Theses and Dissertations from UMD
Permanent URI for this communityhttp://hdl.handle.net/1903/2
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
More information is available at Theses and Dissertations at University of Maryland Libraries.
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Item Lab-on-CMOS Sensors and Real-time Imaging for Biological Cell Monitoring(2019) Senevirathna, Bathiya; Abshire, Pamela; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Monitoring biological cell growth and viability is essential for in vivo biomedical diagnosis and therapy, and in vitro studies of pharmaceutical efficacy and material toxicity. Conventional monitoring techniques involve the use of dyes and markers that can potentially introduce side effects into the cell culture and often function as end-point assays. This eliminates the opportunity to track fast changes and to determine temporal correlation between measurements. Particularly in drug screening applications, high-temporal resolution cell viability data could inform decisions on drug application protocols that could lead to better treatment outcomes. This work presents development of a lab-on-chip (LoC) sensor for real-time monitoring of biological cell viability and proliferation, to provide a comprehensive picture of the changes cells undergo during their lifecycle. The LoC sensor consists of a complementary metal-oxide-semiconductor (CMOS) chip that measures the cell-to-substrate coupling of adherent cells that are cultured directly on top. This technique is non-invasive, does not require biochemical labeling, and allows for automated and unsupervised cell monitoring. The CMOS capacitance sensor was designed to addresses the ubiquitous challenges of sensitivity, noise coupling, and dynamic range that affect existing sensors. The design includes on-chip digitization, serial data output, and programmable control logic in order to facilitate packaging requirements for biological experiments. Only a microcontroller is required for readout, making it suitable for applications outside the traditional laboratory setting. An imaging platform was developed to provide time-lapse images of the sensor surface, which allowed for concurrent visual and capacitance observation of the cells. Results showed the ability of the LoC sensor to detect single cell binding events and changes in cell morphology. The sensor was used in in vitro experiments to monitor chemotherapeutic agent potency on drug-resistant and drug-sensitive cancer cell lines. Concentrations higher than 5 μM elicited cytotoxic effects on both cell lines, while a dose of 1 μM allowed discrimination of the two cell types. The system demonstrates the use of real-time capacitance measurements as a proof-of-concept tool that has potential to hasten the drug development process.Item Lab-on-a-Chip Integration of Size-based Separation Techniques for Isolation of Bacteria from Blood(2018) Han, Jung Yeon; DeVoe, Don L; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Clinical sample preparation is an essential process in modern diagnostics for maximizing sensitivity and specificity of detection and for ensuring reliability of assay readout. In general, sample preparation typically involves isolating and concentrating a population of target molecules, cells, or particles together with the removal of undesired components from specimen that could otherwise interfere with target detection. The identification of bacteria from complex clinical matrices such as blood presents a particular sample preparation challenge. Conventional culture-based methods typically require at least 24 h of incubation time, making this approach unsuitable for use in rapid diagnostics. Therefore, the development of sample preparation methods for bacteria with rapid processing time, high purification efficiency, and large volumetric throughput to enable analysis of low bacteria concentrations in blood remains a key challenge. This dissertation is focused on realizing a universal platform for preparing microbial sample from blood that is free lysis buffer, electric field, or affinity-based capture methods. First, we developed the porous silica monolith elements integrated into thermoplastic devices for isolation of intact bacteria from blood, enabling the application of emerging detection methods that supports bacterial identification from purified cell populations. Second, to support high throughput analysis of blood samples procured in resource-limited environments, microfluidics elements integrated directly into a syringe are demonstrated by utilizing the deterministic lateral displacement technique and the Dean flow focusing methods. Through these approaches blood cell reduction prior to bacteria isolation can be achieved, thereby increasing the overall sample volume that may be processed by the system. Additionally, a miniaturized hydrocylone capable of operating at tens of milliliters per minute feed rate is presented. Complex microstructures successfully realized at a hundred-micron scale by 3D printing technique presented a promising route to the unconventional microfluidic systems. Lastly, we demonstrated ancillary microfluidic components required to enable full operation of the system in a low-cost lab-on-a-chip format suitable for implementation in resource-limited environments and optimize overall operation of the platform to achieve throughput, sensitivity, and selectivity suitable for clinical application when coupling the platform with downstream detection methods designed for assay readout from intact bacteria.Item Thermoplastic microfluidic technologies for portable and disposable bioanalytical and diagnostic platforms(2015) Rahmanian, Omid David; DeVoe, Don L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Portable and cost-effective medical diagnostic technologies that require minimal external infrastructure for their operation are highly desirable for on-field military operations, defense against acts of bioterrorism, and infectious disease screening in resource-limited environments. Miniaturized Total Analysis Systems (µTAS) have the potential to fulfill this un-met need via low-cost, portable, and disposable point-of-care (POC) diagnostic devices. Inherent advantages of µTAS systems can be utilized to transform diagnostic technologies that currently require significant investment in centralized laboratories and highly trained personnel into automated, integrated, and miniaturized platforms. This dissertation addresses the development of microfabrication techniques and resulting component technologies that are realized in low-cost thermoplastic substrates. A thermoplastic microfabrication technique termed orogenic microfabrication, based on a non-reversible solvent-assisted swelling mechanism, is developed to provide unique capabilities for microscale and nanoscale patterning in rigid thermoplastics with minimal infrastructure. Orogenic microfabrication is compatible with multiple masking techniques including photolithography, chemical surface modification, contact and noncontact spotting, and inkjet deposition techniques, with each masking method offering unique influence on resulting orogenic structures that can be applied to microfluidic and µTAS systems. Direct ink masking is further explored as a low-cost rapid prototyping tool for fabrication of simple microfluidic devices where channel formation and bonding are combined into a single step, resulting in fully enclosed microfluidic channels within 30 minutes. Chemical surface passivation by UV-ozone treatment is utilized in combination with orogenic swelling and thermocompression bonding to develop single-use burst valves with tunable burst pressures. In addition to assisting in on-chip fluid manipulation, the normally closed burst valves enable on-chip reagent packaging and hermetic sealing of bioactive material in lyophilized format, and can be used for delivery of stored reagents for a range of disposable point-of-care assays. On-chip integrated micropumps are also developed, using simple fabrication process compatible with conventional thermoplastic fabrication techniques such as direct micromilling or injection molding. Direct displacement of liquid reagents using screw-assisted pumping can be operated either automatically or manually, with on-demand delivery of liquid reagents in a wide range of flow rates typically used in microfluidic applications. Collectively, the technologies developed in this dissertation may be applied to the future development of simple, disposable, and portable diagnostic devices that have the potential to be operated without off-chip instrumentation. On-chip storage of buffers and reagents in either dry or liquid format, and on-demand delivery of liquid reagents is packaged in a miniaturized, portable, and automated platform that can be operated in resource-constrained settings by practitioners with minimal expertise.