Fischell Department of Bioengineering Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/6628
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Item DEVELOPMENT OF AN INTEGRATED CAPSULE SYSTEM FOR GASTROINTESTINAL-TARGETED BIOSENSING(2019) Banis, George Efstratios; Ghodssi, Reza; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Non-invasive microsystems are emerging as a means to address diagnostics challenges in healthcare due to the potential to retrieve information at the source and in a personalized approach. The gastrointestinal (GI) tract is a hub of information that alters in composition during both homeostatic and pathological conditions, and often manifests as varying biochemical concentrations in cell and tissue-sourced secretions. Thus, innovative strategies to sample molecular information from these secretions would be of significant benefit to physicians in establishing an appropriate prognosis. This dissertation describes the development of a film-based capacitive sensing strategy and subsequent integration into a capsule-based microsystem that is designed to travel through the GI tract upon ingestion until it passes through the stomach, where it is designed to measure model analytes in duodenal secretions. Subsequently, the measurements are processed into signals for wireless transmission, enabling external analysis for potential clinical utility. To achieve a system that can be safely ingested by patients, design features must be implemented that follow previously established standards in device requirements such as geometry and biocompatibility. In this work, I aid in the design, integration, and characterization of a capsule-embedded sensing system using commercial off-the-shelf components that interface capacitive transducers (range: 0.8-220 pF; sensitivity: 7.3x10-3) with a smart phone via Bluetooth Low Energy (2.4 GHz). The transducers are designed to measure the change in dielectric constant of interfacing media, which transitions when specific environmental (pH) characteristics are met. The system, including the power supply, are manufactured on a printed circuit board and packaged within a 3D-printed capsule structure (13 mm x 35 mm) that maintains dimensions of other clinically utilized ingestible capsule devices. The system is cost effective, user-friendly, biocompatible, and can serve as a highly customizable platform for measuring a variety of desired targets. Secretions from various GI organs can be distinguished by pH, as is demonstrated in the pharmaceutical industry via enteric coatings that dissolve in target pH ranges but maintain structural stability in others. I employ such coatings for protecting our system until targeting the pH, and therefore GI region, of interest for sampling. Once dissolved, microfluidic inlets allow access for the media to interface with the sensors. I studied coatings that respond to both acidic (pH 6), as well as pH sequences via hierarchical coatings. Because the target analytes react with naturally occurring substrates, I investigate label-free sensing of model enzymes such as pancreatic trypsin (20-40 μM) and lipase (10 μM-1 mM), as well as bile salts (0.07-7 %w/v) as a model emulsifier, using films composed of biomaterials, including gelatin and stearin. To integrate these materials with the desired microsystem, I investigate various film deposition and modification strategies. Studies performed with our platform suggest the potential for the ability to sample the target fluid, as well as sense the analyte of interest in different concentrations by comparing the rate of capacitance change upon fluid entry compared to uncoated controls. Using this system, I characterize its potential for utility as a non-invasive platform for targeting multiple GI regions and detecting sensor-compatible biomarkers.Item Optical and Thermal Systems for Automation of Point-of-Care Assays(2018) Goertz, John; White, Ian M; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Modern medicine has detailed 70,000 different diagnoses; the 21st century challenge is bringing those diagnoses to over 7 billion people. This phenomenal feat requires precision biosensing strategies that minimize necessary training and manual effort while maximizing portability and affordability. Microfluidic strategies, both fabricated chips and paper-based devices, held the promise to facilitate point-of-care diagnostics but have been inadequate for many applications due to the trade-off between bulky pumps or limited control and complexity. This dissertation details novel strategies that control the progression of biochemical reactions with high functionality, portability, and ease-of-use. First, I will describe an amplified signaling reaction that leverages both positive and negative feedback loops to achieve optically-regulated control. This assay, termed “Peroxidyme-Amplified Radical Chain Reaction” enables naked-eye detection of catalytic reporter DNA structures at concentrations across five orders of magnitude down to 100 pM while eliminating the need for manual addition of hydrogen peroxide common to other such detection reactions. Next, I will describe the development of a platform for thermal regulation of generic reactions. To address the need for a broadly capable automation platform that provides equal utility in the lab and field alike, we recently developed “phase-change partitions”. In our system, purified waxes segregate reagents until incremental heating melts the partitions one by one, causing the now-liquid alkane to float and allowing the desired reagents to interact with the sample on demand. This tight control over reaction progression enabled us to construct hands-free detection systems for isothermal DNA amplification, heavy metal contamination, and antibiotic resistance profiling. My work has demonstrated a broadly capable suite of assay control systems with the potential to enable simple, inexpensive automation of a broad array of chemical and biological analysis across human medicine, environmental surveillance, and industrial chemical synthesis.