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

Dedy Septiadi,Valentin Barna,Damiano Genovese,Riccardo Sapienza,Luisa De Cola,Dhruv Saxena

doi:10.1002/adom.201901573

Abstract

AbstractLasing 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.

Highlights

Lasing from cells has recently been subject of thorough investigation because of feedback, stimulated emission can overthe potential for sensitive and fast biosensing
The observation system is composed of a 100 μm thick chamber delimited by two facing poly(methyl methacrylate) (PMMA) walls, resulting in very weak reflection at the system interfaces
Numerical calculations demonstrate the role of refractive index contrast in cells in triggering light amplification, while a broader analogy with random lasing as observed from weakly scattering matrices[24] remains limited because of the low probability of multiple scattering

Summary

Introduction

Lasing from cells has recently been subject of thorough investigation because of feedback, stimulated emission can overthe potential for sensitive and fast biosensing. Introduction individual cells, has been proposed as a promising novel concept with potential for enhanced sensing.[16,17] It has been achieved as a result of the amplification taneous emission is used to monitor in real time and real provided by laser cavities[12] or microresonators[13,14,15] while space the activity of cells, organelles, and biomolecules[1] with lasing from an isolated individual cell has proven to be elusive, high resolution and sensitivity.[2] in the presence and only observed in isolated adipocytes featuring very large oil. For cells inside a cavity composed of two reflective mirrors, the refractive index contrast between a cell and its surrounding medium has been found to lower the threshold for lasing, due to the so-called “lens-effect”.[18,19] In these conditions, the laser threshold has been reported to carry information on cellular properties (such as the hydration level)[18] and it has been used to discriminate cancer from healthy cells.[20]

Results

Discussion

Conclusion