微流控芯片集成的管内固相微萃取与高效液相色谱联用装置的研究及应用

We propose to develop a novel microchip device that integrates in-tube solid-phase microextraction and high performance liquid chromatography (IT-SPME-HPLC) in a single chip, and achieves on-line coupling IT-SPME and μ-HPLC to increase both separation performance and detection sensitivity. The microchip-based IT-SPME-HPLC can perform sample loading, concentration, separation and detection on-chip, which restrains band broadening resulted from the intrinsic large dead volumes in the interfaces while off-chip sample loading is applied. A four "T"-shaped connecting and meandering extraction channel is designed, and freeze/thaw valves are used for controlling flow paths. These innovative improvement designs could eliminate the inherent systematic error existing wildly in automated in-tube solid-phase microextraction by using an autosampler coupled with HPLC. Functional nanomaterials with high specific surface area are applied to immobilize in extraction channels to improve the extraction capacity. Microchip-based electroosmotic pumps as a driving force of mobile phases to carry out the HPLC separation. The above novel device fulfills the miniaturization and integration of the IT-SPME-HPLC system. The study of this technology will have important significance for environmental analysis, food analysis, and pharmaceutical analysis.

本项目提出构建一种新颖的微流控芯片管内固相微萃取-高效液相色谱（IT-SPME-HPLC）装置，将管内固相微萃取和高效液相色谱技术集成到单个芯片上，实现IT-SPME和μ-HPLC的在线联用，提高分离效率和检测灵敏度。芯片IT-SPME-HPLC将实现在片的试样引入、富集、分离和检测，消除了离片进样时由于外界接口的死体积所导致色谱峰谱带加宽的现象；通过设计4"T"型接口的蜿蜒状微萃取通道，结合冻融阀来控制流路，用以消除目前广泛使用的自动化管内固相微萃取与商业液相色谱仪联用技术中存在的固有的系统误差；通过在微萃取通道内固载高比表面积的纳米功能材料，提高萃取容量；采用芯片电渗泵作为μ-HPLC流动相的驱动力，实现IT-SPME-HPLC系统的微型化和集成化。此技术的研究对于环境检测、食品分析和药物分析具有重要的意义。

本项目设计和制备了4“T”型的阵列微萃取通道，结合冻融阀控制流路，构建了微流控芯片管内固相微萃取-高效液相色谱（IT-SPME-HPLC）系统，避免了样品和流动相、解析溶剂和流动相等各流路的相互污染问题，用以消除目前广泛使用的自动化管内固相微萃取与液相色谱联用技术中存在的固有的系统误差，以提高分析的准确度。4“T”型接口的设计是为了清洗掉由于样品与流动相接触混合而导致的残留积累；用4“T”型接口和冻融阀结合替代传统IT-SPME-HPLC中的六通阀，实现流路的切换，由于冻融阀是非介入式阀，它可以实现对流路进行无损、无痕、无残留的控制，避免了六通阀中样品残留的问题。将所构建的芯片IT-SPME-HPLC系统成功应用于磷酸肽的萃取富集和分析。.已发表标注基金资助SCI论文15篇，其中影响因子大于10.0的3篇；另有1篇论文刚被录用。已获授权发明专利4项，其中1项美国发明专利。