Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Intracellular microlasers

Nature Photonics volume 9, pages 572–576 (2015)Cite this article

Subjects

Abstract

Optical microresonators1, which confine light within a small cavity, are widely exploited for various applications ranging from the realization of lasers2 and nonlinear devices3,4,5 to biochemical and optomechanical sensing6,7,8,9,10,11. Here we use microresonators and suitable optical gain materials inside biological cells to demonstrate various optical functions in vitro including lasing. We explore two distinct types of microresonator—soft and hard—that support whispering-gallery modes. Soft droplets formed by injecting oil or using natural lipid droplets support intracellular laser action. The laser spectra from oil-droplet microlasers can chart cytoplasmic internal stress (∼500 pN μm–2) and its dynamic fluctuations at a sensitivity of 20 pN μm–2 (20 Pa). In a second form, whispering-gallery modes within phagocytized polystyrene beads of different sizes enable individual tagging of thousands of cells easily and, in principle, a much larger number by multiplexing with different dyes.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Injected oil droplet laser.
Figure 2: Adipocyte lasers.
Figure 3: Three different types of solid intracellular microcavity.
Figure 4: Tagging and sensing applications of solid intracellular microcavities.
Figure 5: Size of intracellular microlasers.

References

  1. Vahala, K. J. Optical microcavities. Nature 424, 839–846 (2003).

    ADS  Article  Google Scholar 

  2. Qian, S. X., Snow, J. B., Tzeng, H. M. & Chang, R. K. Lasing droplets—highlighting the liquid–air interface by laser-emission. Science 231, 486–488 (1986).

    ADS  Article  Google Scholar 

  3. Hill, M. T. et al. A fast low-power optical memory based on coupled micro-ring lasers. Nature 432, 206–209 (2004).

    ADS  Article  Google Scholar 

  4. Kippenberg, T. J., Holzwarth, R. & Diddams, S. A. Microresonator-based optical frequency combs. Science 332, 555–559 (2011).

    ADS  Article  Google Scholar 

  5. Spillane, S. M., Kippenberg, T. J. & Vahala, K. J. Ultralow-threshold Raman laser using a spherical dielectric microcavity. Nature 415, 621–623 (2002).

    ADS  Article  Google Scholar 

  6. Armani, A. M., Kulkarni, R. P., Fraser, S. E., Flagan, R. C. & Vahala, K. J. Label-free, single-molecule detection with optical microcavities. Science 317, 783–787 (2007).

    ADS  Article  Google Scholar 

  7. Vollmer, F. & Arnold, S. Whispering-gallery-mode biosensing: label-free detection down to single molecules. Nature Methods 5, 591–596 (2008).

    Article  Google Scholar 

  8. Zhu, J. G. et al. On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator. Nature Photon. 4, 46–49 (2010).

    ADS  Article  Google Scholar 

  9. Fan, X. D. & White, I. M. Optofluidic microsystems for chemical and biological analysis. Nature Photon. 5, 591–597 (2011).

    ADS  Article  Google Scholar 

  10. Baaske, M. D., Foreman, M. R. & Vollmer, F. Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform. Nature Nanotech. 9, 933–939 (2014).

    ADS  Article  Google Scholar 

  11. Himmelhaus, M. & Francois, A. In-vitro sensing of biomechanical forces in live cells by a whispering gallery mode biosensor. Biosens. Bioelectron. 25, 418–427 (2009).

    Article  Google Scholar 

  12. Zhang, J., Campbell, R. E., Ting, A. Y. & Tsien, R. Y. Creating new fluorescent probes for cell biology. Nature Rev. Mol. Cell Biol. 3, 906–918 (2002).

    Article  Google Scholar 

  13. Gather, M. C. & Yun, S. H. Single-cell biological lasers. Nature Photon. 5, 406–410 (2011).

    ADS  Article  Google Scholar 

  14. Jonáš, A. et al. In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities. Lab. Chip 14, 3093–3100 (2014).

    Article  Google Scholar 

  15. Shambat, G. et al. Single-cell photonic nanocavity probes. Nano Lett. 13, 4999–5005 (2013).

    ADS  Article  Google Scholar 

  16. Fan, X. & Yun, S.-H. The potential of optofluidic biolasers. Nature Methods 11, 141–147 (2014).

    Article  Google Scholar 

  17. Hill, M. T. & Gather, M. C. Advances in small lasers. Nature Photon. 8, 908–918 (2014).

    ADS  Article  Google Scholar 

  18. Zhang, Y. & Yu, L. C. Microinjection as a tool of mechanical delivery. Curr. Opin. Biotechnol. 19, 506–510 (2008).

    ADS  Article  Google Scholar 

  19. Campàs, O. et al. Quantifying cell-generated mechanical forces within living embryonic tissues. Nature Methods 11, 183–189 (2014).

