Abstract

Concentrations down to 3 nM of the rhS100A4 protein, associated with human tumor development, have been detected in undiluted urine using an integrated sensor based on microring resonators in the emerging Al2O3 photonic platform. The fabricated microrings were designed for operation in the C-band (λ = 1565 nm) and exhibited a high-quality factor in air of 3.2 × 105. The bulk refractive index sensitivity of the devices was ~100 nm/RIU (for TM polarization) with a limit of detection of ~10−6 RIU. A surface functionalization protocol was developed to allow for the selective binding of the monoclonal antibodies designed to capture the target biomarker to the surface of the Al2O3 microrings. The detection of rhS100A4 proteins at clinically relevant concentrations in urine is a big milestone towards the use of biosensors for the screening and early diagnosis of different cancers. Biosensors based on this microring technology can lead to portable, multiplexed and easy-to-use point of care devices.

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

Full Article  |  PDF Article
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2018 (6)

F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA Cancer J. Clin. 68(6), 394–424 (2018).
[Crossref] [PubMed]

E. Luan, H. Shoman, D. M. Ratner, K. C. Cheung, and L. Chrostowski, “Silicon photonic biosensors using label-free detection,” Sensors (Basel) 18(10), E3519 (2018).
[Crossref] [PubMed]

N. Li, E. S. Magden, Z. Su, N. Singh, A. Ruocco, M. Xin, M. Byrd, P. T. Callahan, J. D. B. Bradley, C. Baiocco, D. Vermeulen, and M. R. Watts, “Broadband 2-µm emission on silicon chips: monolithically integrated Holmium lasers,” Opt. Express 26(3), 2220–2230 (2018).
[Crossref] [PubMed]

Z. Su, N. Li, H. C. Frankis, E. S. Magden, T. N. Adam, G. Leake, D. Coolbaugh, J. D. B. Bradley, and M. R. Watts, “High-Q-factor Al2O3 micro-trench cavities integrated with silicon nitride waveguides on silicon,” Opt. Express 26(9), 11161–11170 (2018).
[Crossref] [PubMed]

M. de Goede, M. Dijkstra, R. O. Núñez, E. Martínez, and S. M. García-Blanco, “High quality factor Al2O3 microring resonators for on-chip sensing applications,” Proc. SPIE 10535, 1053504 (2018).
[Crossref]

J. Scheuer, “White light cavity formation and superluminal lasing near exceptional points,” Opt. Express 26(24), 32091–32102 (2018).
[Crossref] [PubMed]

2017 (6)

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, “Fluorescent and lasing whispering gallery mode microresonators for sensing applications,” Laser Photonics Rev. 11, 1600265 (2017).
[Crossref]

W. Pongruengkiat and S. Pechprasarn, “Whispering-gallery mode resonators for detecting cancer,” Sensors (Basel) 17(9), 2095 (2017).
[Crossref] [PubMed]

E. Kim, M. D. Baaske, and F. Vollmer, “Towards next-generation label-free biosensors: recent advances in whispering gallery mode sensors,” Lab Chip 17(7), 1190–1205 (2017).
[Crossref] [PubMed]

F. Fei, J. Qu, M. Zhang, Y. Li, and S. Zhang, “S100A4 in cancer progression and metastasis: A systematic review,” Oncotarget 8(42), 73219–73239 (2017).
[Crossref] [PubMed]

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, “Urine S100 proteins as potential biomarkers of lupus nephritis activity,” Arthritis Res. Ther. 19(1), 242 (2017).
[Crossref] [PubMed]

L. Gounaridis, P. Groumas, E. Schreuder, G. Tsekenis, A. Marousis, R. Heideman, H. Avramopoulos, and C. Kouloumentas, “High performance refractive index sensor based on low Q-factor ring resonators and FFT processing of wavelength scanning data,” Opt. Express 25(7), 7483–7495 (2017).
[Crossref] [PubMed]

2016 (4)

N. Bansal, A. K. Gupta, A. Gupta, S. N. Sankhwar, and A. A. Mahdi, “Serum-based protein biomarkers of bladder cancer: A pre- and post-operative evaluation,” J. Pharm. Biomed. Anal. 124, 22–25 (2016).
[Crossref] [PubMed]

A. Samusenko, R. Guider, L. Pavesi, G. Pucker, T. Chalyan, D. Gandolfi, and M. Ghulinyan, “A SiON Microring Resonator-Based Platform for Biosensing at 850 nm,” J. Lit. Technol. 34(3), 969–977 (2016).
[Crossref]

G. Besselink, R. Heideman, E. Schreuder, L. Wevers, F. Falke, and H. Van den Vlekkert, “Performance of arrayed microring resonator sensors with the TriPleX platform,” J. Biosens. Bioelectron. 7(2), 1000209 (2016).

A. L. Washburn, W. W. Shia, K. A. Lenkeit, S.-H. Lee, and R. C. Bailey, “Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays,” Analyst (Lond.) 141(18), 5358–5365 (2016).
[Crossref] [PubMed]

2015 (1)

A. R. Bresnick, D. J. Weber, and D. B. Zimmer, “S100 proteins in cancer,” Nat. Rev. Cancer 15(2), 96–109 (2015).
[Crossref] [PubMed]

2014 (4)

H. Chen, C. Xu, Q. Jin, and Z. Liu, “S100 protein family in human cancer,” Am. J. Cancer Res. 4(2), 89–115 (2014).
[PubMed]

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

S. T. Fard, V. Donzella, S. A. Schmidt, J. Flueckiger, S. M. Grist, P. Talebi Fard, Y. Wu, R. J. Bojko, E. Kwok, N. A. F. Jaeger, D. M. Ratner, and L. Chrostowski, “Performance of ultra-thin SOI-based resonators for sensing applications,” Opt. Express 22(12), 14166–14179 (2014).
[Crossref] [PubMed]

L. Padilla, S. Dakhel, and J. L. Hernández, “S100 to receptor for advanced glycation end-products binding assay: looking for inhibitors,” Biochem. Biophys. Res. Commun. 446(1), 404–409 (2014).
[Crossref] [PubMed]

2013 (5)

E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, “Intra-laser-cavity microparticle sensing with a dual-wavelength distributed-feedback laser,” Laser Photonics Rev. 7(4), 589–598 (2013).
[Crossref]

J. T. Kirk, N. D. Brault, T. Baehr-Jones, M. Hochberg, S. Jiang, and D. M. Ratner, “Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma,” Biosens. Bioelectron. 42(1), 100–105 (2013).
[Crossref] [PubMed]

