Collaborative Research: Ultrasensitive Cancer Biomarker Detection on Biophotonic Chips

合作研究：生物光子芯片上的超灵敏癌症生物标志物检测

• 批准号: 1159453
• 负责人: Holger Schmidt
• 金额: $ 36万
• 依托单位: University of California-Santa Cruz
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1159453&HistoricalAwards=false
• 关键词: Collaborative; Research; Ultrasensitive; Cancer; Biomarker

1159453/1159423Schmidt/HawkinsThe main goal of the proposal is to develop a chip that combines microfluidics with a sensitive fluorescence excitation and detection platform that relies on liquid-core waveguides. This lab-on-a-chip is designed for highly sensitive and specific detection of cell-free nucleic acids (CNAs) that are found in elevated concentrations within the bodily fluids of cancer patients. The high sensitivity of the proposed technology is expected to obviate the need for amplification that is currently required when performing traditional PCR assays for CNAs, which in turn increase the complexity and cost associated with this approach. The investigators propose to initially develop a multi-mode interferometric approach for fluorescence excitation in order to enhance the signal to noise ratio and to enable spectral multiplexing in order to enhance sensitivity and specificity. The second step involves integration of the silicon photonic layer with standard PDMS microfluidics layers for sample preparation and filtering. The integrated device will be tested initially using fluorescent beacons against viral nucleic acids associated with high-risk human papilloma virus (HPV) 18. In the final step, the platform will be tested using blood from 5 melanoma patients, a healthy human and a leukemia patient.Polymerase chain reaction (PCR) methods are the current gold standard in cell-free nucleic acids (CNA) detection and rely on amplifying the genomic material to produce a sufficiently large signal for optical readout.. The PIs propose to demonstrate and validate a biophotonic platform for multiplexed, amplification-free analysis of cell-free DNA. At its core will be liquid-core optical waveguides that have a limit of detection of single fluorescing molecules of DNA/RNA at clinically relevant concentrations. The project will address key innovations at all levels of the detection system, and, if successful, create a transformative step for cancer diagnosis, enabling non-invasive and quantitative analysis of biomarker panels from cell-free DNA.

该提案的主要目标是开发一种将微流体与依赖液核波导的敏感荧光激发和检测平台相结合的芯片。这种芯片实验室设计用于对癌症患者体液中浓度升高的无细胞核酸（CNAs）进行高灵敏度和特异性检测。所提出的技术的高灵敏度有望避免目前在对CNAs进行传统PCR分析时需要的扩增，这反过来又增加了与该方法相关的复杂性和成本。研究人员建议首先开发一种多模干涉法用于荧光激发，以提高信噪比，并使光谱复用，以提高灵敏度和特异性。第二步涉及硅光子层与标准PDMS微流体层的集成，用于样品制备和过滤。该集成设备将首先使用荧光信标对与高危人类乳头瘤病毒（HPV） 18相关的病毒核酸进行测试。在最后一步，该平台将使用5名黑色素瘤患者、一名健康人和一名白血病患者的血液进行测试。聚合酶链反应（PCR）方法是目前无细胞核酸（CNA）检测的金标准，它依赖于扩增基因组物质来产生足够大的光学读出信号。pi建议演示和验证一个生物光子平台，用于多路复用，无扩增分析无细胞DNA。其核心将是液核光波导，它对临床相关浓度的DNA/RNA单个荧光分子的检测有限制。该项目将在检测系统的各个层面进行关键创新，如果成功，将为癌症诊断迈出革命性的一步，使无细胞DNA生物标志物面板的非侵入性和定量分析成为可能。