Abstract

We proposed and demonstrated a label-free imaging method for living cells using a GaInAsP H0-type photonic crystal nanolaser array. We integrated 441 nanolasers in an arrayed configuration and achieved photopumped lasing with a 100% yield. Then, we attached HeLa cells on it, measured the wavelengths of all nanolasers and used them as pixel information. We acquired cell images, which partially corresponds to optical micrographs and probably reflects the attachment condition of the cells. We improved the refractive index resolution from ~10−2 to 2 × 10−3 by incorporating a nanoslot into each nanolaser and compensating the nonuniformity of each index sensitivity.

© 2015 Optical Society of America

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References

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  1. C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
    [Crossref] [PubMed]
  2. K. J. Moh, X. C. Yuan, J. Bu, S. W. Zhu, and B. Z. Gao, “Surface plasmon resonance imaging of cell-substrate contacts with radially polarized beams,” Opt. Express 16(25), 20734–20741 (2008).
    [PubMed]
  3. Y. Fang, A. M. Ferrie, N. H. Fontaine, J. Mauro, and J. Balakrishnan, “Resonant waveguide grating biosensor for living cell sensing,” Biophys. J. 91(5), 1925–1940 (2006).
    [Crossref] [PubMed]
  4. L. L. Chan, S. L. Gosangari, K. L. Watkin, and B. T. Cunningham, “A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation,” Apoptosis 12(6), 1061–1068 (2007).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  6. Y. Fang, “Non-invasive optical biosensor for probing cell signaling,” Sensors (Basel Switzerland) 7(10), 2316–2329 (2007).
    [Crossref]
  7. A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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2014 (3)

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
[Crossref]

A. F. Coskun, A. E. Cetin, B. C. Galarreta, D. A. Alvarez, H. Altug, and A. Ozcan, “Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view,” Sci. Rep. 4, 6789 (2014).
[Crossref] [PubMed]

T. Watanabe, H. Abe, Y. Nishijima, and T. Baba, “Array integration of thousands of photonic crystal nanolasers,” Appl. Phys. Lett. 104(12), 121108 (2014).
[Crossref]

2013 (1)

2012 (1)

M. Narimatsu, S. Kita, H. Abe, and T. Baba, “Enhancement of vertical emission in photonic crystal nanolasers,” Appl. Phys. Lett. 100(12), 121117 (2012).
[Crossref]

2011 (2)

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
[Crossref]

S. Kita, S. Hachuda, S. Otsuka, T. Endo, Y. Imai, Y. Nishijima, H. Misawa, and T. Baba, “Super-sensitivity in label-free protein sensing using a nanoslot nanolaser,” Opt. Express 19(18), 17683–17690 (2011).
[Crossref] [PubMed]

2010 (1)

Y. Yanase, T. Hiragun, S. Kaneko, H. J. Gould, M. W. Greaves, and M. Hide, “Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging,” Biosens. Bioelectron. 26(2), 674–681 (2010).
[Crossref] [PubMed]

2008 (2)

K. J. Moh, X. C. Yuan, J. Bu, S. W. Zhu, and B. Z. Gao, “Surface plasmon resonance imaging of cell-substrate contacts with radially polarized beams,” Opt. Express 16(25), 20734–20741 (2008).
[PubMed]

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

2007 (2)

Y. Fang, “Non-invasive optical biosensor for probing cell signaling,” Sensors (Basel Switzerland) 7(10), 2316–2329 (2007).
[Crossref]

L. L. Chan, S. L. Gosangari, K. L. Watkin, and B. T. Cunningham, “A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation,” Apoptosis 12(6), 1061–1068 (2007).
[Crossref] [PubMed]

2006 (1)

Y. Fang, A. M. Ferrie, N. H. Fontaine, J. Mauro, and J. Balakrishnan, “Resonant waveguide grating biosensor for living cell sensing,” Biophys. J. 91(5), 1925–1940 (2006).
[Crossref] [PubMed]

1978 (1)

1962 (1)

I. H. Goldverg, M. Rabinowitz, and E. Reichi, “Basis of actinomycin action, I. DNA binding and inhibition of RNA-polymerase synthetic reactions by actionomycin,” Proc. Natl. Acad. Sci. U. S. A. 48, 2094–2101 (1962).

