纸芯片基底的定制化构筑及其可视图案化显示性能研究

Paper-based sensor has emerged as a new generation of cost-effective platform with great potential for diagnostics and analysis in low-resource settings. Although there have been significant advances in the fabrication of device and introduction of analytical techniques in recent years, the attempts regarding to use engineered cellulose fiber matrix with desirable physical and chemical property for improving a specific detection is limited. Our previous study has proved that the fiber composition and the structure & property of paper substrate have significant influence on the penetration and spreading of biological samples, and directly impact the sensitivity and specificity of analytical assays. In this project, the interaction between biological fluids and multiscale cellulose fiber/matrix structure will be firstly investigated, followed by the mechanisms of the penetration, spreading, adhesion and reaction of different samples and reagents in paper matrix. According to the findings from these studies, the physical and chemical property of paper will be specially adjusted in order to improve the sensitivity and specificity of different paper-based assays. Moreover, direct patterning methods such as printing and writing will be employed to establish a new method that can display results in text or digital code without hydrophobic barriers. Based on the innovative use of different kinds of technology, a new generation of bioactive paper-based assay platform can be built up, which meets the user-friendly and convenient criteria from World Health Organization. This project provides an example for the future research on the fabrication of paper–based sensors with great performance on specific applications, and therefore, has important scientific purpose.

纸基传感芯片已逐渐成为一种新型的平台技术，在低资源配置地区的快速诊断检测领域具有较大的应用潜力。尽管纸基芯片在其制造技术和检测技术等方面发展迅速，但是鲜有针对纸基纤维阵列，进行定制化设计，旨在构建优良纸基传感器的系统研究。申请人前期工作发现纸基的纤维组成和结构性质，与生物样品的传输和分布行为密切相关，直接影响检测的灵敏度和特异性。本项目将研究生物流体与多尺度木质纤维及纤维间结构单元的相互作用机制，根据生物样品在纤维阵列内流动、分布、粘附和反应的特点及规律，调控纸基的物理、化学性质，构建针对不同反应的最优纸基，提高检测的灵敏度和特异性。此外，本项目将运用印刷书写原理，交叉生物化学修饰及固定技术，提出在定制纸基上实现非疏水限域的文字及编码显示的新方法，建立新一代可图案化显示检测结果的生物活性纸基平台。这种从纸基优化定制到芯片雏形组装的系统研究模式，有望在纸基检测诊断领域中得到广泛的应用。

纸作为一种来源丰富，造价低廉的纤维材料，因其易于加工、生物相容性好、过滤性能良好等诸多优点，常作为承载分析测试的基底材料，应用于医学快速诊断、食品安全快速检测以及环境质量监控等多个领域，在低资源配置地区的快速诊断显示出较大的应用潜力。纸基的物理结构与表面化学性质，影响着生物分子、细胞、检测试剂的修饰、固定、分离、凝聚、流动和反应。本项目研究了多种生化流体在木质纤维阵列中的流动行为和相互作用，并通过纸基底纸基的物理、化学性质的优化设计，在不同检测应用中，提高了纸基检测芯片的灵敏度和特异性；研究了多种因素对血液“咖啡环”界面效应的形成的影响规律，并以定量和血比容为变量因素，建立了“咖啡环” 形成的敏感因素预测模型；通过对纸基表面浸润性的调控，实现了在非疏水限域条件下，实现了单步骤到多步骤的检测结果的图案化显示以及QR二维码检测结果显示的效果，提高了纸芯片的制造简便性和用户友好性；优化了纸芯片比色结果的读取方法，提出了基于印刷中常用的手持型透射光密度仪的结果分析方法，与常规的光反射密度分析方法相比，提高了检测结果的线性显示范围。本项目体现了制浆造纸工程、印刷工程、分析化学、生物医学检验等多学科基础理论交叉与技术融合，为纸芯片基底的优化构建和半定量/定量检测功能的集成，提供了科学依据。