Abstract

Whispering gallery mode resonator lasers hold the promise of an ultralow intrinsic limit of detection. However, the widespread use of these devices for biosensing applications has been hindered by the complexity and lack of robustness of the proposed configurations. In this work, we demonstrate biosensing with an integrated microdisk laser. Al2O3doped with Yb3+ was utilized because of its low optical losses as well as its emission in the range 1020–1050 nm, outside the absorption band of water. Single-mode laser emission was obtained at a wavelength of 1024 nm with a linewidth of 250 kHz while the microdisk cavity was submerged in water. A limit of detection of 300 pM (3.6 ng/ml) of the protein rhS100A4 in urine was experimentally demonstrated, showing the potential of the proposed devices for biosensing.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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References

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2019 (4)

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M. Pollnau and J. D. B. Bradley, Opt. Express 26, 24164 (2018).
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A. Meldrum, W. Morrish, S. Lane, W. Wu, T. M. Monro, and A. François, Phys. Status Solidi A 215, 1700619 (2018).
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2014 (3)

2013 (2)

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2012 (1)

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2011 (2)

2010 (1)

2009 (1)

K. Worhoff, J. D. B. Bradley, F. Ay, D. Geskus, T. P. Blauwendraat, and M. Pollnau, IEEE J. Quantum Electron. 45, 454 (2009).
[Crossref]

2008 (2)

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, Anal. Chim. Acta 620, 8 (2008).
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I. M. White and X. Fan, Opt. Express 16, 1020 (2008).
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2007 (1)

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2006 (1)

J. Yang and L. J. Guo, IEEE J. Sel. Top. Quantum Electron. 12, 143 (2006).
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2002 (1)

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1995 (1)

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J. D. B. Bradley, F. Ay, K. Wörhoff, and M. Pollnau, Appl. Phys. B 89, 311 (2007).
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M. Pollnau and J. D. B. Bradley, Opt. Express 26, 24164 (2018).
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J. D. B. Bradley, E. S. Hosseini, Z. Su, T. N. Adam, G. Leake, D. Coolbaugh, and M. R. Watts, Opt. Express 22, 12226 (2014).
[Crossref]

K. Worhoff, J. D. B. Bradley, F. Ay, D. Geskus, T. P. Blauwendraat, and M. Pollnau, IEEE J. Quantum Electron. 45, 454 (2009).
[Crossref]

J. D. B. Bradley, F. Ay, K. Wörhoff, and M. Pollnau, Appl. Phys. B 89, 311 (2007).
[Crossref]

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J. L. Turnier, N. Fall, S. Thornton, D. Witte, M. R. Bennett, S. Appenzeller, M. S. Klein-Gitelman, A. A. Grom, and H. I. Brunner, Arthritis Res. Ther. 19, 242 (2017).
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Chang, L.

J. Mu, M. Dijkstra, Y. S. Yong, M. de Goede, L. Chang, and S. M. G. Blanco, IEEE J. Sel. Top. Quantum Electron. 25, 8200911 (2019).
[Crossref]

C. I. Emmerik, M. Dijkstra, M. de Goede, L. Chang, J. Mu, and S. M. García-Blanco, Opt. Mater. Express 8, 3049 (2018).
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[Crossref]

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[Crossref]

de Goede, M.

de Ridder, R. M.

E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, Laser Photon. Rev. 7, 589 (2013).
[Crossref]

E. H. Bernhardi, H. A. G. M. Van Wolferen, K. Wörhoff, R. M. De Ridder, and M. Pollnau, Opt. Lett. 36, 603 (2011).
[Crossref]

Dietzel, B.

P. Steglich, M. Hülsemann, B. Dietzel, and A. Mai, Molecules 24, 519 (2019).
[Crossref]

Dijkstra, M.

Durkan, G. C.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, J. Pathol. 196, 292 (2002).
[Crossref]

Emmerik, C. I.

Fall, N.

J. L. Turnier, N. Fall, S. Thornton, D. Witte, M. R. Bennett, S. Appenzeller, M. S. Klein-Gitelman, A. A. Grom, and H. I. Brunner, Arthritis Res. Ther. 19, 242 (2017).
[Crossref]

Fan, X.

