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Development of electronics setup & readout method for Transepithelial/transendothelial electrical resistance (TEER)-based measurements of tissue barrier function on microfluidic organ-on-a-chip device
We offer a project where you will develop a novel system for real-time TEER-based assessment of barrier function of human in vitro tissue models (e.g., bladder, lung) in microfluidic organ-on-a-chip device developed in the Bioengineering Lab.
Keywords: TEER, electrodes, impedance, microfluidics, in vitro barrier models; organ-on-chips.
Measurement of transepithelial electrical resistance (TEER) is a commonly used quantitative method for assessment of tight junction integrity within in vitro culture of barrier models without causing cellular and barrier damage. Various commercial TEER measurement systems have been developed, which are mainly tailored for use with a limited number of static in vitro culture platforms (e.g., transwell inserts) and are not able to monitor the real-time response of cellular barriers to the changing of external factors.
In the scope of NCCR Antiresist consortium, our team has developed a novel microfluidic platform for generation of physiologically relevant tissue models of human-derived cell lines. The device serves as a platform for seamless transition of the transwell-based tissue cultures from static growth conditions to more physiologically relevant environment via introduction of microfluidic perfusion capabilities. Currently, the assessment of the tissue barrier integrity is carried out via 1) high-resolution confocal microscopy imaging and 2) permeability assay with fluorescently-labeled tracer molecules. However, both methods generate only limited number of readouts set only at fixed time-points throughout an experiment.
In collaboration with Infection biology groups in Biozentrum, the chip is used to develop physiologically relevant models of human upper airway infection and bladder infection. Pathogen proliferation in the host tissue is known to be characterized by various extents of damage in the tissue barrier integrity, and can be modulated by treatment with relevant antibiotic compounds. Use of TEER-based real-time readout would thus improve the time-resolution of studies on pathophysiology of the bacterial infection, as well as improve the pharmacodynamic studies on antibiotic susceptibility tests.
Your main role involves development of a custom-built system for microfluidic implementation of TEER-based readout. Based on the analogous systems that were already developed in the group as well as published alternatives, you will design and fabricate an electronic setup (electrodes, connections) integrated with the PMMA-based microfluidic device. You will then extensively characterize the system with the tissue models of both healthy and compromised barrier integrity. TEER measurement will be performed with frequency-sweep, fitting the frequency derived TEER value will be an alternatives task.
While there is some flexibility in how to tailor the scope and focus of the project to your interest and background, generally, you should expect this project to be fairly interdisciplinary. As such, we offer ample opportunities to collaborate and train with team members from diverse backgrounds. You will potentially gain experiences in a host of practical skillsets: cell culture techniques, cleanroom work, confocal microscopy, electrical instrumentation.
Required background (at least two of the followings): Good understandings of electronics, Some programming knowledge, Cleanroom/microfabrication expertise is a plus.
Measurement of transepithelial electrical resistance (TEER) is a commonly used quantitative method for assessment of tight junction integrity within in vitro culture of barrier models without causing cellular and barrier damage. Various commercial TEER measurement systems have been developed, which are mainly tailored for use with a limited number of static in vitro culture platforms (e.g., transwell inserts) and are not able to monitor the real-time response of cellular barriers to the changing of external factors.
In the scope of NCCR Antiresist consortium, our team has developed a novel microfluidic platform for generation of physiologically relevant tissue models of human-derived cell lines. The device serves as a platform for seamless transition of the transwell-based tissue cultures from static growth conditions to more physiologically relevant environment via introduction of microfluidic perfusion capabilities. Currently, the assessment of the tissue barrier integrity is carried out via 1) high-resolution confocal microscopy imaging and 2) permeability assay with fluorescently-labeled tracer molecules. However, both methods generate only limited number of readouts set only at fixed time-points throughout an experiment.
In collaboration with Infection biology groups in Biozentrum, the chip is used to develop physiologically relevant models of human upper airway infection and bladder infection. Pathogen proliferation in the host tissue is known to be characterized by various extents of damage in the tissue barrier integrity, and can be modulated by treatment with relevant antibiotic compounds. Use of TEER-based real-time readout would thus improve the time-resolution of studies on pathophysiology of the bacterial infection, as well as improve the pharmacodynamic studies on antibiotic susceptibility tests.
Your main role involves development of a custom-built system for microfluidic implementation of TEER-based readout. Based on the analogous systems that were already developed in the group as well as published alternatives, you will design and fabricate an electronic setup (electrodes, connections) integrated with the PMMA-based microfluidic device. You will then extensively characterize the system with the tissue models of both healthy and compromised barrier integrity. TEER measurement will be performed with frequency-sweep, fitting the frequency derived TEER value will be an alternatives task.
While there is some flexibility in how to tailor the scope and focus of the project to your interest and background, generally, you should expect this project to be fairly interdisciplinary. As such, we offer ample opportunities to collaborate and train with team members from diverse backgrounds. You will potentially gain experiences in a host of practical skillsets: cell culture techniques, cleanroom work, confocal microscopy, electrical instrumentation.
Required background (at least two of the followings): Good understandings of electronics, Some programming knowledge, Cleanroom/microfabrication expertise is a plus.
- Design and fabrication of TEER sensors that can be integrated in microfluidic chips;
- Design and implement a readout unit;
- Monitoring of cellular barrier formation and disruption with the integrated TEER sensors;
- Get a fitting method that works for muti-frequency TEER values;
- Design and fabrication of TEER sensors that can be integrated in microfluidic chips; - Design and implement a readout unit; - Monitoring of cellular barrier formation and disruption with the integrated TEER sensors; - Get a fitting method that works for muti-frequency TEER values;