M. K. Park, J. S. Kee, J. Y. Quah, V. Netto, J. Song, Q. Fang, E. M. La Fosse, and G. Q. Lo, “Label-free aptamer sensor based on silicon microring resonators,” Sens. Actuators B Chem. 176, 552–559 (2013).
[Crossref]

Y. Shin, A. P. Perera, and M. K. Park, “Label-free DNA sensor for detection of bladder cancer biomarkers in urine,” Sens. Actuators B Chem. 178, 200–206 (2013).
[Crossref]

J. T. Kindt and R. C. Bailey, “Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening,” Curr. Opin. Chem. Biol. 17(5), 818–826 (2013).
[Crossref] [PubMed]

2012 (3)

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
[Crossref]

S. K. Mishra, H. R. Siddique, and M. Saleem, “S100A4 calcium-binding protein is key player in tumor progression and metastasis: preclinical and clinical evidence,” Cancer Metastasis Rev. 31(1-2), 163–172 (2012).
[Crossref] [PubMed]

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

2011 (2)

L. He, Ş. K. Özdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol. 6(7), 428–432 (2011).
[Crossref] [PubMed]

Y. Sun and X. Fan, “Optical ring resonators for biochemical and chemical sensing,” Anal. Bioanal. Chem. 399(1), 205–211 (2011).
[Crossref] [PubMed]

2010 (4)

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

E. H. Bernhardi, H. A. G. M. van Wolferen, L. Agazzi, M. R. H. Khan, C. G. H. Roeloffzen, K. Wörhoff, M. Pollnau, and R. M. de Ridder, “Ultra-narrow-linewidth, single-frequency distributed feedback waveguide laser in Al2O3:Er3+ on silicon,” Opt. Lett. 35(14), 2394–2396 (2010).
[Crossref] [PubMed]

J. D. Bradley, R. Stoffer, L. Agazzi, F. Ay, K. Wörhoff, and M. Pollnau, “Integrated Al2O3:Er3+ ring lasers on silicon with wide wavelength selectivity,” Opt. Lett. 35(1), 73–75 (2010).
[Crossref] [PubMed]

Y. Sagara, Y. Miyata, T. Iwata, S. Kanda, T. Hayashi, H. Sakai, and H. Kanetake, “Clinical significance and prognostic value of S100A4 and matrix metalloproteinase-14 in patients with organ-confined bladder cancer,” Exp. Ther. Med. 1(1), 27–31 (2010).
[PubMed]

2009 (4)

A. L. Washburn, L. C. Gunn, and R. C. Bailey, “Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators,” Anal. Chem. 81(22), 9499–9506 (2009).
[Crossref] [PubMed]

A. L. Washburn, M. S. Luchansky, A. L. Bowman, and R. C. Bailey, “Quantitative, label-free detection of five protein biomarkers using multiplexed arrays of silicon photonic microring resonators,” Anal. Chem. 82(1), 69–72 (2009).
[PubMed]

J. Hu, X. Sun, A. Agarwal, and L. C. Kimerling, “Design guidelines for optical resonator biochemical sensors,” J. Opt. Soc. Am. B 26(5), 1032–1041 (2009).
[Crossref]

W. R. McKinnon, D. X. Xu, C. Storey, E. Post, A. Densmore, A. Delâge, P. Waldron, J. H. Schmid, and S. Janz, “Extracting coupling and loss coefficients from a ring resonator,” Opt. Express 17(21), 18971–18982 (2009).
[Crossref] [PubMed]

2008 (2)

I. M. White and X. Fan, “On the performance quantification of resonant refractive index sensors,” Opt. Express 16(2), 1020–1028 (2008).
[Crossref] [PubMed]

S. F. Shariat, J. A. Karam, Y. Lotan, and P. I. Karakiewizc, “Critical evaluation of urinary markers for bladder cancer detection and monitoring,” Rev. Urol. 10(2), 120–135 (2008).
[PubMed]

2007 (1)

J. D. B. Bradley, F. Ay, K. Wörhoff, and M. Pollnau, “Fabrication of low-loss channel waveguides in Al2O3 and Y2O3 layers by inductively coupled plasma reactive ion etching,” Appl. Phys. B 89, 311–318 (2007).
[Crossref]

2006 (1)

S. C. Garrett, K. M. Varney, D. J. Weber, and A. R. Bresnick, “S100A4, a mediator of metastasis,” J. Biol. Chem. 281(2), 677–680 (2006).
[Crossref] [PubMed]

2002 (1)

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, “Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer,” J. Pathol. 196(3), 292–299 (2002).
[Crossref] [PubMed]

1996 (1)

G. N. van den Hoven, R. J. I. M. Koper, A. Polman, C. van Dam, J. W. M. van Uffelen, and M. K. Smit, “Net optical gain at 1.53 μm in Er-doped Al2O3 waveguides on silicon,” Appl. Phys. Lett. 68(14), 1886–1888 (1996).
[Crossref]

1995 (1)

1984 (1)

G. Este, “Reactive deposition of low loss Al2O3 optical waveguides by modified dc planar magnetron sputtering,” J. Vac. Sci. Technol., A 2(3), 1238–1247 (1984).

Adam, T. N.

Agarwal, A.

Agazzi, L.

Appenzeller, 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, “Urine S100 proteins as potential biomarkers of lupus nephritis activity,” Arthritis Res. Ther. 19(1), 242 (2017).
[Crossref] [PubMed]

Avramopoulos, H.

Ay, F.

J. D. Bradley, R. Stoffer, L. Agazzi, F. Ay, K. Wörhoff, and M. Pollnau, “Integrated Al2O3:Er3+ ring lasers on silicon with wide wavelength selectivity,” Opt. Lett. 35(1), 73–75 (2010).
[Crossref] [PubMed]

J. D. B. Bradley, F. Ay, K. Wörhoff, and M. Pollnau, “Fabrication of low-loss channel waveguides in Al2O3 and Y2O3 layers by inductively coupled plasma reactive ion etching,” Appl. Phys. B 89, 311–318 (2007).
[Crossref]

Baaske, M. D.

E. Kim, M. D. Baaske, and F. Vollmer, “Towards next-generation label-free biosensors: recent advances in whispering gallery mode sensors,” Lab Chip 17(7), 1190–1205 (2017).
[Crossref] [PubMed]

Baehr-Jones, T.