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, Laser Photon. Rev. 11, 1600265 (2017).
[Crossref]

I. M. White and X. Fan, Opt. Express 16, 1020 (2008).
[Crossref]

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, Anal. Chim. Acta 620, 8 (2008).
[Crossref]

Faye, D.

S. Lozenko, D. Faye, H. Zhang, M. Lebental, J. Lautru, J. Zyss, J. P. Lefevre, and I. Leray, Appl. Phys. B 117, 501 (2014).
[Crossref]

François, A.

W. Morrish, N. Riesen, S. Stobie, A. François, and A. Meldrum, Phys. Rev. Appl. 10, 051001 (2018).
[Crossref]

A. Meldrum, W. Morrish, S. Lane, W. Wu, T. M. Monro, and A. François, Phys. Status Solidi A 215, 1700619 (2018).
[Crossref]

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, Laser Photon. Rev. 11, 1600265 (2017).
[Crossref]

García-Blanco, S.

García-Blanco, S. M.

Geskus, D.

K. Worhoff, J. D. B. Bradley, F. Ay, D. Geskus, T. P. Blauwendraat, and M. Pollnau, IEEE J. Quantum Electron. 45, 454 (2009).
[Crossref]

Grom, A. A.

J. L. Turnier, N. Fall, S. Thornton, D. Witte, M. R. Bennett, S. Appenzeller, M. S. Klein-Gitelman, A. A. Grom, and H. I. Brunner, Arthritis Res. Ther. 19, 242 (2017).
[Crossref]

Guha, B.

Guo, L. J.

J. Yang and L. J. Guo, IEEE J. Sel. Top. Quantum Electron. 12, 143 (2006).
[Crossref]

Guo, X.

L. Ren, X. Zhang, X. Guo, H. Wang, and X. Wu, IEEE Photon. Technol. Lett. 29, 639 (2017).
[Crossref]

Hall, J. M. M.

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, Laser Photon. Rev. 11, 1600265 (2017).
[Crossref]

Hare, J.

Haroche, S.

Herek, J. L.

Hollink, A. J. F.

E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, Laser Photon. Rev. 7, 589 (2013).
[Crossref]

Hosseini, E. S.

Hülsemann, M.

P. Steglich, M. Hülsemann, B. Dietzel, and A. Mai, Molecules 24, 519 (2019).
[Crossref]

Kharas, D.

G. N. West, W. Loh, D. Kharas, C. Sorace-Agaskar, K. K. Mehta, J. Sage, J. Chiaverini, and R. J. Ram, APL Photon. 4, 026101 (2019).
[Crossref]

Kikuchi, K.

T. Okoshi, K. Kikuchi, and A. Nakayama, Electron. Lett. 16, 630 (1980).
[Crossref]

Kim, E.

E. Kim, M. D. Baaske, and F. Vollmer, Lab Chip 17, 1190 (2017).
[Crossref]

Klein-Gitelman, M. S.

J. L. Turnier, N. Fall, S. Thornton, D. Witte, M. R. Bennett, S. Appenzeller, M. S. Klein-Gitelman, A. A. Grom, and H. I. Brunner, Arthritis Res. Ther. 19, 242 (2017).
[Crossref]

Kyotoku, B. B. C.

Lane, S.

A. Meldrum, W. Morrish, S. Lane, W. Wu, T. M. Monro, and A. François, Phys. Status Solidi A 215, 1700619 (2018).
[Crossref]

Lautru, J.

S. Lozenko, D. Faye, H. Zhang, M. Lebental, J. Lautru, J. Zyss, J. P. Lefevre, and I. Leray, Appl. Phys. B 117, 501 (2014).
[Crossref]

Leake, G.

Lebental, M.

S. Lozenko, D. Faye, H. Zhang, M. Lebental, J. Lautru, J. Zyss, J. P. Lefevre, and I. Leray, Appl. Phys. B 117, 501 (2014).
[Crossref]

Lefevre, J. P.

S. Lozenko, D. Faye, H. Zhang, M. Lebental, J. Lautru, J. Zyss, J. P. Lefevre, and I. Leray, Appl. Phys. B 117, 501 (2014).
[Crossref]

Lefèvre-Seguin, V.

Leray, I.

S. Lozenko, D. Faye, H. Zhang, M. Lebental, J. Lautru, J. Zyss, J. P. Lefevre, and I. Leray, Appl. Phys. B 117, 501 (2014).
[Crossref]

Li, H.

