Polymer modified paper – on the way to new diagnostic approaches –Fundamental studies on the origin of sensitivity loss in paper-based diagnostic processes and how to avoid them

The non-woven layered structure of paper allows for the transport of aqueous solutions through capillary action. This makes paper a promising candidate for the generation of simple microfluidic devices, which do not require any pumps nor sophisticated electric equipment for fluid transport. However, despite huge efforts, as of today, only rather simple diagnostic devices based on paper strips have been realized. A main reason for this is that a large number of very fundamental problems remain unsolved for paper-based diagnostics. A significant sensitivity loss is observed, once standard immunodiagnostic processes are transferred to microfluidic paper-based devices (µPADs). This sensitivity loss is mainly caused by unspecific adsorption of the analyte (usually proteins or antibodies) to the paper fibers. In addition, sensitivity loss during optical detection due to light scattering impact sensitive readouts negatively as well.

To address these problems, our research project aims to modify the paper fibers with (functional) polymers, which will be covalently attached to the fiber surface via different C,H-insertion reactions. This on the one hand, generates hydrophobic barriers for a micro-structured fluidic layout, while on the other hand allowing for protein repellent properties by fiber surface-attached hydrogels. The latter is meant to minimize non-specific adsorption and accordingly retention of an analyte (e.g. protein) transported through the channel by capillary action. Ideally, non-specific adsorption would be totally suppressed.

Analysis of the retention will be carried out with temporal and spatial resolution in situ, using fluorescent imaging techniques. In a further step, it is planned that a third class of polymers will be deposited in selected areas of the channel. These functional polymers will be covalently attached to the fibers at the surface of the paper sheet during a hot stamping contact process. This will also allow for spatially controlled modification of the paper with probe molecules, which will be studied subsequently in model reactions by means of immunological methods. The immobilization reaction occurs close to the surface and the modification of the fibers will be carried out with an (almost) iso-refractive material. Light scattering will therefore strongly be attenuated and the sensitivity of the sensor will correspondingly be enhanced compared to standard paper-based analytical processes.

Because this project requires both, expertise in paper chemistry as well as surface (polymer) chemistry, the groups of Rühe (Freiburg) and Biesalski (Darmstadt) have joined forces to address the above mentioned challenges.