J. T. Kirk, N. D. Brault, T. Baehr-Jones, M. Hochberg, S. Jiang, and D. M. Ratner, “Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma,” Biosens. Bioelectron. 42(1), 100–105 (2013).
[Crossref] [PubMed]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

Baets, R.

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
[Crossref]

Bailey, R. C.

A. L. Washburn, W. W. Shia, K. A. Lenkeit, S.-H. Lee, and R. C. Bailey, “Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays,” Analyst (Lond.) 141(18), 5358–5365 (2016).
[Crossref] [PubMed]

J. T. Kindt and R. C. Bailey, “Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening,” Curr. Opin. Chem. Biol. 17(5), 818–826 (2013).
[Crossref] [PubMed]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

A. L. Washburn, M. S. Luchansky, A. L. Bowman, and R. C. Bailey, “Quantitative, label-free detection of five protein biomarkers using multiplexed arrays of silicon photonic microring resonators,” Anal. Chem. 82(1), 69–72 (2009).
[PubMed]

A. L. Washburn, L. C. Gunn, and R. C. Bailey, “Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators,” Anal. Chem. 81(22), 9499–9506 (2009).
[Crossref] [PubMed]

Baiocco, C.

Bansal, N.

N. Bansal, A. K. Gupta, A. Gupta, S. N. Sankhwar, and A. A. Mahdi, “Serum-based protein biomarkers of bladder cancer: A pre- and post-operative evaluation,” J. Pharm. Biomed. Anal. 124, 22–25 (2016).
[Crossref] [PubMed]

Barraclough, R.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, “Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer,” J. Pathol. 196(3), 292–299 (2002).
[Crossref] [PubMed]

Bennett, M. R.

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, “Urine S100 proteins as potential biomarkers of lupus nephritis activity,” Arthritis Res. Ther. 19(1), 242 (2017).
[Crossref] [PubMed]

Bernhardi, E. H.

E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, “Intra-laser-cavity microparticle sensing with a dual-wavelength distributed-feedback laser,” Laser Photonics Rev. 7(4), 589–598 (2013).
[Crossref]

E. H. Bernhardi, H. A. G. M. van Wolferen, L. Agazzi, M. R. H. Khan, C. G. H. Roeloffzen, K. Wörhoff, M. Pollnau, and R. M. de Ridder, “Ultra-narrow-linewidth, single-frequency distributed feedback waveguide laser in Al2O3:Er3+ on silicon,” Opt. Lett. 35(14), 2394–2396 (2010).
[Crossref] [PubMed]

Besselink, G.

G. Besselink, R. Heideman, E. Schreuder, L. Wevers, F. Falke, and H. Van den Vlekkert, “Performance of arrayed microring resonator sensors with the TriPleX platform,” J. Biosens. Bioelectron. 7(2), 1000209 (2016).

Bienstman, P.

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
[Crossref]

Bogaerts, W.

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
[Crossref]

Bojko, R. J.

Bowman, A. L.

A. L. Washburn, M. S. Luchansky, A. L. Bowman, and R. C. Bailey, “Quantitative, label-free detection of five protein biomarkers using multiplexed arrays of silicon photonic microring resonators,” Anal. Chem. 82(1), 69–72 (2009).
[PubMed]

Bradley, J. D.

Bradley, J. D. B.

Brault, N. D.

J. T. Kirk, N. D. Brault, T. Baehr-Jones, M. Hochberg, S. Jiang, and D. M. Ratner, “Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma,” Biosens. Bioelectron. 42(1), 100–105 (2013).
[Crossref] [PubMed]

Bray, F.

F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA Cancer J. Clin. 68(6), 394–424 (2018).
[Crossref] [PubMed]

Bresnick, A. R.

A. R. Bresnick, D. J. Weber, and D. B. Zimmer, “S100 proteins in cancer,” Nat. Rev. Cancer 15(2), 96–109 (2015).
[Crossref] [PubMed]

S. C. Garrett, K. M. Varney, D. J. Weber, and A. R. Bresnick, “S100A4, a mediator of metastasis,” J. Biol. Chem. 281(2), 677–680 (2006).
[Crossref] [PubMed]

Brunner, H. I.

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, “Urine S100 proteins as potential biomarkers of lupus nephritis activity,” Arthritis Res. Ther. 19(1), 242 (2017).
[Crossref] [PubMed]

Byrd, M.

Callahan, P. T.

Chalyan, T.

A. Samusenko, R. Guider, L. Pavesi, G. Pucker, T. Chalyan, D. Gandolfi, and M. Ghulinyan, “A SiON Microring Resonator-Based Platform for Biosensing at 850 nm,” J. Lit. Technol. 34(3), 969–977 (2016).
[Crossref]

Chen, H.

H. Chen, C. Xu, Q. Jin, and Z. Liu, “S100 protein family in human cancer,” Am. J. Cancer Res. 4(2), 89–115 (2014).
[PubMed]

Cheung, K. C.

E. Luan, H. Shoman, D. M. Ratner, K. C. Cheung, and L. Chrostowski, “Silicon photonic biosensors using label-free detection,” Sensors (Basel) 18(10), E3519 (2018).
[Crossref] [PubMed]

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Chrostowski, L.

E. Luan, H. Shoman, D. M. Ratner, K. C. Cheung, and L. Chrostowski, “Silicon photonic biosensors using label-free detection,” Sensors (Basel) 18(10), E3519 (2018).
[Crossref] [PubMed]

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

S. T. Fard, V. Donzella, S. A. Schmidt, J. Flueckiger, S. M. Grist, P. Talebi Fard, Y. Wu, R. J. Bojko, E. Kwok, N. A. F. Jaeger, D. M. Ratner, and L. Chrostowski, “Performance of ultra-thin SOI-based resonators for sensing applications,” Opt. Express 22(12), 14166–14179 (2014).
[Crossref] [PubMed]

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Claes, T.

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
[Crossref]

Coolbaugh, D.

Dakhel, S.

L. Padilla, S. Dakhel, and J. L. Hernández, “S100 to receptor for advanced glycation end-products binding assay: looking for inhibitors,” Biochem. Biophys. Res. Commun. 446(1), 404–409 (2014).
[Crossref] [PubMed]

Davies, B. R.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, “Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer,” J. Pathol. 196(3), 292–299 (2002).
[Crossref] [PubMed]

de Goede, M.

M. de Goede, M. Dijkstra, R. O. Núñez, E. Martínez, and S. M. García-Blanco, “High quality factor Al2O3 microring resonators for on-chip sensing applications,” Proc. SPIE 10535, 1053504 (2018).
[Crossref]

De Heyn, P.

