Microfabricated high-performance microwave impedance biosensors for detection of aptamer-protein interactions

Abstract

High-frequency impedance biosensors with nanometer gaps have been prepared for the detection of biomolecular interactions such as protein-antibody and protein-aptamer binding. The sensor principle is based on electrical impedance changes measured at 1.2 GHz due to changes of the effective dielectric constant within the 68 nm gaps between two gold electrodes. As a model system, the specific binding of the blood clotting factor human thrombin with different concentrations to its ribonucleic acid (RNA) α-thrombin aptamer, as well as the immobilization process of the RNA-aptamer, have been detected in real time. By using a similar 68 nm-gap sensor blocked with bovine serum albumin and a reference sensor with 10μm electrode spacing, signal changes due to variations of the bulk dielectric constant due to buffer/analyte solutions, and unspecific binding events have been analyzed.

Electrochemical Aptasensors

“…High frequency nanogap-impedance aptasensors have been reported for the label-free detection of thrombin [69,70] or a smaller size target, Rev peptide (2.4 kDa) [71]. For these structures, the analysis of the full frequency spectrum using appropriate equivalent circuits is not required.…”

Emerging applications of aptamers to micro- and nanoscale biosensing

“…Another method of electroanalytical measurement common in aptasensors is the use of impedance (Degefa and Kwak 2008;Du et al 2008;Lee et al 2008;Li et al 2008;Lohndorf et al 2005;Xu et al 2005Xu et al , 2006. Whereas common electrochemical techniques (e.g., cyclic voltammetry) employ DC current, electrochemical impedance spectroscopy (EIS) uses an identical set of connections with alternating current signals to achieve an accurate measurement of surface charge.…”

Molecularly Bridged Gold Nanoparticle Array for Sensing Applications

“…[24][25][26][27] In particular, the combination of top-down and bottom-up approaches has been a successful strategy for providing the desired configuration, placement of molecules into the nanospace, and realizing promising molecular recognition results. [12][13][14][28][29][30][31][32][33][34] In principle, bottom-up fabrication is achieved through the binding, interaction, self-assembly, and self-organization characteristics of molecules and materials as building blocks. [35][36][37][38][39] Precise control of the spacing between the fabricated electrodes for specific molecules is expected to allow ultrasensitive sensing.…”