Another relevant experimental condition to reveal the AA fingerprints is the chemical interference from impurities or partial functionalization that may leave proton active radicals not originated on the AAs. For example, semiconductor FETs typically build the sensing interface upon an oxide dielectric in which oxide groups exposed to the electrolyte can also exchange protons, resulting in shifting the isoelectric point. Imperfect passivation of the oxide surface provokes these oxide groups to compete with the proton affinity sites of the AAs, resulting in a chemical interference in the system to study the peptide signatures. To overcome this issue, we can include in the simulation a percentage of non-functionalized groups, which could be calibrated a priori. Here, we have studied the case of Carboxyl-terminal immobilized aspartic acid (D) having an amine and carboxylic sidechain with SiO2 as a gate oxide for the FET. We have simulated different partial functionalizations that result in a percentage of silanol groups from the dielectric barrier interfering with the active reactive sites of the AAs. The total surface states (NT) are composed of attached analytes (AA) (NAA) and the free silanol sites (NOH = NT -NAA) which are contributing to the surface charge density ( > ). Figure (a) shows the simulations for δΨo 2 /δpH 2 for Carboxyl-terminal immobilized aspartic acid in the presence of silanol sites where we represent the percentage of silanol groups with colors degradations from 0 (lighter color, perfect functionalization) to 100% (darker color, pure silica groups) in steps of 10% of the total surface states. The presence of silanol sites changes the surface potential and isoelectric point due to the superposition of charge from the protonated/ deprotonated silanol radicals with the AA depending on the pH value. The silanol site (pKa = -2) is more reactive to acquire a negative charge as compared to the carboxylic radical of D (pK = 3.65) but silanol site (pKb = 6) is less effective in protonating as compared to the amine radical of D (pK = 9). As the percentage of the silanol sites increases from a low value (0%) to 10%, the surface potential tends to have lower values due to a more acidic dissociation constant of silanol sites as compared to the carboxyl sites of aspartic acid [Surface potential shown in supplementary material, Figure SI 7]. The zero-crossover point of the double gradient correlates with the isoelectric point of the system with either 100% AA or silanol sites. The isoelectric point shift to acidic values as the percentage of the silanol sites keeps increasing due to the higher effect of smaller dissociation constants of silanol radicals. In the presence of reactive sites from AA and silanol, the zero-crossover point depicts the change in slope of surface potential and the ascendancy of the silanol over the AAs. At lower silanol contributions, D dominates the behaviour in δΨo 2 /δpH 2 , which are more significant in the range of alkaline pH values as compared to the acidic range due to the early deprotonation of silanol radicals. As the isoelectric point shifts to more acidic values, the maxima of δΨo 2 /δpH 2 associated with the amino groups however shift to the right to leave space for changes in convexity that occur because of the contributions from the silanol groups to the electrostatic equilibrium with the double layer capacitance. Because of these contributions, the linearity of the surface potential increases flattening δΨo 2 /δpH 2 , making precisely the most linear contribution at 50% contribution from each of the reactive sites. In the presence of a high contribution of silanol sites that decreases the effective affinity of the surface for protonation as compared to the individual amine sites of D, the behaviour is dominated by the silanol groups and the peaks of δΨo 2 /δpH 2 are then observed in the acidic range of pH.