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
[Crossref]

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, “Intra-laser-cavity microparticle sensing with a dual-wavelength distributed-feedback laser,” Laser Photonics Rev. 7(4), 589–598 (2013).
[Crossref]

E. H. Bernhardi, H. A. G. M. van Wolferen, L. Agazzi, M. R. H. Khan, C. G. H. Roeloffzen, K. Wörhoff, M. Pollnau, and R. M. de Ridder, “Ultra-narrow-linewidth, single-frequency distributed feedback waveguide laser in Al2O3:Er3+ on silicon,” Opt. Lett. 35(14), 2394–2396 (2010).
[Crossref] [PubMed]

De Vos, K.

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
[Crossref]

Delâge, A.

Densmore, A.

Dijkstra, M.

M. de Goede, M. Dijkstra, R. O. Núñez, E. Martínez, and S. M. García-Blanco, “High quality factor Al2O3 microring resonators for on-chip sensing applications,” Proc. SPIE 10535, 1053504 (2018).
[Crossref]

Donzella, V.

S. T. Fard, V. Donzella, S. A. Schmidt, J. Flueckiger, S. M. Grist, P. Talebi Fard, Y. Wu, R. J. Bojko, E. Kwok, N. A. F. Jaeger, D. M. Ratner, and L. Chrostowski, “Performance of ultra-thin SOI-based resonators for sensing applications,” Opt. Express 22(12), 14166–14179 (2014).
[Crossref] [PubMed]

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

Dumon, P.

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
[Crossref]

Durkan, G. C.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, “Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer,” J. Pathol. 196(3), 292–299 (2002).
[Crossref] [PubMed]

Este, G.

G. Este, “Reactive deposition of low loss Al2O3 optical waveguides by modified dc planar magnetron sputtering,” J. Vac. Sci. Technol., A 2(3), 1238–1247 (1984).

Falke, F.

G. Besselink, R. Heideman, E. Schreuder, L. Wevers, F. Falke, and H. Van den Vlekkert, “Performance of arrayed microring resonator sensors with the TriPleX platform,” J. Biosens. Bioelectron. 7(2), 1000209 (2016).

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, “Urine S100 proteins as potential biomarkers of lupus nephritis activity,” Arthritis Res. Ther. 19(1), 242 (2017).
[Crossref] [PubMed]

Fan, X.

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, “Fluorescent and lasing whispering gallery mode microresonators for sensing applications,” Laser Photonics Rev. 11, 1600265 (2017).
[Crossref]

Y. Sun and X. Fan, “Optical ring resonators for biochemical and chemical sensing,” Anal. Bioanal. Chem. 399(1), 205–211 (2011).
[Crossref] [PubMed]

I. M. White and X. Fan, “On the performance quantification of resonant refractive index sensors,” Opt. Express 16(2), 1020–1028 (2008).
[Crossref] [PubMed]

Fang, Q.

M. K. Park, J. S. Kee, J. Y. Quah, V. Netto, J. Song, Q. Fang, E. M. La Fosse, and G. Q. Lo, “Label-free aptamer sensor based on silicon microring resonators,” Sens. Actuators B Chem. 176, 552–559 (2013).
[Crossref]

Fard, S. T.

Fei, F.

F. Fei, J. Qu, M. Zhang, Y. Li, and S. Zhang, “S100A4 in cancer progression and metastasis: A systematic review,” Oncotarget 8(42), 73219–73239 (2017).
[Crossref] [PubMed]

Ferlay, J.

F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA Cancer J. Clin. 68(6), 394–424 (2018).
[Crossref] [PubMed]

Flueckiger, J.

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

S. T. Fard, V. Donzella, S. A. Schmidt, J. Flueckiger, S. M. Grist, P. Talebi Fard, Y. Wu, R. J. Bojko, E. Kwok, N. A. F. Jaeger, D. M. Ratner, and L. Chrostowski, “Performance of ultra-thin SOI-based resonators for sensing applications,” Opt. Express 22(12), 14166–14179 (2014).
[Crossref] [PubMed]

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

François, A.

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, “Fluorescent and lasing whispering gallery mode microresonators for sensing applications,” Laser Photonics Rev. 11, 1600265 (2017).
[Crossref]

Frankis, H. C.

Fry, E. S.

Gandolfi, D.

A. Samusenko, R. Guider, L. Pavesi, G. Pucker, T. Chalyan, D. Gandolfi, and M. Ghulinyan, “A SiON Microring Resonator-Based Platform for Biosensing at 850 nm,” J. Lit. Technol. 34(3), 969–977 (2016).
[Crossref]

García-Blanco, S. M.

M. de Goede, M. Dijkstra, R. O. Núñez, E. Martínez, and S. M. García-Blanco, “High quality factor Al2O3 microring resonators for on-chip sensing applications,” Proc. SPIE 10535, 1053504 (2018).
[Crossref]

Garrett, S. C.

S. C. Garrett, K. M. Varney, D. J. Weber, and A. R. Bresnick, “S100A4, a mediator of metastasis,” J. Biol. Chem. 281(2), 677–680 (2006).
[Crossref] [PubMed]

Ghulinyan, M.

A. Samusenko, R. Guider, L. Pavesi, G. Pucker, T. Chalyan, D. Gandolfi, and M. Ghulinyan, “A SiON Microring Resonator-Based Platform for Biosensing at 850 nm,” J. Lit. Technol. 34(3), 969–977 (2016).
[Crossref]

Gleeson, M. A.

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

Gounaridis, L.

Grist, S.

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Grist, S. M.

S. T. Fard, V. Donzella, S. A. Schmidt, J. Flueckiger, S. M. Grist, P. Talebi Fard, Y. Wu, R. J. Bojko, E. Kwok, N. A. F. Jaeger, D. M. Ratner, and L. Chrostowski, “Performance of ultra-thin SOI-based resonators for sensing applications,” Opt. Express 22(12), 14166–14179 (2014).
[Crossref] [PubMed]

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

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, “Urine S100 proteins as potential biomarkers of lupus nephritis activity,” Arthritis Res. Ther. 19(1), 242 (2017).
[Crossref] [PubMed]

Groumas, P.

Guider, R.

A. Samusenko, R. Guider, L. Pavesi, G. Pucker, T. Chalyan, D. Gandolfi, and M. Ghulinyan, “A SiON Microring Resonator-Based Platform for Biosensing at 850 nm,” J. Lit. Technol. 34(3), 969–977 (2016).
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Gunn, L. C.

