Abstract

We report a refractive index sensing system with a high sensitivity of 1579 dB/RIU and a low refractive index detection limit of 9.7 × 10−6 RIU. The sensing system was based on cascaded-microring resonators (CMRR) using intensity interrogation. The free spectrum range (FSR) for the reference ring was designed to be equal to the sensing ring. The sensing ring of the CMRR was modified with molecularly imprinted polymers (MIPs) for the detection of progesterone. The achieved limit of detection (LOD) was as low as 83.5 fg/mL.

© 2017 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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    [Crossref]
  2. X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
    [Crossref]
  3. M. R. Lee and P. M. Fauchet, “Nanoscale microcavity sensor for single particle detection,” Opt. Lett. 32(22), 3284–3286 (2007).
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  4. C. A. Barrios, “Integrated microring resonator sensor arrays for labs-on-chips,” Anal. Bioanal. Chem. 403(6), 1467–1475 (2012).
    [Crossref] [PubMed]
  5. L. Qin, L. Wang, M. Li, and J.-J. He, “Optical Sensor Based on Vernier-Cascade of Ring Resonator and Echelle Diffraction Grating,” IEEE Photonics Technol. Lett. 24(11), 954–956 (2012).
    [Crossref]
  6. A. Densomore, D. X. Xu, P. Waldron, S. Janz, A. Delâge, and P. Cheben, “Silicon Microphotonic Waveguides for Biological Sensing,” in Proceedings of IEEE Conference on Biophotonics, Nanophotonics and Metamaterials (IEEE, 2006), pp. 15–18.
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    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  22. A. Bossi, F. Bonini, A. P. Turner, and S. A. Piletsky, “Molecularly imprinted polymers for the recognition of proteins: the state of the art,” Biosens. Bioelectron. 22(6), 1131–1137 (2007).
    [Crossref] [PubMed]
  23. L. Jin, M. Li, and J.-J. He, “Analysis of wavelength and intensity interrogation methods in cascaded double-ring sensors,” J. Lightwave Technol. 30(12), 1994–2002 (2012).
    [Crossref]
  24. L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
    [Crossref] [PubMed]
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2016 (1)

W. Yu, W. C. Jiang, Q. Lin, and T. Lu, “Cavity optomechanical spring sensing of single molecules,” Nat. Commun. 7, 12311 (2016).
[Crossref] [PubMed]

2015 (4)

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

J. V. Samsonova, V. A. Safronova, and A. P. Osipov, “Pretreatment-free lateral flow enzyme immunoassay for progesterone detection in whole cows’ milk,” Talanta 132, 685–689 (2015).
[Crossref] [PubMed]

X. Sun, D. Dai, L. Thylén, and L. Wosinski, “High-sensitivity liquid refractive-index sensor based on a Mach-Zehnder interferometer with a double-slot hybrid plasmonic waveguide,” Opt. Express 23(20), 25688–25699 (2015).
[Crossref] [PubMed]

2014 (3)

M. D. Baaske, M. R. Foreman, and F. Vollmer, “Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform,” Nat. Nanotechnol. 9(11), 933–939 (2014).
[Crossref] [PubMed]

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

2013 (1)

2012 (3)

L. Jin, M. Li, and J.-J. He, “Analysis of wavelength and intensity interrogation methods in cascaded double-ring sensors,” J. Lightwave Technol. 30(12), 1994–2002 (2012).
[Crossref]

C. A. Barrios, “Integrated microring resonator sensor arrays for labs-on-chips,” Anal. Bioanal. Chem. 403(6), 1467–1475 (2012).
[Crossref] [PubMed]

L. Qin, L. Wang, M. Li, and J.-J. He, “Optical Sensor Based on Vernier-Cascade of Ring Resonator and Echelle Diffraction Grating,” IEEE Photonics Technol. Lett. 24(11), 954–956 (2012).
[Crossref]

2011 (3)