Lipson, M.

Liu, L.

Loh, W.

G. N. West, W. Loh, D. Kharas, C. Sorace-Agaskar, K. K. Mehta, J. Sage, J. Chiaverini, and R. J. Ram, APL Photon. 4, 026101 (2019).
[Crossref]

Lozenko, S.

S. Lozenko, D. Faye, H. Zhang, M. Lebental, J. Lautru, J. Zyss, J. P. Lefevre, and I. Leray, Appl. Phys. B 117, 501 (2014).
[Crossref]

Mai, A.

P. Steglich, M. Hülsemann, B. Dietzel, and A. Mai, Molecules 24, 519 (2019).
[Crossref]

Maker, A. J.

A. J. Maker and A. M. Armani, Appl. Phys. Lett. 103, 123302 (2013).
[Crossref]

Martínez, E.

Mehta, K. K.

G. N. West, W. Loh, D. Kharas, C. Sorace-Agaskar, K. K. Mehta, J. Sage, J. Chiaverini, and R. J. Ram, APL Photon. 4, 026101 (2019).
[Crossref]

Meldrum, A.

A. Meldrum, W. Morrish, S. Lane, W. Wu, T. M. Monro, and A. François, Phys. Status Solidi A 215, 1700619 (2018).
[Crossref]

W. Morrish, N. Riesen, S. Stobie, A. François, and A. Meldrum, Phys. Rev. Appl. 10, 051001 (2018).
[Crossref]

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, Laser Photon. Rev. 11, 1600265 (2017).
[Crossref]

Mellon, J. K.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, J. Pathol. 196, 292 (2002).
[Crossref]

Mishra, S. K.

S. K. Mishra, H. R. Siddique, and M. Saleem, Cancer Metastasis Rev. 31, 163 (2012).
[Crossref]

Mitjans, F.

Monro, T. M.

A. Meldrum, W. Morrish, S. Lane, W. Wu, T. M. Monro, and A. François, Phys. Status Solidi A 215, 1700619 (2018).
[Crossref]

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, Laser Photon. Rev. 11, 1600265 (2017).
[Crossref]

Morrish, W.

A. Meldrum, W. Morrish, S. Lane, W. Wu, T. M. Monro, and A. François, Phys. Status Solidi A 215, 1700619 (2018).
[Crossref]

W. Morrish, N. Riesen, S. Stobie, A. François, and A. Meldrum, Phys. Rev. Appl. 10, 051001 (2018).
[Crossref]

Mu, J.

J. Mu, M. Dijkstra, Y. S. Yong, M. de Goede, L. Chang, and S. M. G. Blanco, IEEE J. Sel. Top. Quantum Electron. 25, 8200911 (2019).
[Crossref]

C. I. Emmerik, M. Dijkstra, M. de Goede, L. Chang, J. Mu, and S. M. García-Blanco, Opt. Mater. Express 8, 3049 (2018).
[Crossref]

Nakayama, A.

T. Okoshi, K. Kikuchi, and A. Nakayama, Electron. Lett. 16, 630 (1980).
[Crossref]

Neal, D. E.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, J. Pathol. 196, 292 (2002).
[Crossref]

O’Donnell, M.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, J. Pathol. 196, 292 (2002).
[Crossref]

Obregón, R.

Okoshi, T.

T. Okoshi, K. Kikuchi, and A. Nakayama, Electron. Lett. 16, 630 (1980).
[Crossref]

Padilla, L.

Pollnau, M.

M. Pollnau and J. D. B. Bradley, Opt. Express 26, 24164 (2018).
[Crossref]

S. A. Vázquez-Córdova, M. Dijkstra, E. H. Bernhardi, F. Ay, K. Wörhoff, J. L. Herek, S. M. García-Blanco, and M. Pollnau, Opt. Express 22, 25993 (2014).
[Crossref]

E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, Laser Photon. Rev. 7, 589 (2013).
[Crossref]

E. H. Bernhardi, H. A. G. M. Van Wolferen, K. Wörhoff, R. M. De Ridder, and M. Pollnau, Opt. Lett. 36, 603 (2011).
[Crossref]