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

A. L. Washburn, L. C. Gunn, and R. C. Bailey, “Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators,” Anal. Chem. 81(22), 9499–9506 (2009).
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Gunn, W. G.

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
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Gupta, A.

N. Bansal, A. K. Gupta, A. Gupta, S. N. Sankhwar, and A. A. Mahdi, “Serum-based protein biomarkers of bladder cancer: A pre- and post-operative evaluation,” J. Pharm. Biomed. Anal. 124, 22–25 (2016).
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Gupta, A. K.

N. Bansal, A. K. Gupta, A. Gupta, S. N. Sankhwar, and A. A. Mahdi, “Serum-based protein biomarkers of bladder cancer: A pre- and post-operative evaluation,” J. Pharm. Biomed. Anal. 124, 22–25 (2016).
[Crossref] [PubMed]

Hall, J. M. M.

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, “Fluorescent and lasing whispering gallery mode microresonators for sensing applications,” Laser Photonics Rev. 11, 1600265 (2017).
[Crossref]

Hayashi, T.

Y. Sagara, Y. Miyata, T. Iwata, S. Kanda, T. Hayashi, H. Sakai, and H. Kanetake, “Clinical significance and prognostic value of S100A4 and matrix metalloproteinase-14 in patients with organ-confined bladder cancer,” Exp. Ther. Med. 1(1), 27–31 (2010).
[PubMed]

He, L.

L. He, Ş. K. Özdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol. 6(7), 428–432 (2011).
[Crossref] [PubMed]

Heideman, R.

L. Gounaridis, P. Groumas, E. Schreuder, G. Tsekenis, A. Marousis, R. Heideman, H. Avramopoulos, and C. Kouloumentas, “High performance refractive index sensor based on low Q-factor ring resonators and FFT processing of wavelength scanning data,” Opt. Express 25(7), 7483–7495 (2017).
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G. Besselink, R. Heideman, E. Schreuder, L. Wevers, F. Falke, and H. Van den Vlekkert, “Performance of arrayed microring resonator sensors with the TriPleX platform,” J. Biosens. Bioelectron. 7(2), 1000209 (2016).

Hernández, J. L.

L. Padilla, S. Dakhel, and J. L. Hernández, “S100 to receptor for advanced glycation end-products binding assay: looking for inhibitors,” Biochem. Biophys. Res. Commun. 446(1), 404–409 (2014).
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Hochberg, M.

J. T. Kirk, N. D. Brault, T. Baehr-Jones, M. Hochberg, S. Jiang, and D. M. Ratner, “Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma,” Biosens. Bioelectron. 42(1), 100–105 (2013).
[Crossref] [PubMed]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

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, “Intra-laser-cavity microparticle sensing with a dual-wavelength distributed-feedback laser,” Laser Photonics Rev. 7(4), 589–598 (2013).
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Hu, J.

Iqbal, M.

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
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Iwata, T.

Y. Sagara, Y. Miyata, T. Iwata, S. Kanda, T. Hayashi, H. Sakai, and H. Kanetake, “Clinical significance and prognostic value of S100A4 and matrix metalloproteinase-14 in patients with organ-confined bladder cancer,” Exp. Ther. Med. 1(1), 27–31 (2010).
[PubMed]

Jaeger, N. A. F.

S. T. Fard, V. Donzella, S. A. Schmidt, J. Flueckiger, S. M. Grist, P. Talebi Fard, Y. Wu, R. J. Bojko, E. Kwok, N. A. F. Jaeger, D. M. Ratner, and L. Chrostowski, “Performance of ultra-thin SOI-based resonators for sensing applications,” Opt. Express 22(12), 14166–14179 (2014).
[Crossref] [PubMed]

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Janz, S.

Jemal, A.

F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA Cancer J. Clin. 68(6), 394–424 (2018).
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J. T. Kirk, N. D. Brault, T. Baehr-Jones, M. Hochberg, S. Jiang, and D. M. Ratner, “Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma,” Biosens. Bioelectron. 42(1), 100–105 (2013).
[Crossref] [PubMed]

Jin, Q.

H. Chen, C. Xu, Q. Jin, and Z. Liu, “S100 protein family in human cancer,” Am. J. Cancer Res. 4(2), 89–115 (2014).
[PubMed]

Kanda, S.

Y. Sagara, Y. Miyata, T. Iwata, S. Kanda, T. Hayashi, H. Sakai, and H. Kanetake, “Clinical significance and prognostic value of S100A4 and matrix metalloproteinase-14 in patients with organ-confined bladder cancer,” Exp. Ther. Med. 1(1), 27–31 (2010).
[PubMed]

Kanetake, H.

Y. Sagara, Y. Miyata, T. Iwata, S. Kanda, T. Hayashi, H. Sakai, and H. Kanetake, “Clinical significance and prognostic value of S100A4 and matrix metalloproteinase-14 in patients with organ-confined bladder cancer,” Exp. Ther. Med. 1(1), 27–31 (2010).
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S. F. Shariat, J. A. Karam, Y. Lotan, and P. I. Karakiewizc, “Critical evaluation of urinary markers for bladder cancer detection and monitoring,” Rev. Urol. 10(2), 120–135 (2008).
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S. F. Shariat, J. A. Karam, Y. Lotan, and P. I. Karakiewizc, “Critical evaluation of urinary markers for bladder cancer detection and monitoring,” Rev. Urol. 10(2), 120–135 (2008).
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M. K. Park, J. S. Kee, J. Y. Quah, V. Netto, J. Song, Q. Fang, E. M. La Fosse, and G. Q. Lo, “Label-free aptamer sensor based on silicon microring resonators,” Sens. Actuators B Chem. 176, 552–559 (2013).
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Khumwan, P.

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

Kim, E.

E. Kim, M. D. Baaske, and F. Vollmer, “Towards next-generation label-free biosensors: recent advances in whispering gallery mode sensors,” Lab Chip 17(7), 1190–1205 (2017).
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Kim, W.

L. He, Ş. K. Özdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol. 6(7), 428–432 (2011).
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Kimerling, L. C.

Kindt, J. T.

J. T. Kindt and R. C. Bailey, “Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening,” Curr. Opin. Chem. Biol. 17(5), 818–826 (2013).
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S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

Kirk, J. T.

J. T. Kirk, N. D. Brault, T. Baehr-Jones, M. Hochberg, S. Jiang, and D. M. Ratner, “Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma,” Biosens. Bioelectron. 42(1), 100–105 (2013).
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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, “Urine S100 proteins as potential biomarkers of lupus nephritis activity,” Arthritis Res. Ther. 19(1), 242 (2017).
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Kumar Selvaraja, S.

