Integrated opto-nanofluidic biosensors

智能优点：光学无标记生物传感器以其自然形式测量分析物，而无需荧光标记。不幸的是，几乎所有的样品都存在大约1pg/mm2的检测极限瓶颈。与检测附着到单个固-液界面的分析物相比，基于纳米孔的生物传感器能够进行三维检测，因为在检测区域中存在多个固-液界面。因此，有可能达到0.01pg/mm2或更好的检出限。然而，纳米孔传感器的一个主要问题是样品的输送。分子扩散进(出)多孔性检测区域需要极长的时间。当处理复杂介质时，问题会加剧，因为很难从孔内去除不需要的干扰分子，这会导致大量的非特异性结合，并严重恶化传感性能。所提出的光纳米流体传感器克服了上述问题，同时即使在复杂介质中也保持了高灵敏度。它利用放置在法布里-佩罗微腔中的纳米结构毛细管，同时充当流过纳米流体通道、样品浓缩器和光学无标签传感器。它有许多独特的优势。(1)它保持了与纳米孔生物传感器相似的高灵敏度，同时具有更大的Q因子，这使得检测极限达到前所未有的fg/mm2数量级；(2)由于大的表面积与体积比，它保持了高的分析物捕获效率，同时其内置的流过纳米流体通道能够快速且可控地输送样品；(3)从复杂介质中检测分析物变得更加容易。该仪器的主要特点是：(1)可以彻底清洗掉干扰分子，从而最大限度地减少非特异性结合，并提高传感性能；(4)它具有坚固的机械性能，并且可以利用拉丝方法以非常低的成本批量生产；(5)孔尺寸高度均匀，可调整以适应不同大小的分析物和流速；(6)由于其尺寸小且简单，因此可以放大到阵列格式，用于NL尺度上的多路检测；以及(7)它可以很容易地连接到上游样品处理部件和下游样品分析仪进行进一步分析。更广泛的影响：该项目包括面向研究生、本科生和高中生的重要教育组成部分。参与建议项目的学生将获得光子学、纳米/微制造、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生和研究生水平的皮？S教学。此外，PI将与当地的非博士授予机构密切合作，为他们的学生制定一个暑期项目，让他们的学生在PI？S实验室进行研究。最后，与工业公司的合作将有助于光纳米流体传感器的设计、制造、集成和应用，以及对学生的培训。

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.