Nanowire Devices for Ultrasensitive, Multiplexed Detection of Cancer Markers

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DESCRIPTION (provided by applicant): The overall goal of this project is to develop a robust silicon nanowire-based nanoelectronic sensor technology for rapid, ultra-sensitive and quantitative multiplexed detection of cancer marker proteins. Chemically-synthesized silicon nanowires can provide the uniformity needed for assembly of arrays of reproducible field-effect detectors, and modification of the surfaces of these nanodevices with specific receptors will enable real-time, ultra-sensitive electronic detection of cancer markers. The proposed research will address four specific research areas. First, a robust, addressable nanowire sensor chip and effective chip interface will be developed. Large-scale silicon nanowire growth will be coupled with wafer scale assembly, and the results will be optimized to yield an efficient chip fabrication process that enables good device yield and efficient chip through-put. A new chip interface that enables simple `plug-and-play' interconnection to measurement apparatus will be developed and validated. Large-scale device characterization will be carried out to determine statistical reproducibility of the nanowire transistor properties, and to optimize these properties. Second, a reproducible methodology for linking antibody receptor arrays to functional nanowire device arrays will be developed. Monoclonal antibodies arrays for cancer markers will be linked to the nanowire device arrays using a microarrayer, and the fidelity and competence of the receptors arrays will determine using fluorescence and electrical binding assays. Third, key factors and limits on the nanowire sensor performance will be defined. Systematic studies of the antibody-modified nanowire device array chips will be used to determine key performance factors, including (i) device baseline and detection stability, (ii) detection sensitivity as a function of buffer ionic strength, (iii) selectivity and discrimination against false positive/false negative responses, and (iv) methods for quantitative concentration analysis. In addition, limits for multiplexed detection in the nanowire device arrays will be investigated. Fourth, nanowire device chip characteristics and limits for serum samples will be determined. Protein detection limits in serum analysis as a function of ionic strength, and limits for selective multiplexed detection, including discrimination of false positives from nonselective binding and quantitative concentration analysis will be characterized. The proposed research has broad significance and (1) could enable early stage diagnosis and detection of recurrence of cancer using current diagnostic markers, (2) allow for highly robust diagnosis and treatment by detection and monitoring of panels of emerging cancer markers, and (3) could be generally applied for early stage diagnosis and monitoring of other human diseases. PUBLIC HEALTH RELEVANCE The overall goal of this project is to develop a nanoelectronic sensor technology for rapid, ultra-sensitive and quantitative simultaneous detection of multiple cancer marker proteins. The proposed research has broad significance and promises to (1) enable early stage diagnosis and detection of recurrence of cancer using current diagnostic markers, (2) allow for highly robust diagnosis and treatment by detection and monitoring of panels of emerging cancer markers, and (3) become a general technology for rapid early stage diagnosis and monitoring of human disease.