Dual-light microscope captures micro detail and nano motion with 14x expanded range

Researchers at the University of Tokyo have developed a microscope that captures signals across an intensity range fourteen times wider than conventional systems. The device records both forward and backward scattered light without using dyes. It operates gently on living cells and supports long-term observations. The team sees strong potential for pharmaceutical and biotech testing.

Bridging micro and nano gaps Microscopy has advanced significantly over the centuries, but modern tools still face trade-offs. Quantitative phase microscopy utilizes forward-scattered light to detect features above approximately 100 nanometers. Researchers rely on it for detailed cellular structures, but it struggles with smaller targets. Illustration of the dual-light quantitative scattering microscope.

Credit University of Tokyo Interferometric scattering microscopy reads back-scattered light to track single proteins, yet it cannot deliver a broad, cell-wide view. “I would like to understand dynamic processes inside living cells using non-invasive methods,” says Kohki Horie. That aim prompted the team to integrate both approaches into a single system. Horie and colleagues, Keiichiro Toda, Takuma Nakamura, and Takuro Ideguchi, wanted to remove size limitations and capture micro and nano motion in the same frame.

They built a microscope that measures both light directions at once. They tested it by observing programmed cell death. The team recorded a single image that encoded information from both channels. The setup allowed them to study changes across scales while preserving cellular health.

“Our biggest challenge,” Toda explains, “was cleanly separating two kinds of signals from a single image while keeping noise low and avoiding mixing between them.” The researchers refined their optics and analysis methods until the two signals remained distinct. Capturing motion across scales The device detected the movement of large cell structures and tiny particles at the same time. It also helped the team estimate particle size and refractive index by comparing forward and backward scattering. The refractive index describes how much light bends when passing through a particle.

That measurement gives clues about the particle’s composition or condition. The team saw clear advantages in this unified approach. It reduces the need for multiple imaging tools. It also shortens the analysis pipeline, which often slows research.

The absence of labels makes the method more compatible with long studies where dyes can interfere with cellular behavior. Toda sees large opportunities ahead. “We plan to study even smaller particles,” he says. His goal includes exosomes and viruses in various samples.

He and his colleagues also hope to map how cells move toward death. They plan to control cell conditions and verify findings with other techniques. The researchers believe the method can support drug development and cell-quality checks. Long-term, label-free imaging can monitor how cells respond to treatments.

It can also help detect subtle structural changes that other tools miss. The team continues to refine the system and expects broader adoption as labs look for ways to bridge micro and nano observations without damaging samples.

The study is published in the journal Nature Communications.