基于表面等离激元微胶囊的单细胞代谢物分析检测新技术研究

Tumor heterogeneity is an important reason for the complexity and diversity of cancer, and has become a hot and difficult point in the field of cancer research. The overcome of tumor heterogeneity research requires high throughput, high sensitivity and accurate single cell analysis. In this project, a novel method based on surface plasmon microcapsule was proposed for direct single cell signal obtaining, in situ enhancement and high-throughput detection, which could solve the problems of low throughput, low sensitivity and target single. A new high throughput detection platform for single cell metabolites was established by combining the droplet-based microchip with the SERS spectrum. The developed new single cell analysis technology will be applied for the analysis of tumor cells, in order to find new phenomenon of tumor heterogeneity, provide new means and theoretical basis for diagnosis, treatment and drug research.

肿瘤异质是癌症复杂性和多样性的重要原因，已成为癌症研究领域的热点和难点。肿瘤异质性研究的攻克需要高通量、高灵敏、准确的单细胞分析技术。申请项目拟发展一种微纳尺度下获取单细胞微弱信号的新方式，构建新型的单细胞SERS检测基底——纳米表面等离激元微胶囊，以解决单细胞分析中取样困难、样品易稀释污染、采样不全等问题。通过对纳米材料的表面修饰，实现单细胞代谢物信号的直接获取、原位增强和直接检测。进一步将液滴微流控与SERS检测相联用，利用微胶囊电磁增强实现单细胞无标记、高灵敏检测的同时构建高通量的单细胞代谢物检测平台。实现对肿瘤异质性规律的研究，为疾病标志物发现、药物研发提供新的研究手段和理论依据。

本项目成功构建了可对单细胞进行封装和操控的纳米表面等离激元微胶囊，并用于了单细胞代谢物的表面增强拉曼检测，取得较好的检测效果。该单细胞封装技术与基质辅助激光解析质谱相联用，成果用于单细胞的质谱检测。构建的拉曼检测方法还能用于束羁状态下细胞的分泌物检测。为肿瘤异质性规律的研究、疾病标志物的发现和药物研发提供新的研究手段。