Integrated optical sensors and nano-structures for biomedical diagnosis applications

本研究的重点是开发基于光子晶体板（PCS）纳米结构的新型高性能无标签折射率传感器，以提高传感检测极限，并将纳米结构表面的光学成像应用于分子的纳米光谱学和评估分子在有限体积内的相互作用。在过去的十年中，纳米结构已经被证明对生物传感非常有用，如荧光、折射率变化、拉曼光谱和等离子体效应。然而，它们的广泛使用受到重复性、检测极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。在本提案中，我们寻求1)通过新的PCS设计和自参考技术提高传感检测极限；2)开发PCS生物传感器成像架构，并行研究多种分子相互作用。在我们的设计中，我们将专注于无标签技术，其中分子与表面的结合或分子相互作用会导致局部质量浓度和折射率的变化，这些变化可以通过图像中的光谱位移或强度变化来检测。我们将探索新的器件物理机会，打破结构和角对称，并引入混合金属/介电结构，以便在传感表面的近距离（< 100 nm）处进行场重塑，以及使用光学成像技术并行评估许多分子疑问。该计划将与生物化学家合作，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际的生物传感器方案。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紧密合作的基础上，我们已经做好了一切准备，使这一提议取得成功。我们相信，提高检测限和稳定性（减少环境对测量的影响）将大大增加生物传感器在有或没有标记剂的生物分子检测中的使用和性能。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，到寻找快速、无标签、便携式检测方法的诊断医生。示例终端用户应用包括低成本、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，从而可以对一种疾病的许多药物靶点进行并行评估。加拿大病人将有机会获得准确、敏感和负担得起的诊断工具，这些工具可以在许多地方诊所使用，而不仅仅是在大型医院环境中使用。此外，该研究将在学员、我们实验室成员之间的跨学科互动以及与多伦多大学和加拿大其他实验室的合作中茁壮成长。

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.