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W. Morrish, N. Riesen, S. Stobie, A. François, and A. Meldrum, Phys. Rev. Appl. 10, 051001 (2018).
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G. N. West, W. Loh, D. Kharas, C. Sorace-Agaskar, K. K. Mehta, J. Sage, J. Chiaverini, and R. J. Ram, APL Photon. 4, 026101 (2019).
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S. K. Mishra, H. R. Siddique, and M. Saleem, Cancer Metastasis Rev. 31, 163 (2012).
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G. N. West, W. Loh, D. Kharas, C. Sorace-Agaskar, K. K. Mehta, J. Sage, J. Chiaverini, and R. J. Ram, APL Photon. 4, 026101 (2019).
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P. Steglich, M. Hülsemann, B. Dietzel, and A. Mai, Molecules 24, 519 (2019).
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W. Morrish, N. Riesen, S. Stobie, A. François, and A. Meldrum, Phys. Rev. Appl. 10, 051001 (2018).
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J. Su, Sensors 17, 540 (2017).
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E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, Laser Photon. Rev. 7, 589 (2013).
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E. H. Bernhardi, H. A. G. M. Van Wolferen, K. Wörhoff, R. M. De Ridder, and M. Pollnau, Opt. Lett. 36, 603 (2011).
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J. D. B. Bradley, F. Ay, K. Wörhoff, and M. Pollnau, Appl. Phys. B 89, 311 (2007).
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A. Meldrum, W. Morrish, S. Lane, W. Wu, T. M. Monro, and A. François, Phys. Status Solidi A 215, 1700619 (2018).
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L. Ren, X. Zhang, X. Guo, H. Wang, and X. Wu, IEEE Photon. Technol. Lett. 29, 639 (2017).
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X. Zhang, L. Ren, X. Wu, H. Li, L. Liu, and L. Xu, Opt. Express 19, 22242 (2011).
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J. Yang and L. J. Guo, IEEE J. Sel. Top. Quantum Electron. 12, 143 (2006).
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Zhang, X.

L. Ren, X. Zhang, X. Guo, H. Wang, and X. Wu, IEEE Photon. Technol. Lett. 29, 639 (2017).
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X. Zhang, L. Ren, X. Wu, H. Li, L. Liu, and L. Xu, Opt. Express 19, 22242 (2011).
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X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, Anal. Chim. Acta 620, 8 (2008).
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S. Lozenko, D. Faye, H. Zhang, M. Lebental, J. Lautru, J. Zyss, J. P. Lefevre, and I. Leray, Appl. Phys. B 117, 501 (2014).
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Anal. Chim. Acta (1)

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, Anal. Chim. Acta 620, 8 (2008).
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APL Photon. (1)

G. N. West, W. Loh, D. Kharas, C. Sorace-Agaskar, K. K. Mehta, J. Sage, J. Chiaverini, and R. J. Ram, APL Photon. 4, 026101 (2019).
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Appl. Phys. B (2)

S. Lozenko, D. Faye, H. Zhang, M. Lebental, J. Lautru, J. Zyss, J. P. Lefevre, and I. Leray, Appl. Phys. B 117, 501 (2014).
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J. D. B. Bradley, F. Ay, K. Wörhoff, and M. Pollnau, Appl. Phys. B 89, 311 (2007).
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Appl. Phys. Lett. (1)

A. J. Maker and A. M. Armani, Appl. Phys. Lett. 103, 123302 (2013).
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Arthritis Res. Ther. (1)

J. L. Turnier, N. Fall, S. Thornton, D. Witte, M. R. Bennett, S. Appenzeller, M. S. Klein-Gitelman, A. A. Grom, and H. I. Brunner, Arthritis Res. Ther. 19, 242 (2017).
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Cancer Metastasis Rev. (1)

S. K. Mishra, H. R. Siddique, and M. Saleem, Cancer Metastasis Rev. 31, 163 (2012).
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Electron. Lett. (1)

T. Okoshi, K. Kikuchi, and A. Nakayama, Electron. Lett. 16, 630 (1980).
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IEEE J. Quantum Electron. (1)

K. Worhoff, J. D. B. Bradley, F. Ay, D. Geskus, T. P. Blauwendraat, and M. Pollnau, IEEE J. Quantum Electron. 45, 454 (2009).
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IEEE J. Sel. Top. Quantum Electron. (2)

