Progress in biomedical research and drug development is currently strongly constrained by the high costs and ethical limitations of in vivo animal studies, as well as by the high costs and long duration of clinical trials. Organ-on-a-Chip (OoC) technologies have recently been proposed as a valid alternative for studying pathophysiological processes in vitro using mammalian cells and customized devices. Conventional OoC systems are typically designed and manufactured at the laboratory scale and assembled through complex manipulation steps. To make OoC technology readily available for high-throughput biological experimentation, it is essential to develop robust fabrication approaches that enable customizable and sustainable production at accessible costs.

The main objective of the MITO project is to design and develop an efficient chain of microfabrication processes for the production of an innovative Organ-on-a-Chip (OoC) microfluidic platform—namely, a structured system for the in vitro culture and perfusion of mammalian cells. Thanks to this process chain, it will be possible to develop efficient, structured, ready-to-use, and scalable systems for culturing cells in conditions similar to the microphysiological environment, allowing the reproduction of cellular functions that are absent in conventional cell-culture systems.

The overall goal is to develop efficient, integrated, ready-to-use, and scalable systems for culturing cells in conditions that resemble the microphysiological environment, in order to recapitulate cellular functions not present in standard cell-culture platforms. These microfluidic devices will make it possible to study human disease biology at both the patient-specific and the cellular/molecular level. Using this integrated system for drug discovery will enable faster, cheaper, and more accurate studies than ever before, while reducing animal experimentation. Conventional OoC systems are generally designed and fabricated in the laboratory and assembled into units through complex handling steps. To make OoC technology readily available for high-throughput biological investigations, it is crucial to develop robust production methods that support large-scale, cost-effective manufacturing.

An integrated, compact OoC device—and its associated perfusion system—will be designed, prototyped, manufactured, and validated, featuring advanced characteristics that will define future systems of this kind. The proposed project will have a multilayer architecture based on polymer layers and elastomeric membranes. Microchannels, valves, and pumps will be fabricated and assembled on the main chip, leveraging the different material properties and using specially developed micro-support grids for the cells. State-of-the-art microproduction technologies will be adapted and refined to enable mass production of such a complex product. In particular, micro-milling and micro-EDM processes will be optimized to produce mold microfeatures such as smooth, thin walls, pins, and shaped cavities; thin polymer microgrids will be fabricated and integrated into the layers to promote periodic stretching of the biological substrate and to reproduce chemical and physical stimuli on co-culture layers. The injection micro-molding process will be optimized to produce micro-structured layers and micro-components. Robust strategies will be identified for the metrological characterization of molds, inserts, and microfluidic devices. As an important outcome of the successful completion of the project, a unique set of expertise in precision tooling, micro-manufacturing, and mass production through replication will become available. This project will strengthen a new research stream focused on micro-manufacturing technologies for large-scale production of OoCs and bioengineering. It will create a network of excellence in scientific research on tooling and micro-manufacturing technologies within the European landscape, in line with strategic priorities for the competitiveness of European industry.