Microfluidic extraction is a promising alternative for existing extraction methods of radioisotopes due to the high surface-to-volume ratio. When assessing the compatibility of microfluidic material with the extraction system, there are three critical aspects—compatibility with organic solvents, compatibility with the radiochemistry, and, most importantly, the resistance to radiation-induced damage. Resistance to radiation-induced damage includes the primary reactions of the radiation with the matter, such as bond cleavage and the indirect damage caused by radiation due to free radicals. On the other hand, polymers are an interesting alternative as they are cheap and suitable for producing microfluidic chips. Therefore, in this experimental study, multiple interactions with polymers and quartz caused by radiation are assessed. In general, most radiation-induced modifications can be traced back to changes taking place in the structure of the material. Some of the changes have been attributed to the scission of the polymer chains, promotion of cross-linkages, breaking of covalent bonds, formation of carbon clusters, and liberation of volatile products. However, these materials must not lose their mechanical and chemical properties to maintain a well-functioning microfluidic extraction system. Atomic layer deposition (ALD) is an interesting surface modification method due to its self-limiting nature and atomic precision control. With ALD, it is possible to deposit a nano-scale layer of metal oxide that reduces surface-induced damage without changing much of its bulk properties. Furthermore, with ALD, it is possible to change the wettability of the material to make them suited for microfluidic liquid-liquid extraction. This study showed that a 40nm T iO2 thin-film was able to stabilize the surface modifications during high flux electron irradiation. A similar pattern is found between the samples coated with VALD as radiation-induced surface activation is achieved. Briding oxygen that usually is present on the surface gets replaced by carboxyl groups and increases the surface energy to increase the hydrophilicity of the surface. Furthermore, polycarbonate, quartz, and high-density polyethylene showed impressive radiation resistance up to 5MGy as Young’s modulus showed no significant difference. With this study, it is possible to use nano-coating to stabilize the radiation-induced surface activation and can be helpful for surface modifications in multiple fields.