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

用于基础科学和转化医学的无标记单分子检测

基本信息

批准号：
10649704
负责人：
Judith Su
金额：
$ 36.46万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-06-30
项目状态：
未结题

项目摘要

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.

项目摘要。我们最近开发了一种无标记的生物和化学传感系统，作为频率锁定的光学回音消逝谐振器（FLOWER），其集成了微环形光学元件，具有频率锁定反馈控制的谐振器，这有助于抑制噪声。花目前能够高灵敏度和快速（30秒以下）无标记检测到单个大分子水平，如通过检测单个人白细胞介素-2（IL-2）分子所证实。到目前为止，花使用固定在微环上的抗IL-2抗体层，捕获IL-2。除了灵敏度高之外，FLOWER还具有其他纳米级传感的优势平台，如悬臂梁或纳米线，因为它拥有相对大的捕获面积，增加了分析物检测概率。我们建议（1）使用FLOWER针对大量当前的生物医学问题，受益于快速、灵敏和准确的方法来识别关键的微观、纳米级或分子特定于问题的标记;（2）将FLOWER进行分类和多路复用，并使其成为自包含的、紧凑的便携式设备，以快速建立各种状况的预后;以及（3）进一步提高FLOWER的灵敏度和选择性，使其能够检测更小的分子，例如胰岛素或更能够检测（1）中提到的小信号变化的社会兴趣。因此，在本发明的一个方面， FLOWER可用于理解合成光学鼻的嗅觉过程或疾病进展老年痴呆症FLOWER是一种新的方法，以前没有应用于这些问题，并证明的概念，有很大的潜力，以推动几个领域。如果成功，该项目将允许一个强大的，非常敏感的，便携式设备，可以提供给EMT或士兵，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使公民科学家能够监测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转移到其他实验室，从而实现对药物库的强大分析筛选、细胞信号传导研究和临床测定。最终，我们设想这些设备将在药店遍布全国，创造了一个方便，廉价，例行，可访问，和非侵入性意味着影响许多疾病的诊断和治疗，包括阿尔茨海默氏症，癌症，多种疼痛硬化症、糖尿病、成瘾和抑郁症。