Nanogap Dielectric Spectroscopy for Aptamer-Based Protein Detection

Abstract

Among the various label-free methods for monitoring biomolecular interactions, capacitive sensors stand out due to their simple instrumentation and compatibility with multiplex formats. However, electrode polarization due to ion gradient formation and noise from solution conductance limited early 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. To minimize electrode polarization effects, capacitive sensors with 20 nm electrode separation were fabricated using silicon dioxide sacrificial layer techniques. The nanoscale separation of the capacitive electrodes in the sensor results in an enhanced overlapping of electrical double layers, and apparently a more ordered "ice-like" water structure. Such effects in turn reduce low frequency contributions from bulk sample resistance and from electrode polarization, and thus markedly enhance sensitivity toward biomolecular interactions. Using these nanogap capacitive sensors, highly sensitive, label-free aptamer-based detection of protein molecules is achieved.

An impedance-based integrated biosensor for suspended DNA characterization

“…1b). In contrast with the parallel electrode architecture described in the literature2122, which measures the direct (as opposed to fringing) capacitance, the planar electrodes used in this work, take advantage of the fringing field capacitance in the solution (see Supplementary Note online). The sensing electrode was connected to the surrounding circuits.…”

Fabrication of a Horizontal and a Vertical Large Surface Area Nanogap Electrochemical Sensor

“…It is well reported that the low-frequency dielectric response is dominated by the ionic relaxation of the buffer [32,41,42,43], complicating detection. The complex composition of the PBS buffer (0.01 M phosphate buffer, 2.7 mM KCl, 0.137 M NaCl) may be the source of this behaviour.…”

Inkjet-printed Ag electrodes on paper for high sensitivity impedance measurements

“…These sensors are now widely applied in detections of various scales, e.g. DNA [21][22][23] , proteins 24,25 , cells 26,27 and bacteria 28 . For impedance-based measurements, an electrode-electrolyte double layer will be formed at the electrode surface, and this double layer capacitance behaves as a parasitic component to reduce the sensitivity 29 .…”