SBIR Topic 243-Novel and Improved Methods To Measure Cancer Epigenetic Biomarkers

拟议的工作将通过创建纳米电子甲基化检测系统来推进甲基化诊断。目前用于检测特定位点CpG甲基化的大多数方法需要硫酸氢盐处理、PCR扩增和其他常规生物分子测定，这些方法耗时且缺乏准确性。最近，基于纳米线场效应晶体管的电子器件在DNA分子的检测中显示出有希望的结果，其具有无标记和超灵敏的吸引人的特征。基于提出团队在开发用于DNA甲基化检测的纳米晶体管生物传感器方面的先前研究，本文提出开发用于分析癌细胞DNA甲基化谱的集成电子器件。拟议的研究涉及三个领域：a）产生特定的电子信号，同时报告许多基因启动子中的DNA甲基化事件（第一阶段）; B）改善纳米晶体管的设计，制造质量和产量（第一阶段）;和c）开发纳米晶体管与深亚微米电子集成器件（第二阶段）。一个独特的分子信号转导系统，将分子识别事件转化为电子信号将用于多个DNA检测。纳米晶体管检测器耦合到一组专门设计用于分子电子电荷检测的微电子器件。

The proposed work will advance methylation diagnosis through the creation of a nano electronic methylation detection system. Most methods currently used in the detection of CpG methylation at specific sites require a bisulfate treatment, PCR amplification and other conventional bio-molecular assays which are time-consuming and lack accuracy. Recently, nanowire field effect transistor based electronic devices have shown promising results in the detection of DNA molecules with attractive features of being label-free and ultra-sensitive. Based on the previous research by the proposing team in the development of nano-transistor biosensor for DNA methylation detection, it is proposed herein to develop integrated electronic devices for analyzing the DNA methylation profiles for cancer cells. Proposed research involves three areas: a) generate specific electronic signals to report DNA methylation events in numerous gene promoters simultaneously (PhaseI); b) improve nano-transistor design, fabrication quality and yield (Phase I); and c) develop integrated devices of nano-transistors with deep submicron electronics (Phase II). A unique molecular signal transduction system which transforms molecular recognition events into electronic signals will be used for multiple DNA detection. Nano-transistor detectors are coupled to a set of microelectronic devices specifically designed for molecular electronic charge detection.