Development of a conducting polymer sensing- and stimulation platform for organoid guidance

The regulation of most physiological processes in the human body relies on homeostasis, a state of equilibrium. This is achieved through a biological control loop involving physiological sensors and actuators, connected from the central nervous system, connected to local tissue and organs through the peripheral nervous- and vascular systems. However, tissue damage, disease and aging can disrupt these control loops, leading to impaired homeostasis and connection between these systems. Bioelectronic devices offer the opportunity to interface artificial technology with biological systems, enabling the measurement, stimulation and control of specific processes using sensors and actuators.

Bioelectronics is the emerging field that aspires to couple two seemingly very different worlds, the world of Biology and the world of Electronics. The benefits of this coupling are numerous as it allows for the creation of a two-direction biotic/abiotic pathway. In one direction, events in the biological world are sensed and recorded by electronic devices. In the reverse direction, electronic devices can be used to trigger biological phenomena. The challenge in this endeavor, though, is the miscommunication between the two worlds due to their different natures. Biology is dynamic, with ionic fluxes dominating their processes, while electronics are stiff and rigid, with electrons and holes transporting signals and information. This creates a communication mismatch which has tremendous effects on the quality of the coupling.

Recently organic electronic materials have emerged as a promising candidate for interfacing with biology, with numerous applications both in sensing and stimulation, due to their unique set of features. This set includes improved mechanical compatibility to biological tissue, thanks to their “soft” nature, enhanced biocompatibility which favors the biotic/abiotic interplay and drug delivery capabilities. Organics can be easily modified chemically, which gives them a plethora of on demand functionalities, and they form oxide free interfaces with aqueous electrolytes, and therefore they can be in direct contact with biological tissue. In addition, they are compatible with low temperature processing, which can lead to low-cost fabrication. Last, but not least, they support mixed ionic/electronic conductivity which is of great importance due to the role ion fluxes play in biology. Consequently, conducting polymer devices have been exploited lately in various applications concerning neural interfacing, drug delivery, neuromorphics and biosensing.

The goal of this PhD research is the microfabrication of conducting polymer in vitro devices for organoid guidance. The work will build on state-of-the-art technology in the field of organic devices and organoids, to deliver conducting polymer “Organoid-on-a-chip” platforms with novel form factors and enhanced capabilities. The set up will be able to stimulate, sense and guide organoids, which will lead to a better understanding regarding the role of bioelectronics in human homeostasis and disease, and hence pave the way for new biomedical applications. By leveraging the characteristics of conducting polymers, novel devices, endowed with multimodal functionalities, will be fabricated, various stimulation paradigms will be tested and their effect on the function of the organoids will be recorded and quantified, creating new routes in understating their biology.

In the first phase of the project, the student will be trained in the microfabrication processes in the Leuven cleanroom facilities. They will learn how to use modern microfabrication techniques to fabricate microscale in vitro devices relevant to biological systems. They will also work with conducting polymers and leverage the advantages offered by the latter in producing devices for bioelectronic applications. In the second phase, organoids will be integrated in the in vitro platforms and sophisticated stimulating impulses and/or chemical agents will be used to trigger them and to measure the effects on their physiology followed by validation in pre-clinical models in the final phase.