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、高灵敏度的光学方法开发新一代无标签生物传感器。在过去的十年中，无标签光学生物传感器已经成为临床和军事用途以及药物发现的宝贵工具。它们是一系列应用的重要设备，从检测传染性病原体、毒素、蛋白质和DNA到研究整个细胞行为（例如动物细胞在固体表面的附着、扩散和增殖），再到定量测定分子之间的结合亲和力和相互作用动力学。现代无标签光学生物传感器，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倏逝光场，探测沉积在表面的目标材料。通过利用介电微球的窄线宽光子共振，即所谓的低语廊模式（WGMs），可以实现一种基于倏逝场耦合的更灵敏的生物传感器，在这种模式下，场被限制在靠近球体内表面的地方，并通过全内反射绕球体传播。光在逃离谐振器之前可以绕轨道运行数千次，使消失的光场与目标分子之间的有效相互作用长度比分子沉积的球体表面的物理长度长许多个数量级（其SPR类似于一米多长的平面芯片！）。这种方法应该显示出前所未有的灵敏度，但要充分探索可能的应用范围，仍然缺乏适当的理论模型。我们最近开始了基于抗体-抗原相互作用的免疫传感原型WGM生物传感器的构建和实验研究，其中许多涂有不同抗体的微球可以通过它们与在衬底表面附近传播的平面波导模式的倏变耦合并行寻址。在目前的项目中，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敏感检测的适用性。通过将这一严格的理论研究与已经进行的实验相结合，我们的目标是实现高通量免疫测定的最佳无标签生物传感器的设计。

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.