At the heart of this technological breakthrough lies the principle of solid-state nanopores—nanoscale holes embedded in thin membranes that serve as portals through which individual biomolecules such as proteins translocate. As these molecules pass through the nanopores, they transiently disrupt an ionic current, generating electrical signatures that reflect their physical and chemical properties. While nanopore sensing has revolutionized nucleic acid sequencing by reading the DNA and RNA sequences directly, its application to proteins has been substantially more complicated. Proteins exhibit a more diverse and dynamic range of conformations compared to nucleic acids, leading to signals that are both complex and variable, thereby complicating their direct interpretation.

To overcome the inherent limitations of single-voltage nanopore measurements traditionally employed, the researchers devised a strategy of systematically varying the transmembrane voltage applied during molecular translocation. This multivoltage approach produces a rich dataset of signal responses under different electrical driving forces, capturing both stable and voltage-dependent molecular behaviors. By compiling these distinct signal patterns into a structured voltage matrix, the team unlocks a multidimensional profile of each protein’s electrical fingerprint. This matrix serves as an input for sophisticated machine learning models, which classify and discriminate proteins with remarkable accuracy, even amidst intricate mixtures.

The experimental rigor of this novel methodology was demonstrated on biologically significant cancer biomarkers—carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3). These proteins, pivotal in cancer diagnostics, were analyzed both in isolation and as components of mixed samples. By recording nanopore signals under six discrete voltage settings, distinct electrical response profiles were identified that uniquely correspond to each protein. Notably, the method could detect molecular population shifts upon the binding of an aptamer, a synthetic DNA sequence that selectively interacts with CEA, underscoring the sensitivity of the voltage-matrix approach to subtle molecular modifications.

Beyond purified protein mixtures, the researchers extended their investigation to biologically complex fluids such as mouse serum. Through comparative analysis of serum samples subjected to centrifugation versus untreated controls, the voltage-matrix framework was capable of distinguishing nuanced compositional changes induced by sample processing. This pivotal result underscores the technique’s robustness and its potential utility in analyzing real-world clinical and environmental specimens, where molecular heterogeneity often confounds conventional analytical methods.

Professor Sotaro Uemura, leading the initiative at the University of Tokyo’s Department of Biological Sciences, emphasized the transformative potential of integrating multivoltage nanopore sensing with machine learning. “Our methodology transcends traditional protein detection by systematically exploring the voltage-dependent electrical landscape of biomolecules,” he explained. “The voltage matrix not only captures inherent, voltage-invariant features but also reveals subtle structural dynamics responsive to changes in the electric field, enabling a comprehensive representation of molecular individuality.”

This advancement ushers in a new paradigm where nanopore technology evolves from a nucleic acid sequencing tool into a versatile platform for general molecular profiling. The capacity to visualize and quantify the compositional complexity of protein mixtures without reliance on labels or chemical modifications heralds a significant leap forward in bioanalytical science. Such a label-free, high-precision approach holds promise for accelerating biomarker discovery, enhancing diagnostic accuracy, and facilitating personalized medicine.

From a technical perspective, the voltage-matrix nanopore profiling technique capitalizes on the interplay between applied voltage and molecular conformation dynamics. By recording ionic current disruptions over a spectrum of transmembrane potentials, the system effectively probes different energetic states and interactions of the molecules inside the nanopore. This multidimensional data matrix enriches feature extraction processes integral to the machine learning classifiers, thus refining their discriminatory power.

Looking ahead, the research team envisions scaling and parallelizing this platform to enable real-time and multiplexed molecular profiling. By integrating arrays of nanopores operating under tailored voltage sequences, simultaneous analysis of multiple targets could be realized, dramatically increasing throughput and diagnostic relevance. Such innovations may ultimately contribute to the development of portable, rapid diagnostic devices for clinical settings, environmental monitoring, and beyond.

The implications of this research extend far beyond immediate protein detection. Voltage-matrix nanopore profiling illuminates the pathway toward understanding molecular individuality at unprecedented resolution. By facilitating the characterization of subtle structural variants and complex mixture compositions, the technology could impact a broad range of disciplines, including immunology, pharmacology, and proteomics. Moreover, it could catalyze new insights into disease mechanisms where protein heterogeneity plays a critical role.

In summary, this breakthrough from the University of Tokyo embodies a confluence of nanotechnology, electrical engineering, and artificial intelligence, culminating in a novel analytical framework that promises to redefine molecular diagnostics. With its capacity to discern complex protein mixtures sensitively and accurately, voltage-matrix nanopore profiling stands poised to become an indispensable tool in the scientific and medical toolbox, heralding a new era of molecular discernment and diagnostic precision.

Subject of Research:
Voltage-matrix nanopore profiling and machine learning-based classification of proteins in complex mixtures.

