MESOSCALE EMBEDDED SENSOR-INTEGRATED SYSTEMS FOR LOCALIZED BIOMEDICAL MONITORING

Abstract

Advancements in micro- and meso-scale manufacturing and fabrication technologies have revolutionized the development of miniature sensor-integrated devices for embedded applications in the biomedical and biopharmaceutical domains. However, biological environments impose significant constraints on device miniaturization and complexity. Often, system integration challenges limit the functional capabilities and accessibility of capsule-like devices making them unable to detect relevant analytes of interest, requiring assistance from external systems for localization or operation. In this dissertation, a unifying workflow for designing capsule prototypes was developed to address pervasive system integration and manufacturing challenges associated with device scaling, localized sensing, and electrochemical detection of complex biologics. The approach is predicated on modular sensor integration, Bluetooth-enabled front end (FE) electronics, and biocompatible packaging to enable localized and unassisted remote sensing. This concept is demonstrated through two case study applications featuring capsule prototypes. A bio-processing monitoring capsule, or bPod, was realized to detect spatial distributions of dissolved oxygen (DO) within cell-culture bioreactors to ensure uniform cell proliferation. The device successfully interfaces a microfabricated Clark-type DO sensor with a portable potentiostat and robust package ( = 24-mm) to facilitate amperometric measurements of varying DO saturation levels in a 10-L bioreactor. DO sensors achieved a sensitivity of 6.3 mV/DO% and a 5-s response time. Building upon the bPod concept, the prescribed workflow was applied to further scale the system, achieving the first ingestible capsule prototype capable of detecting intraluminal hydrogen sulfide (H2S) in the gastrointestinal (GI) tract. The device employs a Nafion-coated gold electrochemical sensor and bioimpedance sensor to investigate sources of chronic inflammatory responses in the small intestines. FE electronics were designed on a flex-rigid printed circuit board (PCB) and molded in a silicone elastomer (34 mm x 14 mm). electrochemical characterization yielded a linear current response to H2S and improved selectivity (H2S:H2 = 1,340) in the presence of known interferent GI gases. Overall, this thesis contributes to advancing the state-of-the-art for miniaturized capsule manufacturing and assembly, through (1) development of custom 3D-printed mesoscale sensor interfaces that enable facile plug-in-play integration of electrochemical gas sensors for remote sensing, (2) design of Bluetooth-enabled FE electronics that facilitate multiple sensing modalities for real-time detection and localization of target analytes, and (3) a packaging strategy for isolating device electronics with considerations for capsule form factor, robustness, and biocompatibility. Ultimately, the device miniaturization method highlighted in this thesis makes possible the realization of feedback-driven systems with embedded sensing and wireless networking capabilities for potential autonomous device operation and localized biomedical monitoring.