Bloodstream infections are among the most common hospital acquired infections in the United States. Time-consuming diagnosis and limited knowledge of the dynamics of bacterial infections in the bloodstream pose a significant problem for the effective treatment of bacteremia, leading to increased hospital stays, prolonged time to effective treatment, and patient mortality. For this reason, it is imperative that we develop novel strategies to study and rapidly diagnose bacterial bloodstream infections. The research presented herein focuses on using photoacoustic (PA) and photothermal (PT) methods to detect circulating bacteria cells (CBC) in the bloodstream. S. aureus is chosen as the primary model for this research as it was identified as a pathogen of immediate concern by the Infectious Disease Society of America and is commonly associated with bacteremia. PA and PT phenomena have been exploited to detect absorbing particles (such as nanoparticles attached to bacteria) whether on a slide (photothermal microscopy, PTM) or in flow (photoacoustic fluorescent flow cytometry, PAFFC) using various nanoparticles to study CBCs. Our custom PAFFC platform is able to detect a PA signal produced by the absorption of laser energy by the nanoparticle as labeled CBCs pass through a laser path, whether in vitro (capillary tube) or in vivo (blood vessel). This methodology could be vital for early diagnosis of bloodstream infections before they have time to develop into more severe diseases, such as sepsis. Proof-of-concept photoswitchable nanoparticles have been introduced and demonstrated for further development to enhance the detection and research methods. Further, in vitro and in vivo PAFFC methods were developed and improved, creating research tools to study bloodstream infections. Finally, gold nanocages that have been functionalized with antibodies that target protein A on the surface of S. aureus are used as a proof-of-concept platform to detect S. aureus in vivo via pulsed lasers utilizing the photoacoustic effect. This research holds the potential to revolutionize the way we approach bacterial infections both in the lab and in clinical settings.
|Advisor:||Zharov, Vladimir P.|
|Commitee:||Smeltzer, Mark S., Galanzha, Ekaterina I., Dings, Ruud P. M., Biris, Alexandru S.|
|School:||University of Arkansas for Medical Sciences|
|Department:||Interdisciplinary Biomedical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 81/5(E), Dissertation Abstracts International|
|Subjects:||Microbiology, Nanotechnology, Biophysics|
|Keywords:||Detection, Flow cytometry, Nanocage, Nanoparticle, Photoacoustic, S. aureus|
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