Trans-scale-scope to explore rare cellular activity in more than one million cells

Abstract

In many phenomena of biological systems, a minority of cells act on the entire multicellular system causing drastic changes in the system. 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. We have been developing a "trans-scale scope" to realize cellular imaging in an over-one-centimeter field-of-view (FOV) beyond the limitation of conventional microscopes. We demonstrated its ability of time-lapse imaging of multicellular system with capturing the dynamics of 10^5-10^6 cells in the system in a single FOV. Zooming in at any position in the whole image, one can know the distribution and dynamics of the cells in the local region. It has been applied 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.