Molecular Scale Dielectric Sensors for Highly Sensitive Biomolecular Detection

Abstract

Capacitive sensors provide a promising alternative to conventional optical methods of detecting biomolecular interactions, due to their label-free operation, simple instrumentation and ease of miniaturization. Although several configurations of capacitive biosensors have been reported in the literature, physical and electrochemical properties of these structures and the measurement methods used have significantly limited their commercial development as biosensors. The existence of electrode polarization effect and noise from solution conductance limited the earlier dielectric spectroscopic measurements to high frequencies only, which in turn limited their sensitivity to biomolecular interactions, as the applied excitation signals were too fast for the charged macromolecules to respond. The series parasitic impedance from electrode polarization effect masked the dielectric changes occurring due to biomolecular interactions at low frequencies (<1 kHz).To address such challenges, we have developed a molecular scale capacitive sensing device with an electrode separation < 30nm. This nano-scale sensing area provides a window into bio-molecular interactions which was not previously attainable with macro or even micro scale devices. The interaction between the electrical double layers due to the space confinement decreases the potential drop across the electrode spacing and allows dielectric measurements at low frequency. As the double layers from both the capacitive electrodes merge together and occupy a major fraction of the dielectric volume, the contribution from bulk sample resistance in the measured impedance is eliminated. The dielectric properties during nucleic acid-protein interactions were measured using alpha thrombin and its aptamer. A 45-50% change in capacitance was observed due to aptamer-alpha thrombin binding at 10Hz. Highly sensitive capacitive detection of nucleic acid hybridization reactions was also demonstrated.