Theses and Dissertations from UMD
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Item INTEGRATED MICROSYSTEM-BASED APPROACH FOR DETECTION AND TREATMENT OF BACTERIAL BIOFILMS ON URINARY CATHETERS(2020) Huiszoon, Ryan Cornelis; Ghodssi, Reza; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Biofilms are a ubiquitous mode of growth for bacteria and present a significant challenge in healthcare due to their resistant nature towards traditional antibiotic therapy. Particularly, biofilms can form on indwelling urinary catheters, leading to catheter-associated urinary tract infections, which are one of the most prevalent healthcare-acquired infections. In recent years, microsystems-based approaches have been developed to measure and study bacterial biofilms. In this dissertation, microsystems are adapted for the catheterized urinary tract environment to address biofilm infections in situ. Specifically, a proof-of-concept device comprised of gold interdigitated electrodes on a flexible polyimide substrate is fabricated and characterized in vitro. This substrate allows the device to conform seamlessly with the cylindrical surface of a catheter. Real-time impedance sensing is demonstrated, showing an average decrease in impedance of 30.3% following 24 hours of biofilm growth. The device also applies the bioelectric effect, which yields an increase in impedance of 12% and the lowest biomass relative to control treatments. Furthermore, 3D-printed molds and commercial modeling software show that the cylindrical conformation does not have an appreciable impact on performance. This device is integrated with a commercially available Foley catheter using two disparate approaches: (1) integration of the flexible proof-of-concept device using a 3D-printed catheter insert and (2) electroless plating directly onto the catheter lumen. In addition to electrode integration, miniaturized electronic systems are developed to control sensing and treatment wirelessly with a minimal form factor. A smartphone mobile application is developed in conjunction with this effort, to provide a user-friendly interface for the system. Several functions are verified with the integrated system, including biofilm sensing, wireless signal transmission, bladder drainage, and balloon inflation. To decrease the risk associated with this system for future research in vivo and in a clinical setting, sensing and treatment are evaluated under realistic conditions. The biochemical aspect of the catheterized environment is recreated using artificial urine, and the physical aspect is recreated using a silicone model of a human bladder and a programmable pump. A 13.0% decrease in impedance is associated with bacterial growth; this decreased magnitude relative to the proof-of-concept device is due to the reduced degree of growth in artificial urine. The bioelectric effect is demonstrated as well, showing a reduction in planktonic bacteria of 1.50×107 CFU/ml and adhered biomass equivalent to OD590nm = 0.072 relative to untreated samples. This work provides a framework for developing microsystem-based tools for biofilm infection management and research from proof-of-concept to integrated system, particularly for CAUTI. The results demonstrate that the cylindrical conformation does not interfere with device sensing or treatment performance and that the system maintains functionality under realistic conditions, laying the groundwork for future in vivo and clinical testing. The system will provide in situ and real-time data regarding catheter biofilm colonization in a way that is not possible with existing techniques. Finally, the system can serve to reduce reliance on antibiotics and reduce the spread of antibiotic resistance in CAUTI and other vulnerable areas.Item INTEGRATED THRESHOLD-ACTIVATED FEEDBACK MICROSYSTEM FOR REAL-TIME CHARACTERIZATION, SENSING AND TREATMENT OF BACTERIAL BIOFILMS(2016) Subramanian, Sowmya; Ghodssi, Reza; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Biofilms are the primary cause of clinical bacterial infections and are impervious to typical amounts of antibiotics, necessitating very high doses for treatment. Therefore, it is highly desirable to develop new alternate methods of treatment that can complement or replace existing approaches using significantly lower doses of antibiotics. Current standards for studying biofilms are based on end-point studies that are invasive and destroy the biofilm during characterization. This dissertation presents the development of a novel real-time sensing and treatment technology to aid in the non-invasive characterization, monitoring and treatment of bacterial biofilms. The technology is demonstrated through the use of a high-throughput bifurcation based microfluidic reactor that enables simulation of flow conditions similar to indwelling medical devices. The integrated microsystem developed in this work incorporates the advantages of previous in vitro platforms while attempting to overcome some of their limitations. Biofilm formation is extremely sensitive to various growth parameters that cause large variability in biofilms between repeated experiments. In this work we investigate the use of microfluidic bifurcations for the reduction in biofilm growth variance. The microfluidic flow cell designed here spatially sections a single biofilm into multiple channels using microfluidic flow bifurcation. Biofilms grown in the bifurcated device were evaluated and verified for reduced biofilm growth variance using standard techniques like confocal microscopy. This uniformity in biofilm growth allows for reliable comparison and evaluation of new treatments with integrated controls on a single device. Biofilm partitioning was demonstrated using the bifurcation device by exposing three of the four channels to various treatments. We studied a novel bacterial biofilm treatment independent of traditional antibiotics using only small molecule inhibitors of bacterial quorum sensing (analogs) in combination with low