Abstract

Biological cell lasers are promising novel building blocks of future biocompatible optical systems and offer new approaches to cellular sensing and cytometry in a microfluidic setting. Here, we demonstrate a simple method for providing optical gain by using a variety of standard fluorescent dyes. The dye gain medium can be located inside or outside a cell, or in both, which gives flexibility in experimental design and makes the method applicable to all cell types. Due to the higher refractive index of the cytoplasm compared to the surrounding medium, a cell acts as a convex lens in a planar Fabry-Perot cavity. Its effect on the stability of the laser cavity is analyzed and utilized to suppress lasing outside cells. The resonance modes depend on the shape and internal structure of the cell. As proof of concept, we show how the laser output modes are affected by the osmotic pressure.

© 2015 Optical Society of America

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References

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    [Crossref] [PubMed]

2015 (3)

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

M. Humar and S. H. Yun, “Intracellular microlasers,” Nat. Photonics 9(9), 572–576 (2015).
[Crossref] [PubMed]

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

2014 (3)

M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5, 5722 (2014).
[Crossref] [PubMed]

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

X. Fan and S.-H. Yun, “The potential of optofluidic biolasers,” Nat. Methods 11(2), 141–147 (2014).
[Crossref] [PubMed]

2013 (3)

S. Nizamoglu, M. C. Gather, and S. H. Yun, “All-biomaterial laser using vitamin and biopolymers,” Adv. Mater. 25(41), 5943–5947 (2013).
[Crossref] [PubMed]

C. Vannahme, F. Maier-Flaig, U. Lemmer, and A. Kristensen, “Single-mode biological distributed feedback laser,” Lab Chip 13(14), 2675–2678 (2013).
[Crossref] [PubMed]

Q. Chen, X. Zhang, Y. Sun, M. Ritt, S. Sivaramakrishnan, and X. Fan, “Highly sensitive fluorescent protein FRET detection using optofluidic lasers,” Lab Chip 13(14), 2679–2681 (2013).
[Crossref] [PubMed]

2011 (3)

M. C. Gather and S. H. Yun, “Single-cell biological lasers,” Nat. Photonics 5(7), 406–410 (2011).
[Crossref]

X. Fan and I. M. White, “Optofluidic microsystems for chemical and biological analysis,” Nat. Photonics 5(10), 591–597 (2011).
[Crossref] [PubMed]

M. C. Gather and S. H. Yun, “Lasing from Escherichia coli bacteria genetically programmed to express green fluorescent protein,” Opt. Lett. 36(16), 3299–3301 (2011).
[Crossref] [PubMed]

2009 (1)

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

2006 (1)

H. Shao, D. Kumar, and K. L. Lear, “Single-cell detection using optofluidic intracavity spectroscopy,” IEEE Sens. J. 6(6), 1543–1550 (2006).
[Crossref]

2005 (2)

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

P. L. Gourley and R. K. Naviaux, “Optical phenotyping of human mitochondria in a biocavity laser,” IEEE J. Sel. Top. Quantum Electron. 11(4), 818–826 (2005).
[Crossref]

2004 (2)

2003 (1)

P. Gourley, “Biocavity laser for high-speed cell and tumour biology,” J. Phys. D Appl. Phys. 36(14), R228–R239 (2003).
[Crossref]

2002 (1)

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

1999 (1)

J. Homola, S. S. Yee, and G. Gauglitz, “Surface plasmon resonance sensors: review,” Sens. Actuators B Chem. 54(1–2), 3–15 (1999).
[Crossref]

1998 (1)

R. Y. Tsien, “The green fluorescent protein,” Annu. Rev. Biochem. 67(1), 509–544 (1998).
[Crossref] [PubMed]

1997 (1)

P. Decherchi, P. Cochard, and P. Gauthier, “Dual staining assessment of Schwann cell viability within whole peripheral nerves using calcein-AM and ethidium homodimer,” J. Neurosci. Methods 71(2), 205–213 (1997).
[Crossref] [PubMed]

