Yuki Komoto

The biological functions of iodinated biomolecules depend on their degree of iodination, but ensemble measurements cannot resolve iodine-induced electronic differences at the single-molecule level. Here, we investigated the effect of iodine substitution on electron transport using phenol (PhOH), 2-iodophenol (2-I-PhOH), L-tyrosine (Tyr), and 3-iodo-L-tyrosine (3-I-Tyr). Single-molecule current-time traces were measured with mechanically controllable break junction electrodes, and density functional theory (DFT) calculations were used to analyze their electronic structures. Iodine substitution produced distinct tunneling-current signatures in both molecular pairs. DFT showed opposite HOMO energy shifts: upward for PhOH and downward for Tyr, consistent with the measured current changes. These results suggest that HOMO alignment relative to the Au Fermi level is the primary factor governing substitution-induced charge-transport modulation. These findings provide a basis for the label-free electrical identification of iodinated biomolecules.

Chemical modifications of nucleobases regulate genomic stability and therapeutic response, yet identifying individual modified bases remains challenging because subtle structural changes often produce similar electronic properties. Here, we report the label-free single-molecule electrical identification and quantification of O ⁶ -methylguanine ( O ⁶ -MeG) using tunneling-current measurements with mechanically controllable break-junction electrodes. Density functional theory calculations predicted that O ⁶ -MeG and guanine should be difficult to distinguish by conductance alone because of their similar frontier orbital energies. Consistently, both molecules exhibited nearly identical tunneling-current amplitudes. However, transient tunneling-current signals contained reproducible dynamic fingerprints that enabled reliable discrimination of O ⁶ -MeG from guanine, 8-oxoG, and adenine. Predefined O ⁶ -MeG/guanine mixtures were also quantified accurately. These results demonstrate that transient tunneling-current fingerprints provide chemically meaningful information beyond static conductance, offering a promising approach for the label-free electrical analysis of DNA damage.

Life on Earth uses L-amino acids and D-sugars, whereas abiotic processes produce equal abundances of both enantiomers. Detecting enantiomeric excess among molecules of biological interest has therefore been proposed as a potential biosignature for life beyond Earth. However, robust electrical methods for determining the L/D ratios of amino acids and sugars at low concentrations, particularly in chemically complex samples, remain limited. Here we show that quantum tunneling currents electrically distinguish individual L- and D-amino acids and quantify their ratios at the single-molecule level without optical measurements or chiral recognition molecules. Individual enantiomers are distinguished with over 80% accuracy, and a blind test of 39 amino acids identifies both molecular identity and chirality with >50% accuracy, well above random chance. Mixtures containing four amino acids with different chiral compositions are quantified with >66% accuracy. Murchison meteorite and Atacama Desert extracts are analyzed using a targeted panel of 11 amino acids. Confidence-based filtering distinguishes high-confidence target assignments from low-confidence events, and the resulting compositions capture major compositional features observed by LC–MS while highlighting the effects of background and low-abundance signals. These results establish a targeted single-molecule electrical approach for chiral amino acid analysis and provide a foundation for future applications to study chemically complex samples, including those relevant to astrobiological research.

Nanopores provide a direct electrical interface to biomolecules, yet most operate as passive conduits whose sensing state is imposed externally. Here we report an autonomous solid-state nanopore in which voltage-driven precipitation and dissolution repeatedly create and erase transient conductive pathways under constant bias. This reaction cycle generates stochastic ionic spikes and converts the pore into a chemically stateful nanofluidic element whose conductance reflects recent history. As nucleotides and amino acids traverse these transient openings, they reshape the evolving pore state and produce distinct spike amplitudes, durations, and firing statistics. Learning these state-dependent fingerprints enables discrimination of four nucleotides, quantitative readout of mixed populations, and extension to seven amino acids without active gating. Our results reposition the solid-state nanopore as a reaction-programmed molecular interface that integrates sensing, memory, and signal generation within chemically dynamic nanoscale environments for molecular analytics and iontronic information processing.

Electrical single-molecule detection distinguishes all phosphorylated and non-phosphorylated Ser, Thr and Tyr, revealing the conductance mechanism underlying phosphorylation.