J. Yang and L. J. Guo, IEEE J. Sel. Top. Quantum Electron. 12, 143 (2006).
[Crossref]

J. Mu, M. Dijkstra, Y. S. Yong, M. de Goede, L. Chang, and S. M. G. Blanco, IEEE J. Sel. Top. Quantum Electron. 25, 8200911 (2019).
[Crossref]

IEEE Photon. Technol. Lett. (1)

L. Ren, X. Zhang, X. Guo, H. Wang, and X. Wu, IEEE Photon. Technol. Lett. 29, 639 (2017).
[Crossref]

J. Pathol. (1)

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, J. Pathol. 196, 292 (2002).
[Crossref]

Lab Chip (1)

E. Kim, M. D. Baaske, and F. Vollmer, Lab Chip 17, 1190 (2017).
[Crossref]

Laser Photon. Rev. (2)

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, Laser Photon. Rev. 11, 1600265 (2017).
[Crossref]

E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, Laser Photon. Rev. 7, 589 (2013).
[Crossref]

Molecules (1)

P. Steglich, M. Hülsemann, B. Dietzel, and A. Mai, Molecules 24, 519 (2019).
[Crossref]

Opt. Express (7)

Opt. Lett. (2)

Opt. Mater. Express (1)

Phys. Rev. Appl. (1)

W. Morrish, N. Riesen, S. Stobie, A. François, and A. Meldrum, Phys. Rev. Appl. 10, 051001 (2018).
[Crossref]

Phys. Status Solidi A (1)

A. Meldrum, W. Morrish, S. Lane, W. Wu, T. M. Monro, and A. François, Phys. Status Solidi A 215, 1700619 (2018).
[Crossref]

Sensors (1)

J. Su, Sensors 17, 540 (2017).
[Crossref]

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Figures (5)

Fig. 1.
Fig. 1. (a) Photograph of the optofluidic chip on the experimental setup. Both input and output fibers aligned to the sensor chip are shown as well as the inlet/outlet to the microfluidic channel. The inset shows the Al 2 O 3 : Yb 3 + microdisk laser under pump illumination (976 nm). The green luminescence originates from upconversion of Er 3 + ion impurities in the microdisk. (b) Lasing spectrum of the microdisk laser with a DI water cladding at a launched pump power of 27 mW at 976 nm. Spectral resolution is 100 pm. (c) Power characteristics of the laser, which has a slope efficiency of 0.1% and a threshold of 7 mW.
Fig. 2.
Fig. 2. (a) Schematic of the heterodyne detection for monitoring the change of the microdisk laser frequency. (b) RF beatnote between the microdisk laser and the external laser during a flow of synthetic urine (black curve) and synthetic urine spiked with rhS100A4 at a concentration of 30 nM (red curve).
Fig. 3.
Fig. 3. Bulk sensing characterization. (a) Beatnote frequency (between the lower frequency laser peak and the external laser) as a function of time for different chip holder temperatures. DI water was flown through the microfluidic channel during the experiment at a flow rate of 10 μl/min. (b) Temperature slope sensitivity. The dotted line is a linear fit. (c) Beatnote frequency as a function of time as different concentrations of NaCl in DI water (0.0–0.5 wt. %) are flown over the microdisk laser sensor in time steps of 3 min with a flow rate of 30 μl/min. (d) Bulk refractive index slope sensitivity. The dotted line is a linear fit.
Fig. 4.
Fig. 4. (a) Beatnote frequency between both laser modes and the external laser during 3 min of DI water flow. A frequency noise of 7 MHz was determined. (b) Beatnote frequency of the lower laser mode during a 20 min flow of synthetic urine. Four experiments were carried out. The increase in the beatnote frequency at about 1 to 4 min results from the short-time temperature overshoot caused by the introduction of the urine samples. The beatnote frequency returns to the baseline after the overshoot. The frequency noise was determined during the last 10 min of the measurement to be 30 MHz .
Fig. 5.
Fig. 5. Beatnote frequency changes due to binding of the rhS100A4 protein to the antibodies immobilized onto the microdisk laser. The samples were flown at a rate of 40 μl/min for 20 min. The initial bumps at around 1 to 2 min are results of a short-time temperature overshoot caused by the dynamics of the flow system. (a) Data of low protein concentrations. (b) Data of high protein concentrations. (c) Biosensor calibration curve.

Equations (1)

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f beat = c λ 2 λ 1 λ 1 λ 2 ,

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