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.
