INTEGRATED THRESHOLD-ACTIVATED FEEDBACK MICROSYSTEM FOR REAL-TIME CHARACTERIZATION, SENSING AND TREATMENT OF BACTERIAL BIOFILMS

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.

Sonic Movie Memories: Sound, Childhood, and American Cinema

Though the trend rarely receives attention, since the 1970s many American filmmakers have been taking sound and music tropes from children’s films, television shows, and other forms of media and incorporating those sounds into films intended for adult audiences. Initially, these references might seem like regressive attempts at targeting some nostalgic desire to relive childhood. However, this dissertation asserts that these children’s sounds are instead designed to reconnect audience members with the multi-faceted fantasies and coping mechanisms that once, through children’s media, helped these audience members manage life’s anxieties. Because sound is the sense that Western audiences most associate with emotion and memory, it offers audiences immediate connection with these barely conscious longings. The first chapter turns to children’s media itself and analyzes Disney’s 1950s forays into television. The chapter argues that by selectively repurposing the gentlest sonic devices from the studio’s films, television shows like Disneyland created the studio’s signature sentimental “Disney sound.” As a result, a generation of baby boomers like Steven Spielberg comes of age and longs to recreate that comforting sound world. The second chapter thus focuses on Spielberg, who incorporates Disney music in films like Close Encounters of the Third Kind (1977). Rather than recreate Disney’s sound world, Spielberg uses this music as a springboard into a new realm I refer to as “sublime refuge” - an acoustic haven that combines overpowering sublimity and soothing comfort into one fantastical experience. The second half of the dissertation pivots into more experimental children’s cartoons like Gerald McBoing-Boing (1951) - cartoons that embrace audio-visual dissonance in ways that soothe even as they create tension through a phenomenon I call “comfortable discord.” In the final chapter, director Wes Anderson reveals that these sonic tensions have just as much appeal to adults. In films like The Royal Tenenbaums (2001), Anderson demonstrates that comfortable discord can simultaneously provide a balm for anxiety and create an open-ended space that makes empathetic connections between characters possible. The dissertation closes with a call to rethink nostalgia, not as a romanticization of the past, but rather as a reconnection with forgotten affective channels.