微腔增强的光纤免疫传感技术与应用研究

Optical fiber provides a compact, label-free sensing platform, with the capability of in-vivo detection, but its sensitivity is limited by its weak evanescent field outside. Here we propose a novel sensing technique to use a spherical microcavity directly coupled to a side polished fiber, which not only has the capability of in-vivo sensing, but also possesses greatly enhanced sensitivity provided by the cavity resonance. The physical mechanism of this sensing technique relies on measuring changes in both the mode linewidth and intensity of the reflected light from the fiber, induced by the backscattering of the biomolecules to the probe light. In experiment, we will measure the reflection spectrum of the fiber, from which both the mode linewidth and intensity can be obtained. Furthermore, the Raman spectra of the biomolecules will also be measured, which can further specifically recognize the biomolecules. We propose to demonstrate this cavity enhanced fiber probe sensor in two steps. First, using the linewidth broadening, light intensity and Raman spectrum as the sensing signals, we will detect single circulating tumor cell (CTC), which has great biomedical significance. Second, by utilizing plasmonic enhancement provided by metal nanoparticles, we will further perform label-free, high-sensitivity, and high-specificity detection of cancer testis antigens (CTAs). We believe this cavity enhanced fiber probe sensing technique has great potential in early-stage diagnosis and rapid relapse examination of some major diseases like lung cancer.

光纤提供了一种无需标记、结构紧凑且易于在体检测的生物传感手段，在科学研究和临床应用中都展现了极大潜力，但灵敏度受限于较弱的倏逝场。本项目提出利用回音壁光学微腔来增强光纤倏逝场，从而显著提高了光纤免疫传感的灵敏度。通过微球腔与侧面抛磨光纤直接耦合的结构，该传感方法既保留了光纤传感易于在体检测的优势，又具有超高的灵敏度。为了进一步降低噪声，我们利用待测抗原（或者携带抗原的待测粒子）与抗体特异性结合时的散射效应，通过反射谱强度和特征模式线宽的测量获得痕量生物信息；同时，反射谱中的拉曼信号可用来进一步甄别抗原或待测粒子，提高了检测的可靠性。应用方面，我们将使用该光纤探针检测具有重大临床意义的循环肿瘤细胞，达到单细胞水平；进一步结合表面等离激元局域场增强效应，实现超高灵敏度和无标记的肿瘤睾丸抗原传感，并初步探索在体检测。一旦突破，该免疫传感技术将有望成为肺癌等重大恶性肿瘤早期筛查的一种全新光学方法。

光纤提供了一种无需标记、结构紧凑且易于在体检测的生物传感手段，在科学研究和临床应用中都展现了极大潜力，但灵敏度受限于较弱的倏逝场。本项目利用回音壁光学微腔来增强光纤倏逝场，从而显著提高了光纤免疫传感的灵敏度，并保留了光纤传感易于在体检测的优势。该免疫传感技术将有望成为肺癌等重大恶性肿瘤早期筛查的一种全新光学方法。经过5年的努力，本项目完成了主要研究目标，并取得一系列创新性研究成果，发表受基金标注的研究论文42篇，其中包括国际著名期刊Science 1篇，Nature Photonics 1篇，PNAS 1篇，Physical Review Letters 4篇，Advanced Materials 3篇，Light 1篇，Physical Review系列10余篇等。主要成果如下：..(A)发展了基于微腔与微纳光纤的无标记光学传感，并利用微纳光纤以及密集型波导实现了纳米尺度单颗粒传感。(B)建立了微纳光场线性传感的理论框架，发展了模式展宽、耗散型相互作用等传感新方法。(C)实现了超低浓度生物分子的无标记检测，并利用光学微腔和金纳米颗粒的“双增强”达到了单分子级别的响应。(D)将微腔传感检测拓展到非线性相互作用，提出并证明了基于微腔拉曼激光、二次谐波等非线性光学过程的微腔传感新原理。..系列研究涵盖了微腔增强光学传感的多种机制，在微纳传感国际学术界产生了良好的影响力。成果被Phys.org和Materials Views等多家国际科技媒体专题图文报道。