Final Report Summary - SMART (Stimuli-responsive zipper-like nanobioreactors) Nanobioreactors are emerging and advanced devices resulting from the smart integration of nanobiotechnology and nanomaterials. Due to their ultimately small size, high surface area and simulation capacity, they are becoming a versatile tool and platform for making ultra-sensitive and selective novel nanobiosensors, which offers us new phenomena to tackle key medical and environmental issues. The current nanobioreactor research is focused on the fabrication of simple-to-use, inexpensive and ultra-sensitive biodevices mainly biosensors which could be highly selective, sensitive and stable. The novel nanobioreactor was designed to be capable of positively responding by creating unique 'zipper' nanoarchitectures. The zipper consists of a polymeric donor branch and a polymeric receptor branch, which was rationally assembled together based on a stoichiometric donor-receptor interaction. The fundamental design behind the fabrication of stimuli-responsive 'zipper' architectures is attractive and novel. Ideally, at a relatively low temperature the active donor-receptor interaction (ionic hydrogen bonding) creates a coalescence of both polymeric branches, thereby causing considerable shrinkages in the shell network. The access for biosubstrate to the nanobioreactor could be largely restricted, thus causing a decrease in the diffusion of reactants and the activity thereafter. On the contrary, at a relatively high temperature the donor-receptor interaction (ionic hydrogen bonding) was subverted. As a result, the biosubstrate could be freely accessed by the nanobioreactor, thus enabling feasible biosensing applications within the shell. Most importantly, the first example of positively responsive nanoreactors was achieved by controlling the external temperature as an on / off switchable model. As proposed, both branches of the 'zipper' was able to recognise and bind each other basing on the strong and highly complementary interactions. Furthermore, the stoichiometric ratio of donor / acceptor monomers was essentially required in order to produce the optimal 'zipper'. An excessive ratio of donor / acceptor monomers rendered one of the polymeric branches with the spatial mismatch to the other due to an overabundance of functional groups (i.e. binding sites) that distribute randomly throughout the matrix. On the contrary, an underestimated ratio of donor / acceptor monomers resulted in a system with an incomplete extent of self-assembly. Thus, the fundamental goal of this research project was to design, develop and verify a novel bioreactor platform with self-control abilities for advanced applications, e.g. switchable biocatalysis utilising nanotechnology. It was our strong and intense aspiration to design, construct, develop and apply the responsive nanoreactors in this project. By utilising such fascinating technology, we have conducted an investigation on stimuli-responsive zipper-like nanobioreactors, which was positively responsive to the substrate. Furthermore, their advanced applications in switchable biocatalysis and modulated protein processing were explored. In addition, the project was also developed some other novel methodologies and application strategies, which include molecular self-assembly, monitoring of dynamic phase transition and biocatalytic analysis and characterisations.