Label-free single molecule detection for basic science and translational medicine

项目总结。我们最近开发了一种无标记的生物和化学传感系统，已知 作为集成了微环光学的锁频光学耳语消逝谐振器(FLOW) 具有锁频反馈控制的谐振器，有助于抑制噪声。鲜花目前 能够高灵敏、快速(不到30秒)检测到单个大分子 单个人白介素2(IL-2)分子的检测证明了这一点。到目前为止，鲜花已经 使用固定在微环上的抗IL-2抗体层获得5的信噪比 捕获IL-2。除了具有高灵敏度外，FLOW还具有其他纳米级传感器无法比拟的优势 悬臂梁或纳米线等平台，因为它拥有相对较大的捕获区域，增加了 分析物检测的概率。 我们建议(1)使用FLOW来针对当前的大量生物医学问题，这将 利用快速、灵敏、准确的方法识别关键的微观、纳米或分子 特定于问题的标记；(2)微型化和多路复用花，使其成为自我的一部分 包含、紧凑的便携式设备，可快速确定各种情况的预后；以及(3)进一步 提高了FLOW的灵敏度和选择性，使其能够检测到更小的分子 社会兴趣，如胰岛素或更多，能够检测到(1)中提到的小信号变化。因此， FLOW可以用来理解人工光学鼻子的嗅觉过程或疾病进展 在阿尔茨海默氏症中。FLOW是一种以前没有被应用于这些问题的新方法，并且有证据表明 在概念上，有很大的潜力推进几个领域。 如果成功，这个项目将允许一个强大的，极其敏感的和便携的设备，可以 给EMT或士兵的，以便他们快速检测饮用水中的疾病或病毒和细菌 或者食物。这些设备可以让公民科学家监控他们的饮用水供应或呼吸空气。 此外，这些设备可以很容易地移植到其他实验室，从而能够对药物库进行可靠的分析 筛选、细胞信号研究和临床分析。最终，我们设想这些设备将在 全国各地的药店，创造了一个方便、便宜、常规、可及、无创的 影响许多疾病的诊断和治疗的手段，包括阿尔茨海默氏症、癌症、多发性疼痛 硬化症、糖尿病、成瘾和抑郁症。

PROJECT SUMMARY. We have recently developed a label-free biological and chemical sensing system known as a frequency locked optical whispering evanescent resonator (FLOWER) that integrates microtoroid optical resonators with frequency locking feedback control, which aids the suppression of noise. FLOWER is currently capable of highly sensitive and rapid (under 30 seconds) label-free detection down to the single macromolecule level, as demonstrated by the detection of single human interleukin-2 (IL-2) molecules. To date, FLOWER has achieved a signal-to-noise ratio of 5 using an anti-IL-2 antibody layer immobilized on a microtoroid to specifically capture IL-2. In addition to its high sensitivity, FLOWER has an advantage over other nanoscale sensing platforms such as cantilevers or nanowires in that it possesses a relatively large capture area, increasing the probability of analyte detection. We propose (1) using FLOWER to target a large number of current biomedical problems which would benefit from a rapid, sensitive, and accurate means to identify key microscopic, nanoscopic, or molecular markers specific to the problem; (2) miniaturizing and multiplexing FLOWER and making it part of a self- contained, compact portable device to quickly establish the prognosis of various conditions; and (3) further increasing FLOWER’s sensitivity and selectivity, making it capable of detecting even smaller molecules with societal interest such as insulin or more capable of detecting the small signal changes mentioned in (1). As such, FLOWER may be used to understand the process of olfaction in synthetic optical noses or disease progression in Alzheimer’s. FLOWER is a new method that has not been applied to these questions before and, with proof of concept, has great potential to advance several fields. If successful, this project would allow for a robust, extremely sensitive, and portable device that could be given to an EMT or a solider in order for them to rapidly detect diseases or viruses and bacteria in drinking water or food. These devices could empower citizen scientists to monitor their drinking supply or breathing air. Furthermore, these devices could be easily translatable to other labs, enabling robust assays for drug library screening, cell signaling studies, and clinical assays. Eventually, we envision these devices to be prevalent in drug stores throughout the country, creating a convenient, inexpensive, routine, accessible, and non-invasive means to impact the diagnosis and treatment of many diseases, including Alzheimer’s, cancer, pain from multiple sclerosis, diabetes, addiction, and depression.