Semprus Biosciences is developing environmentally benign and permanent modifications to prevent biofouling on Marine and Hydrokinetic (MHK) devices. Biofouling, including growth on external surfaces by bacteria, algae, barnacles, mussels, and other marine organisms, accumulate quickly on MHK devices, causing mechanical wear and changes in performance. Biofouling on crucial components of hydrokinetic devices, such as rotors, generators, and turbines, imposes substantial mass and hydrodynamic loading with associated efficiency loss and maintenance costs. Most antifouling coatings leach toxic ingredients, such as copper and tributyltin, through an eroding process, but increasingly stringent regulation of biocides has led to interest in the development of non-biocidal technologies to control fouling. Semprus Biosciences research team is developing modifications to prevent fouling from a broad spectrum of organisms on devices of all shapes, sizes, and materials for the life of the product. The research team designed and developed betaine-based polymers as novel underwater coatings to resist the attachment of marine organisms. Different betaine-based monomers and polymers were synthesized and incorporated within various coating formulations. The formulations and application methods were developed on aluminum panels with required adhesion strength and mechanical properties. The coating polymers were chemically stable under UV, hydrolytic and oxidative environments. The sulfobetaine formulations are applicable as nonleaching and stable underwater coatings. For the first time, coating formulations modified with highly packed sulfobetaine polymers were prepared and demonstrated resistance to a broad spectrum of marine organisms. Assays for comparing nonfouling performance were developed to evaluate protein adsorption and bacteria attachment. Barnacle settlement and removal were evaluated and a 60-day field test was performed. Silicone substrates including a commercial fouling release coating were used for comparison. Compared with the unmodified silicone substrates, the sulfobetaine-modified formulations were able to exhibit a 98% reduction in fibrinogen adsorption, 97.0% (E. coli), 99.6% (S. aureus), and 99.5% (C. lytica) reduction in bacteria attachment, and 100% reduction in barnacles cyprid attachment. In addition to the significant improvement in fouling resistance of various organisms, the 60-day field test also showed an evident efficacy from visual assessment, foul rating, and fouling removal test. The research confirmed that the novel antifouling mechanism of betaine polymers provides a new avenue for marine coating development. The developed coatings out-performed currently used nontoxic underwater coatings in a broad spectrum of fouling resistance. By further developing formulations and processing methods for specific devices, the technology is ready for the next stage of development with demonstration in MHK systems.