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

我的研究计划围绕着使用物理学创造生物驱动的医学应用，并解决悬而未决的生物医学问题。在这里，我将解决两个关键挑战，我的背景和最近的方向非常适合这两个挑战。 我的第一个目标是利用物理学对植入脑瘤的电极发射的温和但快速变化的电场进行计算机模拟。事实证明，这种电场干扰了细胞分裂，可以阻止脑瘤的生长。我们将确定对大多数脑肿瘤或手术后残留肿瘤有效的最佳电极设计、数量和间距。我们还将开发一种计算机算法来自动优化最佳刺激参数，以最大限度地扩大电极发出的电场范围，以覆盖每个人肿瘤目标的大小和形状。这项工作的结果将传递给我的合作者，以便在细胞培养和动物实验中得到确认。 我的第二个目标是关于“芯片器官”的发展和应用。在细胞培养和实验室动物(例如小鼠)中进行的实验是有局限性的。与细胞培养不同，小动物有器官和血液供应，但研究的细胞不是人类来源的。虽然我们可以在带有支持生物材料的培养皿或井中培养人类细胞，但它们处于静态环境中。我们的实验室最近采用了芯片上实验室微流控设备技术，在动态的血液流动环境中培养人类细胞。在适当的细胞和条件混合下，就会形成器官样组织。 具体地说，我将加强芯片上肺和血脑屏障芯片的制造。然后，我将应用它们来研究由外部辐射或电场刺激引发的细胞和器官水平的反应。这样的应用以前从未做过，拟议的实验将为我们提供一种新的方式来观察器官中细胞的行为，并增强我们对正常组织对这些外部刺激的反应的基本了解。 计算机优化软件是对我的跨学科研究团队的关键物理贡献，使团队能够设计更好的临床前实验并提出相关问题。我们共同努力，继续推进这一新兴研究领域的发展，为医学物理学领域打开大门。芯片上的器官将使我们能够用人类起源的细胞来检查器官对辐射和电场的反应过程。我们对单芯片肺和血脑屏障的增强将使它们的制造效率更高，对我们体内的组织更具代表性。这将使对其他类型的外部刺激感兴趣的研究人员受益，包括可能影响加拿大人生活质量的制剂。

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.