. 2017. Non-canonical mechanisms regulating hypoxia-inducible factor 1 alpha in cancer. Front. Oncol. 7:286
    [Google Scholar]
  21. 21.
    Koritzinsky M, Seigneuric R, Magagnin MG, van den Beucken T, Lambin P, Wouters BG. 2005. The hypoxic proteome is influenced by gene-specific changes in mRNA translation. Radiother. Oncol. 76:2177–86
    [Google Scholar]
  22. 22.
    Uniacke J, Holterman CE, Lachance G, Franovic A, Jacob MD et al. 2012. An oxygen-regulated switch in the protein synthesis machinery. Nature 486:7401126–29
    [Google Scholar]
  23. 23.
    Koumenis C, Wouters BG. 2006.. “ Translating” tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways. Mol. Cancer Res. 4:7423–36
    [Google Scholar]
  24. 24.
    Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT. 1998. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. PNAS 95:2011715–20
    [Google Scholar]
  25. 25.
    Arteel GE, Thurman RG, Yates JM, Raleigh JA. 1995. Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver. Br. J. Cancer 72:4889–95
    [Google Scholar]
  26. 26.
    Koch CJ, Evans SM, Lord EM. 1995. Oxygen dependence of cellular uptake of EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide]: analysis of drug adducts by fluorescent antibodies vs bound radioactivity. Br. J. Cancer 72:4869–74
    [Google Scholar]
  27. 27.
    Koch CJ, Evans SM. 2015. Optimizing hypoxia detection and treatment strategies. Semin. Nucl. Med. 45:2163–76
    [Google Scholar]
  28. 28.
    Koch CJ. 2002. Measurement of absolute oxygen levels in cells and tissues using oxygen sensors and 2-nitroimidazole EF5. Methods Enzymol 352:3–31
    [Google Scholar]
  29. 29.
    Winter SC, Buffa FM, Silva P, Miller C, Valentine HR et al. 2007. Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers. Cancer Res 67:73441–49
    [Google Scholar]
  30. 30.
    Buffa FM, Harris AL, West CM, Miller CJ. 2010. Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene. Br. J. Cancer 102:2428–35
    [Google Scholar]
  31. 31.
    Durand RE, Aquino-Parsons C. 2006. The fate of hypoxic (pimonidazole-labelled) cells in human cervix tumours undergoing chemo-radiotherapy. Radiother. Oncol. 80:2138–42
    [Google Scholar]
  32. 32.
    Wadsworth BJ, Lee C-M, Bennewith KL. 2022. Transiently hypoxic tumour cell turnover and radiation sensitivity in human tumour xenografts. Br. J. Cancer. In press. https://doi.org/10.1038/s41416-021-01691-5
    [Crossref] [Google Scholar]
  33. 33.
    Rafajová M, Zatovicová M, Kettmann R, Pastorek J, Pastoreková S. 2004. Induction by hypoxia combined with low glucose or low bicarbonate and high posttranslational stability upon reoxygenation contribute to carbonic anhydrase IX expression in cancer cells. Int. J. Oncol. 24:4995–1004
    [Google Scholar]
  34. 34.
    Vordermark D, Kaffer A, Riedl S, Katzer A, Flentje M. 2005. Characterization of carbonic anhydrase IX (CA IX) as an endogenous marker of chronic hypoxia in live human tumor cells. Int. J. Radiat. Oncol. Biol. Phys. 61:41197–1207
    [Google Scholar]
  35. 35.
    Erapaneedi R, Belousov VV, Schäfers M, Kiefer F. 2016. A novel family of fluorescent hypoxia sensors reveal strong heterogeneity in tumor hypoxia at the cellular level. EMBO J 35:1102–13
    [Google Scholar]
  36. 36.
    Schmitz C, Pepelanova I, Seliktar D, Potekhina E, Belousov VV et al. 2020. Live reporting for hypoxia: hypoxia sensor-modified mesenchymal stem cells as in vitro reporters. Biotechnol. Bioeng. 117:113265–76
    [Google Scholar]
  37. 37.
    Rivera KR, Yokus MA, Erb PD, Pozdin VA, Daniele M 2019. Measuring and regulating oxygen levels in microphysiological systems: design, material, and sensor considerations. Analyst 144:103190–215
    [Google Scholar]
  38. 38.
    Brennan MD, Rexius-Hall ML, Elgass LJ, Eddington DT. 2014. Oxygen control with microfluidics. Lab Chip 14:224305–18
    [Google Scholar]
  39. 39.
    Thomas PC, Raghavan SR, Forry SP. 2011. Regulating oxygen levels in a microfluidic device. Anal. Chem. 83:228821–24
    [Google Scholar]
  40. 40.
    Kane BJ, Zinner MJ, Yarmush ML, Toner M. 2006. Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes. Anal. Chem. 78:134291–98
    [Google Scholar]
  41. 41.
