ULTRASENSITIVE NANOLASERS FOR EPIGENETICS INVESTIGATIONS

用于表观遗传学研究的超灵敏纳米激光

基本信息

批准号：
8629287
负责人：
Andrea Martin Armani
金额：
$ 14.82万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2015-06-30
项目状态：
已结题

项目摘要

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.

摘要：该项目的目标是开发一种能够检测和定量 DNA 甲基化的新型无标记传感方式。该传感器平台基于稀土掺杂光学腔，形成纳米激光器，并结合基于受体的表面功能化。这种光学传感器可以在光学或电学领域进行检测，将被开发用于检测和量化 DNA 序列中多个位点的 CpG 甲基化，而无需使用 PCR。其在早期卵巢癌检测和监测中的应用将通过检测 RASS F1A 和 BRCA1 中的多个 CpG 甲基化位点得到证明。外周血和肿瘤组织中的表观遗传标记物的分析在癌症的早期检测、预后和治疗方面显示出了前景。然而，由于当前检测技术缺乏敏感性、特异性和重现性，这些标记物的分析受到阻碍。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的检测和监测，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，使用多种标记物将有助于筛选和监测治疗效果。 PI 之前的纳米传感器研究已开发出基于光学谐振腔的无标记单蛋白分子传感技术，该技术在缓冲液和血清中均起作用。据建议，纳米激光传感器将可用于检测血清 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通用平台。