CAREER: Optical Sensing and Imaging of Bacterial Infection to Improve Global Health
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Cell culture based methods for the detection and quantification of bacterial pathogens remain the gold standard. However, depending on the pathogen, this method can take anywhere from one day to one month to form colonies and can have high variability and limited sensitivity. The development of genetically-modified fluorescent bacteria for use in whole-animal imaging systems has enabled more rapid quantification of bacterial infection and real-time evaluation of therapeutic agents and vaccines. However, detection of fluorescent bacteria and resolution of regions of infection inside a host animal is limited due to tissue absorption and scattering, especially deep inside the animal, such as in the lungs in the case of tuberculosis. Consequently, a greater number of bacteria are required; however, high dose infections are not physiologically normal. The research proposed here will build on our preliminary work to develop optical fiber based technology to increase sensitivity in whole-animal imaging by bringing a novel diffusing fiber excitation source closer to the pathogen in the lungs, enable high resolution imaging in vivo in the lung co-registered with whole-animal imaging using an innovative miniaturized fiber microendoscope, and sense fluorescent bacteria at unprecedented levels using a diffuser-based probe for excitation with integrated fibers for fluorescence collection. The fiber sensor will be developed to exploit the recent development of a near infrared reporter enzyme fluorescence probe that has potential to be used for sensitive, real-time detection of tuberculosis in humans.