Seeing both the forest and the trees: Trans-scale scope shows big picture of tiny targets

In biology, scientists are often interested in the outliers of a population, such as cells with a rare function that may appear in fewer than one in a million individuals. These experiments have been hampered by the inherent tradeoff with microscopes between seeing cells at a sufficient spatial resolution while still maintaining a large enough field of view to capture unusual specimens. Scientists often spend several minutes moving slides in search of just the right cells to study.

Now, a team of scientists led by Osaka University has devised a system that can produce an image containing up to a million cells at once. "Conventional biological microscopes can observe at most 1,000 cells, with a field of view limited to a few millimeters. Our setup uses machine vision powered by a high-pixel camera with a macro lens," first author Taro Ichimura says. The team built the optical imaging system with a 120-megapixel camera and a telecentric macro lens. This provided a much larger field of view than conventional microscopes, up to about one and half by one centimeter, while still resolving individual cells and the interactions between them that characterize the population. The team termed the imaging technology "trans-scale scope," which signifies that the technology can be applied to imaging from the micrometer-scale to the centimeter-scale. "As a technological singularity for a powerful cell measurement, our trans-scale scope system AMATERAS is expected to contribute to a wide range of applications, from basic research for understanding the operating mechanism of multicellular systems, to medical applications such as the quality control of artificial cell sheets," senior author Takeharu Nagai says.

The team tested the AMATERAS by dynamically imaging calcium ions in cultured cells and successfully detected anomalies that occurred in less than 0.01% of specimens. This work may accelerate research in a wide range of fields that deal with large cell populations, such as neuroscience, oncology, and immunology.