Santermans Sybren, Schanovsky Franz, Gupta Mihir, Hellings Geert, Heyns Marc, Van Roy Willem, Martens Koen
IMEC, Kapeldreef 75, 3001 Leuven, Belgium.
Department of Materials Engineering, University of Leuven, Kasteelpark Arenberg 44, 3001 Leuven, Belgium.
ACS Sens. 2021 Mar 26;6(3):1049-1056. doi: 10.1021/acssensors.0c02285. Epub 2021 Jan 26.
Electrolyte screening is well known for its detrimental impact on the sensitivity of liquid-gated field-effect transistor (FET) molecular sensors and is mostly described by the linearized Debye-Hückel model. However, charged and pH-sensitive FET sensing surfaces can limit the FET molecular sensitivity beyond the Debye-Hückel screening formalism. Pre-existing surface charges can lead to the breakdown of Debye-Hückel screening and induce enhanced nonlinear Poisson-Boltzmann screening. Moreover, the charging of the pH-sensitive surface groups interferes with biomolecule sensing resulting in a pH interference mechanism. With analytical equations and TCAD simulations, we highlight that the Debye-Hückel approximation can underestimate screening and overestimate FET molecular sensitivity by more than an order of magnitude. Screening strengthens significantly beyond Debye-Hückel in the proximity of even moderately charged surfaces and biomolecule charge densities (≥1 × 10 q/cm). We experimentally show the strong impact of both nonlinear screening and the pH interference effect on charge-based biomolecular sensing using a model system based on the covalent binding of single-stranded DNA on silicon FET sensors. The DNA signal increases from 24 mV at pH 7 to 96 mV at pH 3 in 1.5 mM PBS for a DNA density of 7 × 10 DNA/cm. Our model quantitatively explains the signal's pH dependence with roughly equal nonlinear screening and pH interference contributions. This work shows the importance of reducing the net charge and the pH sensitivity of the sensing surface to improve molecular sensing. Therefore, tailoring the gate dielectric and functional layer of FET sensors is a promising route to strong silicon FET molecular sensitivity boosts.
电解质筛选因其对液栅场效应晶体管（FET）分子传感器灵敏度的不利影响而广为人知，并且大多由线性化的德拜 - 休克尔模型描述。然而，带电且对pH敏感的FET传感表面会限制FET分子灵敏度，超出德拜 - 休克尔筛选形式理论的范畴。预先存在的表面电荷会导致德拜 - 休克尔筛选失效，并引发增强的非线性泊松 - 玻尔兹曼筛选。此外，pH敏感表面基团的带电会干扰生物分子传感，从而产生pH干扰机制。通过解析方程和TCAD模拟，我们强调德拜 - 休克尔近似可能会低估筛选作用，并高估FET分子灵敏度超过一个数量级。在即使是适度带电的表面和生物分子电荷密度（≥1×10 q/cm）附近，筛选作用会显著增强，远超德拜 - 休克尔理论范围。我们通过基于单链DNA在硅FET传感器上共价结合的模型系统，实验证明了非线性筛选和pH干扰效应对基于电荷的生物分子传感的强烈影响。对于DNA密度为7×10 DNA/cm的情况，在1.5 mM PBS中，DNA信号从pH 7时的24 mV增加到pH 3时的96 mV。我们的模型定量解释了信号的pH依赖性，其中非线性筛选和pH干扰贡献大致相等。这项工作表明降低传感表面的净电荷和pH敏感性对于改善分子传感的重要性。因此，定制FET传感器的栅极电介质和功能层是大幅提高硅FET分子灵敏度的一条有前景的途径。