    Lam RHW, Kim M-C, Thorsen T. 2009. Culturing aerobic and anaerobic bacteria and mammalian cells with a microfluidic differential oxygenator. Anal. Chem. 81:145918–24
    [Google Scholar]
  42. 42.
    Mehta G, Mehta K, Sud D, Song JW, Bersano-Begey T et al. 2007. Quantitative measurement and control of oxygen levels in microfluidic poly(dimethylsiloxane) bioreactors during cell culture. Biomed. Microdevices 9:2123–34
    [Google Scholar]
  43. 43.
    Chen Y-A, King AD, Shih H-C, Peng C-C, Wu C-Y et al. 2011. Generation of oxygen gradients in microfluidic devices for cell culture using spatially confined chemical reactions. Lab Chip 11:213626–33
    [Google Scholar]
  44. 44.
    Oppegard SC, Nam K-H, Carr JR, Skaalure SC, Eddington DT. 2009. Modulating temporal and spatial oxygenation over adherent cellular cultures. PLOS ONE 4:9e6891
    [Google Scholar]
  45. 45.
    Oppegard SC, Blake AJ, Williams JC, Eddington DT. 2010. Precise control over the oxygen conditions within the Boyden chamber using a microfabricated insert. Lab Chip 10:182366–73
    [Google Scholar]
  46. 46.
    Ferrari E, Palma C, Vesentini S, Occhetta P, Rasponi M. 2020. Integrating biosensors in organs-on-chip devices: a perspective on current strategies to monitor microphysiological systems. Biosensors 10:9110
    [Google Scholar]
  47. 47.
    Kim M-C, Lam RHW, Thorsen T, Asada HH. 2013. Mathematical analysis of oxygen transfer through polydimethylsiloxane membrane between double layers of cell culture channel and gas chamber in microfluidic oxygenator. Microfluid. Nanofluid. 15:3285–96
    [Google Scholar]
  48. 48.
    Grist SM, Schmok JC, Liu M-CA, Chrostowski L, Cheung KC. 2015. Designing a microfluidic device with integrated ratiometric oxygen sensors for the long-term control and monitoring of chronic and cyclic hypoxia. Sensors 15:820030–52
    [Google Scholar]
  49. 49.
    Ochs CJ, Kasuya J, Pavesi A, Kamm RD. 2014. Oxygen levels in thermoplastic microfluidic devices during cell culture. Lab Chip 14:3459–62
    [Google Scholar]
  50. 50.
    Funamoto K, Zervantonakis IK, Liu Y, Ochs CJ, Kim C, Kamm RD. 2012. A novel microfluidic platform for high-resolution imaging of a three-dimensional cell culture under a controlled hypoxic environment. Lab Chip 12:224855–63
    [Google Scholar]
  51. 51.
    Mills A. 1997. Optical oxygen sensors. Platinum Metals Rev 41:3115–27
    [Google Scholar]
  52. 52.
    Demas JN, DeGraff BA, Coleman PB. 1999. Oxygen sensors based on luminescence quenching. Anal. Chem. 71:23793A–800A
    [Google Scholar]
  53. 53.
    Wang X, Wolfbeis OS. 2014. Optical methods for sensing and imaging oxygen: materials, spectroscopies and applications. Chem. Soc. Rev. 43:103666–761
    [Google Scholar]
  54. 54.
    Wolfbeis OS. 2015. Luminescent sensing and imaging of oxygen: fierce competition to the Clark electrode. Bioessays 37:8921–28
    [Google Scholar]
  55. 55.
    Amao Y. 2003. Probes and polymers for optical sensing of oxygen. Microchim. Acta 143:11–12
    [Google Scholar]
  56. 56.
    Quaranta M, Borisov SM, Klimant I. 2012. Indicators for optical oxygen sensors. Bioanal. Rev. 4:2–4115–57
    [Google Scholar]
  57. 57.
    Lehner P, Staudinger C, Borisov SM, Klimant I. 2014. Ultra-sensitive optical oxygen sensors for characterization of nearly anoxic systems. Nat. Commun. 5:4460
    [Google Scholar]
  58. 58.
    Papkovsky DB, Dmitriev RI. 2013. Biological detection by optical oxygen sensing. Chem. Soc. Rev. 42:228700–32
    [Google Scholar]
  59. 59.
    Grist SM, Chrostowski L, Cheung KC. 2010. Optical oxygen sensors for applications in microfluidic cell culture. Sensors 10:109286–316
    [Google Scholar]
  60. 60.
    Sun S, Ungerböck B, Mayr T. 2015. Imaging of oxygen in microreactors and microfluidic systems. Methods Appl. Fluoresc. 3:3034002
    [Google Scholar]
  61. 61.
