1. Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope
- Author
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Tom Quinn, Annya Bruce, Alicia Megia-Fernandez, Emma Scholefield, Sheelagh Duncan, Gareth O. S. Williams, Jonathan Knight, Tim A. Birks, Michael G. Tanner, James M. Stone, Ahsan R. Akram, Nikola Krstajić, Muhammed Ucuncu, Christopher Haslett, Harry A. C. Wood, Mark Bradley, Kerrianne Harrington, Adam Marshall, Tushar R. Choudhary, Helen E. Parker, Bethany Mills, Kevin Dhaliwal, Irene Young, and Dominic Norberg
- Subjects
0301 basic medicine ,Staphylococcus aureus ,Fluorescence-lifetime imaging microscopy ,Optical fiber ,Endoscope ,Gram-positive bacteria ,Gram-Positive Bacteria ,01 natural sciences ,Optical imaging ,Fluorescence ,law.invention ,010309 optics ,Gram-positive ,03 medical and health sciences ,law ,0103 physical sciences ,Endomicroscopy ,Humans ,Radiology, Nuclear Medicine and imaging ,Optical endomicroscopy ,Lung ,Optical Fibers ,Endoscopes ,Bacteria ,biology ,Chemistry ,General Medicine ,biology.organism_classification ,Imaging agent ,030104 developmental biology ,Original Article ,Molecular imaging ,Ex vivo ,Biomedical engineering - Abstract
Purpose The relentless rise in antimicrobial resistance is a major societal challenge and requires, as part of its solution, a better understanding of bacterial colonization and infection. To facilitate this, we developed a highly efficient no-wash red optical molecular imaging agent that enables the rapid, selective, and specific visualization of Gram-positive bacteria through a bespoke optical fiber–based delivery/imaging endoscopic device. Methods We rationally designed a no-wash, red, Gram-positive-specific molecular imaging agent (Merocy-Van) based on vancomycin and an environmental merocyanine dye. We demonstrated the specificity and utility of the imaging agent in escalating in vitro and ex vivo whole human lung models (n = 3), utilizing a bespoke fiber–based delivery and imaging device, coupled to a wide-field, two-color endomicroscopy system. Results The imaging agent (Merocy-Van) was specific to Gram-positive bacteria and enabled no-wash imaging of S. aureus within the alveolar space of whole ex vivo human lungs within 60 s of delivery into the field-of-view, using the novel imaging/delivery endomicroscopy device. Conclusion This platform enables the rapid and specific detection of Gram-positive bacteria in the human lung.
- Published
- 2020
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