1996 (1)

P. L. Gourley, “Semiconductor microlasers: A new approach to cell-structure analysis,” Nat. Med. 2(8), 942–944 (1996).
[Crossref] [PubMed]

1994 (1)

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, “Green fluorescent protein as a marker for gene expression,” Science 263(5148), 802–805 (1994).
[Crossref] [PubMed]

1993 (1)

O. V. Braginskaja, V. V. Lazarev, I. N. Pershina, K. V. Petrov, L. B. Rubin, and O. V. Tikhonova, “Sodium fluorescein accumulation in cultured cells,” Gen. Physiol. Biophys. 12(5), 453–464 (1993).
[PubMed]

1979 (1)

C. L. Bashford and J. C. Smith, “The use of optical probes to monitor membrane potential,” Methods Enzymol. 55, 569–586 (1979).
[Crossref] [PubMed]

1971 (1)

M. H. Gassman and H. Weber, “Flashlamp-pumped high gain laser dye amplifiers,” Opt. Quantum Electron. 3(4), 177–184 (1971).

Aas, M.

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

Anand, S.

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

Ananthakrishnan, R.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Badizadegan, K.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

Bandres, M. A.

Bashford, C. L.

C. L. Bashford and J. C. Smith, “The use of optical probes to monitor membrane potential,” Methods Enzymol. 55, 569–586 (1979).
[Crossref] [PubMed]

Bayraktar, H.

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

Bilby, C.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Braginskaja, O. V.

O. V. Braginskaja, V. V. Lazarev, I. N. Pershina, K. V. Petrov, L. B. Rubin, and O. V. Tikhonova, “Sodium fluorescein accumulation in cultured cells,” Gen. Physiol. Biophys. 12(5), 453–464 (1993).
[PubMed]

Brott, L. L.

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

Campbell, E. C.

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

Chalfie, M.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, “Green fluorescent protein as a marker for gene expression,” Science 263(5148), 802–805 (1994).
[Crossref] [PubMed]

Chen, Q.

Q. Chen, X. Zhang, Y. Sun, M. Ritt, S. Sivaramakrishnan, and X. Fan, “Highly sensitive fluorescent protein FRET detection using optofluidic lasers,” Lab Chip 13(14), 2679–2681 (2013).
[Crossref] [PubMed]

Choi, W.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

Cochard, P.

P. Decherchi, P. Cochard, and P. Gauthier, “Dual staining assessment of Schwann cell viability within whole peripheral nerves using calcein-AM and ethidium homodimer,” J. Neurosci. Methods 71(2), 205–213 (1997).
[Crossref] [PubMed]

Dasari, R. R.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

Decherchi, P.

P. Decherchi, P. Cochard, and P. Gauthier, “Dual staining assessment of Schwann cell viability within whole peripheral nerves using calcein-AM and ethidium homodimer,” J. Neurosci. Methods 71(2), 205–213 (1997).
[Crossref] [PubMed]

Dennis, W. M.

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

Ebert, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Erickson, H. M.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Euskirchen, G.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, “Green fluorescent protein as a marker for gene expression,” Science 263(5148), 802–805 (1994).
[Crossref] [PubMed]

Fan, X.

X. Fan and S.-H. Yun, “The potential of optofluidic biolasers,” Nat. Methods 11(2), 141–147 (2014).
[Crossref] [PubMed]

Q. Chen, X. Zhang, Y. Sun, M. Ritt, S. Sivaramakrishnan, and X. Fan, “Highly sensitive fluorescent protein FRET detection using optofluidic lasers,” Lab Chip 13(14), 2679–2681 (2013).
[Crossref] [PubMed]

X. Fan and I. M. White, “Optofluidic microsystems for chemical and biological analysis,” Nat. Photonics 5(10), 591–597 (2011).
[Crossref] [PubMed]

Feld, M. S.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

Gassman, M. H.