Abe, H.

T. Watanabe, H. Abe, Y. Nishijima, and T. Baba, “Array integration of thousands of photonic crystal nanolasers,” Appl. Phys. Lett. 104(12), 121108 (2014).
[Crossref]

M. Narimatsu, S. Kita, H. Abe, and T. Baba, “Enhancement of vertical emission in photonic crystal nanolasers,” Appl. Phys. Lett. 100(12), 121117 (2012).
[Crossref]

Altug, H.

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
[Crossref]

A. F. Coskun, A. E. Cetin, B. C. Galarreta, D. A. Alvarez, H. Altug, and A. Ozcan, “Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view,” Sci. Rep. 4, 6789 (2014).
[Crossref] [PubMed]

Alvarez, D. A.

A. F. Coskun, A. E. Cetin, B. C. Galarreta, D. A. Alvarez, H. Altug, and A. Ozcan, “Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view,” Sci. Rep. 4, 6789 (2014).
[Crossref] [PubMed]

Arita, Y.

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
[Crossref]

Baba, T.

T. Watanabe, H. Abe, Y. Nishijima, and T. Baba, “Array integration of thousands of photonic crystal nanolasers,” Appl. Phys. Lett. 104(12), 121108 (2014).
[Crossref]

S. Hachuda, S. Otsuka, S. Kita, T. Isono, M. Narimatsu, K. Watanabe, Y. Goshima, and T. Baba, “Selective detection of sub-atto-molar Streptavidin in 1013-fold impure sample using photonic crystal nanolaser sensors,” Opt. Express 21(10), 12815–12821 (2013).
[Crossref] [PubMed]

M. Narimatsu, S. Kita, H. Abe, and T. Baba, “Enhancement of vertical emission in photonic crystal nanolasers,” Appl. Phys. Lett. 100(12), 121117 (2012).
[Crossref]

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
[Crossref]

S. Kita, S. Hachuda, S. Otsuka, T. Endo, Y. Imai, Y. Nishijima, H. Misawa, and T. Baba, “Super-sensitivity in label-free protein sensing using a nanoslot nanolaser,” Opt. Express 19(18), 17683–17690 (2011).
[Crossref] [PubMed]

Balakrishnan, J.

Y. Fang, A. M. Ferrie, N. H. Fontaine, J. Mauro, and J. Balakrishnan, “Resonant waveguide grating biosensor for living cell sensing,” Biophys. J. 91(5), 1925–1940 (2006).
[Crossref] [PubMed]

Bu, J.

Cetin, A.

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
[Crossref]

Cetin, A. E.

A. F. Coskun, A. E. Cetin, B. C. Galarreta, D. A. Alvarez, H. Altug, and A. Ozcan, “Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view,” Sci. Rep. 4, 6789 (2014).
[Crossref] [PubMed]

Chan, L. L.

L. L. Chan, S. L. Gosangari, K. L. Watkin, and B. T. Cunningham, “A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation,” Apoptosis 12(6), 1061–1068 (2007).
[Crossref] [PubMed]

Coskun, A. F.

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
[Crossref]

A. F. Coskun, A. E. Cetin, B. C. Galarreta, D. A. Alvarez, H. Altug, and A. Ozcan, “Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view,” Sci. Rep. 4, 6789 (2014).
[Crossref] [PubMed]

Cunningham, B. T.

L. L. Chan, S. L. Gosangari, K. L. Watkin, and B. T. Cunningham, “A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation,” Apoptosis 12(6), 1061–1068 (2007).
[Crossref] [PubMed]

Endo, T.

Fang, Y.

Y. Fang, “Non-invasive optical biosensor for probing cell signaling,” Sensors (Basel Switzerland) 7(10), 2316–2329 (2007).
[Crossref]

Y. Fang, A. M. Ferrie, N. H. Fontaine, J. Mauro, and J. Balakrishnan, “Resonant waveguide grating biosensor for living cell sensing,” Biophys. J. 91(5), 1925–1940 (2006).
[Crossref] [PubMed]

Ferrie, A. M.

