纳米蛋白纤维传感器作癌症标记物的检测及其于疾病诊断中的应用

MicroRNA (miRNA) has recently emerged as a new and important class of cellular regulators. Strong evidence that aberrant expression of miRNA is associated with a broad spectrum of human diseases, such as cancer, diabetes, cardiovascular and psychological disorders. However, the short length and low abundance of miRNA place great challenges for conventional techniques in the miRNA quantitation and expression profiling. In this work, we propose a direct and ultrasensitive and multiplex detection assay for miRNA without sample amplification. A self-assembled protein nanofibril acts as an online preconcentrating sensor to the target miRNA. Lock-nucleic acid (LNA) modified molecular beacon (MB) is the probe and signal generator. This work will further extend to clinical samples of Nasopharyngeal Carcinoma (NPC) patients' tumor tissue, as well as blood and saliva such that a non-invasive sampling approach is adapted for early clinical disease diagnosis and prognosis, and clinical new drugs testing. The success of this project will certainly open up new avenues for development of highly sensitive and accurate detection systems to both biomedical researches and a wide variety of clinical applications.

最近，微核糖核酸(miRNA)被视作一种新型的细胞调节剂。有强力的科研证据证明人体内miRNA水平的异常表达与多种不同疾病，如癌症、糖尿病、心血管病等，都有着密切的关系。因此，miRNA能够作为一种疾病的生物标记物，透过测量miRNA的水平及其表达可能有助诊断早期疾病的形成。可惜，基于miRNA的短序列以及其于体内极低的浓度令传统的定量及表达谱分析带来很大挑战。本项目拟开发一种直接、超敏、而且省却样品预处理的多元miRNA检测方法。自组制淀粉样蛋白纤维将作为检测靶miRNA的生物传感器。作为检测探针的锁核酸分子信标将捕捉溶液中的靶miRNA，而杂交体将于蛋白纤维上预富集从而提高荧光信号于荧光显微镜下的信噪比。为提高检测平台的应用能力，鼻咽癌病人的血液及唾液样品将会被收集作为此平台的临床测试物。研究成功的话，此高敏且准确的平台将为生物医学研究及临床检测应用上带来全新的发展。

小分子核糖核酸(miRNA)是一种新型的细胞调节剂。有研究表面明人体内miRNA水平的异常表达与不同疾病密切关联，如癌症、糖尿病、心血管病等。因此miRNA能作为疾病诊断特征标志物，通过测量miRNA的含量及其表达可有助疾病的早期诊断。然而miRNA序列短以及体内浓度极低，使得基于传统方法的定量分析具有很大挑战。本项目开发了快速、高灵敏且无需样品预处理的多元miRNA检测方法。为衡量该检测方法的实际样本应用能力，鼻咽癌病人的血液样本被应用为此方法的临床测目标。我们成功实现了对目标样本的高灵敏且准确的分析检测,这将为生物医学研究及临床检测应用带来新的机遇。