L. Chen, S. Xu, and J. Li, “Recent advances in molecular imprinting technology: current status, challenges and highlighted applications,” Chem. Soc. Rev. 40(5), 2922–2942 (2011).
[Crossref] [PubMed]

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

L. Jin, M. Li, and J.-J. He, “Highly sensitive optical sensor based on two cascaded micro-ring resonators with an LED light source,” Proc. SPIE 7943, 794307 (2011).
[Crossref]

2008 (2)

J. Homola, “Surface plasmon resonance sensors for detection of chemical and biological species,” Chem. Rev. 108(2), 462–493 (2008).
[Crossref] [PubMed]

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: A review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[Crossref] [PubMed]

2007 (3)

E. B. Fonseca, E. Celik, M. Parra, M. Singh, and K. H. Nicolaides, “Progesterone and the risk of preterm birth among women with a short cervix,” N. Engl. J. Med. 357(5), 462–469 (2007).
[Crossref] [PubMed]

A. Bossi, F. Bonini, A. P. Turner, and S. A. Piletsky, “Molecularly imprinted polymers for the recognition of proteins: the state of the art,” Biosens. Bioelectron. 22(6), 1131–1137 (2007).
[Crossref] [PubMed]

M. R. Lee and P. M. Fauchet, “Nanoscale microcavity sensor for single particle detection,” Opt. Lett. 32(22), 3284–3286 (2007).
[Crossref] [PubMed]

2006 (1)

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

2001 (1)

1997 (1)

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

1992 (1)

J. Brolin, L. Skoog, and P. Ekman, “Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue,” Prostate 20(4), 281–295 (1992).
[Crossref] [PubMed]

Baaske, M. D.

M. D. Baaske, M. R. Foreman, and F. Vollmer, “Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform,” Nat. Nanotechnol. 9(11), 933–939 (2014).
[Crossref] [PubMed]

Bao, J.

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

Barrios, C. A.

C. A. Barrios, “Integrated microring resonator sensor arrays for labs-on-chips,” Anal. Bioanal. Chem. 403(6), 1467–1475 (2012).
[Crossref] [PubMed]

Blanco, F. J.

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

Blow, J. J.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Bonini, F.

A. Bossi, F. Bonini, A. P. Turner, and S. A. Piletsky, “Molecularly imprinted polymers for the recognition of proteins: the state of the art,” Biosens. Bioelectron. 22(6), 1131–1137 (2007).
[Crossref] [PubMed]

Borgne, A.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Bossi, A.

A. Bossi, F. Bonini, A. P. Turner, and S. A. Piletsky, “Molecularly imprinted polymers for the recognition of proteins: the state of the art,” Biosens. Bioelectron. 22(6), 1131–1137 (2007).
[Crossref] [PubMed]

Boyd, R. W.

Brolin, J.

J. Brolin, L. Skoog, and P. Ekman, “Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue,” Prostate 20(4), 281–295 (1992).
[Crossref] [PubMed]

Celik, E.

E. B. Fonseca, E. Celik, M. Parra, M. Singh, and K. H. Nicolaides, “Progesterone and the risk of preterm birth among women with a short cervix,” N. Engl. J. Med. 357(5), 462–469 (2007).
[Crossref] [PubMed]

Cheben, P.

A. Densomore, D. X. Xu, P. Waldron, S. Janz, A. Delâge, and P. Cheben, “Silicon Microphotonic Waveguides for Biological Sensing,” in Proceedings of IEEE Conference on Biophotonics, Nanophotonics and Metamaterials (IEEE, 2006), pp. 15–18.

Chen, L.

L. Chen, S. Xu, and J. Li, “Recent advances in molecular imprinting technology: current status, challenges and highlighted applications,” Chem. Soc. Rev. 40(5), 2922–2942 (2011).
[Crossref] [PubMed]

Chen, T.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Chen, Y.

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

Chong, J. P. J.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Dai, D.

Delâge, A.

