Periodic Reporting for period 1 - 2D-MES (Two Dimensional Molecular Electronics Spectroscopy for DNA/RNA Mutation Recognition)
Periodo di rendicontazione: 2020-07-01 al 2022-06-30
In this project, a combination of quantum mechanical and classical methods has been used with electronic transport techniques to evaluate the sensing capabilities of two-dimensional (2D) based biosensors to identify DNA and RNA nucleobases (NB) and mutations. Developing fast, reliable, and cost effective, yet practical DNA/RNA sequencing methods and devices is a must. The ability to sequence (i.e. determine the precise order of NBs within a DNA molecule) an organism’s genome and detect probable mutations has radically changed many aspects of molecular biology and genetics in both the academic and private sectors, with applications in molecular medicine, bio-archaeology, anthropology, evolution, forensics, agriculture and livestock breeding. One significant benefit is investigating various diseases and genetic illnesses caused by mutations, for which inexpensive and accurate methods for DNA sequencing are essential. Several computational methodologies, such as simulations of electronic transport in nanopore, or nanochannel-based biosensors, have been fruitfully used to address important phenomena related to DNA sequencing and detection at the molecular level. However, they generally either rely on quantum mechanics (QM) approaches, and are hence limited to small systems, or they employ molecular mechanics (MM) methods, which lack accuracy in certain sensitive cases. The market for next-generation approaches is expected to grow by up to $14 billion by 2024. Some of these approaches exploit the extraordinary properties of (2D) materials to recognize mutated DNA (or mRNA, messenger RNA that conveys the genetic information from DNA) bases at the single molecule level.) In this project, the new concept of Fano resonance-driven 2D molecular electronic spectroscopies (2D-MES), has been employed to enable the recognition of single NBs attached to a 2D material based nanoribbon (2DMNR), and expand it to study, not only isolated NBs, but a more realistic system which includes a complete DNA/RNA sequence in a solvent. In the 2D-MES method, the electrical conductance is calculated against both bias and gate voltages. Sharp dips and/or peaks in the electronic transmission due to the Fano resonance with such MOs represent the molecular fingerprints, which are different for each molecule. Mutation alters the MOs energy levels and their coupling strengths. Consequently, the 2D-MES method is able to distinguish mutated NBs from normal ones with high spatial resolution in a fast and non-expensive way.
In this project the molecular fingerprints of normal and mutated DNA/RNA nucleobases on various 2DMNR have been determined using the 2D-MES method, as well as determining the influence of the 2DMNR characteristics such as its width and the potential defects on the molecular adsorption and transport properties. The selected NBs are adenine (A), cytosine (C), guanine (G), thymine (T), uracil, 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC), in which the latter two were selected because of their potential role in cancer cell growth. The DFT codes VASP, SIESTA, and TranSIESTA have been utilized in the 2D-MES to firstly calculate the most stable conformation of the NB-2DMNR systems, and, subsequently calculate its transport characteristics.
To this end, transmission profiles of the introduced NB–2DMNR systems were calculated and it was shown that once a DNA/RNA base is adsorbed onto the 2DMNR's surface, the ballistic electron transfer mode exhibits a new path with dips at certain energies. To investigate the possibility of uniquely assigning the emerged Fano dips as molecular fingerprints to each nucleobase in 2DMNR based sequencing device, we calculate and plot the differential conductance (Δg) spectra of each NB–2DMNR system for a certain range of bias and gate voltages were calculated. Comparing the obtained 2D and three-dimensional (3D) Δg maps indicated that 2DMNR can be employed to unambiguously recognize and distinguish various NBs provided 2DMES is applied. By calculating the conductance sensitivity, it was also shown that 2DMNR is able to recognize various nucleobases with acceptable sensitivity under the application of 2DMES technique.
Motivated by the successful application of 2DMES method on graphene nanoribbon (GNR), the capability of germanene nanoribbons (GeNRs) and graphdiyne nanoribbons (AGDNRs) as a feasible, accurate, and ultra-fast sequencing device under the application of 2DMES was investigated. The calculated 2D and 3D Δg maps (Figure 1) for different studied systems, in contrast with 1D current–voltage profiles, exhibited explicitly distinct features which enable unambiguous recognition of nucleobases. This means that, in practice, providing the Δg spectrum for each NB while the NB is translocating the width of nanoribbon can be utilized for unambiguous molecular recognition. The provided Δg maps for various nucleobases can be stored in a data set for DNA/RNA sequencing purpose. Also, in order to demonstrate the admissible susceptibility of the introduced nano bio-sensors to recognize various bases, the conductance sensitivity of the proposed system was calculated and it was shown that the proposed devices can provide large sensitivities for different nucleobases at different gate voltage values, making it applicable for molecular sensing usages.
