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甲基化的方法大多需要硫酸氢盐处理、PCR扩增和其他传统的生物分子分析，这些方法耗时长且缺乏准确性。近年来，基于纳米线场效应晶体管的电子器件以其无标记、超灵敏等特点在DNA分子检测中显示出了良好的应用前景。在前期研究团队开发用于DNA甲基化检测的纳米晶体管生物传感器的基础上，本文提出了开发用于分析癌细胞DNA甲基化图谱的集成电子设备。拟议的研究涉及三个领域：a)产生特定的电子信号以同时报告多个基因启动子中的DNA甲基化事件(阶段I)；b)改进纳米晶体管的设计、制造质量和产量(阶段I)；以及c)开发具有深亚微米电子学的纳米晶体管的集成器件(阶段II)。一种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，将用于多重DNA检测。纳米晶体管探测器与一套专门为分子电子电荷检测而设计的微电子设备相耦合。

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.