Electrochemical sensors for organ-on-chips: RuO2 for amperometric and potentiometric sensors

Research output: ThesisPhD Thesis - Research UT, graduation UT

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Abstract

Organs-on-chips are new promising in vitro models of human tissue. They were developed to improve drug screening, by providing a realistic, predictive model of human (patho)phyiology with high-throughput and less ethical concerns. In organ-on-chip models, human cells are cultured and perfused in microfluidic devices, where cues can be applied to mimic the in vivo microenvironment of the living organ. In response, the cells have shown more realistic phenotypes, as well as self-organisation to depict organ-like architecture and functions. During experiments using organs-on-chips, the cells are hidden away in the microdevices. This makes it difficult to know the status of the cells. One emerging feature, to solve this problem, is the inclusion of (micro)sensors for real-time readout capability. These microsensors can be placed inside the device, close to the cells. They would then enable evaluation of the cells’ conditions without the need to terminate or interrupt the experiment.
This work developed ruthenium oxide (RuOx) electrode as on-chip chemical sensors that are robust, reusable/regenerable, versatile, and suitable for organ-on-chip research. The RuOx electrode was presented as a pH-sensitive and selective electrode when operated potentiometrically. The RuOx pH electrode is robust against oxygen interference, making it suitable for organ-on-chips. The same electrode could be operated amperometrically to quantify O2 concentration. We demonstrated the use of the RuOx pH and O2 sensing in inferring different types of metabolism of cardiomyocytes. The RuOx electrode is a versatile and powerful tool in in vitro cell metabolism studies, especially in comparative settings.
The same electrode was tested to quantify nitric oxide (NO). Tests using chemical donor, whose NO generation was experimentally confirmed, showed that oxidation of NO occurred at a lower potential as well as delivered higher current densities on the RuOx electrode than on bare Pt electrode. The electrode also successfully monitored NO as generated by a colony of endothelial cell culture. The RuOx electrode proves to be an electrocatalytic NO sensing electrode, that is suitable for organ-on-chip studies.
We also showed the RuOx electrode can monitor contractile hPSC-CMs using electrochemical impedance spectroscopy. This mode of operation adds to the versatility of the RuOx electrode’s use. Finally, we addressed the demands on the miniaturisation and on-chip integration of the RuOx electrodes. The RuOx electrodes could be reliably miniaturised down to ø 100 μm dimension. Furthermore, the RuOx electrode and fabrication method was highly transferrable for biologically-relevant on-chip format/studies. The tested RuOx electrode would allow for low-cost on-chip NO sensing at the proximity of biological cells, suitable for organ-on-chip studies.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • Olthuis, Wouter, Supervisor
  • van den Berg, Albert, Supervisor
Award date19 Feb 2021
Place of PublicationEnschede
Publisher
Print ISBNs978-90-365-5103-8
DOIs
Publication statusPublished - 19 Feb 2021

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