Effect of Ionic Atmosphere around DNA/Electrolyte Interface on Potentiometric Signal

Abstract

Biomolecular recognitions with an ion sensitive field effect transistor (ISFET) are mostly reported to strongly depend on the structure and dynamics of the electric double layer (EDL) at the gate electrode/electrolyte interface, while the effect of an ionic behavior around a biomolecule/electrolyte interface on the potentiometric detection has not been clarified. In this study, we investigated the behavior of water and ions around a DNA/electrolyte interface using molecular dynamics (MD) simulations, where the charge distribution may induce a field effect contributing to electrical signals of a DNA-modified ISFET sensor. As a result, MD simulations showed that the interfacial charge distribution with a gentle slope (ionic atmosphere) was more clearly found around the DNA duplex at a lower concentration of NaCl electrolyte, while the counter ion condensation was observed nearby the DNA duplex with increasing the concentration of NaCl electrolyte. This means the EDL structure was found at the DNA/electrolyte interface. Such an ionic atmosphere around the DNA duplex would cause the shift in the threshold voltage for DNA molecular recognition events such as hybridization on the gate of ISFET. Our knowledge based on the MD simulation for the biomolecule/electrolyte interface contributes to design and develop an optimum device on potentiometric biosensors.

In Situ Electrical Monitoring of Methylated DNA Based on Its Conformational Change to G-Quadruplex Using a Solution-Gated Field-Effect Transistor

“…According to eq , the Debye length increases with decreasing ionic strength. The effect of ionic strength on the electrical signals of FET-based sensors has been analyzed in previous studies. , The Debye length could be roughly calculated as a few nanometers in the measurement solution used in this study. However, this estimation is doubtful because the effect of the polymer brush grafted onto the Au gate surface was not considered.…”

Biologically Coupled Gate Field-Effect Transistors Meet in Vitro Diagnostics

“…On the other hand, the ionic environment around DNA molecules was considered to affect the equilibrium reaction between hydrogen ions and hydroxy groups at the oxide surface according to the results of a molecular dynamics (MD) simulation. 45 This may mean that biomolecules such as DNA have a diffusion layer around themselves, although the effect of such an ionic environment on the electrical signal should also depend on the ionic strength in the electrolyte solution. That is, various biomolecular recognition events may be detected as a change in pH at the oxide gate when the ISFET sensors are used, as shown in Figure 2c.…”

“…Although the effect of the ionic environment around biomolecules may still be experimentally unclear, MD simulation is a good tool for predicting such ionic behaviors at electrolyte solution/biomolecule/gate interfaces. 42,43,45,46…”

“…(d) Genotyping analysis based on the DNA extension reaction with ISFET. Credit: from ref (24), reprinted with permission from Wiley (a); from ref (28), reprinted with permission from Elsevier (b, d); from ref 45 reproduced with permission from The Electrochemical Society (c).…”

“…The distance from the gate surface at which molecular detection can occur strongly depends on the ionic strength in an electrolyte solution and is known as the Debye length based on an electric double layer (EDL). Ionic behaviors, which contribute to electrical signals, are often discussed by considering an EDL composed of two layers: the Stern layer of the ionic monolayer and the diffusion layer, which balances electrical forces with ion diffusivity. − As shown in Figure a, 17-base target DNA, the length of which was ideally calculated as 5.78 nm, was detected as a change in threshold voltage of Δ V T = 12 mV owing to hybridization in a 25 mM phosphate buffer solution, where the Debye length was roughly calculated to be ∼2 nm at most. In addition, extended DNA molecules with 21–61 bases obtained by the enzymatic reaction with DNA polymerase were detected as Δ V T in a 25 mM phosphate buffer solution, but the electrical signals were not quantitatively obtained for the extended DNA molecules with a base length of over 51 (>17.34 nm), as shown in Figure b .…”