Organic electronics and microphysiological systems to interface, monitor, and model biology

Biological processes in the human body are regulated through complex and precise arrangements of cell structures and their interactions. In vivo models serve as the most accurate choice for biological studies to understand these processes. However, they are costly, time-consuming, and raise ethical issues. Microphysiological systems have been developed to create advanced in vitro models that mimic in vivo-like microenvironments. They are often combined with integrated sensing technologies to perform real-time measurements to gain additional information. However, conventional sensing electrodes, made of inorganic materials such as gold or platinum, differ fundamentally from biological materials. Organic bioelectronic devices made from conjugated polymers are promising alternatives for biological sensing applications and aim to improve the interconnection between abiotic electronics and biotic materials. The widespread use of these devices is partly hindered by the limited availability of materials and low-cost fabrication methods. In this thesis, we provide new tools and materials that facilitate the use of organic bioelectronic devices for in vitro sensing applications. We developed a method to pattern the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate and to fabricate organic microelectronic devices using wax printing, filtering, and tape transfer. The method is low-cost, time-effective, and compatible with in vitro cell culture models. To achieve higher resolution, we further developed a patterning method using femtosecond laser ablation to fabricate organic electronic devices such as complementary inverters or biosensors. The method is maskless and independent of the type of conjugated polymer. Besides fabrication processes, we introduced a newly synthesized material, the semiconducting conjugated polymer p(g42T-T)-8%OH. This polymer contains hydroxylated side chains that enable surface modifications, allowing control of cell adhesion. Using the new femtosecond laser-based patterning method, we could fabricate p(g42T-T)-8%OH-based organic electrochemical transistors to monitor cell barrier formations in vitro. Microphysological systems are further dependent on precise compartmentalization to study cellular interaction. We used femtosecond laser 3D printing to develop a co-culture neurite guidance platform to control placement and interactions between different types of brain cells. In summary, the thesis provides new tools to facilitate the fabrication of organic electronic devices and microphysiological systems. This increases their accessibility and widespread use to interface, monitor, and model biological systems.

List of scientific papers

I. Rapid prototyping of heterostructured organic microelectronics using wax printing, filtration, and transfer. L. Ouyang*, S. Buchmann*, T. Benselfelt, C. Musumeci, Z. Wang, S. Khaliliazar, W. Tian, H. Li, A. Herland, M. Hamedi. Journal of Materials Chemistry C. 9.41 (2021): 14596-14605. *Equal contribution.
https://doi.org/10.1039/d1tc03599a

II. Cleanroom-free direct laser micropatterning of polymers for organic electrochemical transistors in logic circuits and glucose biosensors. A. Enrico*, S. Buchman*, F. De Ferrari, Y. Lin, Y. Wang, W. Yue, G. Mårtensson, G. Stemme, M.Hamedi, F. Niklaus, A. Herland, and E Zeglio. Advanced Science. (2024): 2307042. *Equal contribution.
https://doi.org/10.1002/advs.202307042

III. In situ functionalization of polar polythiophene based organic electrochemical transistor to interface in vitro models. S. Buchmann, P. Stoop, K. Roekevisch, S. Jain, R. Kroon, C. Müller, M. Hamedi, E. Zeglio, and A. Herland. [Manuscript]

IV. Probabilistic cell seeding and non-autofluorescent 3D-printed structures as scalable approach for multi-level co-culture modelling. S. Buchmann*, A. Enrico*, M. Holzreuter, M. Reid, E. Zeglio, F. Niklaus, G. Stemme, A. Herland. Materials Today Bio. (2023): 100706. *Equal contribution.
https://doi.org/10.1016/j.mtbio.2023.100706