Microlasers Track Cells from the Inside

Embedded microlasers could allow scientists to track and distinguish between large numbers of cells simultaneously.

Two laboratories have published results independently, each showing that cells can absorb whispering gallery mode resonators — tiny plastic beads that trap light within a small volume by forcing it onto a circular path along their circumference.

The spectral composition of the light they emit depends on their size and refractive index, meaning that different types of resonators can be used to generate unique, barcode-like signatures.

Artist rendering of a group of cells that have absorbed microlasers. The spectral composition of the laser light from each cell is different, which provides a barcode-type tag and enables reliable noncontact optical tracking of a large number of cells of prolonged periods of time. Courtesy of Malte Gather and Marcel Schubert/University of St. Andrews.

Researchers at the University of St. Andrews said the approach could enable new forms of cell tracking, intracellular sensing and adaptive imaging.

"This miniaturization paves the way to applying cell lasers as a new tool in biophotonics," said St. Andrews professor Malte Gather. "In the future, these new lasers can help us understand important processes in biomedicine. For instance, we may be able to track — one by one — a large number of cancer cells as they invade tissue or follow each immune cell migrating to a site of inflammation."

Pumped with nanojoule light sources, the resonators lase without causing cell damage. Cells implanted with microlasers remain viable for several weeks, according to Gather's team.

Fluorescent dyes used in biomedical research and diagnosis today emit a broad spectrum of light, which means only a handful can be used at one time in a given sample, according to a team at the Wellman Center for Photomedicine at Massachusetts General Hospital in the U.S. that produced similar results.

"The narrowband spectrum of light emitted by these intracellular lasers would allow us to label thousands — in principal up to a trillion — of cells individually," said Wellman research fellow Matjaž Humar.

In the St. Andrews study, cells were induced to "swallow" the microlasers through endocytosis, the process through which cells absorb molecules such as proteins.

Certain types of cell were particularly quick to absorb the microlasers, the St. Andrews team said. Macrophages, a type of immune cell, internalized the resonators in less than five minutes. But even cells without pronounced capacity for endocytosis readily internalized the microresonators, showing that laser barcodes are applicable to many different cell types.

Previously reported cell lasers required optical resonators that were much larger than the cell itself, meaning that the cell had to be inserted into these resonators, the researchers said.

Future research will explore how microlasers embedded in cells could run on biologically generated energy rather than external pump sources, said Wellman professor Seok-Hyun Yun.

"Cells are smart machines, and we are interested in exploiting their amazing capabilities by developing smart-cell lasers that might be able to find diseases and fire light at them on their own," he said. "We can envision lasers completely made out of materials that are safe for use within the human body, which could enable remote sensing within the body or be used in laser-light therapies."

The research was published in Nano Letters (doi: 10.1021/acs.nanolett.5b02491) and Nature Photonics (doi: 10.1038/nphoton.2015.129).

For more information, visit www.st-andrews.ac.uk and www2.massgeneral.org/wellman.