A. Densomore, D. X. Xu, P. Waldron, S. Janz, A. Delâge, and P. Cheben, “Silicon Microphotonic Waveguides for Biological Sensing,” in Proceedings of IEEE Conference on Biophotonics, Nanophotonics and Metamaterials (IEEE, 2006), pp. 15–18.

Delcros, J.-G.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Densomore, A.

A. Densomore, D. X. Xu, P. Waldron, S. Janz, A. Delâge, and P. Cheben, “Silicon Microphotonic Waveguides for Biological Sensing,” in Proceedings of IEEE Conference on Biophotonics, Nanophotonics and Metamaterials (IEEE, 2006), pp. 15–18.

Domínguez, C.

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

Duan, Y.

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

Ekman, P.

J. Brolin, L. Skoog, and P. Ekman, “Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue,” Prostate 20(4), 281–295 (1992).
[Crossref] [PubMed]

Fan, X.

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: A review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[Crossref] [PubMed]

Fauchet, P. M.

Flagan, R. C.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Fonseca, E. B.

E. B. Fonseca, E. Celik, M. Parra, M. Singh, and K. H. Nicolaides, “Progesterone and the risk of preterm birth among women with a short cervix,” N. Engl. J. Med. 357(5), 462–469 (2007).
[Crossref] [PubMed]

Foreman, M. R.

M. D. Baaske, M. R. Foreman, and F. Vollmer, “Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform,” Nat. Nanotechnol. 9(11), 933–939 (2014).
[Crossref] [PubMed]

Fraser, S. E.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Han, X.

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

He, J.-J.

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

X. Jiang, J. Ye, J. Zou, M. Li, and J.-J. He, “Cascaded silicon-on-insulator double-ring sensors operating in high-sensitivity transverse-magnetic mode,” Opt. Lett. 38(8), 1349–1351 (2013).
[Crossref] [PubMed]

L. Jin, M. Li, and J.-J. He, “Analysis of wavelength and intensity interrogation methods in cascaded double-ring sensors,” J. Lightwave Technol. 30(12), 1994–2002 (2012).
[Crossref]

L. Qin, L. Wang, M. Li, and J.-J. He, “Optical Sensor Based on Vernier-Cascade of Ring Resonator and Echelle Diffraction Grating,” IEEE Photonics Technol. Lett. 24(11), 954–956 (2012).
[Crossref]

L. Jin, M. Li, and J.-J. He, “Highly sensitive optical sensor based on two cascaded micro-ring resonators with an LED light source,” Proc. SPIE 7943, 794307 (2011).
[Crossref]

Heebner, J. E.

Herchak, S.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Homola, J.

J. Homola, “Surface plasmon resonance sensors for detection of chemical and biological species,” Chem. Rev. 108(2), 462–493 (2008).
[Crossref] [PubMed]

Inagaki, M.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Inagaki, N.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Janz, S.

A. Densomore, D. X. Xu, P. Waldron, S. Janz, A. Delâge, and P. Cheben, “Silicon Microphotonic Waveguides for Biological Sensing,” in Proceedings of IEEE Conference on Biophotonics, Nanophotonics and Metamaterials (IEEE, 2006), pp. 15–18.

Jiang, W. C.

W. Yu, W. C. Jiang, Q. Lin, and T. Lu, “Cavity optomechanical spring sensing of single molecules,” Nat. Commun. 7, 12311 (2016).
[Crossref] [PubMed]

Jiang, X.

Jin, L.

L. Jin, M. Li, and J.-J. He, “Analysis of wavelength and intensity interrogation methods in cascaded double-ring sensors,” J. Lightwave Technol. 30(12), 1994–2002 (2012).
[Crossref]

L. Jin, M. Li, and J.-J. He, “Highly sensitive optical sensor based on two cascaded micro-ring resonators with an LED light source,” Proc. SPIE 7943, 794307 (2011).
[Crossref]

Jing, L.

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

Kim, J. H.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Lechuga, L. M.

