EAGER: High precision molecular spectroscopy and detection using microtoroid optical resonators

准确检测少量生物和化学分子对于广泛的应用非常重要，包括病毒和细菌的公共卫生监测、化学威胁监测、疾病诊断、治疗评估以及食品和水安全监测。虽然已经证明了对非常低浓度的分子的检测，但是在肮脏的现实世界样品（诸如河水、体液、污染的空气和食物）中检测如此低浓度的分子仍然是一个挑战。在这项工作中，将创建一个超灵敏的光学检测系统，它能够同时快速分子识别和检测。这解决了复杂混合物中低浓度检测的问题。将进行概念验证实验，以确定该系统的准确性。此外，我们将使用成熟和成熟的二次技术来验证我们的结果。这项工作将通过亚利桑那大学生物5研究所运行的“让青年参与科学”高中项目吸引当地社区的参与。在课程结束时，学生们将在一个公共研究展示会上展示他们的成果。让学生在职业生涯早期参与可以直接影响他们社区的项目可以帮助解决管道泄漏问题，即没有足够的学生进入并留在科学和技术领域，以满足美国对此类工作的需求。 本计画的研究目标是建立一种非成像的单分子光谱感测器。在这里，提出了一种新的系统，称为FLOWERS（锁频耳语倏逝谐振器光谱），它结合了双梳状频率光谱与锁频微环光学谐振器的分子识别以及检测。其中的一个主要组成部分是使用频率锁定反馈机制来跟踪我们先前已经证明的纳米颗粒和单分子的结合事件。这项技术前所未有的灵敏度将被应用于粒子结合时的光谱测量。FLOWERS的概念验证将使用罗丹明B和蓝色、绿色、橙子和暗红色荧光纳米球来完成，这些纳米球具有清晰的光谱特征。将在不同浓度下对所有样品进行实验，以确定检测限和工作范围。光谱测量的准确度和噪声将被表征为粒度和浓度的函数。预计FLOWERS具有比现有技术光谱系统更高的精度，从而能够实现很少的假阴性。此外，FLOWERS可能比传统的基于显微镜的单分子光谱系统更便携和自动化。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The accurate detection of low numbers of biological and chemical molecules is important for a wide range of applications including public health monitoring of viruses and bacteria, chemical threat monitoring, disease diagnostics, treatment evaluation, and food and water safety monitoring. While the detection of very low concentrations of molecules has been demonstrated, the detection of such low concentrations of molecules in dirty real-world samples such as river water, bodily fluids, polluted air, and food remains a challenge. In this work, an ultra-sensitive optical detection system will be created which is capable of simultaneous rapid molecular identification and detection. This addresses the problem of detection of low concentrations in complex mixtures. Proof-of-concept experiments will be performed to determine the accuracy of this system. In addition, we will verify our results using well-established and proven secondary techniques. This work will engage the local community through the Keep Engaging Youth in Science high school program which is run by the BIO5 Institute at the University of Arizona. At the end of the program, students present their results at a public research showcase. Engaging students early in their career on projects that can directly impact their community can help with the leaky pipeline issue, which is that not enough students are entering and staying in science and technology to satisfy the demand for such jobs in the United States. The research objective of this proposal is to create a non-imaging single molecule spectroscopic sensor. Here, a new system is proposed called FLOWERS (Frequency Locked Whispering Evanescent Resonator Spectroscopy), which incorporates dual comb frequency spectroscopy with frequency locked microtoroid optical resonators for molecular identification as well as detection. A major component of this is the use of a frequency locking feedback mechanism to track the binding events of nanoparticles and single molecules which we have previously demonstrated. The unprecedented sensitivity of this technique will be applied to spectroscopic measurements of particles as they bind. A proof-of-concept of FLOWERS will be done using rhodamine B and blue, green, orange, and dark-red fluorescent nanospheres, which have a clear spectroscopic signature. Experiments will be done at varying concentrations for all samples in order to determine the limit of detection and working range. The accuracy and noise in the spectral measurements will be characterized as a function of particle size and concentration. FLOWERS is expected to have higher precision than current state of the art spectroscopy systems enabling few false negatives. In addition, FLOWERS can potentially be more portable and automated than traditional microscopy-based single molecule spectroscopy systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.