ULTRASENSITIVE NANOLASERS FOR EPIGENETICS INVESTIGATIONS

描述（由申请人提供） 翻译后摘要：本项目的目标是开发一种新的无标记的传感方式能够检测和量化DNA甲基化。传感器平台基于稀土掺杂的光学腔，其形成纳米激光器，结合基于受体的表面功能化。这种光学传感器，它可以在光学或电学领域进行检测，将被开发用于检测和定量CpG甲基化在DNA序列中的多个位点，而不使用PCR。它在早期卵巢癌检测和监测中的应用将通过检测RASS F1 A和BRCA 1中的多个CpG甲基化位点来证明。外周血和肿瘤组织中表观遗传标记物的分析在癌症的早期检测、预后和治疗中显示出希望。然而，这些标志物的分析受到当前检测技术缺乏灵敏度、特异性和再现性的阻碍。这项拟议的研究将开发一种全新的传感器平台，具有前所未有的检测表观遗传变化的能力，并将其应用于早期卵巢癌检测和监测，以及研究癌症进展的基本机制。目前使用单一血清蛋白生物标志物筛查卵巢癌的技术尚未成功。然而，越来越多的证据表明，使用多种标志物将具有筛选和监测治疗效果的实用性。PI先前的纳米传感器研究已经导致了基于光学谐振腔的无标记单蛋白质分子传感技术的发展，该技术在缓冲液和血清中均起作用。纳米激光传感器将有助于检测血清DNA的表观遗传变化，为利用蛋白质和表观遗传变化检测和监测卵巢癌提供一个通用平台。 公共卫生相关性：外周血和肿瘤组织中表观遗传标记物的分析在卵巢癌的早期检测、预后和治疗中显示出希望;然而，这些标记物的分析受到当前检测技术缺乏灵敏度、特异性和可重复性的阻碍。我们的目标是开发一种新的传感模式，能够检测和表征卵巢癌的表观遗传标志物，并将其用于研究表观遗传事件的频率。由于性能的改善，外差纳米激光传感器将能够检测和量化癌症相关的甲基化，特别是RASSF 1A和BRCA 1启动子中的CpG甲基化位点。

DESCRIPTION (Provided by the applicant) Abstract: The objective of this project is to develop a new label-free sensing modality capable of detecting and quantifying DNA methylation. The sensor platform is based on a rare- earth doped optical cavity, which forms a nanolaser, in combination with a receptor- based surface functionalization. This optical sensor, which can perform detection in either the optical or electrical domain, will be developed to detect and to quantify CpG methylation at multiple sites in DNA sequences without the use of PCR. Its application to early ovarian cancer detection and monitoring will be demonstrated with the detection of multiple CpG methylation sites in RASS F1A and BRCA1. Analysis of epigenetic markers in peripheral blood and tumor tissue has shown promise in the early detection, prognosis, and treatment of cancer. However, the analysis of these markers is hampered by the lack of sensitivity, specificity, and reproducibility of current detection techniques. This proposed research will develop a completely novel sensor platform with unprecedented capabilities for detecting epigenetic changes, and applies it to early ovarian cancer detection and monitoring, and to studying the fundamental underlying mechanisms of cancer progression. Current techniques to screen for ovarian cancer using single serum protein biomarkers have not been successful. However, there is growing evidence that use of multiple markers will have utility for screening and monitoring therapeutic efficacy. Previous nanosensor research by the PI has resulted in the development of label-free, single protein molecule sensing techniques based on optical resonant cavities which function in both buffer and serum. It is proposed that the nanolaser sensor will be useful in detecting epigenetic changes in serum DNA, providing a universal platform for detecting and monitoring ovarian cancer utilizing both protein and epigenetic changes. Public Health Relevance: Analysis of epigenetic markers in peripheral blood and tumor tissue has shown promise in the early detection, prognosis, and treatment of ovarian cancer; however, the analysis of these markers is hampered by the lack of sensitivity, specificity, and reproducibility of current detection techniques. Our goal is to develop a new sensing modality capable of detecting and characterizing epigenetic markers for ovarian cancer and to develop it for studying the frequency of epigenetic events. As a result of the improved performance, the heterodyned nanolaser sensor will be able to detect and to quantify cancer associated methylation, specifically CpG methylation sites in the RASSF1A and BRCA1 promoters.