Flow cytometry is routinely used as a high-throughput method for characterising and screening cells in biology and medicine. This ranges from identification of suitable drug treatments for patients diagnosed with cancer to biophysical studies of cells with rare (1 in a million) structures or protein expression profiles.
Recently, researchers in the Molecular and Nanoscale Physics Group in Leeds have developed a device that can apply extreme shear to cells. This shear causes cells to deform within a microfluidic platform (or flow cytometer), which can be used as a diagnostic device for identifying tumours in patient cells [1]. Furthermore, this application of high shear stresses has been shown to lead to formation of pores within cells, which can be used for effective delivery of drugs and small molecules. Our understanding of the cell response is limited by the difficulty in imaging cellular structures during the shearing process. Currently, there is no methodology capable of fluorescence microscopy studies within this device, due to the high-speed imaging required to capture biophysical behaviour at such high shear rates.
You will use and optimise a novel high-speed fluorescence light-sheet microscope, within the new Wolfson Imaging Facility at the Bragg Centre for Materials Research in Leeds, to enable high-speed fluorescence imaging flow cytometry. The aim will be to facilitate 200,000 fps imaging of 100,000 cells/minute flowing at speeds up to 1 m/s, which will require careful optimisation of optics, fluorescent labelling and development of novel control systems and analysis tools. This interdisciplinary work spans multiple research areas including: optical engineering, computational work (novel analysis tools) and biophysics (understanding the behaviour of cellular structures under high shear). This offers flexibility in terms of tailoring the research direction to your interests.
This project will take place in the Molecular and Nanoscale Physics Group within the School of Physics and Astronomy, under joint supervision with Prof. Steven Evans and Dr. Kevin Critchley as well as collaborators in the Schools of Engineering, Biology and Medicine. Candidates should have a background in physics, engineering, chemistry or a closely related field and a keen interest in method development.