基于光学量子弱测量的表面等离子体共振生物分子传感方法研究

The optical quantum weak measurement occurs when the interaction between light and matter is weak and by choosing appropriate observable and measuring pointer, an abnormal amplified measurement result can be achieved combining approximately orthogonal pre- and post-selections. As a new measurement theory, weak measurements have become one of the international research hotspots since it can amplify tiny signals hundreds of times from technical noises, thus improving sensitivity. Weak measurements can achieve results more than two orders of magnitude higher than the classical methods in detecting the phase of light. Surface plasmon resonance (SPR) is a highly sensitive, label-free biomolecular dynamic sensing technology. However, compared with the state-detecting (concentration-detecting) methods, such as ELISA, PCR, SPR’s resolution is still insufficient. This project intends to combine the quantum weak measurements with SPR techniques to study the ultrahigh-sensitivity biosensing method. This project will focus on the research of the theoretical sensing model based on the weak measurement and SPR and use the weak value amplification principle to demodulate the SPR phase, in order to obtain a biomolecular sensor inheriting higher detection capability. At the same time, a multi-channel weak measurement SPR sensing system is proposed to eliminate the interference caused by non-specific adsorption thus improving system robustness.

光学量子弱测量利用光与物质微弱作用时，选择适当的可观测量与测量指针，结合近似正交的前后选择态，可以得到异常放大的测量结果。作为一种新的测量理论，弱测量可以将微小信号从技术噪声中放大数百倍，提高测量灵敏度，已成为国际研究热点之一。在检测光的相位方面可以得到比经典方法高出2个量级以上的结果。表面等离子共振(SPR)是一种高灵敏的非标记生物分子动态传感技术，但与检测状态（浓度）的ELISA、PCR等方法相比，SPR检测分辨率仍然不足。本项目拟结合量子弱测量与表面等离子共振(SPR)技术，研究超高灵敏度的生物分子传感方法。本项目将重点研究基于弱测量SPR传感理论模型，利用弱值放大原理对SPR的相位进行解调，以期获得更高检测能力的生物分子传感方法。同时，研制多通道的弱测量SPR传感系统，排除非特异性吸附带来的干扰，提高系统鲁棒性。

近年来食品卫生安全、药物筛查等生物检测领域快速发展，其中光学检测技术凭借无损、非标记、高灵敏等特点在其中扮演者重要的角色，其核心在于利用光学手段对生物分子相互作用进行检测。针对于界面上生物分子相互作用时微弱信号的采集，关键在于尽可能多获取信号的同时降低其他测量噪声。光学弱测量方法基于新的测量原理，将原本的测量仪器也当做量子态进行处理，同时选择合适的可观测量与前后选择态，将原本的直接测量转换成与测量仪器指针结合的间接测量。利用其特有的放大机制，可以用相对简单的光路设计对原本微弱的信号进行放大测量。本项目提出了基于弱测量表面等离子共振的生物分子传感理论模型，搭建了检测光路并进行了参数优化。研制了同轴光路的弱测量传感系统原型机及关键技术模块。通过表面场增强的方法使提高了信号强度，同时在弱测量近似正交的前后选择态后，使得一些技术噪声比信号得到更好的抑制。最后开展相关生物应用研究，验证了所提出的模型与原型系统的有效性。