Programmable ion-sensitive transistor interfaces. III. Design considerations, signal generation, and sensitivity enhancement

Abstract

We report on factors that affect DNA hybridization detection using ion-sensitive field-effect transistors (ISFETs). Signal generation at the interface between the transistor and immobilized biomolecules is widely ascribed to unscreened molecular charges causing a shift in surface potential and hence the transistor output current. Traditionally, the interaction between DNA and the dielectric or metal sensing interface is modeled by treating the molecular layer as a sheet charge and the ionic profile with a Poisson-Boltzmann distribution. The surface potential under this scenario is described by the Graham equation. This approximation, however, often fails to explain large hybridization signals on the order of tens of mV. More realistic descriptions of the DNA-transistor interface which include factors such as ion permeation, exclusion, and packing constraints have been proposed with little or no corroboration against experimental findings. In this study, we examine such physical models by their assumptions, range of validity, and limitations. We compare simulations against experiments performed on electrolyte-oxide-semiconductor capacitors and foundry-ready floating-gate ISFETs. We find that with weakly charged interfaces (i.e., low intrinsic interface charge), pertinent to the surfaces used in this study, the best agreement between theory and experiment exists when ions are completely excluded from the DNA layer. The influence of various factors such as bulk pH, background salinity, chemical reactivity of surface groups, target molecule concentration, and surface coatings on signal generation is studied. Furthermore, in order to overcome Debye screening limited detection, we suggest two signal enhancement strategies. We first describe frequency domain biosensing, highlighting the ability to sort short DNA strands based on molecular length, and then describe DNA biosensing in multielectrolytes comprising trace amounts of higher-valency salt in a background of monovalent saline. Our study provides guidelines for optimized interface design, signal enhancement, and the interpretation of FET-based biosensor signals.

Dynamic behaviour of the silica-water-bio electrical double layer in the presence of a divalent electrolyte

“…3,21 The EDL structure in turn can be affected by dense biomolecule layers through ion-exclusion; mathematical models incorporating ion-exclusion effects have been shown to describe experimental signal measurements of DNA hybridisation better than more conventional EDL models. 15 Recent experimental work recognises the importance of ion dynamics in BioFET engineering, with deterministic information extracted from BioFET signals in the frequency domain of the response 15,22,23 which has been explained as a result of adsorption-desorption noise of biomolecules 24 and perturbed charge fluctuations in the EDL. 25 Experiments have shown a decrease in low frequency noise with increased ionic strength due to increased screening competition between the EDL and the semiconductor device.…”

“…Not only has the presence of divalent ions recently been shown to increase BioFET sensitivity, [15][16][17] but the electric field and ion-dynamics at the interface are thought to be crucial in determining field effect biosensor response.…”

Field-effect sensors – from pH sensing to biosensing: sensitivity enhancement using streptavidin–biotin as a model system

“…69,74,142 Shalev et al provided evidence to suggest that biomolecular sensing may be a result of biomolecules altering the chemical equilibria of titratable groups on the surface, and therefore for some systems pH-Sensitivity and biomolecular-Sensitivity are expected to be related. 69 In this analysis pH-sensing and biomolecular-sensing Sensitivity have been considered separately.…”

“…Assuming electrostatic gating, the shift in the threshold voltage (ΔV T ) is related to the shift in surface potential at the oxide-electrolyte interface (Δψ o ) (discussed in ESI section 2 †). The precise relationship between the addition of biomolecular charge and the change in surface potential remains one of the most important modelling problems in this field, 20,[140][141][142][149][150][151][152][153][154][155][156][157][158] however an appealing model, due to its simplicity, is to approximate the oxide-electrolyte interface as a parallel plate capacitor (Helmholtz-Perrin Theory). 159 The change in charge on the surfaces of the capacitor, ΔQ, with capacitance C 0 can give the voltage shift simply as:…”

Critical Assessment on Modeling and Design of Nonfaradaic CMOS Electrochemical Sensing

“…As the present study focuses on the physical model extraction instead of device design on a specific analyte of interest [33][34][35][36], such proportional effects in the numerous design tradeoffs are left for future work.…”