High Sensitivity, Label-Free, Interferometric Biosensor for In Vitro Contractility Assessment of HiPSC Cardiomyocytes

The exploration of in vitro cell cultures holds pivotal significance in biological studies, providing a crucial lens through which we examine cellular responses to external stimuli. This is especially pertinent in the field of cardiomyocytes contraction measurement, where the need for accurate and versatile methodologies persists. Past strategies have made strides, yet limitations persist, necessitating innovative solutions in the coming decade. As technology and biology converge, advancements are anticipated in fabrication techniques, sensing materials, and platform designs. The maturation of cardiomyocytes and optimization of culturing protocols promise to refine functional measurements, aligning them more closely with in vivo conditions. Micro- and nanoscale biomaterials have emerged as transformative agents, surmounting the constraints of previous technologies. They lay the groundwork for platforms that interface with electrogenic cells at unprecedented spatiotemporal scales, offering a holistic view of interactions among different cell and organ types. The first chapter of this thesis describes the principal mechanisms governing cardiac tissue contraction, both in vivo and in vitro models. This foundational understanding sets the stage for delving into the challenges inherent in measuring cardiac tissues in vitro. In the second chapter, a comprehensive review unfolds, surveying the current methods employed for measuring cardiomyocyte contraction across diverse biological models. From single-cell analyses to intricate 3D organoid models, a spectrum of approaches is scrutinized, highlighting the nuances and limitations of each. The third chapter marks a pivotal turn, introducing a novel device designed for measuring the contraction force of a 2D monolayer of cardiomyocytes. This technological innovation stands as a testament to the evolving landscape of cardiac research tools. The fourth chapter navigates the translation of this technology from whole cell culture to single-cell resolution.