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

Lee, H.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Lee, M. R.

Li, J.

L. Chen, S. Xu, and J. Li, “Recent advances in molecular imprinting technology: current status, challenges and highlighted applications,” Chem. Soc. Rev. 40(5), 2922–2942 (2011).
[Crossref] [PubMed]

Li, M.

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

X. Jiang, J. Ye, J. Zou, M. Li, and J.-J. He, “Cascaded silicon-on-insulator double-ring sensors operating in high-sensitivity transverse-magnetic mode,” Opt. Lett. 38(8), 1349–1351 (2013).
[Crossref] [PubMed]

L. Jin, M. Li, and J.-J. He, “Analysis of wavelength and intensity interrogation methods in cascaded double-ring sensors,” J. Lightwave Technol. 30(12), 1994–2002 (2012).
[Crossref]

L. Qin, L. Wang, M. Li, and J.-J. He, “Optical Sensor Based on Vernier-Cascade of Ring Resonator and Echelle Diffraction Grating,” IEEE Photonics Technol. Lett. 24(11), 954–956 (2012).
[Crossref]

L. Jin, M. Li, and J.-J. He, “Highly sensitive optical sensor based on two cascaded micro-ring resonators with an LED light source,” Proc. SPIE 7943, 794307 (2011).
[Crossref]

Liedberg, B.

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

Lin, Q.

W. Yu, W. C. Jiang, Q. Lin, and T. Lu, “Cavity optomechanical spring sensing of single molecules,” Nat. Commun. 7, 12311 (2016).
[Crossref] [PubMed]

Lu, T.

W. Yu, W. C. Jiang, Q. Lin, and T. Lu, “Cavity optomechanical spring sensing of single molecules,” Nat. Commun. 7, 12311 (2016).
[Crossref] [PubMed]

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Lu, Z.

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

Mayora, K.

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

Meijer, L.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Moreno, M.

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

Moulinoux, J.-P.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Mulner, O.

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

Nicolaides, K. H.

E. B. Fonseca, E. Celik, M. Parra, M. Singh, and K. H. Nicolaides, “Progesterone and the risk of preterm birth among women with a short cervix,” N. Engl. J. Med. 357(5), 462–469 (2007).
[Crossref] [PubMed]

Osipov, A. P.

J. V. Samsonova, V. A. Safronova, and A. P. Osipov, “Pretreatment-free lateral flow enzyme immunoassay for progesterone detection in whole cows’ milk,” Talanta 132, 685–689 (2015).
[Crossref] [PubMed]

Parra, M.

E. B. Fonseca, E. Celik, M. Parra, M. Singh, and K. H. Nicolaides, “Progesterone and the risk of preterm birth among women with a short cervix,” N. Engl. J. Med. 357(5), 462–469 (2007).
[Crossref] [PubMed]

Piletsky, S. A.

A. Bossi, F. Bonini, A. P. Turner, and S. A. Piletsky, “Molecularly imprinted polymers for the recognition of proteins: the state of the art,” Biosens. Bioelectron. 22(6), 1131–1137 (2007).
[Crossref] [PubMed]

Qin, L.

L. Qin, L. Wang, M. Li, and J.-J. He, “Optical Sensor Based on Vernier-Cascade of Ring Resonator and Echelle Diffraction Grating,” IEEE Photonics Technol. Lett. 24(11), 954–956 (2012).
[Crossref]

Ren, J.

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

Ren, Y.

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

Río, J. S.

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

Safronova, V. A.

J. V. Samsonova, V. A. Safronova, and A. P. Osipov, “Pretreatment-free lateral flow enzyme immunoassay for progesterone detection in whole cows’ milk,” Talanta 132, 685–689 (2015).
[Crossref] [PubMed]

Samsonova, J. V.

