面向癌症精准诊疗的高密度微腔阵列式多重数字PCR芯片

项目名称： 面向癌症精准诊疗的高密度微腔阵列式多重数字PCR芯片

项目编号： No.61771078

项目类型： 面上项目

立项/批准年度： 2018

项目学科： 无线电电子学、电信技术

项目作者： 李刚

作者单位： 重庆大学

项目金额： 16万元

中文摘要： 获取患者的基因变异信息是实现癌症精准治疗的关键。近年来具有简便、无创优势的循环肿瘤DNA（ctDNA）检测被视为实现癌症精准诊疗突破的重要手段。但是由于患者外周血中ctDNA含量极低且肿瘤遗传变异存在异质性和复杂性，目前常规基因诊断技术的灵敏度和准确性还难以满足ctDNA临床检测的需求。最近，高灵敏度的数字PCR技术的出现，为基于ctDNA检测的癌症精准治疗带来了希望，显示了很好的临床应用前景。但是现有数字PCR平台存在一些严重不足，如昂贵的仪器装备、复杂的操作流程和较弱的多重检测能力等，影响了该技术在临床实际中的应用。本项目拟研究一种新型多重数字PCR芯片，该芯片利用高密度微腔阵列结合无源微流体驱动技术实现样品的数字化分解，同时采用分区预存引物实现多重PCR检测，可很好地克服现有数字 PCR 技术在临床实际应用中的关键瓶颈问题，有望为临床肿瘤的精准医疗提供一种有效的分子生物学检测手段。

中文关键词： 微流控技术；多重数字PCR；循环肿瘤DNA；精准医疗；高密度微腔阵列

英文摘要： The identification of genetic mutations in cancer patients is key to cancer precision therapy. Recently, the analysis of circulating tumor DNA (ctDNA) in plasma is regarded as one of the most important diagnostic tools for cancer precision therapy due to its non-invasive, convenient, and specific properties. However the conventional ctDNA detection methods have insufficient sensitivity or patient coverage for broad clinical applicability due to very low ctDNA level and tumor heterogeneity. Now, the advent of digital PCR has greatly improved the precision and sensitivity of mutated gene measurements, which shows promise for the noninvasive detection of cancers. Although digital PCR technique has been shown to be promising, it still has some shortcomings for the clinical practices, such as expensive instrumentation, complicated procedure, and poor multiplexing capability. This program presents a novel digital PCR chip based on the high-density and multi-area microcavity array combined with a power-free pumping to overcome the bottlenecks of the current digital PCR. Without requiring any external connections or pumping equipments, this chip allows low-cost and easy-to-use detection of ctDNA, which greatly improves the clinical practicability of digital PCR. Such simple and efficient approach holds promise to provide an efficient tool for cancer precision therapy.

英文关键词： Microfluidics;Multiplex digital PCR;Circulating tumor DNA;Precision medicine;High-density microcavity arrays