Integrated optical sensors and nano-structures for biomedical diagnosis applications

本研究的重点是开发新型的高性能无标记的光学折射率传感器的基础上光子晶体板（PCS）的纳米结构，将提高传感检测限，并应用纳米结构表面的光学成像的纳米光谱的分子和评估分子相互作用在一个封闭的体积。在过去的十年中，纳米结构已经被证明是非常有用的生物传感技术，如荧光，折射率的变化，拉曼光谱和等离子体效应。然而，它们的广泛应用受到重复性、检测限和对外部环境波动（如温度、振动、液体处理）的高灵敏度的挑战的限制。在这个提案中，我们寻求1）增加传感检测限与新的PCS设计和自参考技术; 2）开发成像架构在PCS生物传感器并行研究许多分子的相互作用。在我们的设计中，我们将专注于无标记技术，其中分子与表面或分子相互作用的结合导致局部质量浓度和折射率变化，这些变化可以通过图像中的光谱偏移或强度变化来检测。我们将探索新的器件物理机会，打破结构和角度对称性，并引入混合金属/电介质结构，用于在传感表面附近（< 100 nm）进行场重塑，并使用光学成像技术并行评估许多分子询问。拟议的计划伴随着我们与生物化学家的合作努力，并寻求在纳米光子学和生物检测的基础和应用研究方面取得突破，并将我们的发现转化为实用的生物传感器方案。在过去的几年里，我们的团队已经掌握了开发新的生物传感器设计的技能，并在我们过去的工作和与多伦多当地医院和斯坦福大学的密切合作的基础上，我们已经准备好了使这项提案取得成功的一切。我们相信，提高检测限和稳定性（降低环境对测量的影响）将大大增加生物传感器的使用和性能的生物分子检测与标记剂。该项目的成功将对广泛的受众产生重大影响-从寻求实时研究生理过程的细胞生物学家到寻求快速，无标记，便携式检测的诊断医生。最终用户应用的例子包括低成本、敏感和环境稳定的血液和尿液诊断测试，快速评估病毒感染，以及在有限体积内研究分子相互作用，从而允许对疾病的许多药物靶标进行平行评估。加拿大患者将有机会获得准确、敏感和负担得起的诊断工具，这些工具不仅可以在大型医院使用，而且可以在许多当地诊所使用。此外，拟议的研究将蓬勃发展，从学员之间的跨学科互动，我们的实验室成员和合作与其他实验室在多伦多大学和加拿大。

This research focuses on developing novel high performance label-free optical index of refraction sensors based on Photonic Crystal Slab (PCS) nanostructures that will improve the sensing detection limit, and apply optical imaging of nano-structured surfaces for nano-spectroscopy of molecules and evaluating molecular interactions within a confined volume. Nanostructures have proven to be extremely useful for biosensing in the past decade using techniques such as Fluorescence, Index of refraction changes, Raman spectroscopy and Plasmonic effects. Nevertheless, their broad use is limited by challenges in repeatability, their detection limit and their high sensitivity to external environment fluctuations (such as temperature, vibrations, liquid handling). In this proposal we seek to 1) increase sensing detection limit with new PCS designs and self-referencing techniques; 2) develop imaging architectures in PCS biosensors to investigate many molecular interactions in parallel. In our designs, we will focus on label-free techniques where binding of a molecule to a surface or molecular interactions result in localized mass concentration and index of refraction changes that can be detected through spectral shifts or intensity changes in an image. We will explore new device physics opportunities in breaking structural and angular symmetry and introducing hybrid metal/dielectric structures for field re-shaping in close proximity (< 100 nm) of the sensing surfaces as well as evaluate many molecular interrogations in parallel, using optical imaging techniques. The proposed program is accompanied by our collaboration efforts with bio-chemists and seeks to accomplish breakthroughs in both fundamental and applied research in nano-photonics and bio-detection and translate our findings to practical bio-sensor schemes. In the past years, our group has acquired skills in developing new biosensors designs and building on our past work and strong collaborations with Toronto local hospitals and Stanford University we have everything in place to bring this proposal to success. We believe that improved detection limit and stability (reduced environmental effect on measurements) will greatly increase the use and performances of biosensors for bio-molecule detection with and without labeling agents. The success of this project will have significant impacts on a broad audience – from cell biologists seeking to study physiological processes in real-time, to diagnosticians searching for rapid, label-free, portable assays. Example end-user applications include low cost, sensitive and environmentally stable blood and urine diagnostic tests, evaluating viral infections quickly and studying molecular interactions within a confined volume that allows parallel evaluation of many drug targets for a disease. Canadian patients will have access to accurate, sensitive and affordable diagnostic tools that can be used in many local clinics and not only in large hospital settings. Furthermore, the research proposed will thrive from cross-disciplinary interaction between the trainees, members of our lab and collaborations with other labs at the University of Toronto and in Canada.