Rapid, compact, and cost effective phonon endoscopy using time-stretching

The measurement of ultrafast phenomena such as phonon, electronic, and optical dynamics allows us to probe nature at largely unexplored time and length scales. Technologies that can access these regimes, e.g. time-resolved pump-probe spectroscopy, improve understanding of our universe and its underlying physics, but have not yet been exploited for addressing real-world challenges particularly in clinical healthcare. A range of biological processes play out on ultrashort and ultrafast scales, for example: changes in fluorescence lifetime on the nanosecond scale due to changes in cell chemistry, or the mechanical straining of subcellular structures due to the presence of nanosecond period acoustic waves. Techniques that are sensitive to the latter reveal mechanical material properties of biological cells and tissue, and these play a crucial role in the progression of a range of cancers as they progress from single cells to complex metastatic tumours (often characterised as “stiff”). Minimally invasively characterising disease at the single-cellular scale is a major global challenge, that if solved would enable clinicians to fundamentally understand and diagnose disease at its earliest stages. Current state-of-the-art technologies for studying mechanical properties of microscopic systems are expensive, low resolution (elastography), and/or cumbersome requiring large clinically-incompatible infrastructure (atomic force microscopy). Optical pump-probe technologies, such as Brillouin spectroscopy, also access these material properties yet have a key differentiator: they are endoscopically viable for future in-body diagnostics. However, similarly, these technologies are currently prohibitively expensive (~£500k), cumbersome (10m2), and slow (seconds per measurement). In this New Investigator Award, I will engineer an optical pump-probe technology that is cheaper (£50k), portable (fits on a trolley), endoscopically deployable, and fast (hundreds to thousands of measurements per second). Typical pump-probe systems require multiple metre-long laser cavities and take seconds to record signals due to long laser synchronisation and signal averaging times. To improve these by several orders of magnitude, my time-stretched phononic spectroscopy technology will leverage several engineering breakthroughs that up until recently have not been possible: Miniature (pocketbook-sized) ultrafast fibre lasers. A new optical sensing paradigm, “time-stretching”, which trades extremely fast temporal information for modest changes in the light’s spectrum. Highly dispersive optical systems (e.g. fibre optic-based) that stretch light in time and colour. High dynamic range sensor arrays for astronomy and NIR spectroscopy that detect faint changes in light intensity from large background signals. Advancements in fibre optic imaging probes that enable needle- or endoscope-based microscopy. I will marry these technologies to engineer a new endoscopically viable pump-probe device that brings microscopic tissue-mechanical information to clinicians for the first time while remaining practical, cheap, small, and fast. Time-stretched phononic spectroscopy will redefine state-of-the-art for pump-probe spectroscopy and therefore will find applications in the study of electronic and thermal physics. However, this breakthrough will finally unlock applications of ultrafast pump-probe spectroscopy to the clinical and life sciences. For instance, we will investigate the ultrafast responses of single- and multi-cellular tissue in cancer biology, whole organism analytics, and plant sciences.