    Clarke GA, Hartse BX, Niaraki Asli AE, Taghavimehr M, Hashemi N et al. 2021. Advancement of sensor integrated organ-on-chip devices. Sensors 21:41367
    [Google Scholar]
  62. 62.
    Nock V, Blaikie RJ, David T, Alkaisi M 2014. Optical oxygen sensors for micro- and nanofluidic devices. Smart Sensors for Industrial Applications K Iniewski, S Selimovic 129–53 Boca Raton, FL: CRC Press
    [Google Scholar]
  63. 63.
    Gruber P, Marques MPC, Szita N, Mayr T. 2017. Integration and application of optical chemical sensors in microbioreactors. Lab Chip 17:162693–712
    [Google Scholar]
  64. 64.
    Nock V, Murray LM, Alkaisi MM, Blaikie RJ. 2010. Patterning of polymer-encapsulated optical oxygen sensors by electron beam lithography. 2010 International Conference on Nanoscience and Nanotechnology237–40 New York: IEEE
    [Google Scholar]
  65. 65.
    Lehner P, Staudinger C, Borisov SM, Regensburger J, Klimant I. 2015. Intrinsic artefacts in optical oxygen sensors—how reliable are our measurements?. Chem. Eur. J. 21:103978–86
    [Google Scholar]
  66. 66.
    Stern O, Volmer M. 1919. The fading time of fluorescence. Phys. Z. 20:183–88
    [Google Scholar]
  67. 67.
    Wilson DF, Vinogradov SA 2003. Tissue oxygen measurements using phosphorescence quenching. Handbook of Biomedical Fluorescence M-A Mycek, BW Pogue 637–62 New York: Marcel Dekker
    [Google Scholar]
  68. 68.
    Demas JN, DeGraff BA, Xu W 1995. Modeling of luminescence quenching-based sensors: comparison of multisite and nonlinear gas solubility models. Anal. Chem. 67:81377–80
    [Google Scholar]
  69. 69.
    Ungerböck B, Charwat V, Ertl P, Mayr T. 2013. Microfluidic oxygen imaging using integrated optical sensor layers and a color camera. Lab Chip 13:81593–601
    [Google Scholar]
  70. 70.
    Li F, Wei Y, Chen Y, Li D, Zhang X. 2015. An intelligent optical dissolved oxygen measurement method based on a fluorescent quenching mechanism. Sensors 15:1230913–26
    [Google Scholar]
  71. 71.
    Taylor BN. 1994. Guidelines for Evaluating and Expressing the Uncertainty of NIST Measurement Results Gaithersburg, MD: Natl. Inst. Stand. Technol.
    [Google Scholar]
  72. 72.
    Heckert N, Filliben J, Croarkin C, Hembree B, Guthrie W et al. 2002. NIST/SEMATECH e-Handbook of Statistical Methods Gaithersburg, MD: Natl. Inst. Stand. Technol.
    [Google Scholar]
  73. 73.
    Heckert N, Filliben J, Croarkin C, Hembree B, Guthrie W et al. 2002. 2.3.6.7.1. Uncertainty for quadratic calibration using propagation of error. NIST/SEMATECH e-Handbook of Statistical Methods Gaithersburg, MD: Natl. Inst. Stand. Technol. https://www.itl.nist.gov/div898/handbook/mpc/section3/mpc3671.htm
    [Google Scholar]
  74. 74.
    Heckert N, Filliben J, Croarkin C, Hembree B, Guthrie W et al. 2002. 4.5.2.1. Single-use calibration intervals. NIST/SEMATECH e-Handbook of Statistical Methods Gaithersburg, MD: Natl. Inst. Stand. Technol https://www.itl.nist.gov/div898/handbook/pmd/section5/pmd521.htm
    [Google Scholar]
  75. 75.
    Datta R, Heaster TM, Sharick JT, Gillette AA, Skala MC. 2020. Fluorescence lifetime imaging microscopy: fundamentals and advances in instrumentation, analysis, and applications. J. Biomed. Opt. 25:7071203
    [Google Scholar]
  76. 76.
    Stich MIJ, Schaeferling M, Wolfbeis OS. 2009. Multicolor fluorescent and permeation-selective microbeads enable simultaneous sensing of pH, oxygen, and temperature. Adv. Mater. 21:212216–20
    [Google Scholar]
  77. 77.
    Kalinina S, Breymayer J, Schäfer P, Calzia E, Shcheslavskiy V et al. 2016. Correlative NAD(P)H-FLIM and oxygen sensing-PLIM for metabolic mapping. J. Biophoton. 9:8800–11
    [Google Scholar]
  78. 78.
    Nock V, Blaikie RJ, David T. 2008. Patterning, integration and characterisation of polymer optical oxygen sensors for microfluidic devices. Lab Chip 8:81300–7
    [Google Scholar]
  79. 79.
