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

这项提议旨在开发基于光刻定义的具有纳米功能单分子层的半导体量子线的分子规模的生化场效应晶体管或FET，以研究蛋白质和DNA的单分子检测。单分子与NW相互作用的研究是通过物理限制单个或少数分子在自组装单分子膜的纳米点上的附着来实现的。利用这一传感器平台，将全面了解电子生物传感机制、最终灵敏度和生物-生物界面，直至单分子水平。将在分子尺度上研究器件物理、表面化学和传感器性能之间的相关性。这些洞察力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定活性与交叉反应的映射，以提高检测特异性。如果成功，所提出的方法将导致创新和可制造的纳米电子生物芯片，用于无标记生物传感，具有单分子灵敏度和高特异性。智力优势：对电子生物传感器极限能力的研究将极大地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和可靠的生物传感器实现的，该传感器使用图案化的单层纳米点作为光刻定义的量子线晶体管的结合界面。使用纳米光刻技术来定义尺寸(2-10 nm)与化学合成的纳米线相当的纳米线将提供更好的一致性、器件可靠性和可制造性。它允许与芯片上的CMOS电路进行原位集成。所提出的技术结合了蛋白质滴定特征(pH依赖)和调制偏置，以及数据分析和蛋白质比活性和混杂活性的半正交映射来提高特异性，是新的和高度变革性的。通过结合最终灵敏度和特异度的研究，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。提出的分子尺度生物传感器和在单分子水平上全面了解纳米电子器件和生物分子之间的电子相互作用将有助于生物传感器、纳米电子学、纳米制造和分子电子学领域的发展。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、全血分析以及家园土地安全。它提供了护理点检测和诊断所需的单芯片生物传感解决方案，以克服当前光学传感器需要笨重和昂贵的设备、贴标签、复杂的样品制备和长处理时间的限制。该计划将利用电子生物传感器发现工具包的概念。为了产生重大的教育影响，包括整合研究和教育，促进多样性，并扩大到K-12，UTD和当地社区学院的代表不足的妇女和拉美裔学生团体以及达拉斯和沃斯堡地区的劳动力。

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.