Set-Reset Flip-Flop Memory Based on Enzyme Reactions: Toward Memory Systems Controlled by Biochemical Pathways

The enzyme-based set-reset flip-flop memory system was designed with the core part composed of horseradish peroxidase and diaphorase biocatalyzing oxidation and reduction of redox species (2,6-dichloroindophenol or ferrocyanide). The biocatalytic redox reactions were activated by H2O2 and NADH produced in situ by different enzymatic reactions allowing transformation of various biochemical signals (glucose, lactate, D-glucose-6-phosphate, ethanol) into reduced or oxidized states of the redox species. The current redox state of the system, controlled by the set and reset signals, was read out by optical and electrochemical means. The multiwell setup with the flip-flop units separately activated by various set/reset signals allowed encoding of complex information. For illustrative purposes, the words Clarkson and then University were encoded using ASCII character codes. The present flip-flop system will allow additional functions of enzyme-based biocomputing systems, thus enhancing the performance of multisignal biosensors and actuators controlled by logically processed biochemical signals. The integrated enzyme logic systems and flip-flop memories associated with signal-responsive chemical actuators are envisaged as basic elements of future implantable biomedical devices controlled by immediate physiological conditions.