DNA Sequencing with Single-Stranded DNA Rectification in a Nanogap Gated by N-Terminated Carbon Nanotube Electrodes

Abstract

Fast, reliable, and inexpensive DNA sequencing is an important pursuit in healthcare, especially in personalized medicine with possible deep societal impacts. Despite significant progress in various nanopore-based sequencing configurations, challenges that remain in resolution and chromosome-size-long readout call for new approaches. Here we found strong rectification in the transversal current during single-stranded DNA translocation through a nanopore with side-embedded N-terminated carbon nanotube electrodes. Employing density functional theory and nonequilibrium Green's function formalisms, we show that the rectifying ratio (response to square pulses of alternating bias) bears high nucleobase specificity. Rectification arises because of bias-dependent resistance asymmetry on the deoxyribonucleotide−electrode interfaces. The asymmetry induces molecular charging and highest occupied molecular orbital pinning to the electrochemical potential of one of the electrodes, assisted by an in-gap electric-field effect caused by dipoles at the terminated electrode ends. We propose the rectifying ratio, due to its order-of-magnitude-difference nucleobase selectivity and robustness to electrode-molecule orientation, as a promising readout quantifier for single-base resolution and chromosome-size-long single-read DNA sequencing. The proposed configurations are within experimental reach from the viewpoint of both nanofabrication and small current measurement.

Field Effect and Local Gating in Nitrogen‐Terminated Nanopores (NtNP) and Nanogaps (NtNG) in Graphene

“…For ⊥ orientation this perturbation is negligible, while it is notable for ∥ orientation, because of negative charge excess Q and reduced distance of benzene from gap edges. In accordance with References [17] and, [37] we have previously shown [12] that even a small partial charge residing on the molecule in the gap (not in a weak coupling or quantum dot regime) can cause large energy shifts of molecular levels: negative charge on the molecule will result in positive energy shift of molecular energy levels [38] . Indeed, returning to Figure S2a, for ∥ orientation of benzene in the gap there is an upshift of HOMO energy compared to ⊥ orientation, E ⊥ HOMO ( X )< E ∥ HOMO ( X ), except for H termination, for which E ⊥ HOMO (H)= E ∥ HOMO (H).…”

“…Using a simple model we will show that termination‐dependent in‐gap electrostatic potential energy and, consequently, the HOMO shift, originates from dipoles formed at the interfaces of graphene sheets (Figures 3a,b) [12] . From TranSIESTA Hirshfeld population analysis of NtNG, it can be seen that dipoles are formed by negative charge accumulated on the N termination atomic row and positive charge located on the adjacent row of C atoms (Figure 3a), while in the HtNG case, positive charge resides on H atoms while negative is located on the adjacent row of C atoms (Figure 3b).…”

“…Tunneling current may vary by several orders of magnitude depending on whether molecular levels participate in transport or not. Resonant transport is commonly accomplished by a careful selection of electrode termination species either for weak interaction between the molecule and electrodes (hydrogen bonding or Van der Waals interaction) [7,9,10] and/or for inducing an electrostatic field with electrode interface dipoles [11,12] …”

Detecting Single Molecule Deoxyribonucleic Acid in a Cell Using a Three‐Dimensionally Integrated Nanopore

“…[ 51 ] Alternatively, it would be promising to embed nanoelectrodes to identify the nucleobase sequence by measuring the transverse electron transport through individual nucleotides. [ 52,53 ] Besides the genome analysis, the versatility of the nanopore sensor can allow to investigate intracellular materials other than DNA such as proteins [ 54 ] and vesicles [ 55 ] at a single‐molecule level, the ability of which may offer a powerful tool for multi‐omics.…”

Single-Entity Detection With TEM-Fabricated Nanopores

“…Djurišić et al achieved strong transversal current rectification of single-stranded DNA in N-terminated carbon nanotube (CNT) electrodes (Figure 2D) based on non-equilibrium (finite bias) Green's function (NEGF) + density functional theory (DFT). They developed a new sequencing approach with high nucleobase specificity (Djurišić et al, 2020). Likewise, the Leburton group used a combined theoretical-experimental method to analyze the variations (resistive effects) of the transverse current response during the translocation of protein and DNA molecules (Figure 2E) through a MoS 2 membrane nanoribbon (Xiong et al, 2020).…”