Elucidating Human Disease Mechanisms Using Innovative Open Microfluidic Platforms

Abstract

Open microfluidic technologies are innovative research tools that offer unique advantages in chemical and biomedical research. This thesis explores the diverse biomedical applications of open microfluidic platforms in understanding the complex mechanisms underlying human diseases. Chapter 1 introduces the concept of open microfluidic systems, discussing their design principles, fabrication methods, and distinctive advantages over traditional macroscale systems or closed microfluidic systems. Chapter 2 presents the application of a novel open microfluidic coculture device for investigating mechanisms of airway inflammation by coculturing fibroblasts and eosinophils. The results show the induction of a proinflammatory phenotype of primary human lung fibroblasts following the coculture with degranulating eosinophils. This model enables the discovery of new analytes in the fibroblast-eosinophil signaling that were not found in previous conditioned media studies. Chapter 3 discusses another application of the same coculture device for examining injury-induced paracrine effects on the podocyte's transcriptome in glomerular disease. Transcriptomic analysis revealed shared and unique pathways between three common forms of podocyte injury inducers. This model is the first to allow direct measurements of the paracrine signals derived from injured podocytes and their effects on a healthy podocyte population. Chapter 4 describes the application of homeRNA, a remote blood collection and stabilization device, as a flexible and responsive approach to assess the effects of wildfire smoke exposure. The flexibility of the homeRNA kits allows participants to collect blood samples throughout the year, even during emergency evacuations. Ongoing transcriptomic analysis will reveal information on the overall health of participants from a mechanistic perspective, particularly on systemic inflammation. Chapter 5 concludes the thesis by proposing future directions of the work presented and discussing exciting opportunities in biomedical research with open microfluidic technologies. Through these chapters, this thesis demonstrates the pivotal role of open microfluidic technologies in advancing biomedical research by offering unique insights into disease mechanism studies.