Abstract
Physiological sensing deep in tissue remains a clinical challenge. Here a flexible miniaturised sensing optrode providing a platform to perform minimally invasive in vivo in situ measurements is reported. Silica microspheres covalently coupled with a high density of ratiometrically configured fluorophores were deposited into etched pits on the distal end of a 150 µm diameter multicore optical fibre. With this platform, photonic measurements of pH and oxygen concentration with high precision in the distal alveolar space of the lung are reported. We demonstrated the phenomenon that high-density deposition of carboxyfluorescein covalently coupled to silica microspheres shows an inverse shift in fluorescence in response to varying pH. This platform delivered fast and accurate measurements (±0.02 pH units and ±0.6 mg/L of oxygen), near instantaneous response time and a flexible architecture for addition of multiple sensors.
Highlights
Alterations in the physiological environment in tissues can drastically impact biological processes
The platform consists of novel pH sensors and oxygen sensors[1] covalently attached to silica microspheres (10 μm diameter) loaded into pits etched into the distal facet of a 19 core (10 μm core diameter) multicore fibre
Following the pioneering work of Walt[2], fluorescent reporters covalently coupled to 10 μm amino modified silica microspheres were used as an optically robust solution to enable in vivo multiplexed pH and oxygen sensing
Summary
Alterations in the physiological environment in tissues can drastically impact biological processes. Despite the presumption of tightly regulated levels of key physiological parameters such as [H+] and oxygen, in many areas of the human body the environmental physiology is unknown due to the paucity of miniaturised clinically compatible technologies. The aim of this study was to develop a flexible microendoscopic optrode for the accurate, robust and multiplexed sensing of pH and oxygen, which could be passed into remote regions of the human body. We demonstrate in this study that the distal alveolar acinar gas exchanging units of the lung can be accessed, where pH and oxygen play a critical role in maintaining homeostasis and are potential biomarkers of pathological processes, clearly the platform technology is widely applicable to other regions. Fluorescence is excited through selective coupling of light to a single core at the proximal end of the fibre, from which the spectrum is measured, enabling multiplexing of sensors across the multi-core fibre
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