CAREER:Molecular scale electronic biosensor for single molecule sensitivity and high specificity

摘要本研究的目的是发展分子尺度的生化场效应晶体管或场效应晶体管，其基于光刻限定的半导体量子线和纳米图案化的功能单层，以研究蛋白质和DNA的单分子检测。单分子与NW相互作用的研究通过物理限制仅单个或几个分子在自组装单层的纳米点上的附着来实现。使用这个传感器平台，电子生物传感机制，最终的灵敏度，和生物无机界面下降到单分子水平的全面理解将被开发。器件物理，表面化学和传感器性能之间的相关性将在分子尺度上进行研究。这些见解将被用来开发先进的调制传感策略，如pH调制传感，多通道检测和蛋白质特异性活性与交叉反应性的映射，以提高检测特异性。如果成功的话，所提出的方法将导致一个创新的和可制造的纳米电子生物芯片，用于无标记的生物传感，具有单分子灵敏度和高特异性。智力优点：对电子生物传感器的极限性能进行深入研究，将大大促进对电子生物传感的理解，并为未来的传感器设计提供指导。这项具有挑战性的研究是由一种创新的和可靠的生物传感器，使用图案化的单层纳米点作为结合界面的量子线晶体管定义的光刻。使用纳米光刻来限定具有与通过化学合成的纳米线相当的尺寸（2-10 nm）的纳米线将提供更好的均匀性、器件可靠性和可制造性。它允许与芯片上的CMOS电路原位集成。所提出的技术将蛋白质滴定特征（pH依赖性）与调制偏置和数据分析与蛋白质比活性和混杂活性的半正交映射相结合以提高特异性是新颖的并且高度变革性的。通过结合对极限灵敏度和特异性的研究，研究它们之间的相关性，从而建立电子生物传感器的关键设计规则。更广泛的影响提出的分子尺度的生物传感器和纳米电子器件和生物分子之间的电子相互作用在单分子水平上的全面理解将有助于生物传感器，纳米电子学，纳米纤维和分子电子学领域。改进的电子传感器作为一个通用平台，可以对广泛的生化检测和疾病诊断产生相当大的影响，包括病原体/病毒检测、基因表达、免疫筛查、全血分析以及国土安全。它提供了一种单芯片生物传感解决方案，可用于即时检测和诊断，以克服当前光学传感器的局限性，这些传感器需要庞大而昂贵的设备、标记、复杂的样品制备和长的处理时间。该计划将利用一个概念？e-Biosensor Discovery Kit？产生重大的教育影响，包括研究和教育的整合，促进多样性，并推广到K-12，代表性不足的妇女和西班牙裔学生团体在UTD和当地社区学院以及劳动力在达拉斯和沃斯堡地区。

ABSTRACTThis proposal aims to develop molecular-scale biochemical field effect transistors or FETs based on lithographically defined semiconducting quantum wires with nanopatterned functional monolayer to study single-molecule detection of protein and DNA. Study of single-molecule interaction with NW is enabled by physically limiting attachment of only single or few molecules on the nano-dot of self-assembled monolayers. Using this sensor platform, a comprehensive understanding of electronic biosensing mechanisms, ultimate sensitivity, and bio-abio interfaces down to single-molecule level will be developed. Correlations between device physics, surface chemistry, and sensor performance at molecular scale will be investigated. These insights will be leveraged to develop advanced modulated sensing strategies, such as pH-modulated sensing, multi-channel detection and mapping of protein specific activity vs. cross-reactivity, to improve detection specificity. If successful, the proposed methods will lead to an innovative and manufacturable nanoelectronic bio-chip for label-free biosensing with single-molecule sensitivity and high specificity. Intellectual merits: The proposed study of ultimate capability of electronic bio-sensor down to the single-molecule level will significantly advance the understanding of electronic biosensing and provide guidance for future sensor design. This challenging study is enabled by an innovative and reliable biosensor using a patterned monolayer nano-dot as binding interface for a quantum wire transistor defined by lithography. The use of nanolithography to define the nanowires with size (2-10 nm) comparable to those by chemical synthesis will provide better uniformity, device reliability, and manufacturability. It allows in-situ integration with CMOS circuitry on chip. The proposed techniques combining protein titration signature (pH-dependence) with modulated biasing and data analysis with semi-orthogonal mapping of protein specific activity and promiscuous activity to improve specificity are novel and highly transformative. By combining the studies of ultimate sensitivity and specificity, the correlation between them will be investigated, leading to the establishment of critical design rules for electronic biosensor. Broader impactsThe proposed molecular-scale biosensor and comprehensive understanding of electronic interaction between nanoelectronic devices and bio-molecules at single-molecule level will contribute to the fields of biosensors, nanoelectronics, nanofabrication, and molecular electronics. Improved electronic sensors as a general platform could have a considerable impact on a wide-range of biochemical detection and disease diagnostics including pathogen/virus detection, gene expression, immune-screening, whole blood analysis, as well as home land security. It provides a single-chip biosensing solution desired for point of care detection and diagnostics to overcome the limitations of current optical sensors that require bulky and expensive equipment, labeling, complex sample preparation, and long processing time. The program will utilize a concept of ?e-Biosensor Discovery Kit? to generate significant educational impact, including integration of research and education, promoting diversity, and outreach to K-12, underrepresented women and the Hispanic student body at UTD and local community colleges as well as the workforce in the Dallas and Fort/Worth area.