由表面声波驱动的生物样品制备和分析微系统

Biosensors and healthcare devices are types of devices which can detect various diseases and cancers in early stage, hence allow taking measures to prevent and cure them before macrosymptoms appear. Owing to its great importance in science and research,healthcare,drug development,biotechnology and future industry,governments around the world,especially the industrialized nations, have heavily invested in this area, hopefully to become the leading nation in the relevant technologies..Biosensors perform detection through reaction between the probe molecules (Biomarkers) and target molecules which are typically proteins and DNAs. In order to perform the detection,these biological entities must be extracted from the cells, a process called cell lyses.If the detection is based on DNA, then the DNA must be amplified to a certain quantity for analysis, a process called polymerase chain reaction (PCR). Current cell lyses are carried out by mechanical milling, ultrasonic destruction or chemical treatment in a large quantity, not suitable for modern micro-analysis. Furthermore the chemical treatment destroys cell's integrity, unable to be used for detection. These sample preparation processes are time-consuming,label intensive, high cost and potential for cross-contamination,.not suitable for on-time, in-field applications..We have been developing surface acoustic wave (SAW) microfluidics and sensors for a while, and found SAW devices can be used not only as microfluidics to pump/transport liquid, mixing and improve bioreaction, but also as sensors, remote microheater..Here we propose to develop SAW-based biological sample preparation microsystems with.integrated SAW-based cell lyses, filters and flow-through (FT-)PCR. High speed acoustic streaming is utilized to smash cells with built-in microstructures in the microchamber to extract cell contents for analysis, microposts integrated in the channel forms the filters to remove the skins of cells etc. SAW heaters combined with SAW pumps forms a FT-PCR system. All devices are within one system with functions of cell lyses, filtering and DNA amplification. As all devices are operated under the same surface acoustic wave principle, the biosystem is simple in manufacturing and operation,compact, no cross-contamination and fast. Once integrated with SAW or other biosensors, it will become a lab-on-a-chip with full function. Owing to its simplicity and multi-functions,it has great potential for widespread applications in healthcare, biological research, drug development and science. This.project will focus on cell lyses, filter and PCR, not integration with sensors due.to time limitation..SAW-based cell lyses,filtering and SAW FT-PCR are novel and new ideas, an investigation shows there is no relevant patent and publication. Support of this project by NSFC would allow China to develop the technology early and establish the.leadership in technology and industry.

高灵敏度生物传感器可用来检测和诊断各种早期疾病，流行病等，为早日介入.治疗和预防提供可靠的依据，它是一种具有很大应用前景的微纳器件。各国都在加大投入，.开发相关的技术以占据科技和产业的制高点。生物传感器的传感对象主要是细胞内的蛋白质.或 DNA 等，而这些物质被细胞膜所包围，不能直接用于检测。生物取样必须将细胞粉碎，取出细胞物质。本研究独创性的提出了基于表面声波（SAW）的微型细胞粉碎器和 DNA 倍放器 PCR，并将它们与申请人已有的 SAW 微流控技术集成，形成集成生物芯片。利用声波传输液体，由它所产生的声致微流的强大离心力使细胞与微结构碰撞而裂解；并利用声波作加热器、驱动器来倍放 DNA。由于各器件都由表面声波驱动，具有共用性，结构，工艺简单等众多优点，有广泛的应用前景。通过本项目开发出新型的细胞取样器件和 PCR，为下一步开法有自主知识产权的集成芯片大号基础。

高灵敏度生物检测系统可用来检测和诊断各种早期疾病，流行病等，是一种具有很大应用价值的微纳器件。生物检测由样品制备(细胞分离，细胞粉碎提取蛋白质或DNA液，DNA倍放)，微流输送，传感器检测等步续组成。微流控器件和生物传感器已有深入的研究，虽然生物样品制备是生物传感和分析必不可少的工艺，却不太受人关注。.本项目主要内容及目标是研制声表面波(SAW)的微型细胞分离，粉碎，SAW非接触式加热器和DNA倍放器（PCR）。通过研制这些SAW执行器以获得理论和实际的依据，为下一步将它们与SAW微流控器件集成，构成单一SAW原理的片上生物检测系统打下基础。SAW对液体中的不同大小的微粒有不同的作用力，可以将癌细胞与其他正常细胞分裂；而声致涡流所产生的强大离心力可以使细胞与微结构碰撞而裂解，来获得细胞的裂解液。利用声波作非接触式加热来开发微型PCR。因为此单一SAW原理的片上生物检测系统由各类表面声波驱动器构成，因此具有结构，工艺制造和控制电路简单等众多优点，应用前景广阔和良好。.通过研究，我们已成功地设计和制作了SAW细胞(微粒)分离器，可以将Hela Cells与其他微粒有效分离，获得了85%以上的分离效率。设计并制作了SAW细胞粉碎器，利用微流将细胞与微结构碰撞裂解细胞，获得了近100%的裂解效率，并由荧光电泳测试获得了确认。虽然没有展开SAW PCR的研究，但已确认SAW非接触式加热可行性，并获得了大于100C的温度，证明完全可以用SAW加热器来制作SAW PCR器件。在本研究期间，本团队还开发了几种极具独创性的器件和工艺：柔性SAW器件，透明SAW器件，任意基板上的FBAR(薄膜体声波谐振器)，基于生物材料的可降解忆阻器和透明摩擦发电机。并利用柔性SAW器件研制了柔性温度，湿度，紫外，应力，压力等传感器，及柔性SAW微流控器件和微粒集聚器，为下一步柔性SAW生物检测系统坚实的基础。