J. V. Samsonova, V. A. Safronova, and A. P. Osipov, “Pretreatment-free lateral flow enzyme immunoassay for progesterone detection in whole cows’ milk,” Talanta 132, 685–689 (2015).
[Crossref] [PubMed]

Sepúlveda, B.

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

Shao, Y.

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

Shopova, S. I.

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: A review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[Crossref] [PubMed]

Singh, M.

E. B. Fonseca, E. Celik, M. Parra, M. Singh, and K. H. Nicolaides, “Progesterone and the risk of preterm birth among women with a short cervix,” N. Engl. J. Med. 357(5), 462–469 (2007).
[Crossref] [PubMed]

Skoog, L.

J. Brolin, L. Skoog, and P. Ekman, “Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue,” Prostate 20(4), 281–295 (1992).
[Crossref] [PubMed]

Song, J.

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

Sun, X.

Sun, Y.

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: A review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[Crossref] [PubMed]

Suter, J. D.

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: A review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[Crossref] [PubMed]

Tang, L.

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

Teng, J.

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

Thylén, L.

Turner, A. P.

A. Bossi, F. Bonini, A. P. Turner, and S. A. Piletsky, “Molecularly imprinted polymers for the recognition of proteins: the state of the art,” Biosens. Bioelectron. 22(6), 1131–1137 (2007).
[Crossref] [PubMed]

Vahala, K.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Vollmer, F.

M. D. Baaske, M. R. Foreman, and F. Vollmer, “Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform,” Nat. Nanotechnol. 9(11), 933–939 (2014).
[Crossref] [PubMed]

Waldron, P.

A. Densomore, D. X. Xu, P. Waldron, S. Janz, A. Delâge, and P. Cheben, “Silicon Microphotonic Waveguides for Biological Sensing,” in Proceedings of IEEE Conference on Biophotonics, Nanophotonics and Metamaterials (IEEE, 2006), pp. 15–18.

Wang, L.

L. Qin, L. Wang, M. Li, and J.-J. He, “Optical Sensor Based on Vernier-Cascade of Ring Resonator and Echelle Diffraction Grating,” IEEE Photonics Technol. Lett. 24(11), 954–956 (2012).
[Crossref]

Wang, Y.

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

Wei, T.

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

White, I. M.

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: A review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[Crossref] [PubMed]

Wosinski, L.

Wu, L.

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

Wu, Z.

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

Xia, C.

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

Xu, C.

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

Xu, D. X.

A. Densomore, D. X. Xu, P. Waldron, S. Janz, A. Delâge, and P. Cheben, “Silicon Microphotonic Waveguides for Biological Sensing,” in Proceedings of IEEE Conference on Biophotonics, Nanophotonics and Metamaterials (IEEE, 2006), pp. 15–18.

Xu, S.

L. Chen, S. Xu, and J. Li, “Recent advances in molecular imprinting technology: current status, challenges and highlighted applications,” Chem. Soc. Rev. 40(5), 2922–2942 (2011).
[Crossref] [PubMed]

Yang, C.

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

Ye, J.

Yu, F.

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

Yu, W.

W. Yu, W. C. Jiang, Q. Lin, and T. Lu, “Cavity optomechanical spring sensing of single molecules,” Nat. Commun. 7, 12311 (2016).
[Crossref] [PubMed]

Zhang, H.

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

Zhang, J.

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

Zhang, Q.

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

Zhao, M.

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

Zhu, H.

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: A review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[Crossref] [PubMed]

Zou, J.