M. H. Gassman and H. Weber, “Flashlamp-pumped high gain laser dye amplifiers,” Opt. Quantum Electron. 3(4), 177–184 (1971).

Gather, M. C.

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5, 5722 (2014).
[Crossref] [PubMed]

S. Nizamoglu, M. C. Gather, and S. H. Yun, “All-biomaterial laser using vitamin and biopolymers,” Adv. Mater. 25(41), 5943–5947 (2013).
[Crossref] [PubMed]

M. C. Gather and S. H. Yun, “Single-cell biological lasers,” Nat. Photonics 5(7), 406–410 (2011).
[Crossref]

M. C. Gather and S. H. Yun, “Lasing from Escherichia coli bacteria genetically programmed to express green fluorescent protein,” Opt. Lett. 36(16), 3299–3301 (2011).
[Crossref] [PubMed]

Gauglitz, G.

J. Homola, S. S. Yee, and G. Gauglitz, “Surface plasmon resonance sensors: review,” Sens. Actuators B Chem. 54(1–2), 3–15 (1999).
[Crossref]

Gauthier, P.

P. Decherchi, P. Cochard, and P. Gauthier, “Dual staining assessment of Schwann cell viability within whole peripheral nerves using calcein-AM and ethidium homodimer,” J. Neurosci. Methods 71(2), 205–213 (1997).
[Crossref] [PubMed]

Gourley, P.

P. Gourley, “Biocavity laser for high-speed cell and tumour biology,” J. Phys. D Appl. Phys. 36(14), R228–R239 (2003).
[Crossref]

Gourley, P. L.

P. L. Gourley and R. K. Naviaux, “Optical phenotyping of human mitochondria in a biocavity laser,” IEEE J. Sel. Top. Quantum Electron. 11(4), 818–826 (2005).
[Crossref]

P. L. Gourley, “Semiconductor microlasers: A new approach to cell-structure analysis,” Nat. Med. 2(8), 942–944 (1996).
[Crossref] [PubMed]

Guck, J.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Gutiérrez-Vega, J. C.

Homola, J.

J. Homola, S. S. Yee, and G. Gauglitz, “Surface plasmon resonance sensors: review,” Sens. Actuators B Chem. 54(1–2), 3–15 (1999).
[Crossref]

Humar, M.

M. Humar and S. H. Yun, “Intracellular microlasers,” Nat. Photonics 9(9), 572–576 (2015).
[Crossref] [PubMed]

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

Jeon, M.

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

Jonáš, A.

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

Karadag, Y.

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

Karl, M.

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

Käs, J.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Kim, K. S.

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

Kim, S.

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

Kiraz, A.

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

Kirkpatrick, S. M.

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

Kristensen, A.

C. Vannahme, F. Maier-Flaig, U. Lemmer, and A. Kristensen, “Single-mode biological distributed feedback laser,” Lab Chip 13(14), 2675–2678 (2013).
[Crossref] [PubMed]

Kronenberg, N. M.

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

Kumar, D.

H. Shao, D. Kumar, and K. L. Lear, “Single-cell detection using optofluidic intracavity spectroscopy,” IEEE Sens. J. 6(6), 1543–1550 (2006).
[Crossref]

Lazarev, V. V.

O. V. Braginskaja, V. V. Lazarev, I. N. Pershina, K. V. Petrov, L. B. Rubin, and O. V. Tikhonova, “Sodium fluorescein accumulation in cultured cells,” Gen. Physiol. Biophys. 12(5), 453–464 (1993).
[PubMed]

Lear, K. L.

H. Shao, D. Kumar, and K. L. Lear, “Single-cell detection using optofluidic intracavity spectroscopy,” IEEE Sens. J. 6(6), 1543–1550 (2006).
[Crossref]

Lee, K. B.

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

Lemmer, U.

