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Natural silk fibroin protein has been used for the fabrication of bio-memristors. The origin of the resistive switching characteristics is investigated in detail. The conduction mechanism in silk protein is found to be controlled by multi-charge transport mechanisms along with filamentary type conduction process. The redox process via hopping mechanism is found to be responsible for charge transport in silk protein. The low-frequency noise (LFN) study reveals that the fluctuation in the current level is due to the traps existing near the conducting filaments (CFs). It is shown for the first time that the amide I region is mainly responsible for the conductivity change in silk fibroin protein-based bio-memristors under appropriate bias (polarity and magnitude) condition.