W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
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M. K. Park, J. S. Kee, J. Y. Quah, V. Netto, J. Song, Q. Fang, E. M. La Fosse, and G. Q. Lo, “Label-free aptamer sensor based on silicon microring resonators,” Sens. Actuators B Chem. 176, 552–559 (2013).
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Lee, S.-H.

A. L. Washburn, W. W. Shia, K. A. Lenkeit, S.-H. Lee, and R. C. Bailey, “Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays,” Analyst (Lond.) 141(18), 5358–5365 (2016).
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Lenkeit, K. A.

A. L. Washburn, W. W. Shia, K. A. Lenkeit, S.-H. Lee, and R. C. Bailey, “Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays,” Analyst (Lond.) 141(18), 5358–5365 (2016).
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Li, N.

Li, Y.

F. Fei, J. Qu, M. Zhang, Y. Li, and S. Zhang, “S100A4 in cancer progression and metastasis: A systematic review,” Oncotarget 8(42), 73219–73239 (2017).
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L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Liu, Z.

H. Chen, C. Xu, Q. Jin, and Z. Liu, “S100 protein family in human cancer,” Am. J. Cancer Res. 4(2), 89–115 (2014).
[PubMed]

Lo, G. Q.

M. K. Park, J. S. Kee, J. Y. Quah, V. Netto, J. Song, Q. Fang, E. M. La Fosse, and G. Q. Lo, “Label-free aptamer sensor based on silicon microring resonators,” Sens. Actuators B Chem. 176, 552–559 (2013).
[Crossref]

Lotan, Y.

S. F. Shariat, J. A. Karam, Y. Lotan, and P. I. Karakiewizc, “Critical evaluation of urinary markers for bladder cancer detection and monitoring,” Rev. Urol. 10(2), 120–135 (2008).
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E. Luan, H. Shoman, D. M. Ratner, K. C. Cheung, and L. Chrostowski, “Silicon photonic biosensors using label-free detection,” Sensors (Basel) 18(10), E3519 (2018).
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Luchansky, M. S.

A. L. Washburn, M. S. Luchansky, A. L. Bowman, and R. C. Bailey, “Quantitative, label-free detection of five protein biomarkers using multiplexed arrays of silicon photonic microring resonators,” Anal. Chem. 82(1), 69–72 (2009).
[PubMed]

Magden, E. S.

Mahdi, A. A.

N. Bansal, A. K. Gupta, A. Gupta, S. N. Sankhwar, and A. A. Mahdi, “Serum-based protein biomarkers of bladder cancer: A pre- and post-operative evaluation,” J. Pharm. Biomed. Anal. 124, 22–25 (2016).
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Marousis, A.

Martínez, E.

M. de Goede, M. Dijkstra, R. O. Núñez, E. Martínez, and S. M. García-Blanco, “High quality factor Al2O3 microring resonators for on-chip sensing applications,” Proc. SPIE 10535, 1053504 (2018).
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McKinnon, W. R.

Meldrum, A.

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, “Fluorescent and lasing whispering gallery mode microresonators for sensing applications,” Laser Photonics Rev. 11, 1600265 (2017).
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Mellon, J. K.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, “Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer,” J. Pathol. 196(3), 292–299 (2002).
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S. K. Mishra, H. R. Siddique, and M. Saleem, “S100A4 calcium-binding protein is key player in tumor progression and metastasis: preclinical and clinical evidence,” Cancer Metastasis Rev. 31(1-2), 163–172 (2012).
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Miyata, Y.

Y. Sagara, Y. Miyata, T. Iwata, S. Kanda, T. Hayashi, H. Sakai, and H. Kanetake, “Clinical significance and prognostic value of S100A4 and matrix metalloproteinase-14 in patients with organ-confined bladder cancer,” Exp. Ther. Med. 1(1), 27–31 (2010).
[PubMed]

Monro, T. M.

T. Reynolds, N. Riesen, A. Meldrum, X. Fan, J. M. M. Hall, T. M. Monro, and A. François, “Fluorescent and lasing whispering gallery mode microresonators for sensing applications,” Laser Photonics Rev. 11, 1600265 (2017).
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Neal, D. E.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, “Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer,” J. Pathol. 196(3), 292–299 (2002).
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Netto, V.

M. K. Park, J. S. Kee, J. Y. Quah, V. Netto, J. Song, Q. Fang, E. M. La Fosse, and G. Q. Lo, “Label-free aptamer sensor based on silicon microring resonators,” Sens. Actuators B Chem. 176, 552–559 (2013).
[Crossref]

Nie, B.

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Núñez, R. O.

M. de Goede, M. Dijkstra, R. O. Núñez, E. Martínez, and S. M. García-Blanco, “High quality factor Al2O3 microring resonators for on-chip sensing applications,” Proc. SPIE 10535, 1053504 (2018).
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O’Donnell, M.

B. R. Davies, M. O’Donnell, G. C. Durkan, P. S. Rudland, R. Barraclough, D. E. Neal, and J. K. Mellon, “Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer,” J. Pathol. 196(3), 292–299 (2002).
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Optical, H.

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
[Crossref]

Ouellet, E.

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Özdemir, S. K.

L. He, Ş. K. Özdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol. 6(7), 428–432 (2011).
[Crossref] [PubMed]

Padilla, L.

L. Padilla, S. Dakhel, and J. L. Hernández, “S100 to receptor for advanced glycation end-products binding assay: looking for inhibitors,” Biochem. Biophys. Res. Commun. 446(1), 404–409 (2014).
[Crossref] [PubMed]

Park, M. K.

Y. Shin, A. P. Perera, and M. K. Park, “Label-free DNA sensor for detection of bladder cancer biomarkers in urine,” Sens. Actuators B Chem. 178, 200–206 (2013).
[Crossref]

M. K. Park, J. S. Kee, J. Y. Quah, V. Netto, J. Song, Q. Fang, E. M. La Fosse, and G. Q. Lo, “Label-free aptamer sensor based on silicon microring resonators,” Sens. Actuators B Chem. 176, 552–559 (2013).
[Crossref]

Pavesi, L.

A. Samusenko, R. Guider, L. Pavesi, G. Pucker, T. Chalyan, D. Gandolfi, and M. Ghulinyan, “A SiON Microring Resonator-Based Platform for Biosensing at 850 nm,” J. Lit. Technol. 34(3), 969–977 (2016).
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W. Pongruengkiat and S. Pechprasarn, “Whispering-gallery mode resonators for detecting cancer,” Sensors (Basel) 17(9), 2095 (2017).
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Perera, A. P.

