Single-biomolecule detection technologies with high throughput and high accuracy can provide vital knowledge that can revolutionize the field of medical science and biology. In fact, such sensors are expected to be utilized as innovative technologies in the future development of medical treatments and drugs. Of the current technologies, the use of nanopores in solid-state membranes has been proven to be compelling in the quest for the fast and accurate biomolecule sensing without labeling or functionalization by monitoring electronic signals. Among all the materials of choice for nanoporous membranes, two-dimensional (2D) solid-state materials such as graphene and transition metal dichalcogenides (TMDs) stand out because of their sub-nanometer thickness comparable to the DNA base pair separation. However, previous research showed graphene nanopores had only partial success; i.e. they were impaired by the strong hydrophobic interaction between the membrane and nucleotides that results in severe sticking and clogging during DNA translocation. As an alternative, DNA translocation through the pore can be detected by variations of the transverse electronic current flowing along semiconducting TMD membranes such as molybdenum disulfide (MoS2) that are less hydrophobic than graphene.
Overall, given the intricacy of nanopore systems involving the electric interaction between: biomolecules, ions in the electrolyte, and the 2D solid-state membranes, three different interpretations have been proposed to explain the origin of the transverse electronic current variations in the 2D membranes caused by the presence of DNA in the nanopore. Nonetheless, no microscopic model has emerged to provide a coherent interpretation of the transverse current response to the DNA translocations in solid-state nanoribbon nanopores. In particular, the recent experimental observation of transverse current variations dependent on the charge sign of the translocating biomolecules has not received a rigorous theoretical foundation. Considering all these, University of Illinois researchers: Dr. Mingye Xiong, Dr. Nagendra Athreya and led by Professor Jean-Pierre Leburton, in collaboration with Dr. Michael Graf and Dr. Aleksandra Radenovic at the Federal Polytechnic of Lausanne designed a systematic microscopic analysis of the various resistive effects involved in the electronic detection of single biomolecules in a nanopore of a MoS2 nanoribbon. Their work is currently published in the research journal, ACS Nano.
In their approach, a comprehensive semiclassical analysis of the electronic current variation in a wide MoS2 nanopore nanoribbon, which combines experimental transport characterization of the membrane with molecular dynamics and Poisson−Boltzmann modeling, was implemented. The model used considered the electrostatic potentials perturbing the charge carriers induced by the combined effect of the biomolecules, electrolyte, and ion screening around the pore rim, which produces variations in the transverse current signal across the membrane.
The research team expounded that the variations of the transverse electronic current along the two-dimensional (2D) membrane due to the translocation of DNA and protein molecules through the pore were obtained by model calculations based on molecular dynamics (MD) and Boltzmann transport formalism, which achieved good agreement with the experimental data. Moreover, their analysis pointed out to a self-consistent interaction among ions, charge carriers around the pore rim, and biomolecules.
In summary, the study utilized a thorough combined experimental−theoretical approach to analyze in detail the biosensing process in a nanopore by transverse electronic current variations in a MoS2 membrane nanoribbon. Remarkably, their microscopic analysis offers a direct connection between the transverse current response to biomolecule translocations in the nanopore and the different components of the electrical resistance of the membrane, i.e., electrolyte, open pore, and DNA motion. In a statement to Advances in Engineering, the lead author, Professor Jean-Pierre Leburton explained that their study provides a comprehensive understanding of the effects of the electrolyte concentration, pore size, nanoribbon geometry, and also the doping polarity of the nanoribbon on the electrical sensitivity of the nanopore in detecting biomolecules. He further added that their results can be utilized for finetuning the design parameters in the fabrication of highly sensitive 2D nanopore biosensors.
Mingye Xiong, Michael Graf, Nagendra Athreya, Aleksandra Radenovic, and Jean-Pierre Leburton. Microscopic Detection Analysis of Single Molecules in MoS2 Membrane Nanopores. ACS Nano 2020: volume 14, page 16131−16139.