Cellular lasers for cell imaging and biosensing

The possibility to produce laser action involving biomaterials, in particular (single) biological cells, has fostered the development of cellular lasers as a novel approach in biophotonics. In this respect, cells that are engineered to carry gain medium (e.g., fluorescent dyes or proteins) are placed inside an optical cavity (i.e., typically a sandwich of highly reflective mirrors), allowing the generation of stimulated emission upon sufficient optical pumping. In another scenario, micron-sized optical resonators supporting whispering-gallery mode (WGM) or semiconductor-based laser probes can be internalized by the cells and support light amplification. This review summarizes the recent advances in the fields of biolasers and cellular lasers, and most importantly, highlights their potential applications in the fields of in vitro and in vivo cell imaging and analysis. They include biosensing (e.g., in vitro detection of sodium chloride (NaCl) concentration), cancer cell imaging, laser-emission-based microscope, cell tracking, cell distinction study, and tissue contraction monitoring in zebrafish. Lastly, several fundamental issues in developing cellular lasers including laser probe fabrication, biocompatibility of the system, and alteration of local refractive index of optical cavities due to protein absorption or probe aggregation are described. Cellular lasers are foreseen as a promising tool to study numerous biological and biophysical phenomena. Statement of significance Biolasers are generation of laser involving biological materials. Biomaterials, including single cells, can be engineered to incorporate laser probes or fluorescent proteins or fluorophores, and the resulting light emission can be coupled to optical resonator, allowing generation of cellular laser emission upon optical pumping. Unlike fluorescence, this stimulated emission is very sensitive and is capable of detecting small alterations in the optical property of the cells and their environment. In this review, recent development and applications of cellular lasers in the fields of in vitro and in vivo cell imaging, cell tracking, biosensing, and cell/tissue analysis are highlighted. Several challenges in developing cellular lasers including probe fabrication and biocompatibility as well as alteration of cellular environment are explained. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

Cellular lasers, which utilize biomaterials to generate laser emissions, have shown great potential in various applications such as cell imaging, tracking, and biosensing. However, challenges in probe fabrication and biocompatibility need to be addressed for further development.