    Byrne MB, Leslie MT, Patel HS, Gaskins HR, Kenis PJA. 2017. Design considerations for open-well microfluidic platforms for hypoxic cell studies. Biomicrofluidics 11:5054116
    [Google Scholar]
  80. 80.
    Feng Y, Cheng J, Zhou L, Zhou X, Xiang H. 2012. Ratiometric optical oxygen sensing: a review in respect of material design. Analyst 137:214885–901
    [Google Scholar]
  81. 81.
    Park EJ, Reid KR, Tang W, Kennedy RT, Kopelman R. 2005. Ratiometric fiber optic sensors for the detection of inter- and intra-cellular dissolved oxygen. J. Mater. Chem. 15:27–28291319
    [Google Scholar]
  82. 82.
    Liebsch G, Klimant I, Frank B, Holst G, Wolfbeis OS. 2000. Luminescence lifetime imaging of oxygen, pH, and carbon dioxide distribution using optical sensors. Appl. Spectrosc. 54:4548–59
    [Google Scholar]
  83. 83.
    Holst G, Kohls O, Klimant I, König B, Kühl M, Richter T. 1998. A modular luminescence lifetime imaging system for mapping oxygen distribution in biological samples. Sens. Actuators B Chem. 51:1–3163–70
    [Google Scholar]
  84. 84.
    Becker W, Shcheslavskiy V, Rück A. 2017. Simultaneous phosphorescence and fluorescence lifetime imaging by multi-dimensional TCSPC and multi-pulse excitation. Adv. Exp. Med. Biol. 1035:19–30
    [Google Scholar]
  85. 85.
    Jenkins J, Dmitriev RI, Papkovsky DB. 2015. Imaging cell and tissue O2 by TCSPC-PLIM. Advanced Time-Correlated Single Photon Counting Applications W Becker 225–47 Cham, Switz: Springer Int.
    [Google Scholar]
  86. 86.
    Jahn K, Buschmann V, Hille C. 2015. Simultaneous fluorescence and phosphorescence lifetime imaging microscopy in living cells. Sci. Rep. 5:14334
    [Google Scholar]
  87. 87.
    Kalinina S, Schaefer PM, Breymayer J, Bisinger D, Chakrabortty S, Rueck A. 2018. Oxygen sensing PLIM together with FLIM of intrinsic cellular fluorophores for metabolic mapping. Proc. SPIE 10497, Imag. Manip. Anal. Biomol. Cells Tissues XVI, 104970F. https://doi.org/10.1117/12.2287429
    [Crossref] [Google Scholar]
  88. 88.
    Schmälzlin E, van Dongen JT, Klimant I, Marmodée B, Steup M et al. 2005. An optical multifrequency phase-modulation method using microbeads for measuring intracellular oxygen concentrations in plants. Biophys. J. 89:21339–45
    [Google Scholar]
  89. 89.
    Wang XF, Uchida T, Coleman DM, Minami S. 1991. A 2-dimensional fluorescence lifetime imaging-system using a gated image intensifier. Appl. Spectrosc. 45:3360–66
    [Google Scholar]
  90. 90.
    Becker W 2015. Advanced Time-Correlated Single Photon Counting Applications, Vol. 111 Cham, Switz: Springer Int.
    [Google Scholar]
  91. 91.
    Sen R, Zhdanov AV, Hirvonen LM, Svihra P, Andersson-Engels S et al. 2020. Characterization of planar phosphorescence based oxygen sensors on a TCSPC-PLIM macro-imager. Sens. Actuators B Chem. 321:128459
    [Google Scholar]
  92. 92.
    Sen R, Zhdanov AV, Bastiaanssen TFS, Hirvonen LM, Svihra P et al. 2020. Mapping O2 concentration in ex-vivo tissue samples on a fast PLIM macro-imager. Sci. Rep. 10:119006
    [Google Scholar]
  93. 93.
    Holst G, Glud RN, Kuhl M, Klimant I. 1997. A microoptode array for fine-scale measurement of oxygen distribution. Sens. Actuators B Chem. 38:1–3122–29
    [Google Scholar]
  94. 94.
    Xiong B, Mahoney E, Lo JF, Fang Q. 2020. A frequency-domain optofluidic dissolved oxygen sensor with total internal reflection design for in situ monitoring. IEEE J. Select. Top. Quantum Electron. 27:6900107
    [Google Scholar]
  95. 95.
    Qiu W, Nagl S. 2021. Automated miniaturized digital microfluidic antimicrobial susceptibility test using a chip-integrated optical oxygen sensor. ACS Sens 6:31147–56
    [Google Scholar]
  96. 96.
    Matsumoto S, Leclerc E, Maekawa T, Kinoshita H, Shinohara M et al. 2018. Integration of an oxygen sensor into a polydymethylsiloxane hepatic culture device for two-dimensional gradient characterization. Sens. Actuators B Chem. 273:1062–69
    [Google Scholar]
  97. 97.
