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Title: Development of a cell-based drug screening platform : extracellular recording and electrochemical impedance spectroscopy on microelectrode array chips
Author: Sörensen, Sören Per
ISNI:       0000 0001 3471 7817
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2007
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Two established methods, Electrochemical Impedance Spectroscopy (EIS) and extracellular recording, were implemented into a technology platform for non-invasive whole-cell biosensing. Electrical activity of cardiomyocytes and cell-substrate interaction of human ovarian cancer cells was monitored on electrode array chips. The performance of cells inside a microfluidic or closed low volume environment was investigated. Prior to the development of the entire microfluidic platform the two transducing methods were evaluated in single experiments. Processes as cellular attachment and detachment were monitored using EIS and single frequency impedance sensing. Electrodes of different size and structure were employed and compared for their impedance response. It was shown that small electrodes (A = 9·10-6 cm²) are more sensitive to cell-substrate interaction than larger ones (A = 9·10-5 cm²) and that the frequency used for analysis has a profound influence on the sensitivity. Data were modelled using a common equivalent circuit that represents a cell layer on an electrode resulting in an increase of the impedance magnitude by <170 % due to cell attachment. In order to demonstrate the potential of this method for biomedical applications, experiments related to anti-cancer strategies were performed. Cell detachment was induced by addition of synthetic integrin ligands and by hypericin mediated photodynamic therapy and monitored with impedance-based biosensing. Electrical activity of cardiomyocytes cultured on microelectrode arrays was monitored inside a microfluidic system. The chronotropic drug isoproterenol was applied using a robotic dispensing machine, and the resulting changes in spike rate and duration were compared with results gained by experiments with a large scale MEA chip. The experimental findings inspired the development of a technology platform that was finally evaluated by monitoring extracellular signals from myocytes in response to Isoproterenol. Another topic was the comparison of cell-substrate interaction monitored on various electrode structures.
Supervisor: Jenkins, Andrew Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: microelectrodes ; drug-screening