集成微流道的微谐振梁生物传感器及其在肿瘤标志物检测中的应用

The liquid damping effect can significantly reduce the resonant frequency and quality factor of micro-beam resonator in solution, which would lower the detecting sensitivity for in situ bio-chemical detection. An effective solution is to imbed the micro-fluidic channel in the resonant micro-beam. As a result, the micro-beam biosensor can resonate at high frequency and quality factor when the solution with biomolecules is flowing in the microfluidic channel. In this project, we carry out a systematic investigation on integrated microfluidic micro-beam biosensor, which includes: structural design and processing; microfluidic biological functionalization; actuation/detection methods; packaging and integration; frequency characterization and mechanism of energy dissipation. Main problem to solve: design and micro-fabrication of integrated microfluidic micro-beam biosensors; surface and fluidic induced energy dissipation mechanism; the simultaneous in-situ detection of several tumor markers in serum by using multiple array of micro-beam resonators. The project is a pioneering interdisciplinary research, and the research results will contribute much to the theoretical and technical field of MEMS-based biosensor.

环境流体阻尼能大幅减小微谐振梁在溶液中的谐振频率和品质因子，是当前制约微谐振梁生物传感器在溶液中原位检测时获得高检测灵敏度的瓶颈问题。一种有效的解决方法是将待测溶液从微谐振梁内部的微流道通过，这样能保证微谐振梁生物传感器既可以原位检测溶液中生化分子，又具有高谐振频率、高品质因子和高检测灵敏度。本项目以集成微流道的微谐振梁生物传感器为研究对象，研究其结构设计与制作、微流道生物功能化、激励/检测方法、封装与集成、频谱特性表征以及能量耗散的机制。重点解决：集成微流道的微谐振梁生物传感器的设计与批量制作、生物功能化表面及流体引起的能量耗散机制、阵列结构同时原位检测多种肿瘤标志物。本项目属于新兴的前沿交叉学科研究，在微机电系统生物传感器应用基础研究方面有一定的开创性，研究成果将为我国微机电系统生物传感器领域奠定理论和技术基础。

本项目研究了微纳谐振梁传感器的制作工艺及其对生化分子的检测性能，取得了一些重要结果。首先，我们通过理论计算设计并优化了微纳谐振梁的结构尺寸，并分析了其检测灵敏度。其次，研究了微纳谐振梁的微加工工艺，制定了器件的微加工工艺流程，并对其进行了生物功能化修饰。最后，用所制得的器件对肿瘤标志物(如AFP)进行了探测，实验表明双端梁对肿瘤标志物具有很高的检测灵敏度。