Optimization of spatiotemporal-modulated electric fields and fabrication of organs-on-chips for applications in Medical Physics

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My research program centres around using physics to create biologically driven medical applications and address unanswered biomedical questions. Here, I will tackle two key challenges for which my background and recent directions are ideally suited. My first objective involves using physics to create computer simulations of mild but rapidly changing electric fields emitted from electrodes which are intended to be implanted in brain tumours. It turns out that such electric fields interfere with cell division, and they can stop the growth of brain tumours. We will determine the best electrode design, number and spacing that will work for most brain tumours or residual tumours after surgery. We will also develop a computer algorithm to automatically optimize the best stimulation parameters to maximize the extent of the electric fields emanating from the electrodes to cover each individual's tumour target size and shape. Results of this work will be passed to my collaborators for experimental confirmation in cell cultures and animals. My second objective relates to the development and application of "organs-on-chips". There are limitations to experiments done in cell cultures and in lab animals (e.g. mice). Unlike cell cultures, small animals have organs and blood supplies, but the cells studied are not of human origin. While we can culture human cells in Petri dishes or wells with supporting biological materials, they are in a static environment. Our lab has recently adopted lab-on-a-chip microfluidic device techniques to culture human cells in a dynamic environment with "blood" flow. Under the right mixture of cells and conditions, organ-like tissues will form. Specifically, I will enhance the fabrication of lung-on-a-chip and blood brain barrier-on-a-chip. I will then apply them to study cellular and organ level responses triggered by external radiation or electric field stimulations. Such applications have not been done before, and the proposed experiments will provide us with a new way to observe behaviours of cells in organs, and enhance our basic understanding of normal tissue response to these external stimulations. The computer optimization software is a critical physics contribution to my interdisciplinary research team, allowing the team to design better pre-clinical experiments and ask relevant questions. Together, we are continuing to build on this emerging research area, opening doors in the field of medical physics. The organs-on-chips will allow us to examine the process of organ response to radiation and electric field with cells from the human origin. Our enhancements to the lung and blood brain barrier-on-a-chip will make them more efficient to fabricate and more representative to the tissues in our bodies. This will benefit researchers interested in other types of external stimuli, including agents that may affect Canadians' quality of life.