Biolasing from Individual Cells in a Low‐Q Resonator Enables Spectral Fingerprinting

Abstract

Lasing from cells has recently been subject of thorough investigation because of the potential for sensitive and fast biosensing. Yet, lasing from individual cells has been studied in high‐quality resonators, resulting in limited dependence of the lasing properties on the cellular microenvironment. Here, lasing is triggered by cells floating in a low quality factor resonator composed of a disposable poly(methyl methacrylate) (PMMA) cell counting‐slide, hence in absence of conventional high‐reflectivity optical cavities. The exceptional spectral narrowing and the steep slope increase in the input–output energy diagram prove occurrence of laser action in presence of cells. The observed biolasing is an intrinsically dynamic signal, with large fluctuations in intensity and spectrum determined by the optical properties of the individual cell passing through the pump beam. Numerical simulations of the scattering efficiency rule out the possibility of optical feedback from either WGM (whispering gallery mode) or multiple scattering within the cell, and point to the enhanced directional scattering field as the crucial contribution of cells to the laser action. Finally, principal component analysis of lasing spectra measured from freely diffusing cells yields spectral fingerprints of cell populations, which allows discriminating cancer from healthy Rattus glial cells with high degree of confidence.

Biophotonic probes for bio-detection and imaging

“…Compared to endogenously expressed fluorescent proteins, a much greater variety of synthetic fluorescent molecules such as 5-chloromethylfluorescein diacetate (CMFDA) 67 , 68 , fluorescein sodium salt 64 , Rhodamine 6G 69 , 70 , Calcein-AM 71 and fluorescein isothiocyanate (FITC) 72 , have been demonstrated as convenient gain medium to generate cell lasers from various cell types. Particularly, the fast dye staining procedures can be completed within an hour, which dramatically reduced the laser preparation time as compared to the time-consuming fluorescent protein transfection methods.…”

Cellular Features Revealed by Transverse Laser Modes in Frequency Domain

“…Thus far, various types of cavities for cellular lasers have been proposed, including whispering gallery mode (WGM)‐based cavities that are embedded into cells, [ 13 , 15 , 16 ] and Fabry–Pérot (FP) cavities which encapsulate the cells in microcavity. [ 17 , 18 , 19 ] The former was utilized to emit WGM‐lasing peaks for precise cell tracking and intracellular analysis. The latter, that is, FP cavity‐type, possesses the advantages of non‐invasiveness and whole‐body interactions between stimulated emission and cells, which may provide intrinsic information of the cell.…”

Single Cell Biological Microlasers Powered by Deep Learning

“…Biological laser, which embeds biological materials into the gain medium and optical cavity, is an emerging technology that offers new ways of using laser light in biomedical applications [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] . Thanks to the strong light-matter interactions provided by an optical cavity, subtle changes in biological gain media could be amplified, leading to distinctive output lasing characteristics.…”

“…Thanks to the strong light-matter interactions provided by an optical cavity, subtle changes in biological gain media could be amplified, leading to distinctive output lasing characteristics. Recent advances in cellular lasers have attracted tremendous interest in cell tracking, intracellular detection, and phenotyping by exploiting various types of cavities [5][6][7][8][9] . In particular, single-cell lasers that utilize Fabry-Pérot (FP) microcavities possess the advantages of whole-body interaction between the electromagnetic field and the gain medium, providing a sensitive approach to study the physical structures and interactions in cells 4,5,19 .…”