    Article  Google Scholar 

  20. Gardan, D., Gondret, F. & Louveau, I. Lipid metabolism and secretory function of porcine intramuscular adipocytes compared with subcutaneous and perirenal adipocytes. Am. J. Physiol. Endocrinol. Metab. 291, E372–E380 (2006).

    Article  Google Scholar 

  21. Cannon, G. J. & Swanson, J. A. The macrophage capacity for phagocytosis. J. Cell Sci. 101, 907–913 (1992).

    Google Scholar 

  22. Kobayashi, S. et al. Artificial induction of autophagy around polystyrene beads in nonphagocytic cells. Autophagy 6, 36–45 (2010).

    Article  Google Scholar 

  23. Gorodetsky, M. L. & Fomin, A. E. Geometrical theory of whispering-gallery modes. IEEE J. Sel. Topics Quantum Electron. 12, 33–39 (2006).

    ADS  Article  Google Scholar 

  24. Livet, J. et al. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450, 56–62 (2007).

    ADS  Article  Google Scholar 

  25. Schultz, S. G. Molecular Biology of Membrane Transport Disorders (Springer, 1996).

    Book  Google Scholar 

  26. Wang, Q. J. et al. Whispering-gallery mode resonators for highly unidirectional laser action. Proc. Natl Acad. Sci. USA 107, 22407–22412 (2010).

    ADS  Article  Google Scholar 

  27. Nizamoglu, S., Gather, M. C. & Yun, S. H. All-biomaterial laser using vitamin and biopolymers. Adv. Mater. 25, 5943–5947 (2013).

    Article  Google Scholar 

  28. Zhang, Z. et al. Visible submicron microdisk lasers. Appl. Phys. Lett. 90, 111119 (2007).

    ADS  Article  Google Scholar 

  29. Choi, M. et al. A terahertz metamaterial with unnaturally high refractive index. Nature 470, 369–373 (2011).

    ADS  Article  Google Scholar 

  30. Stockman, M. I. Spasers explained. Nature Photon. 2, 327–329 (2008).

    ADS  Article  Google Scholar 

Download references

Acknowledgements

This research was supported in part by the US National Science Foundation (NSF; ECCS-1101947, EEC-1358296, ECCS-1505569) and the National Institutes of Health (P41 EB015903). M.H. was supported in part by the Marie Curie International Outgoing Fellowship no. 627274 within the 7th European Community Framework Programme. The authors thank J. Zhao and Wellman Centre Photopathology Core for technical support. Part of this work was performed at the Centre for Nanoscale Systems (CNS) at Harvard University, which is a member of the National Nanotechnology Infrastructure Network (NNIN) and supported by the NSF under award no. ECS-0335765.

Author information

Authors and Affiliations

  1. Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, 65 Landsdowne Street UP-5, Cambridge, 02139, Massachusetts, USA

    Matjaž Humar & Seok Hyun Yun

  2. Condensed Matter Department, J. Stefan Institute, Jamova 39, Ljubljana, SI-1000, Slovenia

    Matjaž Humar

  3. Harvard–MIT Health Sciences and Technology, 77 Massachusetts Avenue Cambridge, Cambridge, 02139, Massachusetts, USA

    Seok Hyun Yun

Authors
  1. Matjaž Humar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seok Hyun Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.H. and S.H.Y. designed the study. M.H. carried out the experiments and analysed the data. M.H. and S.H.Y. wrote the manuscript.

Corresponding author

Correspondence to Seok Hyun Yun.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 3501 kb)

Supplementary information

Supplementary Movie 1 (MOV 330 kb)

Supplementary information

Supplementary Movie 2 (MOV 406 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Humar, M., Hyun Yun, S. Intracellular microlasers. Nature Photon 9, 572–576 (2015). https://doi.org/10.1038/nphoton.2015.129

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nphoton.2015.129

Further reading

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing