基于等离子体Fano共振结构的LSPR-SERS集成传感技术应用基础研究

Ovarian cancer is the most lethal malignant tumor in female reproductive system. Early detection is very difficult for ovarian cancer. Tumor biomarkers are extremely important in detection of early stage ovarian cancer, but the common detection methods usually lack in throughput, sensitivity or specificity because tumor biomarkers usually vary in kinds, and exist in low concentration in complex human body fluid environment. In this study, creatively, LSPR-SERS integrated sensing sensitivity and specificity is augmented by use of Fano resonance structure for its quality of narrow spectrum and strong electromagnetic field locality. Also, microfluid multi-channel technology incorporated LSPR-SERS union sensor based on plasmonic Fano resonance structure is positive to realize rapid detection and high throughput of biosensor devices. Based on previous nano-structure triangle LSPR biosensor, this study plans to design plasma Fano resonance structure with high-quality factor and highly amplified local electric field, analyze the rules of its electromagnetic response, study LSPR-SERS integration methods，optimize the mechanism of biomolecule fixation and signal amplification, construct multi-channel LSPR-SERS integration sensing prototype and exam the quality of detection, thus create a new idea for early detection, relapse forecast and follow-up of ovarian cancer, and provide a theoretical and experimental proof for its practice in clinic disease union detection.

卵巢癌死亡率位居女性生殖器恶性肿瘤第一位，早期诊断尤为困难。肿瘤标志物在其早期诊断中具有重要地位。但肿瘤标记物种类繁多浓度极低，且人体内体液环境复杂，常用检测手段难以满足高通量、高敏感、高特异性检测需求。本研究创新性地提出利用等离子体Fano共振结构的窄线谱和强电磁局域特性实现SERS和LSPR的集成，以提高传感的灵敏度和特异性。同时将微流体多通道技术引入该新型传感器，有望实现生物传感仪器的高通量、快速检测。本项目拟在前期三角形纳米结构LSPR传感技术研究基础上，设计高品质因子、高局域场增强的等离子体Fano共振结构，分析其电磁响应规律，研究LPSR-SERS集成方法，优化生物分子固定法并探索信号放大机理，搭建多通道LSPR-SERS集成传感样机并探讨各项检测性能，为卵巢癌恶性肿瘤的早期诊断、预测复发及随访提供一种新思路，同时也为其应用于临床疾病的联合检测提供理论基础及实验依据。

卵巢癌死亡率位居女性生殖器恶性肿瘤第一位，早期诊断尤为困难。肿瘤标志物在其早期诊断中具有重要地位。但肿瘤标记物种类繁多浓度极低，且人体内体液环境复杂，常用检测手段难以满足高通量、高敏感、高特异性检测需求，且存在传统方法存在放射性污染、步骤繁琐和检测时间长等缺点。纳米生物传感器在疾病诊断中已初步展现了其巨大的应用前景，局域表面等离子体共振（LSPR）已成为生物医学领域的研究热点，基于LSPR的生物传感器结合了纳米技术和光散射特性，有望克服传统检测方法的诸多不足，实现高速且便捷的检测。本项目构建了基于LSPR的多通道实验传感系统，实现了卵巢癌及同期对照患者术前外周血标本中的多种肿瘤标志物（外泌体miR-200b系列、HE4和OPN等）的高通量平行检测，并与传统检测方法ELISA和实时定量PCR比较，客观地评价了生物传感器对临床样本的检测性能，评估了其用于卵巢癌筛检的临床应用前景、操作可行性及技术优势。本项目为基于LSPR的纳米传感技术应用于临床肿瘤标志物检测提供了理论基础和实验依据，为实现卵巢癌患者的早期诊断、复发检测及随访提供了一种新的检测手段。