Changing the game
The ability to capture highly dynamic biomedical processes in real-time inside the human body would be a game changer for biomedical imaging. One approach that stands out is multiphoton lightsheet lensless microscopy, but this method is currently limited by slow scanning speed.
In collaboration with DTU Health Tech, and the Faculty of Health and Medical Sciences at KU we will develop a novel device that will improve the imaging speed by more than 100 times. This new integrated device will allow minimally invasive imaging of fast biological processes that have not so far been visualized in living organisms.
Obtaining insights of fast neurological processes in a large network has the potential to change neuroscience. Hu and his team propose a novel microscopy technique: integrated optical phased array-based multi-photon lightsheet fluorescence microscopy, which has the potential to improve the imaging speed by more than two orders of magnitude. It has the promising potential to revolutionize current biological studies and diagnostic methodology.
Demand
Optical imaging is an important tool for biologists and doctors to understand fundamental biology and diagnose disease. The emerging approach, multiphoton lightsheet fluorescence microscopy (LSFM), can capture images with subcellular resolution in real-time in a minimally invasive manner and generate images comparable to histopathology without the need to cut in tissue. Recently, lensless microscopy has been proposed to adapt LSFM to an optical fiber platform as an important step towards clinical translation.
Lensless microscopy employs wavefront shaping to replace lenses at the distal end of the fiber leading to improved miniaturization. In order to correctly shape and steer the beam at the distal end of the fiber, the wavefront shaping must compensate for the so-called transmission matrix, which describes how the wavefront changes as it propagates through the fiber. The transmission matrix is highly variable as the fiber conformation changes, so the transmission through the fiber must be actively monitored and compensated for imaging in real-world applications. Ultimately, wavefront shaping for lensless and lightsheet microscopy is inherently limited by the slow refresh rate of spatial light modulators and camera-based wavefront sensors.
New approach
Hu and his team propose a new approach of beam shaping for lensless imaging and LSFM based on a novel integrated silicon-nitride optical phased array. Replacing current wavefront shaping techniques with an optical phased array has the potential to improve the imaging speed of light sheet microscopy by more than 100 times.
In combination with compressive sensing-based wavefront monitoring, all speed bottlenecks for multiphoton lightsheet lensless microscopy will be removed. The final implementation of the technology will enable a new suite of biological studies and diagnostic methods based on minimally-invasive fast volumetric scanning.