    Nock V, Blaikie RJ, David T. 2007. Micro-patterning of polymer-based optical oxygen sensors for lab-on-chip applications. Proc. SPIE 6799, BioMEMS Nanotechnol. III, 67990Y. https://doi.org/10.1117/12.759023
    [Crossref] [Google Scholar]
  98. 98.
    Zhu HX, Tian YQ, Bhushan S, Su FY, Meldrum DR. 2010. High throughput micropatterning of optical oxygen sensor. SENSORS 2010:2053–56
    [Google Scholar]
  99. 99.
    Vollmer AP, Probstein RF, Gilbert R, Thorsen T 2005. Development of an integrated microfluidic platform for dynamic oxygen sensing and delivery in a flowing medium. Lab Chip 5:101059–66
    [Google Scholar]
  100. 100.
    Nock V, Alkaisi M, Blaikie RJ. 2010. Photolithographic patterning of polymer-encapsulated optical oxygen sensors. Microelectron. Eng. 87:5–8814–16
    [Google Scholar]
  101. 101.
    Grist SM, Oyunerdene N, Flueckiger J, Kim J, Wong PC et al. 2014. Fabrication and laser patterning of polystyrene optical oxygen sensor films for lab-on-a-chip applications. Analyst 139:225718–27
    [Google Scholar]
  102. 102.
    Bossink EGBM, Slob JVM, Wasserberg D, Segerink LI, Odijk M. 2020. Versatile fabrication and integration method of optical oxygen sensors in organ-on-chips. 2020 IEEE SENSORS1–4 New York: IEEE
    [Google Scholar]
  103. 103.
    Kelbauskas L, Ashili SP, Houkal J, Smith D, Mohammadreza A et al. 2012. Method for physiologic phenotype characterization at the single-cell level in non-interacting and interacting cells. J. Biomed. Opt. 17:3037008
    [Google Scholar]
  104. 104.
    Ehgartner J, Sulzer P, Burger T, Kasjanow A, Bouwes D et al. 2016. Online analysis of oxygen inside silicon-glass microreactors with integrated optical sensors. Sens. Actuators B Chem. 228:748–57
    [Google Scholar]
  105. 105.
    Acosta MA, Ymele-Leki P, Kostov YV, Leach JB. 2009. Fluorescent microparticles for sensing cell microenvironment oxygen levels within 3D scaffolds. Biomaterials 30:173068–74
    [Google Scholar]
  106. 106.
    Acosta MA, Jiang X, Huang P-K, Cutler KB, Grant CS et al. 2014. A microfluidic device to study cancer metastasis under chronic and intermittent hypoxia. Biomicrofluidics 8:5054117
    [Google Scholar]
  107. 107.
    Ando Y, Ta HP, Yen DP, Lee S-S, Raola S, Shen K. 2017. A microdevice platform recapitulating hypoxic tumor microenvironments. Sci. Rep. 7:115233
    [Google Scholar]
  108. 108.
    Wang L, Acosta MA, Leach JB, Carrier RL. 2013. Spatially monitoring oxygen level in 3D microfabricated cell culture systems using optical oxygen sensing beads. Lab Chip 13:81586–92
    [Google Scholar]
  109. 109.
    Lasave LC, Borisov SM, Ehgartner J, Mayr T. 2015. Quick and simple integration of optical oxygen sensors into glass-based microfluidic devices. RSC Adv 5:8770808–16
    [Google Scholar]
  110. 110.
    Zirath H, Rothbauer M, Spitz S, Bachmann B, Jordan C et al. 2018. Every breath you take: non-invasive real-time oxygen biosensing in two- and three-dimensional microfluidic cell models. Front. Physiol. 9:815
    [Google Scholar]
  111. 111.
    Marín-Suárez M, Medina-Rodríguez S, Ergeneman O, Pané S, Fernández-Sánchez JF et al. 2014. Electrophoretic deposition as a new approach to produce optical sensing films adaptable to microdevices. Nanoscale 6:1263–71
    [Google Scholar]
  112. 112.
    Liebisch F, Weltin A, Marzioch J, Urban GA, Kieninger J. 2020. Zero-consumption Clark-type microsensor for oxygen monitoring in cell culture and organ-on-chip systems. Sens. Actuators B Chem 322:128652
    [Google Scholar]
  113. 113.
    Clark LC. 1956. Monitor and control of blood and tissue oxygen tensions. Trans. Am. Soc. Artif. Intern. Org. 2:141–48
    [Google Scholar]
  114. 114.
    Kieninger J, Weltin A, Flamm H, Urban GA. 2018. Microsensor systems for cell metabolism—from 2D culture to organ-on-chip. Lab Chip 18:91274–91
    [Google Scholar]
  115. 115.