Y. Shin, A. P. Perera, and M. K. Park, “Label-free DNA sensor for detection of bladder cancer biomarkers in urine,” Sens. Actuators B Chem. 178, 200–206 (2013).
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Pollnau, M.

E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, “Intra-laser-cavity microparticle sensing with a dual-wavelength distributed-feedback laser,” Laser Photonics Rev. 7(4), 589–598 (2013).
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E. H. Bernhardi, H. A. G. M. van Wolferen, L. Agazzi, M. R. H. Khan, C. G. H. Roeloffzen, K. Wörhoff, M. Pollnau, and R. M. de Ridder, “Ultra-narrow-linewidth, single-frequency distributed feedback waveguide laser in Al2O3:Er3+ on silicon,” Opt. Lett. 35(14), 2394–2396 (2010).
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J. D. B. Bradley, F. Ay, K. Wörhoff, and M. Pollnau, “Fabrication of low-loss channel waveguides in Al2O3 and Y2O3 layers by inductively coupled plasma reactive ion etching,” Appl. Phys. B 89, 311–318 (2007).
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Ratner, D. M.

E. Luan, H. Shoman, D. M. Ratner, K. C. Cheung, and L. Chrostowski, “Silicon photonic biosensors using label-free detection,” Sensors (Basel) 18(10), E3519 (2018).
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J. T. Kirk, N. D. Brault, T. Baehr-Jones, M. Hochberg, S. Jiang, and D. M. Ratner, “Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma,” Biosens. Bioelectron. 42(1), 100–105 (2013).
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L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Resonators, R.

M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
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Schmidt, S. A.

S. T. Fard, V. Donzella, S. A. Schmidt, J. Flueckiger, S. M. Grist, P. Talebi Fard, Y. Wu, R. J. Bojko, E. Kwok, N. A. F. Jaeger, D. M. Ratner, and L. Chrostowski, “Performance of ultra-thin SOI-based resonators for sensing applications,” Opt. Express 22(12), 14166–14179 (2014).
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L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Schreuder, E.

L. Gounaridis, P. Groumas, E. Schreuder, G. Tsekenis, A. Marousis, R. Heideman, H. Avramopoulos, and C. Kouloumentas, “High performance refractive index sensor based on low Q-factor ring resonators and FFT processing of wavelength scanning data,” Opt. Express 25(7), 7483–7495 (2017).
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Shariat, S. F.

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Shi, W.

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Shia, W. W.

A. L. Washburn, W. W. Shia, K. A. Lenkeit, S.-H. Lee, and R. C. Bailey, “Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays,” Analyst (Lond.) 141(18), 5358–5365 (2016).
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E. Luan, H. Shoman, D. M. Ratner, K. C. Cheung, and L. Chrostowski, “Silicon photonic biosensors using label-free detection,” Sensors (Basel) 18(10), E3519 (2018).
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Siddique, H. R.

S. K. Mishra, H. R. Siddique, and M. Saleem, “S100A4 calcium-binding protein is key player in tumor progression and metastasis: preclinical and clinical evidence,” Cancer Metastasis Rev. 31(1-2), 163–172 (2012).
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Smit, M. K.

G. N. van den Hoven, R. J. I. M. Koper, A. Polman, C. van Dam, J. W. M. van Uffelen, and M. K. Smit, “Net optical gain at 1.53 μm in Er-doped Al2O3 waveguides on silicon,” Appl. Phys. Lett. 68(14), 1886–1888 (1996).
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M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, L. C. Gunn, R. Resonators, H. Optical, M. Iqbal, M. A. Gleeson, B. Spaugh, F. Tybor, W. G. Gunn, M. Hochberg, T. Baehr-jones, R. C. Bailey, and L. C. Gunn, “Label-Free biosensor arrays based on silicon scanning instrumentation,” IEEE J. Sel. Top. Quantum Electron. 16(3), 654–661 (2010).
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Thompson, E. R.

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

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F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA Cancer J. Clin. 68(6), 394–424 (2018).
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Turnier, J. L.

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G. N. van den Hoven, R. J. I. M. Koper, A. Polman, C. van Dam, J. W. M. van Uffelen, and M. K. Smit, “Net optical gain at 1.53 μm in Er-doped Al2O3 waveguides on silicon,” Appl. Phys. Lett. 68(14), 1886–1888 (1996).
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G. Besselink, R. Heideman, E. Schreuder, L. Wevers, F. Falke, and H. Van den Vlekkert, “Performance of arrayed microring resonator sensors with the TriPleX platform,” J. Biosens. Bioelectron. 7(2), 1000209 (2016).

van der Werf, K. O.

E. H. Bernhardi, K. O. van der Werf, A. J. F. Hollink, K. Wörhoff, R. M. de Ridder, V. Subramaniam, and M. Pollnau, “Intra-laser-cavity microparticle sensing with a dual-wavelength distributed-feedback laser,” Laser Photonics Rev. 7(4), 589–598 (2013).
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Wang, X.

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

L. Chrostowski, S. Grist, J. Flueckiger, W. Shi, X. Wang, E. Ouellet, H. Yun, M. Webb, B. Nie, Z. Liang, K. C. Cheung, S. A. Schmidt, D. M. Ratner, and N. A. F. Jaeger, “Silicon photonic resonator sensors and devices,” Proc. SPIE 8236, 823620 (2012).

Washburn, A. L.

A. L. Washburn, W. W. Shia, K. A. Lenkeit, S.-H. Lee, and R. C. Bailey, “Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays,” Analyst (Lond.) 141(18), 5358–5365 (2016).
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A. L. Washburn, M. S. Luchansky, A. L. Bowman, and R. C. Bailey, “Quantitative, label-free detection of five protein biomarkers using multiplexed arrays of silicon photonic microring resonators,” Anal. Chem. 82(1), 69–72 (2009).
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Weber, D. J.

A. R. Bresnick, D. J. Weber, and D. B. Zimmer, “S100 proteins in cancer,” Nat. Rev. Cancer 15(2), 96–109 (2015).
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Wevers, L.

G. Besselink, R. Heideman, E. Schreuder, L. Wevers, F. Falke, and H. Van den Vlekkert, “Performance of arrayed microring resonator sensors with the TriPleX platform,” J. Biosens. Bioelectron. 7(2), 1000209 (2016).

White, I. M.

Witte, D.

