Title:  Multimodal and Multifunctional CMOS Cellular Sensing and Actuating Array with Enhanced Electronics-biology Interface

Committee:

Dr. Hua Wang, ECE, Chair, Advisor

Dr. Madhavan Swaminathan, ECE

Dr. Omer Inan, ECE

Dr. Matthieu Bloch, ECE

Dr. Jing Wang, ETH

Abstract: The objective of the research described in this dissertation is to further revolutionize silicon-based multimodality sensor/actuating arrays for emerging applications. In this dissertation, we presented the motivation and researched the approaches toward the next generation of bioelectronic sensors for comprehensive cellular characterization. Biological networks, even when reduced to their most basic building block, cells, are highly sophisticated systems with numerous undiscovered processes involving thousands of molecules operating in hundreds of pathways to maintain their proper functions, morphologies, phenotypes, and physiological behaviors. Therefore, understanding complex multi-physical cellular responses is essential for numerous applications in biological/biomedical science research and technology development such as drug discovery/screening, vaccine development, pathogen virulence, and synthetic exoelectrogen engineering that rely on screening cells or tissues with incredibly high throughput. Therefore, these applications require cell-based biosensors that can detect and characterize various biomolecules using living cells or tissues massively paralleled cell interfacing platforms with multi-parametric sensing. Recently, CMOS platforms for cellular characterization have been reported. However, most CMOS sensors are only single-modal which cannot capture multi-parametric cellular responses, and yield limited cell information. With multimodal sensing, a sensor can real-time monitor cellular potential, impedance, and fluorescence responses to accurately capture cell activities, growth/viability, and physiology states. Furthermore, in a biological/tissue culture composed of a network of many cells, precise characterization providing in-depth insight into the complex biological system will necessitate high spatiotemporal resolution with both subcellular resolution and high sampling rate over a FoV large enough to accommodate tissue growth. To address this, we created and demonstrated a multimodal and multifunctional CMOS cellular sensing and actuating platform with optimized post-CMOS treatment over an ultra-dense pixel array to improve the interface between electronics and biology, allowing for the extraction of various cellular physiological features with sharp features over long periods of time for holistic cellular and tissue characterizations, paving the way for a paradigm shift in numerous biological and biomedical applications.