Design of a novel photonic biosensor based on whispering-gallery modes of dielectric microspheres for high-throughput immunoassays

我们的目标是利用一种简单、通用和高灵敏度的光学方法来开发新一代无标记生物传感器。在过去的十年中，无标记光学生物传感器已经成为临床和军事应用以及药物发现的宝贵工具。它们是一系列应用的重要设备，从检测感染性物质、毒素、蛋白质和DNA到研究整个细胞的行为(例如，动物细胞在固体表面的附着、扩散和增殖)，再到定量确定分子之间的结合亲和力和相互作用动力学。现代无标记光学生物传感器，如广泛使用的表面等离子体共振(SPR)方法，是基于沿平面传播的逝去光场，探测沉积在表面上的目标材料。利用介质微球的窄线宽光子共振，即所谓的回音廊模式(WGMS)，可以实现一种更灵敏的基于逝去场耦合的生物传感器类型，即场被限制在靠近球的内表面，并通过全内反射绕球传播。在离开谐振器之前，光可以绕轨道运行数千次，在消失的光场和目标分子之间产生有效的相互作用长度，比分子沉积的球面上的物理长度长许多个数量级(它的SPR类似于一个超过一米长的平面芯片！)。这种方法应该表现出前所未有的敏感性，但要充分探索可能的应用范围，还缺乏一个合适的理论模型。我们最近已经开始了基于抗体-抗原相互作用的WGM生物传感器原型的构建和实验研究，其中许多涂有不同抗体的微球可以通过它们与靠近衬底表面的平面波导模的逝去耦合来并行寻址。通过本项目，我们希望开发一个理论模型来评估这种光学生物传感器不仅对蛋白质而且对病毒和细菌的灵敏检测的适用性。通过将这一严谨的理论研究与正在进行的实验相结合，我们的目标是实现高通量免疫分析的最佳无标记生物传感器的设计。

Our goal is to develop a new generation of label-free biosensor using a simple, versatile, and highly sensitive optical method. During the last decade, label-free optical biosensors have become valuable tools for clinical and military use as well as drug discovery. They are important devices for a range of applications going from detection of infectious agents, toxins, proteins and DNA to investigation of whole cell behaviour (e.g. attachment, spreading and proliferation of animal cells on solid surfaces), to quantitative determination of binding affinities and interactions kinetics between molecules. Modern label-free optical biosensors, like the widely utilised surface plasmon resonance (SPR) method, are based on an evanescent light field travelling along a planar surface, probing the target material deposited on the surface. A more sensitive type of biosensor based on evanescent field coupling can be realized by exploiting narrow-linewidth photonic resonances of dielectric microspheres, the so called whispering-gallery modes (WGMs), where the field is confined close to the inner surface of the sphere and is travelling around the sphere via total internal reflection. The light can orbit many thousand times before escaping the resonator, giving rise to an effective interaction length between the evanescent light field and the target molecules many orders of magnitude longer than the physical length on the sphere surface where molecules are deposited (its SPR analogous would correspond to a planar chip of more than one meter length!). This method should show unprecedented sensitivity but to fully explore the range of possible applications a proper theoretical model is still missing. We have recently commenced the construction and experimental study of a prototype WGM biosensor for immunosensing based on antibody-antigen interaction where many microspheres coated with different antibodies can be addressed in parallel via their evanescent coupling to planar waveguide modes propagating near a substrate surface. With the present project we want to develop a theoretical modelling to assess the applicability of this optical biosensor toward sensitive detection not only of proteins but also of viruses and bacteria. By combining this rigorous theoretical study with the experiments already ongoing we aim to realize the design of an optimum label-free biosensor for high-throughput immunoassays.