Martino, NicolaKwok, SheldonLiapis, AndreasForward, SarahJang, HoonKim, Hwi-MinWu, SarahWu, JiaminDannenberg, PaulJang, Sun-JooLee, Yong-HeeYun, Seok-Hyun2022-07-282019-07-22Martino, Nicola, Sheldon Kwok, Andreas Liapis, Sarah Forward, Hoon Jang, Kim Hwi-Min, Sarah Wu, Jiamin Wu, Paul Dannenberg, Jang Sun-Joo, and Lee Yong-Hee. 2019. Wavelength-encoded Laser Particles for Massively Multiplexed Cell Tagging. Nature Photonics 13, no. 10: 720-27.1749-48851749-4893https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37372905Large-scale single-cell analyses have become increasingly important given the role of cellular heterogeneity in complex biological systems. However, no current techniques enable optical imaging of uniquely-tagged individual cells. Fluorescence-based approaches can only distinguish a handful of distinct cells or cell groups at a time because of spectral crosstalk between conventional fluorophores. Here we show a novel class of imaging probes emitting coherent laser light, called laser particles. Made of silica-coated semiconductor microcavities, these laser particles have single-mode emission over a broad range from 1170 to 1580 nm with sub-nm linewidths, enabling massive spectral multiplexing. We demonstrate the stability and biocompatibility of these probes in vitro and their utility for wavelength-multiplexed cell tagging and imaging. We demonstrate real-time tracking of thousands of individual cells in a 3D tumor model for several days showing different behavioral phenotypes. We expect laser particles will enable new approaches for single-cell analyses.en-USAtomic and Molecular Physics, and OpticsElectronic, Optical and Magnetic MaterialsJournal Article2022-07-2810.1038/s41566-019-0489-0