    Pettersen EO, Larsen LH, Ramsing NB, Ebbesen P. 2005. Pericellular oxygen depletion during ordinary tissue culturing, measured with oxygen microsensors. Cell Prolif 38:4257–67
    [Google Scholar]
  116. 116.
    Obeidat YM, Evans AJ, Tedjo W, Chicco AJ, Carnevale E, Chen TW 2018. Monitoring oocyte/embryo respiration using electrochemical-based oxygen sensors. Sens. Actuators B 276:72–81
    [Google Scholar]
  117. 117.
    Hsueh A-J, Park S, Satoh T, Shimizu T, Koiwai K et al. 2021. Microdevice with an integrated Clark-type oxygen electrode for the measurement of the respiratory activity of cells. Anal. Chem. 93:135577–85
    [Google Scholar]
  118. 118.
    Luo J, Dziubla T, Eitel R. 2017. A low temperature co-fired ceramic based microfluidic Clark-type oxygen sensor for real-time oxygen sensing. Sens. Actuators B Chem. 240:392–97
    [Google Scholar]
  119. 119.
    Moya A, Zea M, Sowade E, Villa R, Ramon E et al. 2017. Inkjet-printed dissolved oxygen and pH sensors on flexible plastic substrates. Proc. SPIE 10246, Smart Sens. Actuators MEMS VIII, 102460F. https://doi.org/10.1117/12.2264912
    [Crossref] [Google Scholar]
  120. 120.
    Moya A, Ortega-Ribera M, Guimerà X, Sowade E, Zea M et al. 2018. Online oxygen monitoring using integrated inkjet-printed sensors in a liver-on-a-chip system. Lab Chip 18:142023–35
    [Google Scholar]
  121. 121.
    Sticker D, Rothbauer M, Ehgartner J, Steininger C, Liske O et al. 2019. Oxygen management at the microscale: a functional biochip material with long-lasting and tunable oxygen scavenging properties for cell culture applications. ACS Appl. Mater. Interfaces 11:109730–39
    [Google Scholar]
  122. 122.
    Oomen PE, Skolimowski MD, Verpoorte E. 2016. Implementing oxygen control in chip-based cell and tissue culture systems. Lab Chip 16:183394–414
    [Google Scholar]
  123. 123.
    Chapman JD, Sturrock J, Boag JW, Crookall JO. 1970. Factors affecting the oxygen tension around cells growing in plastic petri dishes. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 17:4305–28
    [Google Scholar]
  124. 124.
    Salame M, Steingiser S. 1977. Barrier polymers. Polym. Plast. Technol. Eng. 8:2155–75
    [Google Scholar]
  125. 125.
    Enko B, Borisov SM, Regensburger J, Bäumler W, Gescheidt G, Klimant I. 2013. Singlet oxygen-induced photodegradation of the polymers and dyes in optical sensing materials and the effect of stabilizers on these processes. J. Phys. Chem. A. 117:368873–82
    [Google Scholar]
  126. 126.
    Mahler L, Tovar M, Weber T, Brandes S, Rudolph MM et al. 2015. Enhanced and homogeneous oxygen availability during incubation of microfluidic droplets. RSC Adv 5:123101871–78
    [Google Scholar]
  127. 127.
    Yao M, Walker G, Gamcsik MP. 2021. A multiwell plate-based system for toxicity screening under multiple static or cycling oxygen environments. Sci. Rep. 11:14020
    [Google Scholar]
  128. 128.
    Guenat OT, Geiser T, Berthiaume F. 2020. Clinically relevant tissue scale responses as new readouts from organs-on-a-chip for precision medicine. Annu. Rev. Anal. Chem. 13:111–33
    [Google Scholar]
  129. 129.
    Tonon F, Giobbe GG, Zambon A, Luni C, Gagliano O et al. 2019. In vitro metabolic zonation through oxygen gradient on a chip. Sci. Rep. 9:113557
    [Google Scholar]
  130. 130.
    Bavli D, Prill S, Ezra E, Levy G, Cohen M et al. 2016. Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction. PNAS 113:16E2231–40
    [Google Scholar]
  131. 131.
    Ehgartner J, Wiltsche H, Borisov SM, Mayr T. 2014. Low cost referenced luminescent imaging of oxygen and pH with a 2-CCD colour near infrared camera. Analyst 139:194924–33
    [Google Scholar]
  132. 132.
    Birolli WG, Lima RN, Porto ALM. 2019. Applications of marine-derived microorganisms and their enzymes in biocatalysis and biotransformation, the underexplored potentials. Front. Microbiol. 10:1453
    [Google Scholar]
  133. 133.
    Jalili-Firoozinezhad S, Gazzaniga FS, Calamari EL, Camacho DM, Fadel CW et al. 2019. A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip. Nat. Biomed. Eng. 3:7520–31
    [Google Scholar]
  134. 134.
