CAREER: Nanoelectronic Microfluidic Biochip for Ultrasensitive Detection of Selective Protein Biomarkers

职业：用于选择性蛋白质生物标志物超灵敏检测的纳米电子微流控生物芯片

• 批准号: 0845669
• 负责人: Samir Iqbal
• 金额: $ 40万
• 依托单位: University of Texas at Arlington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0845669&HistoricalAwards=false
• 关键词: CAREER; Nanoelectronic; Microfluidic; Biochip; Ultrasensitive

The objective of this proposal is to develop new modalities for the isolation and detection of selective proteins (biomarkers), by using aptamer-protein interactions in nano/microfluidic channels/chambers with multiplexed nanoscale electrodes and on-chip data processing. To accomplish the goals, a coherent strategy of fabrication and modeling will be adopted: (1) Development of functionalized membranes for isolation of low-abundant disease biomarkers, (2) Design and development of a bio-chip with individually-addressable nano-electrodes, made with high-throughput nanoimprint lithography and functionalized with aptamers for multiplexed detection of biomarkers, (3) Development of novel and rapid fabrication of nano/microfluidic channels, (4) Modeling, analysis and characterization of the electronic properties of biomarker-aptamer interactions measured between the nano-electrodes, and, (5) Real-time low-power noise-free read-out circuit with sequential addressing, actuation, measurement & data analysis of the recognition sites.INTELLECTUAL MERITS: This proposal will transform and create a new area ?proteonics?, building up on the advances in ?proteomics? and ?molecular electronics?. The activities leverage from the molecular scale devices and the in vitro aptamer-protein interactions, and are extendible to a host of other applications. The ideas will overcome bottlenecks of expensive and serial fabrication in molecular electronics and provide alternate to the labor-intensive, poorly-sensitive and lengthy protocols of proteomics. The novel polymer nano/microfluidics will provide proper conditions to retain protein expression and functionality. On-chip circuit will lead the way to prototype point-of-care proteonic bio-chips. The nano-electrodes will provide a 3-D interaction volume for aptamer-protein binding, resulting in higher sensitivity and signal-to-noise ratio than those for planar morphologies. The approach will also overcome sensitivity limitations by removing the effects of device doping, geometry, dimensions, and fluidic environments. The proposed strategies will innovatively transform and revolutionize a number of disciplines: (1) Rapid nano-manufacturing for bio-sensing, (2) Multiplexed detection of disease markers using various aptamers, (3) Ultrasensitive on-chip electrical detection of biomarkers and analysis for early disease detection, (4) Mask-less production of novel nano/microfluidics. BROADER IMPACT: The proposal has direct applications in other biosensor domains, e.g. gene expression analysis, virus/pathogen detection and whole blood analysis. The variations of the propose technology can transform biomolecular sensing with better disease intervention strategies, improved statistical confidence and real-time detection. The PI has engaged women graduate students and minority undergraduate/high school students in his research lab. Innovative educational endeavors will be pursued with this proposal: (1) Development of a graduate course on nano-bio devices, (2) Seminars/Demos/Lab-tours focused on research involvement and retention of undergraduates, (3) One-week summer camp for high school students (primarily African-American and Hispanic) from Arlington school district, integrating MEMS/Nano research and biology concepts, (4) Interactive website/blog for the projection/exposure/discussion of the state of the art in research, (5) Saturday morning live-chat sessions to follow-up/engage K-12 students and teachers, (6) Technology transfer studies to nurture entrepreneurship in students interested in real-world problems, (7) Development of international research collaborations for exchange of students from and to USA. The results of the proposed ideas will be disseminated through peer-reviewed articles, conferences and public media.

该提案的目的是通过在具有多路复用纳米级电极和芯片上数据处理的纳米/微流体通道/腔室中使用适体-蛋白质相互作用，开发分离和检测选择性蛋白质（生物标志物）的新模式。 为了实现这些目标，将采用连贯的制造和建模策略：（1）开发用于分离低丰度疾病生物标志物的功能化膜，（2）设计和开发具有可单独寻址的纳米电极的生物芯片，该生物芯片用高通量纳米压印光刻法制成并用适体功能化，用于生物标志物的多重检测，（3）开发新的和快速制造的纳米/微流体通道，（4）建模，分析和表征纳米电极之间测量的生物标记物-适体相互作用的电子特性，以及（5）实时低功耗无噪声读出电路，具有顺序寻址，驱动，&识别位点的测量数据分析。蛋白质电子学？建立在进步的基础上蛋白质组学？然后呢？分子电子学？。 这些活性利用了分子规模的装置和体外适体-蛋白质相互作用，并且可扩展到许多其他应用。这些想法将克服分子电子学中昂贵和连续制造的瓶颈，并为蛋白质组学的劳动密集型，低灵敏度和冗长的协议提供替代方案。 新型聚合物纳米/微流体将提供适当的条件来保留蛋白质表达和功能。 片上电路将引领定点护理蛋白质生物芯片的原型化。纳米电极将为适体-蛋白质结合提供3-D相互作用体积，导致比平面形态更高的灵敏度和信噪比。 该方法还将通过消除器件掺杂、几何形状、尺寸和流体环境的影响来克服灵敏度限制。提出的策略将创新性地改变和革命性地改变许多学科：（1）用于生物传感的快速纳米制造，（2）使用各种适体的疾病标志物的多重检测，（3）生物标志物的超灵敏芯片上电检测和早期疾病检测分析，（4）新型纳米/微流体的无掩模生产。更广泛的影响：该提议在其他生物传感器领域，例如基因表达分析、病毒/病原体检测和全血分析中具有直接应用。 所提出的技术的变化可以通过更好的疾病干预策略、改进的统计置信度和实时检测来改变生物分子传感。 PI在他的研究实验室中雇用了女研究生和少数民族本科生/高中生。 创新的教育努力将与此建议：（1）开发关于纳米生物装置的研究生课程，（2）侧重于大学生参与研究和保留研究的研讨会/演示/实验室参观，（3）为高中生举办为期一周的夏令营（主要是非洲裔美国人和西班牙裔）从阿灵顿学区，集成MEMS/纳米研究和生物学概念，（4）互动网站/博客，用于投影/曝光/讨论研究领域的最新技术，（5）周六上午的实时聊天会议，以跟踪/吸引K-12学生和教师，（6）技术转让研究，以培养对现实世界问题感兴趣的学生的创业精神，（7）发展国际研究合作，以交换来自美国的学生。 将通过同行审查的文章、会议和公共媒体传播拟议想法的结果。