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Living cell lasers: intracellular lasing induced by natural and polymeric microscopic resonators

Periodic Reporting for period 1 - LIVING LASERS (Living cell lasers: intracellular lasing induced by natural and polymeric microscopic resonators)

Reporting period: 2015-08-01 to 2017-07-31

Biological and living laser are a revolutionary new way to perform optical experiments inside living biological cells. However, current limitations are mostly set by the rigid, synthetic and macroscopic nature of external optical resonators, an essential part of any laser device. The aim of the LIVING LASERS project was to explore new ways to develop fully biocompatible lasers by introducing lasing in living cells independent of external resonators. The main idea was based on a conceptual change of the biolaser design, which aims to transfer the optical feedback directly into the cell.

Due to the challenging restriction with respect to size of the resonators, one of the main activities was related to the screening and development of new microscopic optical resonators. In a next step, the internalisation of resonators into living cells had to be investigated and optimized. Finally, the principle of intracellular lasing had to be shown for different cell types.

The project LIVING LASERS, located at the interface between material sciences, laser physics, photonics and biology, achieved a major breakthrough in demonstrating autonomous single cell lasing for a large variety of cell types. A direct application of this technique is the tagging and tracking of large numbers of cells. In addition, the interaction between the laser light and the cells can reveal intracellular processes in real time and without harming the cells.
A vital part of the project explored the suitability of novel optical resonators for intracellular lasing as well as their biocompatibility. Here, natural and synthetic materials were tested but only the later were found to generate laser light in aqueous environments. It was found that polystyrene-based microbeads stained with a brightly fluorescent green dye can facilitate lasing upon pumping with a nanosecond laser. A size of about 10 µm in diameter was found as the lower boundary to achieve lasing.

Resonator endocytosis, the process describing the internalization of objects by a living cell, was first tested with a specialized type of immune cell called macrophages. It was found that these cells readily internalized PS microbeads with diameters of up to 25 µm. In addition, many other cell types, including cancer cells, neuronal cells and fibroblasts were found to internalize these resonators. We also implemented a way to increase the uptake by introducing special surface coatings.
Generating laser light within single cells displays a major breakthrough in the integration of photonic devices in living cells and biological tissue. Importantly, the LIVING LASERS project has significantly enhanced the range of applications of intracellular lasers by showing that the internalization of resonators can be realized for a number of different cell types. Furthermore, lasing can be achieved and maintained over long periods in time without harming the cells. Overall, the project has clearly demonstrated the innovative potential of intracellular lasing, which will soon be used to track immune and cancer cells over long periods of time to study their function, interactions and diversity. These unique features will lead to entirely new and highly useful applications of intracellular lasers in biomedical research.