A hair-sized probe that performs in vivo measurements of key physiological parameters can detect signs of tissue damage deep inside the lung. Developed by researchers at the Proteus consortium, the technology could pave the way for accurate monitoring of tissue in remote regions of the human body where existing devices cannot reach (Scientific Reports 10.1038/s41598-019-44077-7).
Lung diseases are one of the leading causes of death and disability. But little is known about how disease develops in patients suffering from pneumonia or lung injury, in part due to a lack of miniaturized clinically compatible technologies. The research team, from the University of Edinburgh, Heriot-Watt University and the University of Bath, aims to tackle this challenge by creating a created a flexible micro-endoscopic device that can sense pH and oxygen levels.
The probe consists of fluorescein-based pH sensors and oxygen sensors (based on a palladium porphyrin complex) attached to 10 µm-diameter silica microspheres. These spheres are loaded into pits etched into the far end of a 150 µm-diameter multicore optical fibre containing 19 germanium-doped cores. Each sphere aligns with an individual fibre core.
Fluorescence is excited by coupling 520 nm light into a single core at the other end of the fibre, from which the emission spectrum from the sensor is also measured. Each core thus acts as an independent measurement channel, enabling multiparametric sensing via specific illumination of different cores.
The team tested the miniaturized probe in solutions with different pH values and in water with varying concentrations of dissolved oxygen. They observed high measurement sensitivity, with accuracies of 0.02 pH units for the pH sensor and 0.6 mg/l for the oxygen sensor. The probe’s response to pH and oxygen environments was near-instantaneous (less than 1 s) when it was moved between liquids.
The researchers also tested the fibre probe in perfused and ventilated ex vivo sheep lungs. They passed the probe trans-bronchially into the distal alveolar sacs — where pH and oxygen play a critical role in maintaining homeostasis are potential disease biomarkers. They used the probe to measure changing pH and oxygen levels in the circulating perfusates, while simultaneously monitoring the perfusate using commercial meters.
Both the pH and oxygen sensors responded well to pH and oxygen changes in the lung, with pH and oxygen measurements correlating well with those of the commercial meters.
Having successfully demonstrated pH and oxygen sensing in ex vivo lung models, the team’s next step will be to validate the technology through clinical translation, which will require packaging of the probe in suitable biocompatible materials. They note that the multicore fibre provides a flexible platform technology that can be used in other regions of the body and with different sensors.
“These new methods, if taken to clinic, will lead to novel insights in disease biology,” says co-lead author Michael Tanner. “Our aim now is to expand the number of unique sensors on this miniaturized platform to provide even more information.”