Y. Fang, A. M. Ferrie, N. H. Fontaine, J. Mauro, and J. Balakrishnan, “Resonant waveguide grating biosensor for living cell sensing,” Biophys. J. 91(5), 1925–1940 (2006).
[Crossref] [PubMed]

Fontaine, N. H.

Y. Fang, A. M. Ferrie, N. H. Fontaine, J. Mauro, and J. Balakrishnan, “Resonant waveguide grating biosensor for living cell sensing,” Biophys. J. 91(5), 1925–1940 (2006).
[Crossref] [PubMed]

Freudiger, C. W.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Galarreta, B. C.

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
[Crossref]

A. F. Coskun, A. E. Cetin, B. C. Galarreta, D. A. Alvarez, H. Altug, and A. Ozcan, “Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view,” Sci. Rep. 4, 6789 (2014).
[Crossref] [PubMed]

Gao, B. Z.

Goldverg, I. H.

I. H. Goldverg, M. Rabinowitz, and E. Reichi, “Basis of actinomycin action, I. DNA binding and inhibition of RNA-polymerase synthetic reactions by actionomycin,” Proc. Natl. Acad. Sci. U. S. A. 48, 2094–2101 (1962).

Gosangari, S. L.

L. L. Chan, S. L. Gosangari, K. L. Watkin, and B. T. Cunningham, “A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation,” Apoptosis 12(6), 1061–1068 (2007).
[Crossref] [PubMed]

Goshima, Y.

Gould, H. J.

Y. Yanase, T. Hiragun, S. Kaneko, H. J. Gould, M. W. Greaves, and M. Hide, “Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging,” Biosens. Bioelectron. 26(2), 674–681 (2010).
[Crossref] [PubMed]

Greaves, M. W.

Y. Yanase, T. Hiragun, S. Kaneko, H. J. Gould, M. W. Greaves, and M. Hide, “Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging,” Biosens. Bioelectron. 26(2), 674–681 (2010).
[Crossref] [PubMed]

Hachuda, S.

He, C.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Herman, D.

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
[Crossref]

Hide, M.

Y. Yanase, T. Hiragun, S. Kaneko, H. J. Gould, M. W. Greaves, and M. Hide, “Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging,” Biosens. Bioelectron. 26(2), 674–681 (2010).
[Crossref] [PubMed]

Hiragun, T.

Y. Yanase, T. Hiragun, S. Kaneko, H. J. Gould, M. W. Greaves, and M. Hide, “Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging,” Biosens. Bioelectron. 26(2), 674–681 (2010).
[Crossref] [PubMed]

Holtom, G. R.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Huang, M.

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
[Crossref]

Imai, Y.

Isono, T.

Johnston, A. R.

Kaneko, S.

Y. Yanase, T. Hiragun, S. Kaneko, H. J. Gould, M. W. Greaves, and M. Hide, “Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging,” Biosens. Bioelectron. 26(2), 674–681 (2010).
[Crossref] [PubMed]

Kang, J. X.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Kita, S.

S. Hachuda, S. Otsuka, S. Kita, T. Isono, M. Narimatsu, K. Watanabe, Y. Goshima, and T. Baba, “Selective detection of sub-atto-molar Streptavidin in 1013-fold impure sample using photonic crystal nanolaser sensors,” Opt. Express 21(10), 12815–12821 (2013).
[Crossref] [PubMed]

M. Narimatsu, S. Kita, H. Abe, and T. Baba, “Enhancement of vertical emission in photonic crystal nanolasers,” Appl. Phys. Lett. 100(12), 121117 (2012).
[Crossref]

S. Kita, S. Hachuda, S. Otsuka, T. Endo, Y. Imai, Y. Nishijima, H. Misawa, and T. Baba, “Super-sensitivity in label-free protein sensing using a nanoslot nanolaser,” Opt. Express 19(18), 17683–17690 (2011).
[Crossref] [PubMed]

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
[Crossref]

Lu, S.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Mauro, J.