In order to extend the proposed method to the field of spintronics and the use of spin instead of charge, the structural, electronic, and spintronic properties of graphitic carbon nitride (g-C3N4) monolayers were investigated. Possessing remarkable structural, electronic, and magnetic characteristics, g-C3N4 can be a promising candidate to develop a spin driven nano-biosensor as well as a building block of futuristic nanoelectronics and spintronic systems. Using first-principles calculations, a comprehensive study on the structural stability as well as electronic and magnetic properties of triazine-based g-C3N4 nanoribbons (gt-CNRs) was performed.
To this end, transmission profiles of the introduced NB–2DMNR systems were calculated and it was shown that once a DNA/RNA base is adsorbed onto the 2DMNR's surface, the ballistic electron transfer mode exhibits a new path with dips at certain energies. To investigate the possibility of uniquely assigning the emerged Fano dips as molecular fingerprints to each nucleobase in 2DMNR based sequencing device, we calculate and plot the differential conductance (Δg) spectra of each NB–2DMNR system for a certain range of bias and gate voltages were calculated. Comparing the obtained 2D and three-dimensional (3D) Δg maps indicated that 2DMNR can be employed to unambiguously recognize and distinguish various NBs provided 2DMES is applied. By calculating the conductance sensitivity, it was also shown that 2DMNR is able to recognize various nucleobases with acceptable sensitivity under the application of 2DMES technique.
Motivated by the successful application of 2DMES method on graphene nanoribbon (GNR), the capability of germanene nanoribbons (GeNRs) and graphdiyne nanoribbons (AGDNRs) as a feasible, accurate, and ultra-fast sequencing device under the application of 2DMES was investigated. The calculated 2D and 3D Δg maps (Figure 1) for different studied systems, in contrast with 1D current–voltage profiles, exhibited explicitly distinct features which enable unambiguous recognition of nucleobases. This means that, in practice, providing the Δg spectrum for each NB while the NB is translocating the width of nanoribbon can be utilized for unambiguous molecular recognition. The provided Δg maps for various nucleobases can be stored in a data set for DNA/RNA sequencing purpose. Also, in order to demonstrate the admissible susceptibility of the introduced nano bio-sensors to recognize various bases, the conductance sensitivity of the proposed system was calculated and it was shown that the proposed devices can provide large sensitivities for different nucleobases at different gate voltage values, making it applicable for molecular sensing usages.
In order to extend the proposed method to the field of spintronics and the use of spin instead of charge, the structural, electronic, and spintronic properties of graphitic carbon nitride (g-C3N4) monolayers were investigated. Possessing remarkable structural, electronic, and magnetic characteristics, g-C3N4 can be a promising candidate to develop a spin driven nano-biosensor as well as a building block of futuristic nanoelectronics and spintronic systems. Using first-principles calculations, a comprehensive study on the structural stability as well as electronic and magnetic properties of triazine-based g-C3N4 nanoribbons (gt-CNRs) was performed.
The project provides insight into fundamental physical processes at the interface between solids, liquids and biomolecules, implying a broad knowledge of physics, chemistry, material science and biology. The project helped establish new bridges between the these fields and related communities by disseminating the results in conferences and journals. Usually, the above mentioned fields are separate fields with different methodologies, and researchers working on them belong to different communities sharing little communication. Thus, combining these fields is a distinctive feature of the project. The introduced and successfully employed 2DMES method also provided a new and reliable tool to provide an accurate data set in order to differentiate NBs and their mutated forms unambiguously.
DNA sequencing has been used in medicine including diagnosis and treatment of diseases and epidemiology studies. Sequencing has the power to revolutionize food safety and sustainable agriculture including animal, plant and public health, improving agriculture through effective plant and animal breeding and reducing the risks from disease outbreaks. Additionally, DNA sequencing can be used for protecting and improving the natural environment for both humans and wildlife.
DNA sequencing has been used in medicine including diagnosis and treatment of diseases and epidemiology studies. Sequencing has the power to revolutionize food safety and sustainable agriculture including animal, plant and public health, improving agriculture through effective plant and animal breeding and reducing the risks from disease outbreaks. Additionally, DNA sequencing can be used for protecting and improving the natural environment for both humans and wildlife.