C. Vannahme, F. Maier-Flaig, U. Lemmer, and A. Kristensen, “Single-mode biological distributed feedback laser,” Lab Chip 13(14), 2675–2678 (2013).
[Crossref] [PubMed]

Lenz, D.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Liehm, P.

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

Lincoln, B.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Lue, N.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

Maier-Flaig, F.

C. Vannahme, F. Maier-Flaig, U. Lemmer, and A. Kristensen, “Single-mode biological distributed feedback laser,” Lab Chip 13(14), 2675–2678 (2013).
[Crossref] [PubMed]

Manioglu, S.

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

McGloin, D.

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

Mitchell, D.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Naik, R. R.

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

Naviaux, R. K.

P. L. Gourley and R. K. Naviaux, “Optical phenotyping of human mitochondria in a biocavity laser,” IEEE J. Sel. Top. Quantum Electron. 11(4), 818–826 (2005).
[Crossref]

Nizamoglu, S.

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

S. Nizamoglu, M. C. Gather, and S. H. Yun, “All-biomaterial laser using vitamin and biopolymers,” Adv. Mater. 25(41), 5943–5947 (2013).
[Crossref] [PubMed]

Pershina, I. N.

O. V. Braginskaja, V. V. Lazarev, I. N. Pershina, K. V. Petrov, L. B. Rubin, and O. V. Tikhonova, “Sodium fluorescein accumulation in cultured cells,” Gen. Physiol. Biophys. 12(5), 453–464 (1993).
[PubMed]

Petrov, K. V.

O. V. Braginskaja, V. V. Lazarev, I. N. Pershina, K. V. Petrov, L. B. Rubin, and O. V. Tikhonova, “Sodium fluorescein accumulation in cultured cells,” Gen. Physiol. Biophys. 12(5), 453–464 (1993).
[PubMed]

Pikas, D. J.

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

Polson, R. C.

R. C. Polson and Z. V. Vardeny, “Random lasing in human tissues,” Appl. Phys. Lett. 85(7), 1289–1291 (2004).
[Crossref]

Popescu, G.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

Powis, S. J.

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

Prasher, D. C.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, “Green fluorescent protein as a marker for gene expression,” Science 263(5148), 802–805 (1994).
[Crossref] [PubMed]

Ritt, M.

Q. Chen, X. Zhang, Y. Sun, M. Ritt, S. Sivaramakrishnan, and X. Fan, “Highly sensitive fluorescent protein FRET detection using optofluidic lasers,” Lab Chip 13(14), 2679–2681 (2013).
[Crossref] [PubMed]

Romeyke, M.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Rubin, L. B.

O. V. Braginskaja, V. V. Lazarev, I. N. Pershina, K. V. Petrov, L. B. Rubin, and O. V. Tikhonova, “Sodium fluorescein accumulation in cultured cells,” Gen. Physiol. Biophys. 12(5), 453–464 (1993).
[PubMed]

Schinkinger, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Schubert, M.

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

Schwarz, U. T.

Shao, H.

H. Shao, D. Kumar, and K. L. Lear, “Single-cell detection using optofluidic intracavity spectroscopy,” IEEE Sens. J. 6(6), 1543–1550 (2006).
[Crossref]

Sivaramakrishnan, S.

Q. Chen, X. Zhang, Y. Sun, M. Ritt, S. Sivaramakrishnan, and X. Fan, “Highly sensitive fluorescent protein FRET detection using optofluidic lasers,” Lab Chip 13(14), 2679–2681 (2013).
[Crossref] [PubMed]

Smith, J. C.

C. L. Bashford and J. C. Smith, “The use of optical probes to monitor membrane potential,” Methods Enzymol. 55, 569–586 (1979).
[Crossref] [PubMed]

Steude, A.

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

Stone, M. O.

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

Sun, Y.