Fabrication of pores at the atomic scale remains a significant challenge in modern nanotechnology, hindering the study of ion transport and molecular dynamics in confined spaces. Here, we introduce a chemically controllable break-membrane approach that enables the repeated formation and closure of nanoscale pores in SiN_x membranes through manipulating the in-pore electrochemical reaction conditions by transmembrane voltage. Ionic current measurements reveal distinct conductance features that are consistent with ion dehydration and transport through highly confined channels approaching sub-nanometer dimensions. The scalable nature of this platform, which allows multiple pores to be actuated simultaneously, offers a powerful tool for probing ion transport and fluid dynamics in extreme confinement. Beyond advancing fundamental understanding of ion transport and fluid dynamics, this chemically driven membrane system holds promise for applications in single-molecule sensing, neuromorphic computing, and nanoreactor design.

Efficient heat dissipation at the nanoscale remains a major challenge for high-performance microelectronics. Here, we demonstrate a proof-of-concept approach for ionothermoelectric cooling, the ionic analogue of the Peltier effect, using gate-tunable solid-state nanopores integrated with nanoscale thermocouples. By integrating a nanoscale thermocouple directly adjacent to a gate-tunable solid-state nanopore, we quantitatively map local thermal responses driven by voltage-induced ion transport. We show that ionic heating scales with input power and varies with the ion species, revealing a dependence on the intrinsic heat of transport. Under salt concentration gradients, we observe ionic cooling, a fluidic analogue of the Peltier effect, arising from directional cation transport through negatively charged nanopores. This effect is further enhanced via electrostatic gating, which modulates the pore wall surface potential to tune the permselectivity. Under optimal gating, the system exhibits reversible transitions between heating and cooling regimes with temperature drops exceeding 2 K. Although modest compared to electronic Peltier devices, this effect establishes a viable mechanism for active, electrically tunable thermal management in nanofluidic systems. Given that water-based flow cooling already outperforms solid-state thermoelectrics by orders of magnitude, incorporating ionothermoelectric cooling can further enhance heat-pumping efficiency in micro- and nanofluidic architectures, thereby establishing a scalable on-chip ionic refrigeration strategy for next-generation semiconductor thermal control.

Strand separation is a prerequisite for any genome sequencing method, including the single-molecule approach via solid-state nanopore sensing. Here, we report on the local electrical heating of nanofluidic channels for on-site denaturation to resistive pulse analysis of nucleic acids. We lithographed a Pt nanocoil around a nanopore in a SiN_x membrane. The local temperature at the pore was finely controlled by the voltage applied to the metallic nanowire for the self-heating. The capture-to-translocation motions of DNA were found to be influenced by temperature-gradient-mediated factors, including electrophoresis, viscous dragging, and thermophoresis. Most importantly, we demonstrated unzipping to single-molecule detections of pBR322 plasmid and lambda DNA in the nanopore locally heated with the nanoheater of temperature above 423 and 564 K, respectively. This device concept may be useful for solid-state nanopore sequencing of DNA and proteins.

Simple detection methods for acetyl lysine are essential for diagnosis and understanding of the physiological effects. We have detected and recognized acetyl lysine at the single-molecule level by combining MCBJ measurement and machine learning.

In single-molecule measurements, metal nanogap electrodes directly measure the current of a single molecule. This technique has been actively investigated as a new detection method for a variety of samples. Machine learning has been applied to analyze signals derived from single molecules to improve the identification accuracy. However, conventional identification methods have drawbacks, such as the requirement of data to be measured for each target molecule and the electronic structure variation of the nanogap electrode. In this study, we report a technique for identifying molecules based on single-molecule measurement data measured only in mixed sample solutions. Compared with conventional methods that require training classifiers on measurement data from individual samples, our proposed method successfully predicts the mixing ratio from the measurement data in mixed solutions. This demonstrates the possibility of identifying single molecules using only data from mixed solutions, without prior training. This method is anticipated to be particularly useful for the analysis of biological samples in which chemical separation methods are not applicable, thereby increasing the potential for single-molecule measurements to be widely adopted as an analytical technique.