CAREER: Optical Sensing and Imaging of Bacterial Infection to Improve Global Health

1254767（Maitland）基于细胞培养的细菌病原体检测和定量方法仍然是金标准。然而，根据病原体的不同，这种方法可能需要一天到一个月的时间才能形成菌落，并且具有很高的可变性和有限的灵敏度。用于全动物成像系统的转基因荧光细菌的发展使细菌感染的更快速量化和治疗剂和疫苗的实时评估成为可能。然而，荧光细菌的检测和宿主动物感染区域的分辨受到组织吸收和散射的限制，特别是在动物内部深处，例如在肺结核病例的肺部。因此，需要更多的细菌；然而，高剂量感染在生理上是不正常的。本文提出的研究将建立在我们的初步工作基础上，即开发基于光纤的技术，通过将一种新型弥漫性纤维激发源更接近肺部病原体，从而提高全动物成像的灵敏度，并使用一种创新的小型化纤维显微内窥镜，实现肺内高分辨率成像与全动物成像共同记录。利用基于扩散器的探针进行激发，利用集成纤维进行荧光收集，以前所未有的水平检测荧光细菌。该光纤传感器将利用最近开发的近红外报告酶荧光探针，该探针有可能用于敏感、实时检测人类结核病。

1254767(Maitland) 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.