The success of semiconductor technology over the last few decades has clearly established the importance of photoresists in manufacture of these devices. While the fundamental focus of the development in the photoresists area has often been in obtaining smaller feature size(s) at reduced cost, the toxicity and the environmental impact of these photoresists are not always factored into the design of these resists. Here we report a new family of water-soluble photopolymers that can potentially be useful as environmentally benign “negative working” photoresists. This water-soluble polystyrene copolymer, vinylbenzylthymine−vinylphenylsulfonate (VBT−VPS) can be easily coated on a variety of substrates including flexible plastics such as polyethylterephthalate (PET). The chemistry of the cross-linking and immobilization of these “bio-inspired” photoresists has been derived from a simple photochemical transformation that occurs in nature (2π + 2π photodimerization of thymine). In this study we report the irradiation-dose dependence of cross-linking/immobilization of VBT−VPS films on PET substrates. Noncontact atomic force microscopy has been used to measure the thickness of films formed at various exposure times. In addition, attenuated total reflectance Fourier transform infrared spectroscopy has been used to estimate the dose-dependent progression of film thickness and qualitatively observe the change in composition of the films upon irradiation. It has been demonstrated that these techniques can provide complementary information on photoinduced immobilization of VBT−VPS films that are crucial for developing this new class of environmentally benign materials for photoresist applications.