Exploring rare cellular activity in more than one million cells by a transscale scope

In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.

Automated summary

In biological systems, minority cells can have drastic effects on the entire multicellular system. Understanding the mechanisms behind these phenomena requires observing the spatiotemporal dynamics of a large population of cells at sub-cellular resolution, which is made possible with the imaging system AMATERAS. This system allows for high-resolution imaging and high cell-throughput, enabling the detection of rare cells and observation of multicellular events induced by them.