Responsive interface switchable by logically processed physiological signals: Toward "smart" actuators for signal amplification and drug delivery

Biomarkers characteristic of liver injury, alanine transaminase and lactate dehydrogenase, were processed by an enzyme-based system functioning as a logic AND gate. The NAD⁺ output signal produced by the system upon its activation in the presence of both biomarkers was then biocatalytically converted to a decrease in pH. The acidic pH value biocatalytically produced by the system as a response to the biomarkers triggered the restructuring of a polymer-modified electrode interface. This allowed a soluble redox species to approach the electrode surface, thus switching the electrochemical reaction ON. The redox transformations activated by the biochemical signals resulted in an amplification of signals. This system represents the first example of an integrated sensing-actuating chemical device with the implemented AND Boolean logic for processing natural biomarkers at their physiologically relevant concentrations.