University of Tokyo Unveils Advanced ‘Great Unified Microscope’

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 innovation allows for label-free observations, meaning it does not require additional dyes that can harm cells, making it suitable for long-term studies and quality control in the pharmaceutical and biotechnology sectors. The findings were published on November 14, 2025, in the journal Nature Communications.

Microscopes have been essential tools in scientific advancement since the 16th century. Yet, the demand for more sensitive and accurate equipment has led to the development of specialized techniques that often involve trade-offs. For example, quantitative phase microscopy (QPM) can detect structures over 100 nanometers but lacks the ability to observe smaller entities. This method primarily produces static images of complex cell structures.

On the other hand, interferometric scattering (iSCAT) microscopy detects minute particles, including single proteins, allowing researchers to track dynamic changes within cells. Nevertheless, it does not provide the comprehensive view that QPM offers.

Kohki Horie, a lead author on the study, expressed a desire to understand dynamic processes within living cells through non-invasive techniques. Alongside co-researchers Keiichiro Toda, Takuma Nakamura, and Takuro Ideguchi, they aimed to investigate whether simultaneous measurement of light in both directions could bridge the gap and reveal a broader range of sizes and motions in a single image.

To validate their hypothesis, the team observed cellular processes during cell death. They successfully recorded images that encoded information from both forward and backward-traveling light.

“Our biggest challenge,” Toda explained, “was cleanly separating two kinds of signals from a single image while keeping noise low and avoiding any mixing between them.” This challenge was met, allowing the researchers to quantify the motion of micro-scale cell structures alongside the movements of nano-scale particles. By analyzing both types of scattered light, they could estimate each particle’s size and refractive index, which describes how light bends or scatters when passing through various materials.

Looking ahead, Toda shared aspirations to study even smaller particles, such as exosomes and viruses, to further understand their size and refractive properties in diverse samples. The team also intends to explore how living cells undergo the process of cell death while controlling their states, cross-referencing their findings with other investigative techniques.

The development of the Great Unified Microscope signifies a significant leap forward in microscopy, offering researchers an innovative tool for studying cellular dynamics and enhancing our understanding of complex biological processes.

For more information, refer to the article titled “Bidirectional quantitative scattering microscopy” published in Nature Communications (2025). DOI: 10.1038/s41467-025-65570-w.