In healthy humans, the physiological state in the distal lung alveolar acinar units is tightly regulated by normal homeostatic mechanisms. Pulmonary abnormalities such as chronic obstructive pulmonary disease, that are characterized by recurrent cycles of inflammation and infection involving dense infiltration by myeloid derived peripheral blood cells, may result in significant perturbation of the homeostatic baselines of physiology in addition to host tissue damage. Therefore, the ability to quantify and monitor physiology (e.g. pH, glucose level, oxygen tension) within the alveolar acinar units would provide a key biomarker of distal lung innate defence. Although in vitro modeling of fundamental biological processes show remarkable sensitivity to physiological aberrations, little is known about the physiological state of the distal lung due to the inability to concurrently access the alveolar sacs and perform real-time sensing. Here we report on previously unobtainable measurements of alveolar pH using a fiber-optic optrode and surface enhanced Raman spectroscopy (SERS) and show that alveolar pH changes in response to ventilation. The endoscope-deployable optrode consisted of para-mercaptobenzoic acid functionalized 150 nm gold nanoshells located at the distal end, and an asymmetric dual-core optical fiber designed for spatially separated optical pump delivery and SERS signal collection in order to circumvent the unwanted Raman signal originating from the fiber itself. We demonstrate a ~ 100-fold increase in SERS signal-to-fiber background ratio and pH sensing at multiple sites in the respiratory acinar units of a whole ex vivo ovine lung model with a measurement accuracy of ± 0.07 pH units.
Debaditya Choudhury, Michael G. Tanner, Sarah McAughtrie, Fei Yu, Bethany Mills, Tushar R. Choudhary, Sohan Seth, Thomas Craven, James M. Stone, Ioulia K. Mati, Colin J. Campbell, Mark Bradley, Christopher K.I. Williams, Kevin Dhaliwal, Timothy A. Birks, and Robert R. Thomson, "Endoscopic sensing of pH in the distal lung (Conference Presentation)," Proc. SPIE 10041, Optical Techniques in Pulmonary Medicine II, 100410B (Presented at SPIE BiOS: January 28, 2017; Published: 19 April 2017); https://doi.org/10.1117/12.2251925.5369908509001.
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