Y. Fang, A. M. Ferrie, N. H. Fontaine, J. Mauro, and J. Balakrishnan, “Resonant waveguide grating biosensor for living cell sensing,” Biophys. J. 91(5), 1925–1940 (2006).
[Crossref] [PubMed]

Min, W.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Misawa, H.

Moh, K. J.

Nakada, T.

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
[Crossref]

Narimatsu, M.

Nishijima, Y.

Nozaki, K.

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
[Crossref]

Otsuka, S.

Ozcan, A.

A. F. Coskun, A. E. Cetin, B. C. Galarreta, D. A. Alvarez, H. Altug, and A. Ozcan, “Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view,” Sci. Rep. 4, 6789 (2014).
[Crossref] [PubMed]

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
[Crossref]

Rabinowitz, M.

I. H. Goldverg, M. Rabinowitz, and E. Reichi, “Basis of actinomycin action, I. DNA binding and inhibition of RNA-polymerase synthetic reactions by actionomycin,” Proc. Natl. Acad. Sci. U. S. A. 48, 2094–2101 (1962).

Reichi, E.

I. H. Goldverg, M. Rabinowitz, and E. Reichi, “Basis of actinomycin action, I. DNA binding and inhibition of RNA-polymerase synthetic reactions by actionomycin,” Proc. Natl. Acad. Sci. U. S. A. 48, 2094–2101 (1962).

Saar, B. G.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Saito, Y.

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
[Crossref]

Tsai, J. C.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Watanabe, H.

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
[Crossref]

Watanabe, K.

Watanabe, T.

T. Watanabe, H. Abe, Y. Nishijima, and T. Baba, “Array integration of thousands of photonic crystal nanolasers,” Appl. Phys. Lett. 104(12), 121108 (2014).
[Crossref]

Watkin, K. L.

L. L. Chan, S. L. Gosangari, K. L. Watkin, and B. T. Cunningham, “A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation,” Apoptosis 12(6), 1061–1068 (2007).
[Crossref] [PubMed]

Xie, X. S.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Yanase, Y.

Y. Yanase, T. Hiragun, S. Kaneko, H. J. Gould, M. W. Greaves, and M. Hide, “Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging,” Biosens. Bioelectron. 26(2), 674–681 (2010).
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Yeung, W. F.

Yuan, X. C.

Zhu, S. W.

Apoptosis (1)

L. L. Chan, S. L. Gosangari, K. L. Watkin, and B. T. Cunningham, “A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation,” Apoptosis 12(6), 1061–1068 (2007).
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Appl. Opt. (1)

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T. Watanabe, H. Abe, Y. Nishijima, and T. Baba, “Array integration of thousands of photonic crystal nanolasers,” Appl. Phys. Lett. 104(12), 121108 (2014).
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M. Narimatsu, S. Kita, H. Abe, and T. Baba, “Enhancement of vertical emission in photonic crystal nanolasers,” Appl. Phys. Lett. 100(12), 121117 (2012).
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Biophys. J. (1)

Y. Fang, A. M. Ferrie, N. H. Fontaine, J. Mauro, and J. Balakrishnan, “Resonant waveguide grating biosensor for living cell sensing,” Biophys. J. 91(5), 1925–1940 (2006).
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Biosens. Bioelectron. (1)

Y. Yanase, T. Hiragun, S. Kaneko, H. J. Gould, M. W. Greaves, and M. Hide, “Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging,” Biosens. Bioelectron. 26(2), 674–681 (2010).
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IEEE J. Sel. Top. Quantum Electron. (1)

S. Kita, K. Nozaki, S. Hachuda, H. Watanabe, Y. Saito, S. Otsuka, T. Nakada, Y. Arita, and T. Baba, “Photonic crystal point-shift nanolaser with and without nanoslots—design, fabrication, lasing and sensing characteristics,” IEEE J. Sel. Top. Quantum Electron. 17(6), 1632–1647 (2011).
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Light: Sci. Appl. (1)

