Integrated opto-nanofluidic biosensors

集成光纳米流体生物传感器

• 批准号: 1158638
• 负责人: Xudong Fan
• 金额: $ 36万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1158638&HistoricalAwards=false
• 关键词: Integrated; opto; nanofluidic; biosensors

Intellectual Merit: Optical label-free biosensors measure analytes in their natural form without fluorescence labeling. Unfortunately, nearly all of them suffer from the detection limit bottleneck of approximately 1 pg/mm2. In contrast to detecting analytes attached to a single solid-liquid interface, the nanoporous based biosensor enables 3-dimensional detection, as multiple solid-liquid interfaces are present in the detection region. As a result, 0.01 pg/mm2 or better detection limit can potentially be achieved. However, one major issue with the nanoporous sensor is the sample delivery. It takes extremely long time for molecules to diffuse into (and out of) the porous detection region. The problem exacerbates when one deals with complex media, as it is very difficult to remove the unwanted interfering molecules from inside the pores, which causes large non-specific binding and severely deteriorates sensing performance.The proposed opto-nanofluidic sensor overcomes the aforementioned problems while maintaining high sensitivity even in the presence of complex media. It employs a nanostructured capillary placed in a Fabry-Pérot microcavity, which serves simultaneously as a flow-through nanofluidic channel, sample concentrator, and optical label-free sensor. It has a number of distinctive advantages. (1) It retains high sensitivity similar to that in nanoporous biosensors while having much larger Q-factors, which leads to an unprecedented detection limit on the order of fg/mm2; (2) It retains the high analyte capture efficiency due to the large surface-to-volume ratio and meanwhile its built-in flow-through nanofluidic channels enable quick and controlled sample delivery; (3) Detection of analytes from complex media becomes much easier. The interfering molecules can thoroughly be rinsed off, thus minimizing the non-specific binding and enhancing the sensing performance; (4) It is mechanically robust and can be mass-produced at a very low cost with the fiber drawing method; (5) The hole size is highly uniform and can be adjusted to accommodate different sizes of analytes and flow rates; (6) Due to its small size and simplicity, it can be scaled up to an array format for multiplexed detection on the nL scale; and (7) It can easily be connected to upstream sample processing components and downstream sample analyzers for further analysis. Broader Impact: This project includes prominent education components for graduate, undergraduate, and high school students. The students involved in the proposed project will acquire interdisciplinary knowledge and skills in photonics, nano/microfabrication, chemistry, material sciences, and biotechnology. Furthermore, the results and expertise developed through this project will be directly incorporated into the PI?s teaching at both undergraduate and graduate levels. Additionally, the PI will work closely with local non-Ph.D. granting institutes to develop a summer program for their students to conduct research in the PI?s lab. Finally, the collaboration with industrial companies will be instrumental in opto-nanofluidic sensor design, fabrication, integration, and applications, as well as in student training.

智力优点：无光标记的生物传感器以自然形式测量无荧光标记的分析物。不幸的是，几乎所有人都遭受了大约1 pg/mm2的检测极限瓶颈。与检测单个固液界面附加的分析物相反，基于纳米多孔的生物传感器可以实现3维检测，因为检测区域中存在多个固定液体界面。结果，可以实现0.01 pg/mm2或更好的检测极限。但是，纳米方传感器的一个主要问题是样品输送。分子散布到多孔检测区域中需要很长时间。当人们处理复杂的媒体时，问题会加剧，因为很难从毛孔内部去除有害的干扰分子，这会导致大型非特异性结合和严重检测的敏感性性能。拟议的光 - 纳米流通传感器克服了先前的敏感性，同时维持复杂媒体的敏感性。它采用纳米结构的毛细管放置在Fabry-Pérot微腔中，该毛细管仅用作流通的纳米流体通道，样品浓缩物和无光标记传感器。它具有许多独特的优势。 （1）它保留了与纳米多孔生物传感器相似的高灵敏度，同时具有较大的Q因子，这导致了FG/MM2阶的前所未有的检测极限； （2）由于较大的地表与体积比率，它保留了高分析物捕获效率，同时其内置流通纳米流体通道可快速，控制的样品传递； （3）从复杂媒体中检测分析物变得更加容易。可以彻底冲洗干扰分子，从而最大程度地减少非特异性结合并增强灵敏度性能。 （4）它在机械上很健壮，可以通过纤维制定方法以非常低的成本进行批量生产； （5）孔的大小高度均匀，可以调整以适应不同尺寸的分析物和流速； （6）由于其尺寸较小和简单性，可以将其缩放到阵列格式，以在NL尺度上进行多重检测； （7）它可以很容易地连接到上游样品处理组件和下游样品分析仪以进行进一步分析。更广泛的影响：该项目包括针对研究生，本科和高中生的著名教育组成部分。参与该项目的学生将获得光子学，纳米/微加工，化学，材料科学和生物技术方面的跨学科知识和技能。此外，通过该项目开发的结果和专业知识将直接纳入本科和研究生水平的PI教学中。此外，PI将与局部非PH.D紧密合作。授予机构为学生在PI实验室中进行研究制定夏季计划。最后，与工业公司的合作将在Opt-Nanofluidic传感器设计，制造，集成和应用以及学生培训中发挥作用。