University of Tokyo Develops Advanced Microscope for Cell Analysis

Researchers at the University of Tokyo have developed a groundbreaking microscope capable of detecting signals across a range 14 times wider than conventional models. This innovative device operates without the use of additional dyes, allowing for gentle, label-free observations of living cells. The findings, published on November 14, 2025, in the journal Nature Communications, hold significant potential for applications in pharmaceutical and biotechnology industries, particularly in testing and quality control.

Microscopes have been essential to scientific advancement since their inception in the 16th century. Despite their importance, evolution in microscopy has often involved trade-offs between sensitivity, accuracy, and specialization. Traditional methods, such as quantitative phase microscopy (QPM), excel at imaging microscale structures over 100 nanometers, yet they fall short when it comes to detecting smaller entities. Conversely, interferometric scattering (iSCAT) microscopy can track single proteins, providing insights into dynamic cellular changes but lacking the comprehensive view offered by QPM.

To address these limitations, the research team, including Kohki Horie, Keiichiro Toda, Takuma Nakamura, and Takuro Ideguchi, aimed to create a microscope that could measure both forward and backward light simultaneously. Their goal was to capture a broader range of structures and movements within living cells from a single image.

To validate their concept, the researchers focused on observing the process of cell death. They successfully recorded images that integrated information from both directions of light. “Our biggest challenge,” explained Keiichiro Toda, “was cleanly separating two kinds of signals from a single image while keeping noise low and avoiding mixing between them.” This dual approach allowed them to quantify the movements of both micro and nano-scale structures, enhancing their understanding of cellular dynamics.

Furthermore, by analyzing both forward and back-scattered light, the team was able to estimate the size and refractive index of individual particles. The refractive index indicates how much light bends or scatters when it passes through a substance, a crucial property for understanding cellular composition.

Looking ahead, Toda expressed enthusiasm for future research directions. “We plan to study even smaller particles,” he noted, including exosomes and viruses, and to evaluate their characteristics across different samples. The team also aims to explore the mechanisms of how living cells transition toward death by manipulating their state and cross-verifying their findings with alternative techniques.

This advancement in microscopy represents a significant leap forward in the ability to observe biological processes in real-time without invasive methods. As researchers continue to refine this technology, it may open new avenues for understanding complex cellular behaviors and could be instrumental in developing therapies for various diseases.

For more in-depth details, refer to the original research published in Nature Communications, with the DOI: 10.1038/s41467-025-65570-w.