Polymer modified paper - reducing sensitivity losses in paper-based analytical devices

纸的纤维结构允许水溶液通过毛细作用输送。因此，纸使得微流体装置的产生成为可能，其不需要任何泵来进行流体移动。然而，尽管付出了巨大的努力，但到目前为止，仅实现了基于纸条的相当简单的诊断设备。其主要原因是，即使在今天，对于纸基诊断，仍有大量非常基本的问题未解决，并且当标准免疫诊断过程转移到纸基设备时，观察到灵敏度的严重损失。这些灵敏度损失主要是由光学检测期间的光散射和分析物对高极性纸纤维的非特异性吸附引起的。为了解决这些问题，在本研究项目中提出了用聚合物改性纸纤维，所述聚合物通过C，H-插入反应共价连接到纤维表面。这一方面能够产生用于流体布局的疏水屏障，另一方面允许用蛋白质排斥性聚合物涂覆纸纤维。这将最大限度地减少非特异性吸附，并相应地减少通过毛细管作用通过通道运输的分析物（例如蛋白质）的保留。理想情况下，非特异性吸附将被完全抑制。将使用显微镜技术原位进行保留研究。最后，计划在通道的选定区域沉积第三类聚合物。这些分子将在热冲压步骤期间共价连接到纤维。这些聚合物将允许空间控制的修改与探针分子的纸，这将随后在模型反应中通过免疫学方法进行研究。由于固定化反应发生在表面附近，并且纤维的改性将在（几乎）等折射率材料上进行，因此光散射将被强烈衰减，并且与标准纸基分析过程的读出相比，传感器的灵敏度将相应地增强。

The fibrous structure of paper allows for the transport of aqueous solutions through capillary action. Thus, paper makes the generation of microfluidic devices possible, which do not re-quire any pumps for fluid movement. However, despite huge efforts, as of today only rather simple diagnostic devices based on paperstrips have been realized. A main reason for this is that for paperbased diagostics even today a large number of very fundamental problems re-main unsolved and strong losses of the sensitivity are observed when standard immunodiag-nostic processes are transferred to paper-based devices These sensitivity losses are mainly caused by light scattering during optical detection and unspecific adsorption of analytes to the highly polar paper fibers. To address these problems it is proposed in this research project to modify the paper fibers with polymers, which are covalently attached to the fiber surface by C,H-insertion reactions. This enables on the one hand generation of hydrophobic barriers for the fluidic layout, on the other hand allows coating of the paper fibers with protein repellent polymer. This would minimize the non-specific adsorption and accordingly retention of an ana-lyte (e.g. protein) transported through the channel by capillary action. Ideally, the non-specific adsorption would be totally suppressed. The investigation of the retention will be carried out in situ using microscopy techniques. Finally, it is planned that a third class of polymers will be deposited in selected areas of the channel. These molecules will be covalently attached to the fibers during a hot stamping step. These polymers will allow a spatially controlled modification of the paper with probe molecules, which will be studied subsequently in model reactions by means of immunological methods. Due to the fact that the immobilization reaction occurs close to the surface and the modification of the fibers will be carried out the an (almost) isore-fractive material, light scattering will be strongly attenuated and the sensitivity of the sensor will be correspondingly enhanced compared to read-out of standard paper-based analytical processes.