UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
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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 Motion of elastic capsules in microfluidic channels(2010) Kuriakose, Shugi; Dimitrakopoulos, Panagiotis; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Capsule flow dynamics in microchannels plays a significant role in complex biological phenomena, such as the microcirculation, and in engineering applications, such as in microfluidic devices for drug delivery and cell sorting. In this thesis, we investigate the motion of elastic capsules in wall-bounded flows by extending the Membrane Spectral Boundary Element method developed by Dodson and Dimitrakopoulos for free-suspended flows. First, a validation study of the method is performed for the axisymmetric capsule motion in a cylindrical channel. For a capsule moving along the centerline of a cylindrical channel, our computational model successfully reproduced the parachute shape observed in earlier experimental and computational studies. Next, we investigate the flow dynamics of a strain-hardening Skalak capsule moving along the centerline in a square and a rectangular channel. We examine how the capillary number and capsule size influence the deformation and physical properties of the capsule. For large capsules in a square channel, our investigation reveals that the steady-state capsule shape is non-axisymmetric. The capsule assumes a shape similar to the channel's cross-section i.e. a square shape with rounded edges. Buckling of the capsule's upstream end resulting in a negative edge curvature is observed at higher capillary numbers and for large capsule sizes. For the largest capsules studied, we also observe the development of dimples at the capsule's lateral surface. A comparative study of capsule motion and deformation in cylindrical and square channels shows that the capsule deformation in a cylindrical channel is similar to that in a square channel at a larger capillary number. In a rectangular channel, we observe a three-dimensional (i.e. non-axisymmetric) deformation of the capsule at high capillary numbers resulting in dimpling of the capsule's upstream end at steady state. We also consider the transient motion of a capsule in a converging square microchannel and investigate the influence of viscosity ratio, capillary number and capsule size on the evolution of capsule properties. As the capsule moves through the converging region a fluctuation in the geometric and physical properties of the capsule is observed.Item Dynamics of Erythrocytes and Microcapsules(2008-04-25) Dodson, Walter; Dimitrakopoulos, Panagiotis; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The erythrocytes are the primary carriers of oxygen and carbon dioxide to and from the systemic tissue. The ability of these cells to deform and navigate through the capillary beds is of fundamental importance for proper functioning of the cardiovascular transport system. The erythrocyte is essentially a capsule, and flow-induced erythrocyte deformation involves the interfacial dynamics of a membrane-enclosed fluid volume stressed in a viscous flow. Elastic capsule dynamics is a complicated problem involving the coupling of fluid and membrane forces; it is also found in a variety of scientific and engineering applications. In this work, we investigate the dynamics of elastic capsules and erythrocytes using the Spectral Boundary Element (SBE) method, a high-order / high-accuracy method for capsule and cellular dynamics. For strain-hardening Skalak elastic capsules in an extensional flow, our investigations demonstrate a shape transition in accordance with experimental observations to a cusped conformation at high flow rates, which allows the capsule to withstand the increased hydrodynamic forces. Our computational methodology reveals a region of bifurcation, in which both spindled and cusped steady-state geometries coexist for a single flow rate. The method is also used to investigate the dynamics of strain-softening Neohookean capsules in the same flow pattern. The strain-softening capsules become highly extended at weaker flow rates than strain-hardening capsules, and do not form steady-state cusped shapes. The SBE method has been extended to model the erythrocyte by using a biconcave disc reference geometry and adaptive prestress to enforce area incompressibility. The method accurately reproduces experimental data from erythrocyte ektacytometry, but allows examination of the erythrocyte dynamics beyond the geometric constraints inherent in ektacytometry and other experimental techniques, including observation of the three-dimensional oscillatory behavior over a range of capillary numbers and viscosity ratios. Our results support a prediction by Fischer, Skalak, and coworkers that the erythrocyte shear modulus decreases at small shear deformations. Our work also suggests that cellular deformation is largely independent of the flow pattern, consistent with the findings of experimental investigators.Item Comparative genomic analysis of Vibrio cholerae O31: capsule, O-antigen, pathogenesis and genome(2006-11-21) Chen, Yuansha; Morris, J Glenn; Marine-Estuarine-Environmental Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Vibrio cholerae is the causative agent of cholera. In order to understand the genetic basis underlying the emergence of novel epidemic strains of V. cholerae, the genetics of surface polysaccharide biogenesis, and the role of lateral gene transfer in the evolution of this species, we investigated. NRT36S and A5 are both NAG-ST producing, cholera toxin negative, serogroup O31 V. cholerae. NRT36S is encapsulated and causes diarrhea when administered to volunteers; A5 is acapsular and does not colonize or cause illness in humans. The structure of the capsular (CPS) polysaccharide in NRT36S was determined by NMR. The gene cluster of CPS biogenesis was identified by transposon mutagenesis combined with whole genome sequencing data. The CPS gene cluster shared the same genetic locus as that of the O-antigen of lipopolysaccharide (LPS) biogenesis gene cluster. The LPS biogenesis regions in A5 were similar to NRT36S except that a 6.5 kb fragment in A5 replaced a 10 kb fragment in NRT36S in the middle of the LPS gene cluster. The genome of NRT36S was sequenced to a draft containing 174 contigs plus the superintegron region. Besides confirming the existence of NAG-ST, we also identified the genes for a type three secretion system (TTSS), a putative exotoxin, and two different RTX genes. Four pili systems were also identified. Therefore, the genome of non-O1 Vibrio cholerae NRT36S demonstrates the presence of pathogenic mechanisms that are distinct from O1 V. cholerae. We conclude that lateral gene transfer plays a critical role in the emergence of new strains. The co-location of CPS and LPS could provide a mechanism for simultaneous emergence of new O and K antigens in a single strain. Our data also highlights the apparent mobility within the CPS/LPS region that would provide a basis for the large number of observed V. cholerae serogroups and the emergence of novel epidemic strains.