The molecular origin of the electrostatic gating of single-molecule field-effect biosensors investigated by molecular dynamics simulations


Field-effect biosensors (bioFETs) offer a cutting-edge approach for measuring and monitoring the concentration of ions and various biomarkers such as DNA sequences and antibodies. These sensors can also be ultra-miniaturized to monitor the single-molecule kinetics of biomolecules. These special electronic circuits work based on generating electrical current whose variation correlates to the kinetics of the biomolecule process being studied.

Nanomaterials possess unique features which make them particularly attractive for biosensing medical applications. In particular, carbon nanotubes can serve as scaffolds for immobilization of biomolecules at their surface, and combine several exceptional physical, chemical, electrical, and optical properties which make them one of the most attractive materials for the transduction of signals associated with the recognition of analytes, metabolites, or disease biomarkers. Low-dimensional field-effect transistor, normally made of a single carbon nanotube joining two electrodes, is the main component of single-molecule bioFETs. The electronic properties of this electrical channel are strongly influenced by the local electric field, and its conductance is highly sensitive to the changes in the electrostatic potential (ESP) generated by the biomolecule under study. This makes it possible to determine the biomolecule kinetics by analyzing the kinetics of the measured conductance.

BioFETs, especially those made of a single carbon nanotube, have been used to investigate the kinetics of biomolecules in many studies. These studies have confirmed the strong influence of ESP on the conductance kinetics of bioFETs. Importantly, they have shown the influence of ionic solution concentration on the two-level conductance fluctuations, suggesting that the gating mechanism is naturally electrostatic. To date, there has been remarkable progress in exploring biomolecular structural ensemble and kinetics via experimental simulations. Nevertheless, the single-walled carbon nanotube-biomolecules interactions at the molecular level is yet to be fully explored in the context of carbon nanotube-bioFET devices.

On this account, Dr. Sébastien Côté, Professor Delphine Bouilly and Professor Normand Mousseau from the University of Montreal investigated the molecular origin of the ESP gating of single-molecule bioFETs using all-atom solvent explicit molecular dynamics. They tested two prototypical protein and nucleic acids systems characterized experimentally in previous studies: the sequence hybridization of a 10-nt DNA and the lysozyme protein function. Specifically, the ESP fluctuations on the carbon nanotube surface in response to the changes in the states of these two biomolecules were investigated and related to the experimentally obtained conductance fluctuations. Also, the interactions between the biomolecules and the nanotube and their corresponding impact on the biomolecule structural stability were explored. Their work is currently published in the Physical Chemistry Chemical Physics journal.

The research team showed that the ESP on the nanotube is strongly influenced by the conformational state of these two biomolecules and that the ESP is mostly localized near the anchor/graft point of the biomolecule on the nanotube. For the lysozyme, the two conductance levels previously observed as well as their dependence on salt concentration, were confirmed through the calculated ESP profiles. For the case of DNA, however, the predictions for conductance and its dependence on the salt concentration determined from the ESP profiles were different from those obtained experimentally, suggesting the possible influence of other mechanisms possibly due to specific interactions between the nanotube and the highly charged DNAs.

The researchers also showed that the carbon nanotube didn’t exhibit a significant impact on the lysozyme structural stability. In contrast, the nanotube significantly impacted the structure of single-stranded DNA, indicating again a much stronger non-trivial DNA-device interplay.

In summary, Canadian scientists reported molecular dynamics simulations on the characterization of the ESP generated by biomolecules on the carbon nanotube surface in the context of single-molecule bioFETs. The calculated ESP distributions for the molecular states illustrated the magnitude of the conductance variations measured experimentally. In a statement to Advances in Engineering, the authors stated that their findings strengthened the understanding of the inner working of bioFETs used for measuring and monitoring single-molecule kinetics of biomolecules and paved the way for new simulations to further characterize these devices at the molecular scale.

The molecular origin of the electrostatic gating of single-molecule field-effect biosensors investigated by molecular dynamics simulations - Advances in Engineering

About the author

Sébastien Côté received his PhD in physics from Université de Montréal in 2016. He joined the Cégep de Saint-Jérôme as a professor in physics in 2015. He is also an invited researcher in the Department of physics at Université de Montréal since 2019. His research is focused on using simulations to characterize low-dimensional biosensors. His goal is to support the development of these biosensors for biochemistry and and biomedical applications.



Côté, S., Bouilly, D., & Mousseau, N. (2022). The molecular origin of the electrostatic gating of single-molecule field-effect biosensors investigated by molecular dynamics simulationsPhysical Chemistry Chemical Physics, 24(7), 4174-4186.

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