Theoretical Optimization Method of Buffer Ionic Concentration for Protein Detection Using Field Effect Transistors

Abstract

Field effect transistors (FETs) may respond to charge variations occurring when proteins are adsorbed to the gate surface. The electrolyte electrostatic screening allows a practical detection of charges that are only within a distance of approximately the double layer thickness, which is related to the Debye length in the electrolyte. Hence, operating the FET biomolecular sensors at the highest possible ionic concentration improves reproducibility; however, it may reduce the signal if the concentration is too high. Here, we propose an optimization method of the buffer ionic concentration using a figure of merit “charge number,” Znormald , which is defined as the ratio between the effective number of the surface charges and the number of immobilized molecules. The theoretical Znormald was calculated using a three-dimensional conformation data taken from the Protein Data Bank. The Znormald was obtained from the total number of four charged amino acids of avidin, arginine (positive), lysine (positive), aspartic acid (negative), and glutamic acid (negative), which are within the double layer length from the surface. To verify this model, we chose avidin–biotin interaction. The experimental Znormald , which was obtained for three buffer concentrations, matched the theoretical Znormald . This method shortens the solution calibration time and reduces the analyte amount.

Relation between Effective Charge Numbers and Signals Caused by Protein Adsorption on Field Effect Transistor Detection

“…2). Extending the Debye length resulted in the increase in the charge numbers (3). On the other hand, the charge numbers of a streptavidin molecule were constant with the Debye length, which were about equal to zero (Fig.…”

“…ψ effective ≈ ψ e -κx [3] λ D = κ -1 [4] where ψ effective is the effective electrical potential, ψ the electrical potential, x the distance from the surface, and λ D the Debye length. It is known that Debye length (λ D ) appears as length in which the attenuation of electrical potential, ψ is characterized (6).…”

Improved Model for Nanowire BioFETs on SOI Operating in Electrolyte

“…This can be modelled using sophisticated analysis of the electrostatics (27) or using simple models (28). The pH dependence of the charges on the amino acids easily could be included in the simulations.…”

Biomolecule detection based on Si single-electron transistors for highly sensitive integrated sensors on a single chip

“…To avoid the problem of Debye screening, we chose the ion concentrations in the buffer solution such that the Debye screening length was sufficiently long to enable detection and sufficiently short to screen unbound biomolecules. 16 At the same time, the pH of the buffer solutions was set to 8.0-8.2 since the isoelectric point of streptavidin is pH 5-6. 10 Therefore, the streptavidin was negatively charged in the buffer solution.…”