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

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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.