INTEGRATED MICROSYSTEM-BASED APPROACH FOR DETECTION AND TREATMENT OF BACTERIAL BIOFILMS ON URINARY CATHETERS

Abstract

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.