    Espey MG. 2013. Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota. Free Radic. Biol. Med. 55:130–40
    [Google Scholar]
  135. 135.
    Bohlen HG. 1980. Intestinal tissue PO2 and microvascular responses during glucose exposure. Am. J. Physiol. 238:2H164–71
    [Google Scholar]
  136. 136.
    Grist SM, Nasseri SS, Laplatine L, Schmok JC, Yao D et al. 2019. Long-term monitoring in a microfluidic system to study tumour spheroid response to chronic and cycling hypoxia. Sci. Rep. 9:117782
    [Google Scholar]
  137. 137.
    Grist SM, Nasseri SS, Poon T, Roskelley C, Cheung KC. 2016. On-chip clearing of arrays of 3-D cell cultures and micro-tissues. Biomicrofluidics 10:4044107
    [Google Scholar]
  138. 138.
    Ke M-T, Fujimoto S, Imai T. 2013. SeeDB: a simple and morphology-preserving optical clearing agent for neuronal circuit reconstruction. Nat. Neurosci. 16:81154–61
    [Google Scholar]
  139. 139.
    Kuwajima T, Sitko AA, Bhansali P, Jurgens C, Guido W, Mason C 2013. ClearT: a detergent- and solvent-free clearing method for neuronal and non-neuronal tissue. Development 140:61364–68
    [Google Scholar]
  140. 140.
    Chen F, Tillberg PW, Boyden ES. 2015. Expansion microscopy. Science 347:6221543–48
    [Google Scholar]
  141. 141.
    Tillberg PW. 2016. Expansion microscopy: improving imaging through uniform tissue expansion PhD Thesis, Mass. Inst. Tech. Cambridge, MA:
    [Google Scholar]
  142. 142.
    Lesher-Pérez SC, Kim G-A, Kuo C-H, Leung BM, Mong S et al. 2017. Dispersible oxygen microsensors map oxygen gradients in three-dimensional cell cultures. Biomater. Sci. 5:102106–13
    [Google Scholar]
  143. 143.
    Papkovsky DB, Dmitriev RI. 2018. Imaging of oxygen and hypoxia in cell and tissue samples. Cell. Mol. Life Sci. 75:162963–80
    [Google Scholar]
  144. 144.
    Kocincová AS, Nagl S, Arain S, Krause C, Borisov SM et al. 2008. Multiplex bacterial growth monitoring in 24-well microplates using a dual optical sensor for dissolved oxygen and pH. Biotechnol. Bioeng. 100:3430–38
    [Google Scholar]
  145. 145.
    Lu HG, Jin YG, Tian YQ, Zhang WW, Holl MR, Meldrum DR. 2011. New ratiometric optical oxygen and pH dual sensors with three emission colors for measuring photosynthetic activity in cyanobacteria. J. Mater. Chem. 21:4819293–301
    [Google Scholar]
  146. 146.
    Jenkins J, Borisov SM, Papkovsky DB, Dmitriev RI. 2016. Sulforhodamine nanothermometer for multiparametric fluorescence lifetime imaging microscopy. Anal. Chem. 88:2110566–72
    [Google Scholar]
  147. 147.
    Cohen A, Ioannidis K, Ehrlich A, Regenbaum S, Cohen M et al. 2021. Mechanism and reversal of drug-induced nephrotoxicity on a chip. Sci. Transl. Med. 13:582eabd6299
    [Google Scholar]
  148. 148.
    Kilic T, Navaee F, Stradolini F, Renaud P, Carrara S 2018. Organs-on-chip monitoring: sensors and other strategies. Microphysiol. Syst. 2:1–32
    [Google Scholar]
  149. 149.
    Dornhof J, Kieninger J, Muralidharan H, Maurer J, Urban GA, Weltin A. 2022. Microfluidic organ-on-chip system for multi-analyte monitoring of metabolites in 3D cell cultures. Lab Chip 22:225–39
    [Google Scholar]
  150. 150.
    Azizgolshani H, Coppeta JR, Vedula EM, Marr EE, Cain BP et al. 2021. High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows. Lab Chip 21:81454–74
    [Google Scholar]
  151. 151.
    Kalinina S, Breymayer J, Reeß K, Lilge L, Mandel A, Rück A. 2018. Correlation of intracellular oxygen and cell metabolism by simultaneous PLIM of phosphorescent TLD1433 and FLIM of NAD(P)H. J. Biophoton. 11:10e201800085
    [Google Scholar]
  152. 152.
    Zhang YS, Aleman J, Shin SR, Kilic T, Kim D et al. 2017. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. PNAS 114:12E2293–302
    [Google Scholar]
  153. 153.