electric fields. Studies using the bifurcation-based microfluidic flow cell integrated with real-time transduction methods and macro-scale end-point testing of the combination treatment showed a significant decrease in biomass compared to the untreated controls and well-known treatments such as antibiotics. To understand the possible mechanism of action of electric field-based treatments, fundamental treatment efficacy studies focusing on the effect of the energy of the applied electrical signal were performed. It was shown that the total energy and not the type of the applied electrical signal affects the effectiveness of the treatment. The linear dependence of the treatment efficacy on the applied electrical energy was also demonstrated. The integrated bifurcation-based microfluidic platform is the first microsystem that enables biofilm growth with reduced variance, as well as continuous real-time threshold-activated feedback monitoring and treatment using low electric fields. The sensors detect biofilm growth by monitoring the change in impedance across the interdigitated electrodes. Using the measured impedance change and user inputs provided through a convenient and simple graphical interface, a custom-built MATLAB control module intelligently switches the system into and out of treatment mode. Using this self-governing microsystem, in situ biofilm treatment based on the principles of the bioelectric effect was demonstrated by exposing two of the channels of the integrated bifurcation device to low doses of antibiotics.Item AN INTEGRATED MICROSYSTEM FOR BACTERIAL BIOFILM DETECTION AND TREATMENT(2014) Kim, Young Wook; Ghodssi, Reza; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Bacterial biofilms cause severe infections in clinical fields and contamination problems in environmental facilities. Due to the unique complex structure of biofilms that comprise diverse polysaccharides and bacteria, traditional antibiotic therapies require a thousand times higher concentration compared to non-biofilm associated infections. The early detection of biofilms, before their structures are fully established in a given host/environment, is critical in order to eradicate them effectively. Also, the development of a new innovative biofilm treatment method that can be utilized with a low dose of antibiotic would be extremely important to the medical community. In this dissertation, a biofilm sensor and a new biofilm treatment method were independently developed to detect and treat biofilm communities, respectively. Furthermore, an integrated microsystem was demonstrated as a single platform of the sensor with the treatment method. The sensor was based on the surface acoustic wave (SAW) detection mechanism, which isn extremely sensitive for biofilm monitoring (hundreds of bacterial population detection limit) and consumes very low power (~100 µW). A piezoelectric ZnO layer fabricated by a pulsed laser deposition process was a key material to induce homogeneous acoustic waves. Reliable operation of the sensor was achieved using an Al2O3 film as a passivation layer over the sensor to protect ZnO degradation from the growth media. The sensor successfully demonstrated real-time monitoring of biofilm growth. The new biofilm treatment was developed based on the principles of the bioelectric effect that introduces an electric field along with antibiotics to biofilms, demonstrating significant biofilm inhibition compared to antibiotic treatment alone. Specifically, the new bioelectric effect was implemented with a superpositioned (SP) electric field of both alternating and direct current (AC and DC) and the antibiotic gentamicin (10 µg/mL). With the SP field treatment, significant biofilm reduction was demonstrated in total biomass (~ 71 %) as well as viable bacterial density (~ 400 times respected to the only antibiotic therapy) of the treated biofilms. This method was transferred to a microfluidic system using microfabricated planar electrodes. The microsystem-level implementation of the bioelectric effect also showed enhanced biofilm reduction (~ 140 % total biomass reduction improvement). The integrated system was based on the SAW sensor with the addition of coplanar thin electrodes to apply electric signals for the biofilm treatment. The chip was tested with two bacterial biofilms (Escherichia coli and Pseudomonas aeruginosa) that are clinically relevant strains. In both biofilm experiments, the integrated system demonstrated successful real-time biofilm monitoring and effective biofilm inhibition. This systematic integration of a continuous monitoring method with a novel effective treatment technique is expected to advance the state of the art in the field of managing clinical and environmental biofilms.Item An Optical Density Detection Platform with Integrated Microfluidics for In Situ Growth, Monitoring, and Treatment of Bacterial Biofilms(2012) Mosteller, Matthew Philip; Ghodssi, Reza; Systems Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Systems engineering strategies utilizing platform-based design methodologies are implemented to achieve the integration of biological and physical system components in a biomedical system. An application of this platform explored, in which an integrated microsystem is developed capable of the on-chip growth, monitoring, and treatment of bacterial biofilms for drug development and fundamental study applications. In this work, the developed systems engineering paradigm is utilized to develop a device system implementing linear array charge-coupled devices to enable real time, non-invasive, label-free monitoring of bacterial biofilms. A novel biofilm treatment method is demonstrated within the developed microsystem showing drastic increases in treatment efficacy by decreasing both bacterial biomass and cell viability within treated biofilms. Demonstration of this treatment at the microscale enables future applications of this method for the in vivo treatment of biofilm-associated infections.