Lab-On-a-Chip development for barrier model monitoring

In the context of D3 4 HEALTH Foundation research on digital health technologies, this work contributes to the development of innovative tools for biomedical applications, with potential impact on diagnosis, monitoring and treatment. The aim of this thesis is to optimize a multi-layer microfluidic platform for cell culture and analysis, with the integration of Organic Electrochemical Transistors (OECTs) for real-time monitoring of cellular responses. Starting from a previously developed microfluidic device, the design was modified to enable the culture of a human skin cell model and the incorporation of OECT sensors. The methodology involved the CAD design of the microfluidic platform composed of three different layers: two for cell culture and microfluidic connections, with a central chamber aimed at hosting the barrier model on a porous membrane, and the third one for bottom sealing of the chamber and OECTs integration. Two versions of the device were developed to embed two different membranes to be evaluated, a (38 ± 3) μm thick Polycarbonate (PC) one by Oxyphen and a (210 ± 10) μm thick silk one produced by KLISBio. The manufacturing process involved soft lithography, with the 3D-printing of master molds for the different layers and then the replica molding in PDMS. The final assembly of the multi-layer platform was performed through two techniques to be compared: adhesive bonding with a thin film of PDMS and plasma bonding. The OECTs were fabricated in clean room environment and then completed with the inkjet deposition of PEDOT:PSS, which constitutes the channel material. The OECT chips were complemented by gold gates produced in clean room, which are biocompatible and can be functionalized to enable biosensing. The developed Lab-on-a-Chip (LOC) devices were subjected to microfluidic leakage tests, achieving successful results with the commercial membrane and plasma bonding technique. The silk membrane version requires further optimization to improve the flow and avoid the bending of the membrane to allow hosting the skin model. The integration of OECTs in the multi-layer platform was successfully achieved, with the devices demonstrating stable electrical characteristics and sensitivity to ionic solutions. The future work will involve the seeding of human skin cells on the membranes, the functionalization of OECT gates for specific biomarker detection and the real-time monitoring of cellular responses under various conditions.