Very happy this is finally published, it’s taken a while…..
I think this work really well describes the combination of technologies across a collaboration to do something really nice (and it looks kind of cool!)
A few of my notes on the content below:
High fidelity fibre-based physiological sensing deep in tissue
Scientific Reports, volume 9, Article number: 7713 (2019)
https://www.nature.com/articles/s41598-019-44077-7
https://doi.org/10.1038/s41598-019-44077-7
Lay summary / details
Scientists have created a miniaturised optical probe only a little larger than a human hair capable of measuring key indicators of health deep in the human lung.
The team from the University of Edinburgh, Heriot-Watt University, and the University of Bath have combined exquisite custom multicore optical fibres and novel chemical probes with bespoke optical systems to apply this sensing “optrode” bronchoscopically in whole lungs.
Collaborating as part of the EPSRC funded Proteus IRC, this work brings technologies from research labs one step closer to healthcare implementation.
The size of the sensor allows measurement deep in the distal lungs, the alveolar sacs where gas exchange occurs, critical for health and beyond the reach of standard technologies. Currently the sensing optrode measures oxygen and pH – key indicators of lung tissue health. However, the system is designed to expand to more measurement parameters in the same sized optrode – the sensors can be developed in the chemistry lab and easily combined with the fibre sensing platform.
Clinical need:
Tiny changes in the physiology of tissue in health and disease can have profound impacts on how cells, tissues and drugs function. pH and tissue oxygenation are widely recognised as two environmental parameters that critically regulate cellular physiology. These are largely uninvestigated parameters in situ as it has not previously been possible to perform these measurements. These new methods if taken to clinic, will lead to novel insights in disease biology.
Fibre optrode:
The optical fibre is only ~0.2mm in diameter, yet capable of holding 19 sensors on individual cores of the fibre. Each core is independent, like the many separate wires in an electrical cable, so can measure a different parameter.
The fluorescent sensors are made on 0.01 mm glass spheres, which then sit firmly in concave craters etched in the end of the fibre – self locating with the light guiding fibre cores.
For use in man, the fibre would need further packaging increasing the size, but still well below that of standard endoscopes.
Sensors:
The technology uses fluorescence sensors, which emit changing brightness and colours of light in response to acidity and oxygenation.
We report novel ratiometric sensors for high fidelity sensing that have demonstrated unprecedented and unexpected sensitivity, stability and near instantaneous response time. We also demonstrate a novel fluorescent phenomenon of a commonly used pH reporter – Fluorescein, configured to give an inverse relationship of fluorescent response to pH changes resulting in better sensitivity and resistance to photobleaching that normally limits this type of sensor.
Paper 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.
Wider context:
We are combining this sensing technology with fibre based imaging techniques
https://www.osapublishing.org/boe/abstract.cfm?uri=boe-10-4-1856
utilising fluorescent probes that identify bacteria
https://stm.sciencemag.org/content/10/464/eaal0033
to provide a multifunctional device to improve bedside diagnosis.
Tanner Lab 