Electric sight: mapping tissue barrier function with cellular resolution in organ-on-chip platforms

• Applicants: Professorin Dr. Iordania Constantinou; Thomas Eduard Winkler, Ph.D.
• Subject Area: Microsystems
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536023018

In-vitro biological models are crucial for the advancement of biomedicine and drug development. Yet these models are only as good as the available readout methodologies. With Electric Sight, we seek to add a new dimension to how cellular function can be assayed, specifically using miniaturized electric impedance tomography (microEIT). Our goal is not only to develop microEIT as a technique for electrical imaging at cellular resolution, but also to combine it with advanced microfluidic in-vitro model technology (organs-on-chips; OoC). In particular, we intend to apply our microEIT-OoC platform to study localized biological processes at the blood-brain barrier – both to showcase the unique capabilities of the system, and to answer open questions regarding oxidative stress damage. To take EIT beyond its current minimum scale (cm to mm) and into the micro-scale realm, we plan to holistically optimize the platform; i.e., in terms of electrode array design and fabrication, measurement principle, as well as in terms of image reconstruction algorithms. Integrated into an organ-on-chip model of the blood-brain barrier, microEIT will allow label-free localized monitoring. Even with healthy barriers, this already provides a new metric to assess differences between cellular models – instead of simply average integrity, we can now quantify barrier homogeneity. Of greater interest are, naturally, disturbances, such as by oxidative stress, a common feature of disorders including cancer and traumatic brain injury. Our goal is to reveal not only how different types of oxidative stress affect local barrier integrity, but also how local damage correlates with the local transmigration of immune or cancer cells across the barrier – an open question that our microEIT methodology is uniquely positioned to answer. Overall, Electric Sight will thus establish microEIT – combined with all the typical advantages of organs-on-chips regarding the in-vivo-like microenvironment – as a versatile tool for the label-free study of local biological processes in vitro. Showcasing the platform’s functionality regarding localized cell barrier damage and transmigration is sure to spur further research and insights into neuroinflammation and cancer metastasis, as well as their therapeutic prevention.

• DFG Programme: Research Grants