    Kelbauskas L, Ashili S, Zeng J, Rezaie A, Lee K et al. 2017. Platform for combined analysis of functional and biomolecular phenotypes of the same cell. Sci. Rep. 7:44636
    [Google Scholar]
  154. 154.
    Kelbauskas L, Ashili SP, Lee KB, Zhu H, Tian Y, Meldrum DR. 2018. Simultaneous multiparameter cellular energy metabolism profiling of small populations of cells. Sci. Rep. 8:14359
    [Google Scholar]
  155. 155.
    O'Donnell N, Dmitriev RI. 2017. Three-dimensional tissue models and available probes for multi-parametric live cell microscopy: a brief overview. Adv. Exp. Med. Biol. 1035:49–67
    [Google Scholar]
  156. 156.
    Dmitriev RI, Intes X, Barroso MM. 2021. Luminescence lifetime imaging of three-dimensional biological objects. J. Cell Sci. 134:91–17
    [Google Scholar]
  157. 157.
    Hirvonen LM, Nedbal J, Almutairi N, Phillips TA, Becker W et al. 2020. Lightsheet fluorescence lifetime imaging microscopy with wide-field time-correlated single photon counting. J. Biophoton. 13:2e201960099
    [Google Scholar]
  158. 158.
    Rück AC, Schäfer P, von Einem B, Kritchenkov IS, Kalinina S. 2020. Metabolic NADH/FAD/FMN FLIM and oxygen PLIM: multiphoton luminescence lifetime imaging on the way to clinical diagnosis. Proc. SPIE 11244, Multiphoton Microsc. Biomed. Sci. XX, 112440M. https://doi.org/10.1117/12.2546095
    [Crossref] [Google Scholar]
  159. 159.
    Okkelman IA, Neto N, Papkovsky DB, Monaghan MG, Dmitriev RI. 2020. A deeper understanding of intestinal organoid metabolism revealed by combining fluorescence lifetime imaging microscopy (FLIM) and extracellular flux analyses. Redox Biol 30:101420
    [Google Scholar]
  160. 160.
    Jenkins J, Dmitriev RI, Morten K, McDermott KW, Papkovsky DB. 2015. Oxygen-sensing scaffolds for 3-dimensional cell and tissue culture. Acta Biomater 16:126–35
    [Google Scholar]
  161. 161.
    Elagin V, Kuznetsova D, Grebenik E, Zolotov DA, Istranov L et al. 2020. Multiparametric optical bioimaging reveals the fate of epoxy crosslinked biomeshes in the mouse subcutaneous implantation model. Front. Bioeng. Biotechnol. 8:107
    [Google Scholar]
  162. 162.
    Liu C, Chisholm A, Fu B, Su CT-Y, Şencan İ et al. 2021. Quantitation of cerebral oxygen tension using phasor analysis and phosphorescence lifetime imaging microscopy (PLIM). Biomed. Opt. Express 12:74192–206
    [Google Scholar]
  163. 163.
    Narayanan H, Luna MF, von Stosch M, Cruz Bournazou MN, Polotti G et al. 2020. Bioprocessing in the digital age: the role of process models. Biotechnol. J. 15:1e1900172
    [Google Scholar]
  164. 164.
    Hsu W-T, Aulakh RPS, Traul DL, Yuk IH 2012. Advanced microscale bioreactor system: a representative scale-down model for bench-top bioreactors. Cytotechnology 64:6667–78
    [Google Scholar]
  165. 165.
    Manahan M, Nelson M, Cacciatore JJ, Weng J, Xu S, Pollard J. 2019. Scale-down model qualification of ambr® 250 high-throughput mini-bioreactor system for two commercial-scale mAb processes. Biotechnol. Prog. 35:6e2870
    [Google Scholar]
  166. 166.
    Probst C, Schneider S, Loskill P. 2018. High-throughput organ-on-a-chip systems: current status and remaining challenges. Curr. Opin. Biomed. Eng. 6:33–41
    [Google Scholar]
  167. 167.
    Brunner V, Siegl M, Geier D, Becker T. 2021. Challenges in the development of soft sensors for bioprocesses: a critical review. Front. Bioeng. Biotechnol. 9:722202
    [Google Scholar]
  168. 168.
    Wei Y, Jiao Y, An D, Li D, Li W, Wei Q 2019. Review of dissolved oxygen detection technology: from laboratory analysis to online intelligent detection. Sensors 19:183995
    [Google Scholar]
  169. 169.
    Bittig HC, Fiedler B, Scholz R, Krahmann G, Körtzinger A. 2014. Time response of oxygen optodes on profiling platforms and its dependence on flow speed and temperature. Limnol. Oceanogr. 12:8617–36
    [Google Scholar]
/content/journals/10.1146/annurev-anchem-061020-111458
Loading
/content/journals/10.1146/annurev-anchem-061020-111458
Loading

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error