probes are detected via their fl uorescence, i.e., spontaneous emission. [ 9 ] However, here, we show that integrating these probes into an optical resonator turns them into an optical gain medium supporting effi cient stimulated emission with distinct spectral characteristics. Advantageously, this approach provides a fast and simple method to obtain lasing from normal cells within less than 1 h by using a biocompatible cell-tracker dye that becomes highly fl uorescent upon entering the cytoplasm, thus forming a localized gain volume. We demonstrate lasing with this approach from both spherical cells in suspension and from elongated, adherent cells grown and stained directly on one of the refl ectors forming the cavity. Fluorescent dyes offer a convenient method for transforming normal cells into biolasers for a variety of applications in cell-culture and lab-on-a-chip settings. In the present study, we have exploited 5-chloromethylfl uorescein diacetate (CMFDA, CellTracker Green CMFDA, Invitrogen) to investigate the feasibility of using fl uorescent probes for intracellular gain as a convenient alternative to fl uorescent proteins. The cell tracker dye CMFDA is widely used to stain cells for tracking and monitoring. [ 10 ] Besides bright fl uorescence and good photostability, it offers two further advantageous features in the context of providing optical gain in cells. First, CMFDA molecules are originally nonabsorbing and nonfl uorescent, but transform into a highly fl uorescent form once they enter the cytosol of a cell. This property is due to cleavage of the acetate groups from the molecular core by intracellular esterases, which produces a highly bright, fl uorescein derivative, 5-chloromethylfl uorescein (CMF) ( Figure 1 a). Second, a subsequent reaction of the chloromethyl group of CMF with the thiol groups of intracellular proteins yields a form that can no longer penetrate the cell membrane, thus confi ning the fl uorescent form of the dye to the inside of the cell. We confi rmed that CMF is well retained within the cytosol for over 72 h. By contrast, conventional dyes, such as fl uorescein, leak out of cells within 1 h (Figure 1 b). In terms of its spectral properties, the intracellular form of the dye is similar to the green fl uorescent protein that was previously used for cell lasers, its excitation and emission spectra peak at 493 and 522 nm, respectively (Figure 1 c). The dramatic shift in cell membrane permeability of CMDFA helps achieve high intracellular concentration (Figure S1, Supporting Information), which can provide high gain and, therefore, facilitate lasing. We incubated HeLa cells with 100 × 10 −6 M of CMFDA dye in serum-free medium containing 1% dimethyl sulfoxide (DMSO) for 30 min under standard culture conditions. This concentration is four times higher than the A Simple Approach to Biological Single-Cell Lasers Via Intracellular Dyes