University of Tokyo Develops Advanced Microscope for Cellular Insights

Researchers at the University of Tokyo have unveiled a groundbreaking microscope capable of detecting signals across an intensity range that is 14 times broader than that of traditional microscopes. This innovative device operates without the need for additional dyes, enabling label-free observations that are gentle on cells. This advancement holds significant promise for applications in pharmaceuticals and biotechnology, particularly in testing and quality control settings. The findings were detailed in the journal Nature Communications on November 14, 2025.

Microscopes have been instrumental in scientific progress since the 16th century. As demands for sensitivity and precision have evolved, researchers have faced challenges in balancing these needs with specialized techniques. For instance, quantitative phase microscopy (QPM) can identify structures larger than 100 nanometers but falls short when it comes to smaller entities. Conversely, interferometric scattering (iSCAT) microscopy excels at detecting single proteins, allowing researchers to track particles but lacks the comprehensive imaging capability of QPM.

Kohki Horie, one of the lead authors of the study, expressed a desire to explore dynamic processes within living cells using noninvasive techniques. To achieve this, the research team, which includes Horie, Keiichiro Toda, Takuma Nakamura, and Takuro Ideguchi, aimed to simultaneously measure both forward and backward light to capture a wide range of cellular sizes and movements within a single image.

To validate their concept, the researchers focused on observing the process of cell death. They successfully captured an image that incorporated data from both directions of light. “Our biggest challenge,” noted Toda, “was cleanly separating two kinds of signals from a single image while keeping noise low and avoiding mixing between them.” This approach allowed the team to quantify the motion of both micro-scale structures and nano-scale particles. By analyzing the forward and back-scattered light, they could estimate the size and refractive index of each particle.

Looking ahead, Toda remarked on the potential for future research, stating, “We plan to study even smaller particles, such as exosomes and viruses, and to estimate their size and refractive index in different samples. We also want to reveal how living cells move toward death by controlling their state and double-checking our results with other techniques.”

This pioneering work not only enhances current microscopy capabilities but also sets the stage for deeper insights into cellular dynamics and health-related research. As the field progresses, this technology could prove vital for understanding complex biological processes and improving diagnostic methods.

For further information, refer to the article titled “Bidirectional quantitative scattering microscopy” published in Nature Communications, DOI: 10.1038/s41467-025-65570-w.