Film Bulk Acoustic Resonator-based Ultra-Sensitive Biosensor Array Using Low Cost Piezoelectric Polymer as the Active Material

生物传感器是一种微型装置，能够通过特定的生物结合或化学吸收来测量非常小的生物分子或化学物质浓度。生物传感器在诊断、打击恐怖主义和预防流行病传播方面非常有用。通过检测相关分子，如DNA和抗体抗原，它们在癌症和遗传疾病的早期诊断中非常有希望。这种生物传感器的广泛应用将导致快速和准确的诊断，从而防止不必要的死亡，挽救成千上万的生命。在关键公共场所部署生物传感器，可以及时发现疾病或生物物质，防止疾病或生化附着的传播。高质量的生物传感器必须非常灵敏，易于使用，低成本和快速集成电子。此外，使用阵列对许多分子进行多重检测对于可靠的诊断和检测是必不可少的。尽管已经开发了许多技术，如微阵列和无标签电化学和光学生物传感器。它们有各种缺点：缺乏灵敏度和分辨率，笨重和精确的样品位置控制，或大的设备尺寸和缺乏可扩展性等。剑桥大学（CU）、曼彻斯特大学（MU）和博尔顿大学（BU）组成了一个多学科团队，利用最先进的薄膜体声波谐振器（FBAR）技术开发生化检测技术平台。FBAR器件具有类似石英晶体微天平的结构，但具有亚微米厚的压电（PE）有源层。它由一层薄薄的pe层组成，两侧都有电极。交流信号的应用通过PE效应在两电极之间产生驻波。由于器件尺寸小（因而基质量小）和工作频率高，谐振频率对附着在电极表面的质量极为敏感。通过预先沉积在电极表面的探针分子的特异性生物结合，可以检测到极小浓度的生物分子。该装置具有所有其他生物传感器的综合优点：无标签，超高灵敏度和低检测限，尺寸小，适合使用FBAR阵列进行多次检测，电子输出信号和低成本。由于其相对成熟的技术，该项目最初将重点开发使用压电（PE） ZnO薄膜的高性能fbar。利用前列腺特异性抗原（PSA）和特异性结合这些PSA的肽适体，生物传感技术将同步发展。肽适体具有比蛋白质更好的稳定性和特异性。基于zno的FBAR生物传感器的开发使我们能够澄清设备建模，制造和表征，固定化和生物检测等方面的所有问题。在第二阶段，该项目将使用低成本的pe聚合物在玻璃和塑料基板上开发新型fbar。聚乙烯聚合物如聚偏氟乙烯（PVDF）及其共聚物PVDF/TrFE具有与压电陶瓷相当的压电常数和耦合系数，并且具有生物相容性和化学惰性。由于它们的灵活性，它允许在低成本的玻璃和塑料基板上制造。这些生物传感器的成本将非常低。BU拥有出色的建模和设计设施，以及材料和设备特性。他们将负责建模、设计和特征描述。CU拥有世界级的洁净室，拥有出色的沉积，蚀刻和微加工设备。他们将提供设备制造方面的专业知识和经验。学校拥有一流的生物实验室环境和相关的生物研究设施。他们是蛋白质吸附，界面构象，结构展开，合成和克隆肽适体的专家。

Biosensors are a type of microdevices that are able to measure very small concentration of biological molecules or chemical substances through specific bio-binding or chemical absorption. Biosensors are extremely useful in diagnosis, fighting terrorist and prevention of pandemic disease spread. Through detection of associated molecules such as DNA and antibody-antigen, they are very promising in early diagnosis of cancers and genetic disorder. Widespread applications of thus biosensors will lead to fast and accurate diagnosis, thus preventing unnecessary mortality and saving thousands of lives. Deployment of biosensors at key public locations enables detection of disease or biological substances in time, preventing spread of diseases or biochemical attach. High quality biosensors must be very sensitive, easy to use, low cost and fast with integrated electronics. Also multi-detection of many molecules using arrays is essential for reliable diagnosis and detection. Although many technologies have been developed such as microarrays and label-free electrochemical and optical biosensors. they have various shortages: lack of sensitivity and resolution, bulky and precise control of the sample position, or a large device size and lack of scalability etc. A multi-disciplinary team from Universities of Cambridge (CU), University of Manchester (MU) and University of Bolton (BU) is formed to develop a technology platform for biochemical detection using the most advanced film bulk acoustic wave resonator (FBAR) technology. FBAR device has a structure similar to quartz crystal microbalance but with a submicrometer thick piezoelectric (PE) active layer. It consists of a thin PE-layer with electrodes on both sides. Application of A.C. signals generates a standing wave between the two electrodes through PE effect. The resonant frequency is extremely sensitive to mass attached on the electrode surface owing to small device dimensions (thus the small base mass) and high operating frequency. Extremely small concentration of biomolecules can be detected through specific bio-binding with pre-deposited probe molecules on the electrode surface. The device has the combined merits of all other biosensors: label-free, ultra-high sensitivity and low detection limit, small dimensions, suitability for multi-detection using FBAR arrays, electronic output signal and low cost. The project will initially focus on development of high performance FBARs using piezoelectric (PE) ZnO thin films owing to its relatively mature technology. Biosensing technology will be developed in parallel using prostate-specific antigens (PSA) and peptide aptamers that specifically bind to those PSAs. Peptide aptamers have much better stability and specificity than proteins. Development of ZnO-based FBAR biosensors enables us to clarify all issues in device modelling, fabrication and characterisation, immobilization and biodetection etc. At the second stage, the project will develop novel FBARs on glass and plastic substrates using low cost PE-polymers. PE polymers such as polyvinylidene fluoride (PVDF) and its copolymer PVDF/TrFE have a piezoelectric constant and coupling coefficient comparable to the piezoelectric ceramics, and are biocompatible and chemically inert. Owing to their flexibility, it allows fabrication on low cost glass and plastic substrates. The cost of these biosensors will be extremely low. BU has excellent facilities for modelling and design, and for material and device characterisation. They will be responsible for modelling, design and characterisation. CU has a world-class cleanroom housed with excellent deposition, etch and microfabrication facilities. They will offer the expertise and experiences in device fabrication. The MU has first class biolab environment and relevant facilities for biological research. They are experts in protein adsorption, interfacial conformation, structural unfolding, and synthesis and cloning of peptide aptamers.