基于水凝胶的集成纳米流体器件开发及其在癌症标志物分析中的应用研究

The survival rate of patients suffering from complex ailments such as cancer could immensely benefit from early diagnosis in clinics. Yet robust diagnosis calls for information on genetic and proteomic profiles of multiple markers simultaneously. Single-marker assays generally fall inadequate due to disease heterogeneity, especially in cancer. Moreover, important biomarkers such as proteins are usually present at minute concentrations during early stages of a disease. These lead to conventional methods such as enzyme-linked immunosorbent assays falling in cancer early diagnosis, especially in point-of-care situations, due to shortage in sensitivity, assay duration, and multiplexing capability. Nanofluidic devices, born in the footsteps of nanotechnology, biomedical science and electronic devices, exhibit marked potential in cancer biomarker detection. However, widespread use of these devices is largely limited by their expensive and cumbersome fabrication. Here we propose a convenient and cost-effective method of fabricating nanofluidic devices using polyelectrolyte hydrogel materials, and a pre-concentration strategy based on ion concentration polarization effect in asymmetric nanofluidic systems. Leveraging on this, we then propose a monolithically integrated micro-total-analysis device. The device will be tested for its utility in cancer biomarker pre-concentration and multiplexed detection.

癌症等复杂病症的有效治疗很大程度上依赖于早期诊断，而可靠的早期诊断往往需要多种癌症标志物的信息。在癌症早期，蛋白质等重要癌症标志物通常以极低的浓度存在。由于灵敏度和分析时间等方面的不足，传统的酶联免疫吸附法等方法很难满足癌症早筛，特别是即时检验的需求。由纳米科学、生物医学、电子科学等领域交叉所诞生的纳米流体传感器在传感极限、响应时间等方面具有巨大的优势，但是其昂贵和复杂的制备方法限制了其应用转化的潜力。本项目提出一种运用低成本、易加工的聚电解质水凝胶材料制备纳米流体器件的方法，和基于不对称纳米流体结构中离子浓度极化效应的分子预浓缩策略。在此之上，我们将开发单片集成的纳米流体二极管全微分析系统，并验证其在癌症标志物预浓缩和多重检测中的有效性。

癌症等复杂病症的有效治疗很大程度上依赖于早期诊断，而可靠的早期诊断往往需要核酸等生物标志物的信息。本项目通过对聚电解质水凝胶材料的研究，开发出了一系列的先进生物传感器和传感技术，包括：1）集成化聚电解质水凝胶二极管生物管传感器，2）荧光增强数字聚合酶链式反应（PCR）技术，3）区室化活体细胞生物传感器。基于上述研究成果，我们进一步展示了这些传感器和技术在检测人体复杂病症相关核酸标志物的有效性和先进性。该项目取得的系列创新性成果，有助于降低核酸检测的复杂度并提升其检测时间和灵敏度，为快速早期诊断的发展做出贡献。