Q. Chen, X. Zhang, Y. Sun, M. Ritt, S. Sivaramakrishnan, and X. Fan, “Highly sensitive fluorescent protein FRET detection using optofluidic lasers,” Lab Chip 13(14), 2679–2681 (2013).
[Crossref] [PubMed]

Tewksbury, E.

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

Tikhonova, O. V.

O. V. Braginskaja, V. V. Lazarev, I. N. Pershina, K. V. Petrov, L. B. Rubin, and O. V. Tikhonova, “Sodium fluorescein accumulation in cultured cells,” Gen. Physiol. Biophys. 12(5), 453–464 (1993).
[PubMed]

Tsien, R. Y.

R. Y. Tsien, “The green fluorescent protein,” Annu. Rev. Biochem. 67(1), 509–544 (1998).
[Crossref] [PubMed]

Tu, Y.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, “Green fluorescent protein as a marker for gene expression,” Science 263(5148), 802–805 (1994).
[Crossref] [PubMed]

Ulvick, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Vannahme, C.

C. Vannahme, F. Maier-Flaig, U. Lemmer, and A. Kristensen, “Single-mode biological distributed feedback laser,” Lab Chip 13(14), 2675–2678 (2013).
[Crossref] [PubMed]

Vardeny, Z. V.

R. C. Polson and Z. V. Vardeny, “Random lasing in human tissues,” Appl. Phys. Lett. 85(7), 1289–1291 (2004).
[Crossref]

Ward, W. W.

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, “Green fluorescent protein as a marker for gene expression,” Science 263(5148), 802–805 (1994).
[Crossref] [PubMed]

Weber, H.

M. H. Gassman and H. Weber, “Flashlamp-pumped high gain laser dye amplifiers,” Opt. Quantum Electron. 3(4), 177–184 (1971).

White, I. M.

X. Fan and I. M. White, “Optofluidic microsystems for chemical and biological analysis,” Nat. Photonics 5(10), 591–597 (2011).
[Crossref] [PubMed]

Wottawah, F.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Yaqoob, Z.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

Yee, S. S.

J. Homola, S. S. Yee, and G. Gauglitz, “Surface plasmon resonance sensors: review,” Sens. Actuators B Chem. 54(1–2), 3–15 (1999).
[Crossref]

Yun, S. H.

M. Humar and S. H. Yun, “Intracellular microlasers,” Nat. Photonics 9(9), 572–576 (2015).
[Crossref] [PubMed]

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5, 5722 (2014).
[Crossref] [PubMed]

S. Nizamoglu, M. C. Gather, and S. H. Yun, “All-biomaterial laser using vitamin and biopolymers,” Adv. Mater. 25(41), 5943–5947 (2013).
[Crossref] [PubMed]

M. C. Gather and S. H. Yun, “Single-cell biological lasers,” Nat. Photonics 5(7), 406–410 (2011).
[Crossref]

M. C. Gather and S. H. Yun, “Lasing from Escherichia coli bacteria genetically programmed to express green fluorescent protein,” Opt. Lett. 36(16), 3299–3301 (2011).
[Crossref] [PubMed]

Yun, S.-H.

X. Fan and S.-H. Yun, “The potential of optofluidic biolasers,” Nat. Methods 11(2), 141–147 (2014).
[Crossref] [PubMed]

Zhang, X.

Q. Chen, X. Zhang, Y. Sun, M. Ritt, S. Sivaramakrishnan, and X. Fan, “Highly sensitive fluorescent protein FRET detection using optofluidic lasers,” Lab Chip 13(14), 2679–2681 (2013).
[Crossref] [PubMed]

Adv. Mater. (1)

S. Nizamoglu, M. C. Gather, and S. H. Yun, “All-biomaterial laser using vitamin and biopolymers,” Adv. Mater. 25(41), 5943–5947 (2013).
[Crossref] [PubMed]

Adv. Opt. Mater. (1)

