高分辨共振光隧穿无标记生物传感器

More than 85% of all cancers originate in the epithelium that lines the internal surfaces of organs throughout the body. The exploring of biosensor with ultra-high sensitivity and full-cell detection ability offers an effective way to detect carcinomas and make the clinical diagnosis of precancerous changes in epithelia. To meet the need above, the project proposes the biosensor based on resonant optical tunneling effect (ROTE), which expends the testing range up to micrometer level and achieves the full-cell investigation by measuring the refractive index change of medium in the microfluidic channel. The theoretical resolution of the sensor can be three to four orders higher than current cutting-edge methods. The project will study the mechanism of ROTE as an initial step, propose the optimized structural parameters of the sensor, fabricate the low refractive index thin film with high resolution of thickness and smooth surface, build the experimental setup around the multilayer sensing structure, design the cell screening and trapping structures based on microfluidics, present the offset method for the temperature noise, and characterize the performance of the sensor by analyzing the testing results. This project is expected to carry out the non-contact and real-time component analysis of carcinoma. It will provide the solid support for the investigation of carcinogenesis and related pathological and pharmacological study.

超过85%的癌症源自于人体器官内表面上皮细胞的病变。研究高分辨率、可进行全细胞检测的生物传感器，为解决上皮异质细胞检测及早期癌症诊断难题，提供了一条有效途径。针对上述需求，本项目提出共振光隧穿效应无标记生物传感器，通过检测微流管道内介质的折射率变化，将测试范围扩大至微米量级，实现全细胞检测；同时其理论分辨率比目前的分辨极限高三至四个数量级。本课题拟从共振光隧穿效应机理研究出发，优化传感器设计参数；研制厚度精确控制且表面光滑的低折射率薄膜；以多层隧穿敏感结构为核心，搭建实验测试平台；设计细胞筛选和捕获结构；研究折射率温度交叉敏感分离技术；通过积累和分析实验结果，表征传感器性能指标；实现对人体上皮异质细胞的非接触、实时高灵敏度检测，为揭示上皮细胞的癌化过程及相关病理、药理研究奠定基础。

对介质折射率敏感的光学检测方法，一直是新型生物传感器研究的热点。但是目前主流的光电子传感器，由于倏逝场的空间局域特性，只能测试样品表面的折射率变化，而不能检测如细胞等具有一定体积的生物样品。本项目研制了共振光隧穿效应的折射率计，通过检测微流管道内介质的折射率变化，将测试范围扩大至微米量级，实现了全细胞检测。本项目运用时域有限差分法和平面波展开法分析了共振光隧穿效应的物理机理，揭示了其谐振峰源于二元多层结构的本征模。通过其量子模型，直接获得的谐振峰峰值位置的解析表达式，为共振光隧穿结构的理解提供了一个全新的视角。开发了基于棱镜的薄膜旋涂组装工艺，以制备的多层隧穿敏感结构为核心，搭建了实验测试平台；利用PS小球溶液表征了传感器的各项性能指标，将传感器应用于高灵敏度肝癌细胞浓度检测，传感器的灵敏度可达2.53 nm/(amol/ml)，细胞浓度分辨率为1.2 × 105 cells/ml，达到世界一流水平。该传感器对生物医药检测，饮用水安全和环境保护领域具有巨大的潜在应用价值。