Maximizing the Signal Gain of Electrochemical-DNA Sensors

Abstract

Electrochemical DNA (E-DNA) sensors have emerged as a promising class of biosensors capable of detecting a wide range of molecular analytes (nucleic acids, proteins, small molecules, inorganic ions) without the need for exogenous reagents or wash steps. In these sensors, a binding-induced conformational change in an electrode-bound “probe” (a target-binding nucleic acid or nucleic-acid-peptide chimera) alters the location of an attached redox reporter, leading to a change in electron transfer that is typically monitored using square-wave voltammetry. Because signaling in this class of sensors relies on binding-induced changes in electron transfer rate, the signal gain of such sensors (change in signal upon the addition of saturating target) is dependent on the frequency of the square-wave potential pulse used to interrogate them, with the optimal square-wave frequency depending on the structure of the probe, the nature of the redox reporter, and other features of the sensor. Here, we show that, because it alters the driving force of the redox reaction and thus electron transfer kinetics, signal gain in this class of sensors is also strongly dependent on the amplitude of the square-wave potential pulse. Specifically, we show here that the simultaneous optimization of square-wave frequency and amplitude produces large (often more than 2-fold) increases in the signal gain of a wide range of E-DNA-type sensors.

Interplay of Effective Surface Area, Mass Transport, and Electrochemical Features in Nanoporous Nucleic Acid Sensors

“…When the sensor is challenged with a complementary target, the observed MB redox current decreases significantly. Hybridization induces a large conformational change in the surfaceconfined DNA structure, which in turn significantly alters the electron-transfer tunneling distance between the electrode and the redox label 4,5 . The hybridization event is as such registered as a percent signal suppression.…”

Nanomaterials for molecular signal amplification in electrochemical nucleic acid biosensing: recent advances and future prospects for point-of-care diagnostics

“…27,28 These methods however require system-specific optimization to maximize the signal gain, by tuning the pulse amplitude, frequency, and sampling time. 29…”

Recent Developments of Electrochemical and Optical Biosensors for Antibody Detection

“…Many current biosensor platforms rely on externally labeled biomolecules in order to process a transducing signal [39][40][41][42][43]. A non-label platform was developed to simplify the detection process for pathogens like hantaviruses ( Figure 3c) [44].…”