Title Monitoring Protamine‐Heparin Interactions Using Microcapillary Impedimetric Sensor

We report an impedimetric sensor based on an interdigitated electrode array with electrode digits located at the bottom of microcapillaries formed in silicon dioxide which is used to monitor protamine‐heparin interactions. Modification of the active sensor surface with protamine, a cationic protein used as a high affinity heparin antagonist, permits to register protamine‐heparin complex formation as changes in the surface conductivity determined from the sensor impedance measured in an electrolyte solution. The adsorption curve shows that the detection limit is close to 0.01 U/mL (50 ng/mL) of heparin. The kinetics of the protamine‐heparin complex formation is rather slow and requires at least 15 min to be accomplished. Heparin reaction with protamine is irreversible, however, it is possible to renew the sensor surface putting it in contact with protamine solution and thus use the sensor several times. The future prospects for the proposed sensing strategy are quite wide and can include the grafting of the sensor surface with modified nanoparticles, magnetic particles or self‐assembled structures based on small synthetically‐accessible molecular‐scale building blocks which can act as protamine mimetics.