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, “Urine S100 proteins as potential biomarkers of lupus nephritis activity,” Arthritis Res. Ther. 19(1), 242 (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, “Intra-laser-cavity microparticle sensing with a dual-wavelength distributed-feedback laser,” Laser Photonics Rev. 7(4), 589–598 (2013).
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J. D. Bradley, R. Stoffer, L. Agazzi, F. Ay, K. Wörhoff, and M. Pollnau, “Integrated Al2O3:Er3+ ring lasers on silicon with wide wavelength selectivity,” Opt. Lett. 35(1), 73–75 (2010).
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E. H. Bernhardi, H. A. G. M. van Wolferen, L. Agazzi, M. R. H. Khan, C. G. H. Roeloffzen, K. Wörhoff, M. Pollnau, and R. M. de Ridder, “Ultra-narrow-linewidth, single-frequency distributed feedback waveguide laser in Al2O3:Er3+ on silicon,” Opt. Lett. 35(14), 2394–2396 (2010).
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J. D. B. Bradley, F. Ay, K. Wörhoff, and M. Pollnau, “Fabrication of low-loss channel waveguides in Al2O3 and Y2O3 layers by inductively coupled plasma reactive ion etching,” Appl. Phys. B 89, 311–318 (2007).
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Wu, W.

S. Schmidt, J. Flueckiger, W. Wu, S. M. Grist, S. Talebi Fard, V. Donzella, P. Khumwan, E. R. Thompson, Q. Wang, P. Kulik, X. Wang, A. Sherwali, J. Kirk, K. C. Cheung, L. Chrostowski, and D. Ratner, “Improving the performance of silicon photonic rings, disks, and Bragg gratings for use in label-free biosensing,” Proc. SPIE 9166, 91660M (2014).

Wu, Y.

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F. Fei, J. Qu, M. Zhang, Y. Li, and S. Zhang, “S100A4 in cancer progression and metastasis: A systematic review,” Oncotarget 8(42), 73219–73239 (2017).
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L. He, Ş. K. Özdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol. 6(7), 428–432 (2011).
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S. K. Mishra, H. R. Siddique, and M. Saleem, “S100A4 calcium-binding protein is key player in tumor progression and metastasis: preclinical and clinical evidence,” Cancer Metastasis Rev. 31(1-2), 163–172 (2012).
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W. Bogaerts, P. De Heyn, T. Van Vaerenbergh, K. De Vos, S. Kumar Selvaraja, T. Claes, P. Dumon, P. Bienstman, D. Van Thourhout, and R. Baets, “Silicon microring resonators,” Laser Photonics Rev. 6(1), 47–73 (2012).
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F. Fei, J. Qu, M. Zhang, Y. Li, and S. Zhang, “S100A4 in cancer progression and metastasis: A systematic review,” Oncotarget 8(42), 73219–73239 (2017).
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M. De Goede, L. Chang, M. Dijkstra, R. Obregon, J. Ramon-Azcon, E. Martinez, L. Padilla, J. Adan, F. Mitjans, and S. M. Garcia-Blanco, “Al2O3 Microresonator Based Passive and Active Biosensors,” Int. Conf. Transparent Opt. Networks 2018–July, 1–4 (2018).

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Figures (7)

Fig. 1
Fig. 1 (a) Mode profile of the fundamental mode for respectively TE polarization (I) and TM polarization (II). (b) Scanning electron microscope image of the Al2O3 waveguide cross section. (c) Optical microscope image of the MRRs inside the PDMS microfluidic flow channel.
Fig. 2
Fig. 2 (a) Photograph of the optofluidic chip mounted on the experimental setup. The chip has dimensions of 1.2 × 1.9 cm2. (b) Optical microscope image of the MRR and bus waveguide upon coupling red light from a HeNe laser into the device.
Fig. 3
Fig. 3 (a) Schematic representation showing the developed Al2O3 surface functionalization protocol. (i) Surface activation with O2 plasma. (ii) 6-phosphonohexanoic acid, 500 µM in anhydrous heptane, reacts with the Al2O3 surface to generate a carboxylic acid-terminated surface. (iii) Activation of carboxylic terminals by EDC/NHS and anti-S100A4 antibody immobilization. (iv) Protein recognition. (b) (i) Schematic representation of the fluorescence assay to verify the immobilization of antibody capture probes. (ii) Microscope fluorescent image of Al2O3 ring functionalized with 6-phosphonohexanoic acid and immobilized with an antibody labelled with fluorescein isothiocyanate fluorescence dye (FITC, 495 nm/519 nm excitation/emission). Magnification 40x, acquisition time 2000 ms.
Fig. 4
Fig. 4 (a) MRR transmission spectrum for TE polarized light and a top cladding of air. (b) Lorentzian fit of one of the resonances in (a).
Fig. 5
Fig. 5 (a) Shift of resonance wavelength peak for bulk refractive index variation of the water flow over the MRR for TM polarization. (b) Real-time monitoring of the shift of the resonance wavelength during bulk refractive index sensing for both TE and TM polarization. The flow was switched every 3 minutes between deionized water and NaCl solutions with concentrations ranging from 0.30 wt% down to 0.05 wt%. The flow rate was 100 µl/min. (c) Resonance wavelength shift for variations of the bulk refractive index. (d) Resonance wavelength noise during the bulk refractive index experiment for TM polarization.
Fig. 6
Fig. 6 (a) Real-time monitoring of the shift of the resonance wavelength while varying the stage temperature for both TE and TM polarized light. Deionized water was flown over the MRR at a rate of 100 µl/min. (b) Resonance wavelength shift as function of the stage temperature.
Fig. 7
Fig. 7 (a) MRR sensorgram. The MRR was addressed with PBS 10 mM (I), anti-S100A4 antibody at 50 µg/ml (II), BSA 1% in PBS (III), urine (IV), and rhS100A4 at 25 nM in urine (V). The flow rate was 100 µl/min. (b) Binding of rhS100A4 to the antibodies immobilized onto the MRR’s surface. The initial bumps results from the dynamics of the flow system. (c) Resonance wavelength shift as function of rhS100A4 concentration. (d) Resonance wavelength noise for a blank urine sample. (e) Selectivity assay for anti-S100A4 antibody in urine. Control I: rhS100A4 at 400 nM, without antibody coated on the surface. Control II: neutravidin at 400 nM in urine.

Tables (1)

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Table 1 Summary of Al2O3 MRR optical loss.

Equations (2)

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S= λ n g n eff n
LOD= 3ε S

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