Tooling with light: The art of seeing the "invisible"

Imaging technologies have been an integral part of all modern biomedical research, and major discoveries in biomedicine are made when novel imaging technologies constantly evolve to drive new hypothesis. The first observation of platelets, made by Max Schultze, used a 17th century optical microscope with a moist chamber to reveal individual granulates (particles) during the process of coagulation (formation of a blood clot). It was only until the use of immersion microscope objective by Bizzozero, an Italian microscopist, in 1881 that lead to discovery of the crucial role of platelets in the formation of hemostatic thrombus following a controlled injury to blood vessels.

Platelet's size (~2 μm), rapid activation (milliseconds), and unsuitability for genetic manipulation, means that appropriate imaging tools are limited. Hence, they are almost “invisible” until activated.  Hence, the innate mechanisms that control thrombus propagation, thrombus stability and embolism remains poorly quantified and understood.

Platelets are anucleate blood cells and thus have a relatively stable refractive index. In the first part of my talk, I shall first introduce the use of refractive index (RI) as reliable endogenous label imaging.  In the second part of my talk, I shall describe the high speed 4D RI imaging tools that quantifies individual platelet interactions with nanoscale and picogram precision in a developing thrombus under flow. We conclusively demonstrated that 4D RI imaging tools can capture membrane ruffling and protrusion events in single platelets at adhesion site and quantify mass changes. These crucial quantifications are required to unpack complex biochemical and bio-rheological properties of platelet aggregation. In the final part of the talk, I shall discuss our new combinatory approach (optical physics, 3D laser printing, computational biology, and microfluidic) to understand the biomechanical role of platelets in thrombus formation and embolisation.  

Bio:

Steve leads the ANU Optical Biofluidics Imaging Group (OBIG) that looks to developing optical tools to study 4D dynamics of biofluidic systems. He completed undergraduate training in Electronics Engineering at the Nanyang Technological University (Singapore) and a PhD in Optics at the University of St Andrews (UK) with Kishan Dholakia and Ewan Wright. From 2010-2012, his postdoctoral fellowship was on advanced bioimaging in mice models (NIH, NCI-PSOC) at Harvard Medical School (USA) with Seok-Hyun Andy Yun (NIH Director’s Pioneer Award), that is followed a short stint as Vice Chancellor Fellowship (UNSW). Prior to his PhD studies, he developed commercial laser instruments as a technology consultant with Einst Tech Pte Ltd for Agency for Science, Technology and Research (A*STAR).