Abstract

The notion of lasing with biologics has recently been realized and has rapidly developed with the collective objective of creating lasers in vivo. One major limitation of achieving this is the requirement of exogenous dyes and fluorescent materials. We thus investigate for the first time the possibility of lasing unlabelled cells, using just cell-endogenous fluorophores - the source of cell autofluorescence. In this work, we theoretically studied the lasing potential and efficiency of flavins and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) using a dye lasing model based on coupled rate equations. Analytical solutions for one- and two-photon pumped system were used in multi-parameter studies. We found that at physiological conditions, the more abundant NAD(P)H can be lased with a cavity quality factor of 105. We then recommended the tuning of intersystem crossing to make the lasing of flavins feasible even at their low physiological concentrations. Under conditions of reduced intersystem crossing, we concluded that it is more practical to lase unlabelled cells using flavins, because lasing thresholds and cavity quality factors were both at least an order lower. We also note the higher threshold requirements and lower efficiencies of two-photon pumping, but recognize its potential for realizing lasing in vivo.

Highlights

  • The notion of lasing with biologics has recently been realized and has rapidly developed with the collective objective of creating lasers in vivo

  • It should be noted that flavins here refer to all three fluorescent derivatives found natively within cells, namely riboflavins (RF), flavin mononucleotides (FMN) and flavin adenine dinucleotide (FAD); while NAD(P)H collectively refers to the fluorescent reduced forms of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)

  • We have theoretically studied the feasibility of lasing with cell-endogenous fluorophores and identified parameters that allow for lasing in cells at physiological conditions

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Summary

Introduction

The notion of lasing with biologics has recently been realized and has rapidly developed with the collective objective of creating lasers in vivo. We theoretically studied the lasing potential and efficiency of flavins and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) using a dye lasing model based on coupled rate equations. Under conditions of reduced intersystem crossing, we concluded that it is more practical to lase unlabelled cells using flavins, because lasing thresholds and cavity quality factors were both at least an order lower. These cell-endogenous fluorophores are the source of autofluorescence, which is often regarded as noise in fluorescence microscopy They are the very machineries responsible for cell functions and metabolic activities[11]. We study the conditions and parameters for lasing two of the most abundant cell-endogenous fluorophores - flavins and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H). We make recommendations for possible approaches to lower threshold requirements so as to mitigate risks of inducing irreversible cell damage

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