S. Nizamoglu, K. B. Lee, M. C. Gather, K. S. Kim, M. Jeon, S. Kim, M. Humar, and S. H. Yun, “A simple approach to biological single‐cell lasers via intracellular dyes,” Adv. Opt. Mater. 3(9), 1197–1200 (2015).
[Crossref]

Annu. Rev. Biochem. (1)

R. Y. Tsien, “The green fluorescent protein,” Annu. Rev. Biochem. 67(1), 509–544 (1998).
[Crossref] [PubMed]

Appl. Phys. Lett. (1)

R. C. Polson and Z. V. Vardeny, “Random lasing in human tissues,” Appl. Phys. Lett. 85(7), 1289–1291 (2004).
[Crossref]

Biophys. J. (1)

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Gen. Physiol. Biophys. (1)

O. V. Braginskaja, V. V. Lazarev, I. N. Pershina, K. V. Petrov, L. B. Rubin, and O. V. Tikhonova, “Sodium fluorescein accumulation in cultured cells,” Gen. Physiol. Biophys. 12(5), 453–464 (1993).
[PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

P. L. Gourley and R. K. Naviaux, “Optical phenotyping of human mitochondria in a biocavity laser,” IEEE J. Sel. Top. Quantum Electron. 11(4), 818–826 (2005).
[Crossref]

IEEE Sens. J. (1)

H. Shao, D. Kumar, and K. L. Lear, “Single-cell detection using optofluidic intracavity spectroscopy,” IEEE Sens. J. 6(6), 1543–1550 (2006).
[Crossref]

J. Neurosci. Methods (1)

P. Decherchi, P. Cochard, and P. Gauthier, “Dual staining assessment of Schwann cell viability within whole peripheral nerves using calcein-AM and ethidium homodimer,” J. Neurosci. Methods 71(2), 205–213 (1997).
[Crossref] [PubMed]

J. Phys. Chem. A (1)

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[Crossref] [PubMed]

J. Phys. Chem. B (1)

D. J. Pikas, S. M. Kirkpatrick, E. Tewksbury, L. L. Brott, R. R. Naik, M. O. Stone, and W. M. Dennis, “Nonlinear saturation and lasing characteristics of green fluorescent protein,” J. Phys. Chem. B 106(18), 4831–4837 (2002).
[Crossref]

J. Phys. D Appl. Phys. (1)

P. Gourley, “Biocavity laser for high-speed cell and tumour biology,” J. Phys. D Appl. Phys. 36(14), R228–R239 (2003).
[Crossref]

Lab Chip (3)

Q. Chen, X. Zhang, Y. Sun, M. Ritt, S. Sivaramakrishnan, and X. Fan, “Highly sensitive fluorescent protein FRET detection using optofluidic lasers,” Lab Chip 13(14), 2679–2681 (2013).
[Crossref] [PubMed]

C. Vannahme, F. Maier-Flaig, U. Lemmer, and A. Kristensen, “Single-mode biological distributed feedback laser,” Lab Chip 13(14), 2675–2678 (2013).
[Crossref] [PubMed]

A. Jonáš, M. Aas, Y. Karadag, S. Manioğlu, S. Anand, D. McGloin, H. Bayraktar, and A. Kiraz, “In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities,” Lab Chip 14(16), 3093–3100 (2014).
[Crossref] [PubMed]

Methods Enzymol. (1)

C. L. Bashford and J. C. Smith, “The use of optical probes to monitor membrane potential,” Methods Enzymol. 55, 569–586 (1979).
[Crossref] [PubMed]

Nano Lett. (1)

M. Schubert, A. Steude, P. Liehm, N. M. Kronenberg, M. Karl, E. C. Campbell, S. J. Powis, and M. C. Gather, “Lasing within live cells containing intracellular optical micro-resonators for barcode-type cell tagging and tracking,” Nano Lett. 15(8), 5647–5652 (2015).
[Crossref] [PubMed]

Nat. Commun. (1)