Article Title:
Voltage-matrix nanopore profiling for the discrimination of protein mixtures

News Publication Date:
6 October 2025

Web References:
http://dx.doi.org/10.1039/D5SC05182G

References:
Ryo Akita, Artem Lysenko, Keith A. Boroevich, Tatsuya Yokota, Daiki Kawai, Ryo Iizuka, Tatsuhiko Tsunoda and Sotaro Uemura, “Voltage-matrix nanopore profiling for the discrimination of protein mixtures,” Chemical Science, October 6, 2025, DOI: 10.1039/D5SC05182G

Image Credits:
Sotaro Uemura, The University of Tokyo

Keywords

Nanopore sensing, solid-state nanopores, protein profiling, voltage-matrix, machine learning, biomarker detection, molecular diagnostics, cancer biomarkers, molecular individuality, label-free analysis, nanopore technology, ionic current signatures

Ferroelectric materials are distinguished by their spontaneous electrical polarization, which can be reversed under the application of an external electric field. These materials are composed of numerous domains—regions where the polarization is uniformly oriented—and are separated by domain interfaces. The electrical properties of these interfaces, which are minuscule yet crucial boundaries, dictate how domain walls move and interact, ultimately influencing the performance of devices such as multilayer ceramic capacitors (MLCCs). Despite their significance, direct experimental observation of the charges trapped at these domain boundaries has remained a formidable challenge, primarily due to the atomic scale and complexity of interactions involved.

Multilayer ceramic capacitors, ubiquitous in modern electronic devices including smartphones, personal computers, and automotive systems, rely heavily on ferroelectric ceramics for their high capacitance and reliability. As consumer electronics evolve towards smaller sizes with enhanced capabilities, understanding and controlling ferroelectric domain behavior becomes imperative. These MLCCs consist of alternating layers of ferroelectric materials and electrodes, housing myriad domains and domain walls at the nanometer scale. Variations in polarization across these domain interfaces lead to the accumulation of bound charges, which can have profound effects on leakage currents and device longevity. Thus, unraveling the charge states at domain interfaces is essential for optimizing device design and function.

The research led by Dr. Takehito Seki leveraged a combination of advanced electron microscopy methodologies, integrating localized charge observations with atomic-scale structural measurements. This technique enables visualization not only of the atomic positions with picometer precision but also of the polarization-induced charges confined within nanometric domain walls. The study’s achievement effectively bridges the gap between structural characterization and electrical property analysis, a correlation that until now was mostly theoretical or indirect in nature. Such direct observations usher in a new era for materials science, where the intricate coupling between atomic displacements and electronic polarization can be empirically examined.

Importantly, the experiment identified and differentiated between head-to-head (H-H) and tail-to-tail (T-T) domain walls at the nanoscale. These domain configurations host oppositely charged polarization bound charges at their cores—positive charges in the former and negative in the latter. These localized charges necessitate electrical compensation from neighboring charges to maintain overall neutrality, influencing domain wall stability and mobility. Given that domain wall dynamics under applied voltages govern the ferroelectric switching properties that make these materials technologically attractive, the ability to observe charge distribution directly allows researchers to conceptualize mechanisms that govern device reliability and efficiency.

At the heart of this research lies the development of an “ultra” atomic resolution electron microscopy technique, a concept realized within the ERATO SHIBATA project, funded by the Japan Science and Technology Agency (JST). This novel microscopy transcends conventional resolution limits by combining structural and electromagnetic field imaging, even under variable temperature conditions ranging from extremely low to high temperatures. The capacity to observe the simultaneous evolution of atomic arrangements and electromagnetic phenomena offers unprecedented insights into material and biological functions that were previously inaccessible.

Furthermore, the elucidation of polarization-induced charge at ferroelectric domain interfaces aids in understanding leakage current generation, a persistent challenge affecting the reliability of ferroelectric devices. Leakage currents arise due to the movement or reconfiguration of domains and the associated free charge carriers. By mapping charge distributions with atomic precision, this study lays the groundwork for engineering domain walls with tailored properties that minimize parasitic currents and enhance device stability and lifespan. This has direct implications for the performance of MLCCs and other ferroelectric-based applications, from sensors to non-volatile memories.

Dr. Seki’s team employed specialized electron microscopy to observe atomic displacements in the sub-picometer range while simultaneously detecting charge accumulation at domain walls. This methodological feat was enabled by integrating physical models with high-resolution imaging, overcoming previous limitations that confined analyses to either structural or electrical domains. The researchers’ success opens pathways for exploring dynamic phenomena, such as domain wall motion and polarization switching, in situ under various external stimuli—a major leap toward functional characterization of ferroelectric materials.

This advancement is instrumental for the continued miniaturization and enhancement of electronic devices, as it uncovers the physical foundations underlying the domain wall behaviors that dictate device performance. The ability to “see” charge accumulation and atomic shifts together allows prototypes and materials to be optimized at an unprecedented level of detail, potentially informing the design of ferroelectric devices that are not only more compact but also more efficient and reliable.

Looking forward, this research heralds the possibility of direct "visualization" of fundamental physical processes that govern the function of a vast array of materials. By revealing the interplay between atomic-scale polarization patterns and local charge compensation mechanisms, it invites new theories and computational models to accurately predict the behavior of ferroelectric devices under operational conditions. This enhanced understanding promises to accelerate breakthroughs in a wide range of applications, including energy harvesting, capacitors, memory devices, and advanced sensors.

The significance of this breakthrough extends beyond ferroelectrics alone. The measurement principles and microscopy techniques developed may be adapted to other complex oxides and functional materials where nanoscale charge distributions govern macroscopic functionality. This could transform fields such as catalysis, superconductivity, and even biomaterials research, where electromagnetic interactions at the atomic level critically influence material performance.

In summary, the successful real-space observation of polarization-induced charges at nanoscale ferroelectric interfaces represents a landmark achievement in condensed matter physics and materials engineering. By marrying unprecedented imaging resolution with electrical characterization, the researchers have provided invaluable insights into domain wall physics and ferroelectric device operation. The implications for the future development of compact, high-performance, and highly reliable electronic components are profound and far-reaching.

This research was conducted under the auspices of the JST Strategic Basic Research Program ERATO project "SHIBATA Ultra-atomic Resolution Electron Microscopy," reflecting a concerted national effort to push the boundaries of measurement science. By developing techniques that can simultaneously observe atomic structures and electromagnetic fields across wide temperature ranges, the project exemplifies how innovative tools can transform fundamental science and pave the way for technological leaps.

As electronic devices continue to shrink and demand ever greater capabilities, the insights provided by this study will be instrumental in driving innovation. The newly acquired ability to directly measure and interpret local charges at ferroelectric domain walls will not only enhance our fundamental understanding of ferroelectricity but will serve as a crucial foundation for engineering the next generation of energy-efficient, durable, and multifunctional electronic components.

Subject of Research:
Not applicable

Article Title:
Real-space observation of polarization induced charges at nanoscale ferroelectric interfaces

News Publication Date:
13-Jun-2025

Web References:
http://dx.doi.org/10.1126/sciadv.adu8021

Image Credits:
Naoya Shibata

Keywords

Ferroelectric materials, domain walls, polarization charges, multilayer ceramic capacitors, electron microscopy, nanoscale imaging, atomic displacement, leakage current, materials science, advanced characterization, SHIBATA project, Japan Science and Technology Agency

Ammonia, an indispensable compound for fertilizer production and various industrial processes, is currently produced at an enormous scale—nearly 200 million tons annually across the globe. However, this widespread synthesis comes with a substantial environmental cost: it consumes about 2% of the world’s total energy and generates commensurate carbon dioxide emissions. This unsustainable energy demand has driven chemists and engineers for decades to design cleaner, more energy-efficient pathways to produce ammonia. The University of Tokyo team’s breakthrough introduces an artificial photosynthetic system that emulates nature’s elegant strategies for nitrogen fixation, potentially transforming industrial practices.

The newly developed system utilizes visible light energy to power the reaction, representing a major departure from conventional methods that rely on high temperature and pressure. Central to this approach are two distinct molecular catalysts: one based on molybdenum, a transition metal known for its role in natural nitrogenase enzymes, and the other using iridium, which facilitates the photochemical activation of water and tertiary phosphines. By orchestrating these catalysts together under sunlight, the reaction effectively converts dinitrogen (N₂) and water (H₂O) into ammonia (NH₃) and oxygen, closing a vital chemical cycle with minimal energy input.

Professor Nishibayashi explained the underlying mechanics of the photocatalytic process: “Upon sunlight absorption, the iridium catalyst achieves an excited state that oxidizes tertiary phosphines. These phosphines, in turn, bond to water molecules, extracting protons through a carefully controlled chemical interaction.” This delicate proton generation is critical because ammonia synthesis requires a source of protons to reduce atmospheric nitrogen. “Then, the molybdenum catalyst facilitates the nitrogen activation, enabling it to combine with these protons and form ammonia,” he added. This mechanistic dance mimics the natural biological nitrogen fixation occurring in symbiotic bacteria associated with plants.

Beyond the elegant design of catalysts, the production scale achieved in this study is particularly remarkable. The reaction was successfully carried out at a volume approximately ten times larger than prior experiments of its kind, signaling readiness for further scaling toward practical applications. However, challenges remain that must be addressed to ensure safety, efficiency, and sustainability. Specifically, the tertiary phosphines used in the process, while stable, possess potential toxicity risks if improperly handled or ingested. The research team is exploring ways to manufacture these organic compounds using solar energy or recycle them from phosphine oxides, striving to close the material loop and minimize environmental hazards.

This discovery also symbolizes the successful translation of a fundamental biological process into an artificial system. In natural ecosystems, ammonia is produced through biological nitrogen fixation conducted by nitrogenase enzymes in certain bacteria, which work symbiotically with plants. This reaction is intricately linked to photosynthesis, which supplies the electrons and protons necessary for the conversion of nitrogen gas to ammonia. The University of Tokyo’s system replicates this concept, using sunlight as the energy source and water as the proton donor, achieving what can be thought of as “artificial photosynthesis” of ammonia at a molecular level.

Technically speaking, the use of visible light rather than ultraviolet opens up new avenues for practical energy harvesting and reaction efficiency. The iridium photocatalyst’s absorption of visible wavelengths permits it to operate under sunlight conditions more akin to real-world settings, circumventing the energy limitations of previous systems reliant on more high-energy wavelengths. This not only enhances the energy efficiency of ammonia synthesis but also bolsters the prospect of integrating such a system into existing solar fuel technologies.

The dual catalyst mechanism is particularly ingenious, as it tackles two chemical obstacles simultaneously. While molybdenum excels at cleaving the notoriously strong bond in atmospheric nitrogen—one of the hardest chemical bonds to break—the iridium complex addresses the challenge of water activation, a necessary step for proton and hydrogen atom generation. The tertiary phosphines bridge these processes, mediating electron transfer and facilitating bond formation between phosphorus and water molecules to liberate protons. This advanced orchestration allows for a highly selective and efficient pathway to ammonia, outperforming prior attempts using similar photocatalytic methods.

From an industrial perspective, the implications of this technology stretch far beyond just cleaner ammonia production. The process’s reduced energy requirements hint at a future where decentralized, small-scale ammonia factories could operate remotely or even on farms, reducing transportation emissions and input costs. Moreover, because ammonia is not only a fertilizer feedstock but also a potential fuel carrier and hydrogen storage medium, efficiently producing ammonia using sunlight and abundant resources like air and water could open a suite of clean energy applications.

Despite the excitement, the research team is mindful of scaling hurdles. The exact lifecycle impacts of the catalysts, particularly the long-term stability and recyclability of iridium and molybdenum complexes, warrant further investigation. Additionally, securing a safe handling protocol for tertiary phosphines and developing sustainable synthetic routes remain high priorities. Addressing these issues will be necessary to transition this technology from laboratory success to practical, commercial deployment.

The findings, published in the prestigious journal Nature Communications, represent a milestone in sustainable chemistry. By demonstrating that photocatalytic ammonia synthesis using atmospheric dinitrogen and water is achievable with visible light and dual catalysts, this research ushers in a new era of green chemistry. As the world seeks to decarbonize and meet increasing fertilizer demands to support a growing population, such innovative routes for ammonia production could become vital tools in global environmental stewardship.

The University of Tokyo team’s work continues to deepen our understanding of how molecular catalysts can be designed and combined to harness solar energy for challenging chemical transformations. It also exemplifies the power of interdisciplinary research, merging ideas from inorganic chemistry, photochemistry, and biology to confront pressing environmental challenges. The prospect of “artificial photosynthesis” producing more than just oxygen but a vital feedstock chemical promises a bright horizon for sustainable industrial chemistry.

As this exciting technology advances toward practical use, further research will explore alternative catalysts to replace precious metals, optimize reaction conditions, and integrate this ammonia-synthesis approach with existing renewable energy infrastructures. The ultimate vision is to establish a fully solar-driven ammonia production cycle that minimizes ecological impact while meeting global demands, offering hope for a cleaner and more sustainable future.

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Subject of Research: Experimental study on catalytic ammonia synthesis

Article Title: Catalytic ammonia formation from dinitrogen, water, and visible light energy

News Publication Date: 22-May-2025

Web References: http://dx.doi.org/10.1038/s41467-025-59727-w

References: Yasuomi Yamazaki, Yoshiki Endo, Yoshiaki Nishibayashi, “Catalytic ammonia formation from dinitrogen, water, and visible light energy”, Nature Communications, DOI: 10.1038/s41467-025-59727-w

Image Credits: ©2025 Nishibayashi et al. CC-BY-ND

Keywords

Green ammonia, photocatalysis, nitrogen fixation, molybdenum catalyst, iridium catalyst, visible light energy, artificial photosynthesis, sustainable chemistry, ammonia synthesis, tertiary phosphines, atmospheric nitrogen, water activation