PhD Defence Aniruddha Paul | Engineering Microphysiological Ecosystems

Engineering Microphysiological Ecosystems

Aniruddha Paul is a PhD student in the Department of Biomedical and Environmental Sensorsystems. (Co)Promotors are prof.dr.ir. M. Odijk and dr. J.T. Loessberg-Zahl from the Faculty of Electrical Engineering, Mathematics and Computer Science and prof.dr. A.D. van der Meer and dr. A.R. Vollertsen from the Faculty of Science & Technology.

This thesis introduces a set of modular and microfabrication based engineering solutions to accelerate adoption of microphysiological systems, such as Organ-on-Chip. By demonstrating the versatility of the proposed concepts and fabrication methods, this work aspires to provide the broader scientific community with approaches that can be integrated into their repertoire when designing models and conducting experiments.

Chapter 2 introduces a standalone modular microfluidic platform (STARTER) that integrates essential components relevant for OoC experiments within a standardized microtiter plate footprint. A standardized design framework and a fluidic circuit board (FCB) is used to develop an architecture that allows tube-less inter-module interactions via arbitrary and reconfigurable fluidic circuits. System flexibility, sensor functionality, and multi‑component integration are validated alongside biological relevance through multi‑day in‑vitro and ex‑vivo experiments.

Chapter 3 reports an integrated microfluidic platform capable of regulating and maintaining gas concentrations for OoC studies. Building on previously established concepts, the platform demonstrates control of physiologically relevant conditions, such as hypoxia, across multiple integrated modules. Gas regulation is validated through in‑line optical sensor readouts and hypoxic cell marker expression.

Chapter 4 explores a strategy for multi‑modal onboard electrochemical sensing in modular microfluidic platforms. This aims to address the complexity of entangling sensor connectors that emerges as more sensors are integrated within a compact footprint. A miniaturized potentiostat is adapted as an add‑on module for STARTER. Conductivity and oxygen measurements validate the approach, while laying the foundation for future integration of additional modalities such as transepithelial electrical resistance (TEER).

Chapter 5 introduces a new OoC architecture by integrating 2PP fabricated porous tubular structures into microfluidic chips. These perfusable tubular membranes better replicate physiology while maintaining controlled permeability. A green‑laser system enables printing with lower power and low‑viscosity biocompatible resins, allowing the fabrication of millimeter‑scale structures with single micron resolution, thereby demonstrating fidelity across length scales. The structures are incorporated into a heart‑on‑chip platform, where functional contracting cardiac tissue forms around the tube, while the internal lumen is seeded with endothelial cells to establish a fluidic barrier. By combining these protocols, a perfusable co‑culture system is demonstrated.

Chapter 6 presents a collection of contributions to the field of micro‑robotics by applying work reported in previous chapters. 2PP fabricated complex structures enabled bubble‑based acoustic and magneto‑acoustic propulsion, while helical microrobots exhibited controllable magnetic response and propulsion. Modular microfluidic platforms were used to validate an artificial cilia‑based micropump for OoC applications. Together, these highlights underscore the interdisciplinary use cases of the work in this thesis.

Chapter 7 provides a concluding summary of the results presented in this thesis. Further context is added with respect to possible improvements and future perspectives.