Kazumichi Yokota

Identifying single nucleotides by tunnelling current

A major goal in medical research is to develop a DNA sequencing technique that is capable of reading an entire human genome at low cost. Recently, it was proposed that DNA sequencing could be performed by measuring the electron transport properties of the individual nucleotides in a DNA molecule. Here, we report electrical detection of single nucleotides using two configurable nanoelectrodes and show that electron transport through single nucleotides occurs by tunnelling. We also demonstrate statistical identification of the nucleotides based on their electrical conductivity, thereby providing an experimental basis for a DNA sequencing technology based on measurements of electron transport.

Fabrication of the gating nanopore device

We synthesized gating nanopores with embedded nanogap electrodes in a solid-state nanopore using an 11-step nanofabrication process. We were able to detect Au nanoparticles passing through a 30-nm-diameter gating nanopore via an electric current between nanoelectrodes. The electric current was proportional to the duration of translocation time. The gating nanopore is expected to be a next-generated nanosystem that can be applied to single-molecule sensors.

Detection of post-translational modifications in single peptides using electron tunnelling currents

Post-translational modifications alter the properties of proteins through the cleavage of peptide bonds or the addition of a modifying group to one or more amino acids. These modifications allow proteins to perform their primary biological functions, but single-protein studies of post-translational modifications have been hindered by a lack of suitable analysis methods. Here, we show that single amino acids can be identified using electron tunnelling currents measured as the individual molecules pass through a nanoscale gap between electrodes. We identify 12 different amino acids and the post-translational modification phosphotyrosine, which is involved in the process that switches enzymes on and off. Furthermore, we show that the conductance measurements can be used to partially sequence peptides of an epidermal growth factor receptor substrate, and can discriminate a peptide from its phosphorylated variant.

Inelastic electron tunneling spectroscopy of single-molecule junctions using a mechanically controllable break junction.

We report the use of electrical measurements to identify simultaneously the number and type of organic molecules within metal-molecule-metal junctions. Our strategy combines analyses of single-molecule conductance and inelastic electron tunneling spectra, exploiting a nanofabricated mechanically controllable break junction. We found that the peak linewidth of the inelastic electron tunneling spectrum decreased as the modulation voltage and temperature decreased, and that the selection rule for inelastic electron tunneling spectroscopy agrees with that for Raman spectroscopy. Furthermore, the differential conductance curve of the single-molecule junction suggests that it has asymmetrical electrode-molecule coupling.

Identifying molecular signatures in metal-molecule-metal junctions

Single molecule identification in metal-molecule-metal junctions provides an ultimate probe that opens a new avenue for revolutionary advances in demonstrating single molecule device functions. Inelastic electron tunneling spectroscopy (IETS) is an ultra-sensitive method for probing vibrational characteristics of molecules with atomic resolution. State-of-the-art experiments on the inelastic transport in self-assembled monolayers of organic molecules have demonstrated the utility of the IETS technique to derive structural information concerning molecular conformations and contact configurations. Here we report the vibrational fingerprint of an individual pi-conjugated molecule sandwiched between gold nanoelectrodes. Our strategy combines analyses of single molecule conductance and vibrational spectra exploiting the nanofabricated mechanically-controllable break junction. We performed IETS measurements on 1,4-benzenedithiol and 2,5-dimercapto-1,3,4-thiadiazole to examine chemical discrimination at the single-molecule level. We found distinct IET spectra unique to the test molecules that agreed excellently with the Raman and theoretical spectra in the fingerprint region, and thereby succeeded in electrical identification of single molecule junctions.

Particle Trajectory-Dependent Ionic Current Blockade in Low-Aspect-Ratio Pores

Resistive pulse sensing with nanopores having a low thickness-to-diameter aspect-ratio structure is expected to enable high-spatial-resolution analysis of nanoscale objects in a liquid. Here we investigated the sensing capability of low-aspect-ratio pore sensors by monitoring the ionic current blockades during translocation of polymeric nanobeads. We detected numerous small current spikes due to partial occlusion of the pore orifice by particles diffusing therein reflecting the expansive electrical sensing zone of the low-aspect-ratio pores. We also found wide variations in the ion current line-shapes in the particle capture stage suggesting random incident angle of the particles drawn into the pore. In sharp contrast, the ionic profiles were highly reproducible in the post-translocation regime by virtue of the spatial confinement in the pore that effectively constricts the stochastic capture dynamics into a well-defined ballistic motion. These results, together with multiphysics simulations, indicate that the resistive pulse height is highly dependent on the nanoscopic single-particle trajectories involved in ultrathin pore sensors. The present finding indicates the importance of regulating the translocation pathways of analytes in low-aspect-ratio pores for improving the discriminability toward single-bioparticle tomography in liquid.

Molecule-Electrode Bonding Design for High Single-Molecule Conductance

We report the application of an intermolecular interaction design for organic conductor crystals with a high conductance to a molecule-electrode design for a high single-molecule conductance by using dithiol and diselenol terthiophenes. We found that dithiol and diselenol single-molecule junctions show the highest single-molecule conductance among single-molecule junctions with Au-S and Au-Se bonds, and that diselenol single-molecule junctions have a higher single-molecule conductance than dithiol ones. We demonstrate that replacing S atoms with Se atoms is a promising molecule-electrode bonding design for a high single-molecule conductance.

Electrode-embedded nanopores for label-free single-molecule sequencing by electric currents

Electrode-embedded nanopores have been developed to realize label-free, low-cost, and high-throughput DNA sequencers and are recognized as a promising platform along with solid-state and biological nanopore devices for use in personalized medicine based on genomic information. Rapid and high-speed measurements for single nucleotide molecules are enabled through direct electrical probes and control without either amplification processes or chemical reagents. This new nanoarchitecture can sequence DNA and RNA molecules owing to the changes in the tunneling current conducted via single-base molecules passing through the nanopores. The method for controlling the translocation speed of single DNA and RNA molecules is a critical technology for reading single-base molecules with high accuracy and throughput.

Mechanically-controllable single molecule switch based on configuration specific electrical conductivity of metal–molecule–metal junctions

We report the systematic characterization of configuration-specific electrical conductivity in metal–molecule–metal structures for a demonstration of mechanically controllable contact effect single-molecule switches. Break junction measurements reveal two distinct conductance states of GH ∼ 1.3 mG0 and GL ∼ 0.4 mG0 in an Au–hexanedithiol–Au system. We provide evidence that transitions from GH to GL involve atom scale deformations between two distinct metal–molecule contact configurations by conducting single molecule inelastic electron tunneling spectroscopy. We also examine mechanically controlled binary switching via bistable conductance states, thereby attaining an alkanedithiol single-molecule switch.

Roles of lattice cooling on local heating in metal-molecule-metal junctions

We report a quantitative assessment of the efficacy of lattice cooling on mitigating local heating in a current-carrying single molecule wire connected to gold nanoelectrodes by comparative analyses of high-field effective temperatures at different ambient temperatures. We find substantial local heating in benzenedithiol single molecule junctions raising the local temperatures by ∼320 K from the ambient to ∼400 K at 0.85 V. The intense self-heating are attributable to decreased thermal conductance at low temperatures that leads to deteriorated heat transfer at metal-molecule contacts, thereby manifesting a critical role of lattice cooling for alleviating metal-molecule-metal junction overheating.