FET-based biosensors (bioFETs) are transistors that can detect and quantify charged molecules, such as DNA, RNA, or proteins, in an aqueous environment. The detection is via the electric charge that such molecules intrinsically carry in aqueous environments, so extra labeling molecules and techniques are not required. As such, these devices hold promise for a rapid, portable, and cheap method for measuring biomolecule concentrations in liquid human samples at very low concentrations.

BioFETs have been around for a long time, but they really captured the attention of the scientific community in 2001, when a nanowire-shaped bioFET demonstrated protein detection at concentrations much lower than what had been demonstrated before. The invention was hailed as a breakthrough, and the extreme sensitivity of the nanowire bioFET compared to its non-nanoscale ancestors was attributed to the high surface-area-to volume ratio of the nanowire structure.

The surface-area-to-volume ratio argument has been put into very simple mathematical terms using basic electrostatic arguments. These arguments show that nanowire bioFETs become ever more sensitive as the size of the nanowire shrinks. This result has been widely accepted by the scientific community. Almost every new paper published on the topic cites the surface-area-to-volume ratio argument in its introduction as the justification for using a bioFET with a nanowire structure.

These mathematical equations fail to take into account the effect of Debye screening, which is detrimental to sensor performance because it screens the electric field emanating from the charged biomolecules. Using basic electrostatic arguments, and including the effect of Debye screening, we prove that when a nanowire is surrounded from all sides by the aqueous medium, its sensitivity actually decreases as its diameter shrinks, even while its surface-area-to-volume ratio increases. This result effectively disproves the justification given for the enhanced sensitivity of the nanowires.

We go a bit further, and use simulations to study nanowires that are placed on insulating substrates, as is more commonly encountered in experimental works. We show that within the concave corners created between the sides of the nanowire and the surface on which it sits, Debye screening is significantly weakened, so much so that the majority of the response of the nanowire bioFET is due to the detection of electric charges in these corners. In our simulations, the sensitivity of nanowires decreases with decreasing size when the nanowire is suspended in, and surrounded by, the aqueous medium, in agreement with analytical calculations. However, the trend is reversed for nanowires placed on insulating substrates, in qualitative agreement with experimental results reported in the literature.

These results disprove the surface-area-to-volume ratio argument as the cause of the enhanced sensitivity seen in nanowire bioFETs, and suggest that the concave corners are responsible instead.