M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5, 5722 (2014).
[Crossref] [PubMed]

Nat. Med. (1)

P. L. Gourley, “Semiconductor microlasers: A new approach to cell-structure analysis,” Nat. Med. 2(8), 942–944 (1996).
[Crossref] [PubMed]

Nat. Methods (1)

X. Fan and S.-H. Yun, “The potential of optofluidic biolasers,” Nat. Methods 11(2), 141–147 (2014).
[Crossref] [PubMed]

Nat. Photonics (3)

X. Fan and I. M. White, “Optofluidic microsystems for chemical and biological analysis,” Nat. Photonics 5(10), 591–597 (2011).
[Crossref] [PubMed]

M. Humar and S. H. Yun, “Intracellular microlasers,” Nat. Photonics 9(9), 572–576 (2015).
[Crossref] [PubMed]

M. C. Gather and S. H. Yun, “Single-cell biological lasers,” Nat. Photonics 5(7), 406–410 (2011).
[Crossref]

Opt. Lett. (2)

Opt. Quantum Electron. (1)

M. H. Gassman and H. Weber, “Flashlamp-pumped high gain laser dye amplifiers,” Opt. Quantum Electron. 3(4), 177–184 (1971).

Science (1)

M. Chalfie, Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher, “Green fluorescent protein as a marker for gene expression,” Science 263(5148), 802–805 (1994).
[Crossref] [PubMed]

Sens. Actuators B Chem. (1)

J. Homola, S. S. Yee, and G. Gauglitz, “Surface plasmon resonance sensors: review,” Sens. Actuators B Chem. 54(1–2), 3–15 (1999).
[Crossref]

Other (2)

M. Humar and S.-H. A. Yun, “Microlasers inside live cells,” in Proceedings of CLEO: QELS_Fundamental Science (Optical Society of America, 2015), paper JTh5A. 2.
[Crossref]

A. E. Siegman, Lasers (Mill Valley, 1986).

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Figures (8)

Fig. 1
Fig. 1

Experimental configuration and parameters. A cell with radius R is placed in between mirrors with spacing L. The cell laser spot sizes at the top and bottom mirror are w1 and w2 respectively.

Fig. 2
Fig. 2

Configuration of the cell laser experiments. (a) Cell lasers are pumped by an external laser through a microscope objective. The fluorescent light collected through the same objective, separated by a dichroic mirror and sent to the spectrometer and the camera. (b) Cells are placed in between two highly reflective mirrors and sink to the surface of the bottom mirror. The cell is illuminated in such way that the entire cell or a group of cells is pumped. Three gain configurations are proposed: The fluorescent dye can be situated either (c) only inside the cell (Type I), (d) only on the outside (Type II) or (e) both inside and on the outside of the cell (Type III).

Fig. 3
Fig. 3

Cell lasers employing different fluorescent dyes and different gain configurations. HeLa cells were suspended in a buffer containing one of four different fluorescent dyes. Top panels show an overlay of the bright field image of cells and laser emission. Lower panels show lasing spectra. (a) Calcein-AM lasing in Type I configuration where the dye is localized within the cell. (b) The very long dextran-FITC molecules do not penetrate the cell membrane forming a Type II laser. (c) Lasing of cells filled with and immersed in the green emitting dye fluorescein (Type III configuration). (d) Using the cell penetrating Rhodamine 6G, a Type III cell laser with emission in the red part of the spectrum is obtained. Scale bars, 20 µm.

Fig. 4
Fig. 4

Light output characteristics of a single cell shows typical threshold behavior when the pump energy is increased.

Fig. 5
Fig. 5

Dye concentration in the cells relative to the dye concentration in the medium where the cells were incubated for different incubation times.

