Methods and applications of label-free cell-based systems


Label-free monitoring of living cells is used in various applications such as drug development, toxicology, regenerative medicine or environmental monitoring. The most prominent methods for monitoring the extracellular acidification, oxygen consumption, electrophysiological activity and morphological changes of living cells are described. Furthermore, the intelligent mobile lab (IMOLA) – a computer controlled system integrating cell monitoring and automated cell cultivation – is described as an example of a cell-based system for microphysiometry. Results from experiments in the field of environmental monitoring using algae are presented. An outlook toward the development of an organ-on-chip technology is given.

[1] Y. Fang, Non-Invasive Optical Biosensor for Probing Cell Signaling, Sensors (Basel), 7, 2316–2329, (2007).

[2] Q. Liu, C. Wu, H. Cai, N. Hu, J. Zhou, and P. Wang, Cell-based biosensors and their application in biomedicine, Chem Rev, 114, 6423–6461, (2014).

[3] P. Bergveld, Thirty years of ISFETOLOGY – What happened in the past 30 years and what may happen in the next 30 years, Sens Actuators B Chem, 88, 1–20, (2003).

[4] M. Brischwein, H. Grothe, J. Wiest, et al., Planar Ruthenium Oxide Sensors for Cellon-a-chip Metabolic Studies, Chem Anal Warsz, 54, 1193–1200, (2009).

[5] J. Wiest, M. Brischwein, J. Ressler, A. M. Otto, H. Grothe, and B. Wolf, Cellular Assays with Multiparametric Bioelectronic Sensor Chips, Chimia (Aarau), 59, 243– 246, (2005).

[6] Y. Eminaga, M. Brischwein, J. Wiest, J. Clauss, et al., Self calibration of a planar dissolved oxygen sensor, Sens Actuators B Chem, 177, 785–791, (2013).

[7] L. Doerr, U. Thomas, D. R. Guinot, C. T. Bot, S. Stoelzle-Feix, M. Beckler, M. George, and N. Fertig, New Easy-to-Use Hybrid System for Extracellular Potential and Impedance Recordings, J Lab Autom, 1–14, (2014).

[8] T. Schwarzenberger, P. Wolf, M. Brischwein, R. Kleinhans, F. Demmel, A. Lechner, B. Becker, and B. Wolf, Impedance sensor technology for cell-based assays in the framework of a high-content screening system, Physiol Meas, 32, 977–993, (2011).

[9] H. M. McConnell, J. C. Owicki, J. W. Parce, D. L. Miller, G. T. Baxter, H. G. Wada, and S. Pitchford, The cytosensor microphysiometer: biological applications of silicon technology, Science, 257, 1906–1912, (1993).

[10] T. Hartung, L. Bruner, R. Curren, C. Eskes, A. Goldberg, P. McNamee, L. Scott, and V. Zuang, First alternative method validated by a retrospective weight-ofevidence approach to replace the Draize eye test for the identification of nonirritant substances for a defined applicability domain, ALTEX, 27, 43–51, (2010).

[11] P. Mestres and A. Morguet, The Bionas technology for anticancer drug screening, Expert Opin Drug Discov, 4, 785–797, (2009).

[12] F. Demmel, M. Brischwein, P. Wolf, F. Huber, C. Pfister, and B. Wolf, Nutrient depletion and metabolic profiles in breast carcinoma cell lines measured with a label-free platform, Physiol Meas, 36, 1367–1381, (2015).

[13], (2015).

[14] Y. Eminaga, J. Wiest, M. Brischwein, H. Grothe, and B. Wolf, in Multiparametric Microsensors on Lab-on-chip Systems for the Detection of Dissolved Substances, IMCS14 Booklet, 83, AMA Services GmbH, Nuremberg, 2012.

[15] D. Weiss, M. Brischwein, H. Grothe, B. Wolf, and J. Wiest, Label-free monitoring of whole cell vitality, Engineering in Medicine and Biology Society (EMBC), 2013 35th Annual International Conference of the IEEE, 1607-1610, 3-7 July 2013.

[16] J. Wiest, T. Stadthagen, M. Schmidhuber, M. Brischwein, J. Ressler, U. Raeder, H. Grothe, A. Melzer, and B. Wolf, Intelligent Mobile Lab for Metabolics in Environmental Monitoring, Anal Lett, 39, 1759–1771, (2006).

[17] L. Umar, F. A. Alexander, and J. Wiest, Application of Algae-Biosensor for Environmental Monitoring, 37th Annual International Conference of the IEEE EMBS, Milano, Italy, 25– 9 August, 2015, 7099-7102.

[18] F. A. Alexander and J. Wiest, Online, Label-free Monitoring of Organ-on-a-Chip Models: The case for Microphysiometry, 37th Annual International Conference of the IEEE EMBS, Milano, Italy, 25–29 August, 2015, 7091-7094.