A. Cetin, A. F. Coskun, B. C. Galarreta, M. Huang, D. Herman, A. Ozcan, and H. Altug, “Handheld high-throughput plasmonic biosensor using computational on-chip imaging,” Light: Sci. Appl. 3(1), e122 (2014).
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Opt. Express (3)

Proc. Natl. Acad. Sci. U. S. A. (1)

I. H. Goldverg, M. Rabinowitz, and E. Reichi, “Basis of actinomycin action, I. DNA binding and inhibition of RNA-polymerase synthetic reactions by actionomycin,” Proc. Natl. Acad. Sci. U. S. A. 48, 2094–2101 (1962).

Sci. Rep. (1)

A. F. Coskun, A. E. Cetin, B. C. Galarreta, D. A. Alvarez, H. Altug, and A. Ozcan, “Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view,” Sci. Rep. 4, 6789 (2014).
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Science (1)

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
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Sensors (Basel Switzerland) (1)

Y. Fang, “Non-invasive optical biosensor for probing cell signaling,” Sensors (Basel Switzerland) 7(10), 2316–2329 (2007).
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Figures (12)

Fig. 1
Fig. 1 Nanolaser array on which cells are cultured. Left shows optical micrograph of nanolaser arrays and HeLa cells. Middle is a schematic of a cell on the nanolaser array. Right shows the scanning electron micrograph of fabricated H0-type nanolaser.
Fig. 2
Fig. 2 Fabrication process. (a) Epitaxial wafer. (b) E-beam lithography. (c) HI inductively coupled plasma etching. (d) Silica deposition into holes. (e) Bonding using PDMS resin. (f) Wet etchings.
Fig. 3
Fig. 3 Pulsed lasing characteristics of single nanolaser formed on PDMS and immersed in water. Right lowest panel shows the spontaneous emission spectrum at unpatterned slab on PDMS, which was obtained by pumping harder with a larger pump spot. It indicates that the spontaneous emission peak was around 1.50 μm and that the noisy background in the second lowest panel arose from the spontaneous emission.
Fig. 4
Fig. 4 Fabricated nanolaser array. (a) Optical micrograph of nanolaser array, SEM image of one nanolaser, and pumping scheme. (b) Near-field pattern of laser emission from the 441-nanolaser array.
Fig. 5
Fig. 5 Spectral characteristics of the nanolaser array. (a) Wavelength controlled by changing diameters of the shifted holes in a test sample in water. (b) Laser spectra of the 441 nanolasers in water, where the intensities are normalized.
Fig. 6
Fig. 6 Observation of resist pattern on a nanolaser array. (a) Optical micrograph of resist pattern and organic substance. (b) Δλ image.
Fig. 7
Fig. 7 Observation of HeLa cells attached on a nanolaser array. (a) Snapshots for samples A–D. Left and right panels for each sample show the optical micrographs and Δλ images, respectively. Dashed lines depict the cell boundaries. (b) Time evolution.
Fig. 8
Fig. 8 FDTD calculation of wavelength shift for the distance between nanolaser and cell. The distance is set at zero when the cell is attached on the top surface of the nanolaser. The negative distance means that the cell partially penetrates into holes of the nanolaser.
Fig. 9
Fig. 9 Spectral shifts in nanolasers when Actinomycin D was injected at the time indicated by the arrow. Plot colors present different nanolasers.
Fig. 10
Fig. 10 Fabricated NS nanolaser. (a) SEM image of a single nanolaser. (b) Near-field pattern of the 144-nanolaser array.
Fig. 11
Fig. 11 Sensing characteristics of the nanolaser array with and without an NS. (a) Lasing spectra. (b) Sensitivity. (c) Index absolute accuracy of the index shift after calibrating the sensitivity. Its dispersion determines the index resolution. Green, purple, yellow, and blue plots represent liquid indices of 1.33, 1.35, 1.37, and 1.39, respectively.
Fig. 12
Fig. 12 Time evolution of moving HeLa cell observed in the NS nanolaser array. Left and right panels are optical micrographs and others are Δn images. (a) Moving cell. (b) Cell finally desorbed.

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