CMOS-enabled Cellular and Bio-molecular Sensing Systems: From In-vitro Diagnostics to Ingestible Electronics

Abstract

The COVID-19 pandemic has certainly highlighted the importance of a strong and reliable healthcare system in society, without which millions of people remain vulnerable to the next pandemic. Among many ways to fight against the disease, such as quarantine, patient care, and vaccination, early detection plays a vital role to slow down the spread. The key technology to realize early detection is point-of-care (POC) diagnostics. This technology could allow rapid detection of viral and bacterial infections on the spot or performing health predictions from the collected body fluids without requiring visits to the centralized testing locations. The challenge of enabling POC diagnosis is to miniaturize lab-grade testing instruments to portable form factors with convenience and affordability available to the individuals. In the past decades, the field of lab-on-a-chip has demonstrated significant advancements towards proteomic, genomic, and cytomic sensing on millimeter-sized chip-scale systems. However, the complete integration of fluid collection, processing, bio-molecular/cellular detection and, data communication in a single device still remains unseen, all of which are essential to complete an end-to-end medical diagnosis. To address the challenges above, this thesis introduces three novel ultra-compact and low-power biosensing platforms based on complementary metal-oxide-semiconductor (CMOS) technologies: 1) an external pneumatic-and-instrumentation-free all-in-one handheld microfluidic biosensing platform capable of performing cellular sensing and immunoassay, 2) an ingestible bio-pill compatible to the FDA-approved capsule size that provides health information through gut microbiome monitoring and nucleic acid sensing using on-chip optics, 3) a packaged smart bandage that monitors the wound healing process through cytokine detection using label-free impedance spectroscopy. The three proposed biosensing platforms investigate deeply into novel ways of integrating sample fluid collection, processing, detection, data processing, and wireless data communication features into a single and unified system for in-vitro and in-vivo sensing applications. The proposed approaches eliminate the usage of external instrumentation while achieving new performance and integration levels in their own classes.