| dc.description.abstract | This thesis explores the development and application of microsystems to advance our understanding of disease biology. The overarching goal is to enhance diagnostic and therapeutic strategies through precise and physiologically relevant models that bridge the gap between traditional in-vitro/animal models and human clinical outcomes.
The first part of the study delves into the dynamic behaviour of micro-resonators in fluid environments and their application in analysing the rheological properties of blood plasma samples. Initially, we examine the enhancement of the quality factor (Q-factor) of 2D micro resonators when loaded with a fluid, achieving a Q-factor of 602 in water with the D4000 PMUT, significantly surpassing its in-air performance. This unusual enhancement, confirmed through experimental investigations and simulations, indicates the potential of these devices in sensing applications for biological fluids.
Building on these findings, we leverage the fluid-loaded resonators to measure the viscosity and density of blood plasma samples from various patient groups. Calibrating the MEMS-based devices with varied glycerol-water mixtures for fluid density and viscosity measurements, we achieved accurate results from blood plasma samples that differentiated between breast cancer, diabetes, and healthy individuals. By integrating machine learning algorithms, we improved classification accuracy to 92.1%, demonstrating the potential of combining rheological data with cytokine profiles for enhanced diagnostics in clinical settings.
The second part of the thesis focuses on the development of microfluidic devices to study cancer cell behaviour and organ-specific responses. This section presents a microfluidic device designed to replicate multiple biophysical stresses experienced by circulating tumour cells (CTCs) in the vasculature. This device allowed us to assess the viability and re-attachment capabilities of various breast cancer cell lines post-exposure to these stresses. Our findings highlight the device's utility in evaluating metastatic potential. This study has significant implications for patient risk stratification and personalized treatment strategies.
Expanding on the microfluidic approach, we developed an Organ-on-Chip (OoC) designed to emulate organ-specific environments and investigate organotropism in solid cancers. By optimizing the extracellular matrix composition and integrating physiological fluid dynamics, we successfully integrated multiple organ models offering a novel approach to study cancer metastasis. We also delved into the translational aspects of the OoC platforms by shifting from traditional PDMS-based devices to industry acceptable biocompatible plastics and have demonstrated a proof-of-concept design, fabrication and optimized cell growth.
Collectively, these studies underscore the potential of microsystems in disease biology, offering powerful tools for diagnostics, risk assessment, and therapeutic development. Future work will enhance the complexity and versatility of these platforms, bridging the gap between laboratory research and clinical application, and ultimately improving patient outcomes through personalized medicine. | en_US |
