基于声表面波微流驱动与传感一体化PSA生物芯片机制的研究

Prostate cancer is nowadays one of biggest risk on man health. There is a great demand on a novel PSA sensor which is portable, low cost and fast response. SAW biosensors possess the advantage of fast, accurate detection of an analyte without the use of labels, and thus show a great potentiality of disease diagnostics, monitoring and theranostics. However, most SAW biosensors suffer from the issue of non-specific binding. It degrades the sensitivity and reliability of the sensors, and moreover can lead to detection failure when they are used for actual body fluidic samples. In this project, a preferred orientation (1120) ZnO film will be investigated in terms of its growth mechanism and fabrication. Further, a structure consisting of two orthogonal delay lines based on (1120) ZnO film multi-layered structure will be designed in order to generate two distinct SAW modes. One propagating orthogonal to c-axis with shear horizontal polarization is used for bio-sensing while the other along c-axis as Rayleigh mode is used to actuate liquid sample streaming which not only can accelerate the specific binding but also can remove the loosely bound non-specific proteins. Therefore, the technology can improve the sensitivity, detect limit and reliability and realize the real time detection of actual body fluidic samples. It has great scientific significance for SAW biosensors in point of care applications.

前列腺癌是威胁男性健康的常见肿瘤之一，迫切需要研究新型、便携、快速的PSA检测技术。声表面波（SAW）生物传感器能够在无需标记物的情况下，实时、快速和精确地实现对待测物质的检测，在疾病预防、监控与治疗等方面有着巨大的应用潜力。但是大部分SAW生物传感器在实际应用中存在非特异性蛋白分子结合干扰问题，不但直接影响到传感器的灵敏度和可靠性，甚至无法直接对体液样品进行检测。本项目针对具有（1120）择优取向的ZnO生长机理和工艺开展研究，并基于这种薄膜的相互垂直双延迟线结构开展研究：垂直c轴方向的Love波模式用于液相环境的传感；而在c轴方向则激励Rayleigh波模式来产生微流，不但加快待测物质的吸附，而且对液体样品中由非特异性蛋白与敏感膜产生的吸附进行冲洗，从而提高传感器的灵敏度，检测下限和可靠性，并使得这种结构的传感器能应用于直接对血清，尿液等体液样品的现场快速检测。

本课题旨在研究基于压电薄膜ZnO的新型生物声表面波（SAW）传感器，解决提高传感器灵敏度，稳定性、检测下限的这一科学问题，通过项目的实施，验证了一种基于（1120）晶相的ZnO薄膜可以在正交方向分别激发出Rayleigh波与Love波模式，通过利用Rayleigh波模式对微腔道中的液体样品产生微流，可以有效地对抗体与抗原的结合过程进行调控，从而改善了Love波模式下的生物传感器的检测过程。通过对该项目中的结构进行理论建模和优化，得到了出了具有最优性能的声表面波传感器器件参数，并通过结合微流控技术和抗体-抗原-抗体纳米金的三明治结构明显提升了质量灵敏度和检测下限，通过实验验证，SAW生物传感器的质量灵敏度>10kHz/ng，检测极限达10-10mM，芯片对 PSA检测的结果与 ELISA检测的 结果比较接近，表明实验室制作SAW生物传感器在血清样品中能够实现 PSA可靠检测。研究成果对SAWB的小型化、灵敏度、可靠性、低成本和检测下限体现出了新的优势。对新型的ZnO压电薄膜材料和双声表面波模式的结构开展研究具有较重要的科学意义和广阔的应用前景，对开发新型现场实时检测SAW生物传感器提供关键的技术支撑。