Fig. 6
Fig. 6

Cell laser threshold with different resonator parameters. Thresholds were measured using a suspension of HeLa cells in fluorescein containing medium (Type III), either illuminating a single cell (▪) or an area of the resonator without any cells (●). Lines represent calculated thresholds for cell laser (solid red) and empty resonator (dashed black). (a) The lasing threshold gradually increases with increasing resonator gap for both cell containing and empty resonator. Concentration of fluorescein was 1 mM. (b) The threshold generally decreases with increasing fluorescein concentration, but slightly increases again at higher concentrations. Resonator gap was 30 µm. (c) For the cell laser, the threshold is nearly unaffected by the tilt angle. However, for an empty cavity the threshold increases considerably with angle and above ~0.4° lasing is not observed any longer. Resonator gap was kept constant at 50 µm and the concentration of fluorescein was 1 mM. (d) Illustration of wedged resonator design, made by tilting one mirror by a small amount (3°) with respect to the other. When a cell is present in between mirrors, the resonator remains stable, whereas with no cell present the light quickly escapes from the gain region.

Fig. 7
Fig. 7

Hyperspectral images of lasing modes in different cell geometries. (a-c) Overlays of bright field images and lasing images (left). Hyperspectral images of lasing modes showing both wavelength and spatial pattern of the different transverse modes (right). Lines above spectra represent groups of different transversal modes corresponding to the same longitudinal mode order. In all three cases fluorescein was used (Type III configuration) (a) Nearly spherical EL4 cell shows Laguerre-Gaussian like modes with rotational symmetry. (b) An elongated NIH3T3 cell attached to one of the mirrors lases in Hermite-Gaussian modes that resemble the elongated shape of the cell. (c) A biconcave disc shaped red blood cell also shows Laguerre-Gaussian modes. However, in this case only one of the lowest order modes with a doughnut shape is observed. Here, one mirror was tilted by 0.5° to suppress background lasing. (d) Bright-field image of a group of EL4 cells immersed in pyrromethene 556 doped buffer (Type III configuration). (e) Lasing of the same EL4 cells when illuminated by an expanded 475 nm laser beam. Scale bars, 10 µm in a, b and c, 20 µm in d and e.

Fig. 8
Fig. 8

Tracking changes in cell laser modes as the osmolarity of the surrounding medium is changed. Lasing modes of a single NIH3T3 cell attached to one mirror at different time points. All the modes in each case correspond to different transversal modes in a single longitudinal mode group. (a) The solution of FITC-dextran in PBS was exchanged with a solution of FITC-dextran in pure water causing the mode pattern to change dramatically, with completely different transversal modes present at the end of the experiment compared to the start. (b) Control experiment with no changes made to the solution. Modes remain stable over time, only showing a small amount of photobleaching. (c) Further control experiment in which the original solution of FITC-dextran in PBS was exchanged for an identical one. Modes change only slightly over the course of the experiment. When the flow of medium ceases, the modes return to their original structure, although at a slightly shifted wavelength due to a minute change in overall cavity thickness. Scale bars, 10 µm.

Equations (12)

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M=( A B C D )
1<( A+D 2 )<1.
M 1 =( 1 L2R 0 1 )( 1 0 n cell n 0 R n 0 n cell n 0 )( 1 2R 0 1 )( 1 0 n 0 n cell R n cell n 0 n cell )
M 2 =( 1 0 n cell n 0 R n 0 n cell n 0 )( 1 2R 0 1 )( 1 0 n 0 n cell R n cell n 0 n cell )( 1 L2R 0 1 )
f cell =R[ n cell n 0 2( n cell n 0 1 ) ]
w 1 2 = Lλ π 1 g 1 (1 g 1 )
w 2 2 = w 0 2 = Lλ π g 1 1 g 1 .
Nλ=2( ( L2R ) n 0 +2R n cell ).
g( z )=N[ W( z )τ( B c + σ ss ) σ ss ],
B= λ 4 E( λ )n 8πτ     and    W( z )= J( z ) σ 0 hν ,
0 E( λ )dλ=ϕ,
dI dz =I( z )g( z )

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