Microscopic intracellular lasers tag individual cells over several generations

Abstract

The ability to track individual cells among the trillions that are present in the human body is critical to advancing our understanding of many important biomedical questions. For example, tracking individual cells could enable us to study the function of neuronal networks, follow the inflammation response of immune cells, and unravel the way in which circulating tumor cells contribute to the formation of cancer metastasis. Among the techniques that have recently been developed to achieve single-cell resolution in tissue samples or whole animals, light sheet microscopy,1 transgenic labeling of cellular subsets,2 and genetic barcodes3 hold particular promise. However, as powerful as these methods are, they either rely critically on highly transparent samples, are strongly limited by the total number of unique cell tags, or are highly invasive. We recently developed a radically different approach to track large populations of cells over extended periods of time.4 Our method is based on tiny fluorescent plastic beads that are placed inside of each cell. These beads have diameters of about 15 m and are made of polystyrene doped with a brightly fluorescent green dye. Natural phagocytosis has proven very efficient for transferring the beads into immune cells (macrophages), where they act as microresonators (that is, they trap and amplify light by forcing it onto a circular path along the circumference of the bead).4, 5 When optically pumped, the green dye in the beads provides optical gain that leads to the emission of laser light within the living cell, thus enabling their detection. Furthermore, because the emitted laser frequency depends critically on the size of the bead, inherent size variations create unique, barcode-like laser spectra (see Figure 1) that allow the identification of Figure 1. Representative montage showing the operation of our microscopic intracellular lasers. Microlasers (green spheres) located inside live cells provide optical barcodes that can be used to identify and track individual cells within large populations of cells.