Dr WM (Steve) Lee, Senior Lecturer/ARC DECRA, ANU College of Engineering and Computer Science
Since Antonie Leeuwenhoek and Robert Hooke opened our eyes to an animated world of microbes using polished lenses, light microscopy has become an indispensable tool in life science. High resolution light microscopy presents the opportunity to capture processes while it is occurring. The ability to do conduct in vivo imaging in living samples presents opportunity to answer outstanding questions that are physiologically relevant. First, I shall describe how subtle distortions of light can be used to achieve volumetric imaging of single cells at high resolution. Using these techniques, it has become possible to conduct quantitative real-time deformability measurements of flowing and adhered cells. This presents a method to extract biomechanical properties of diseased cells (cancer cells, malaria infected RBC etc) within a microfluidic environment. As cells organized into tissues, these subtle distortions begin to randomize the properties of light and reduce imaging performance. Next, I shall describe how optical heterogeneity in thick biological tissues restrict light traveling in tissue and how light can be made to overcome these heterogeneity. This is followed by a short discussion on how new laser and optical techniques are engineered to delved deeper within the tissues of a living mouse, at a temporal and spatial resolution that is sufficient to pick out cellular behaviors and molecular signals underlying them. In particular we will touch on the next generation polygon laser scanning microscope systems engineered to deliver targeted dose of light for creating thrombosis or measuring molecular diffusions. While conventional laser scanning microscopes achieve good imaging resolution, field of view and acquisition speed. For large volume imaging, it is much slower and requires more light. In the last section, I shall introduce light sheet microscopy that has lifted the restrictions of conventional laser scanning microscope whilst maintaining high cellular imaging resolution with low photo -toxicity over an extended volume. Lastly, I shall introduce the next generation of light-sheet systems that can robustly optimizes imaging performance during large-scale morphogenetic changes in living organisms.
W M (Steve) Lee completed his undergraduate training in Engineering at the Nanyang Technological University (Singapore) and a PhD in Optics at Optical Trapping Group at the University of St Andrews (UK) with Prof Kishan Dholakia. During his PhD, he built a multimodality bioworkstation for biological cells and nanoparticles. In 2010, he left the UK to pursue a 2-year postdoctoral training at Wellman Photomedicine/Harvard Medical School (USA) with Prof S H Andy Yun, where he developed adaptive intravital endomicroscopy for live small animal imaging. That is followed by a short stint as a Vice Chancellor Fellow at UNSW on nanowire optical manipulation. In mid-2013, he started his own research group (Applied Optics Lab) at ANU Research School of Engineering where he is focused on developing novel optical techniques and instruments that harnesses light for application in biomedicine and nanotechnology. He co-shared the 2014 ANSTO Eureka Prize for developing low cost elastomer optics. In 2015, he receives an ARC Discovery Early Career Research Award (DECRA). He is currently developing the next generation of 3D intravital microscopy for in-vivo imaging with the ARC Centre of Excellence for Advanced Molecular Imaging.