Anal. Bioanal. Chem. (1)

C. A. Barrios, “Integrated microring resonator sensor arrays for labs-on-chips,” Anal. Bioanal. Chem. 403(6), 1467–1475 (2012).
[Crossref] [PubMed]

Anal. Biochem. (1)

Q. Zhang, L. Jing, J. Zhang, Y. Ren, Y. Wang, Y. Wang, T. Wei, and B. Liedberg, “Surface plasmon resonance sensor for femtomolar detection of testosterone with water-compatible macroporous molecularly imprinted film,” Anal. Biochem. 463(1), 7–14 (2014).
[Crossref] [PubMed]

Anal. Chim. Acta (1)

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: A review,” Anal. Chim. Acta 620(1-2), 8–26 (2008).
[Crossref] [PubMed]

Appl. Opt. (1)

Biosens. Bioelectron. (1)

A. Bossi, F. Bonini, A. P. Turner, and S. A. Piletsky, “Molecularly imprinted polymers for the recognition of proteins: the state of the art,” Biosens. Bioelectron. 22(6), 1131–1137 (2007).
[Crossref] [PubMed]

Chem. Rev. (1)

J. Homola, “Surface plasmon resonance sensors for detection of chemical and biological species,” Chem. Rev. 108(2), 462–493 (2008).
[Crossref] [PubMed]

Chem. Soc. Rev. (1)

L. Chen, S. Xu, and J. Li, “Recent advances in molecular imprinting technology: current status, challenges and highlighted applications,” Chem. Soc. Rev. 40(5), 2922–2942 (2011).
[Crossref] [PubMed]

Eur. J. Biochem. (1)

L. Meijer, A. Borgne, O. Mulner, J. P. J. Chong, J. J. Blow, N. Inagaki, M. Inagaki, J.-G. Delcros, and J.-P. Moulinoux, “Biochemical and Cellular Effects of Roscovitine, a Potent and Selective Inhibitor of the Cyclin-Dependent Kinases cdc2, cdk2 and cdk5,” Eur. J. Biochem. 243(1-2), 527–536 (1997).
[Crossref] [PubMed]

IEEE Photonics Technol. Lett. (1)

L. Qin, L. Wang, M. Li, and J.-J. He, “Optical Sensor Based on Vernier-Cascade of Ring Resonator and Echelle Diffraction Grating,” IEEE Photonics Technol. Lett. 24(11), 954–956 (2012).
[Crossref]

J. Lightwave Technol. (1)

J. Opt. A, Pure Appl. Opt. (1)

B. Sepúlveda, J. S. Río, M. Moreno, F. J. Blanco, K. Mayora, C. Domínguez, and L. M. Lechuga, “Optical biosensor microsystems based on the integration of highly sensitive Mach Zehnder interferometer devices,” J. Opt. A, Pure Appl. Opt. 8(7), S561–S566 (2006).
[Crossref]

Monoclon. Antib. Immunodiagn. Immunother. (1)

L. Wu, C. Xu, C. Xia, Y. Duan, C. Xu, H. Zhang, and J. Bao, “Development and Application of an ELISA Kit for the Detection of Milk Progesterone in Dairy Cows,” Monoclon. Antib. Immunodiagn. Immunother. 33(5), 330–333 (2014).
[Crossref] [PubMed]

N. Engl. J. Med. (1)

E. B. Fonseca, E. Celik, M. Parra, M. Singh, and K. H. Nicolaides, “Progesterone and the risk of preterm birth among women with a short cervix,” N. Engl. J. Med. 357(5), 462–469 (2007).
[Crossref] [PubMed]

Nat. Commun. (1)

W. Yu, W. C. Jiang, Q. Lin, and T. Lu, “Cavity optomechanical spring sensing of single molecules,” Nat. Commun. 7, 12311 (2016).
[Crossref] [PubMed]

Nat. Nanotechnol. (1)

M. D. Baaske, M. R. Foreman, and F. Vollmer, “Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform,” Nat. Nanotechnol. 9(11), 933–939 (2014).
[Crossref] [PubMed]

Opt. Commun. (2)

Y. Chen, F. Yu, C. Yang, J. Song, L. Tang, M. Li, and J.-J. He, “Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels,” Opt. Commun. 344, 129–133 (2015).
[Crossref]

X. Han, Y. Shao, X. Han, Z. Lu, Z. Wu, J. Teng, J. Ren, and M. Zhao, “Athermal optical waveguide microring biosensor with intensity interrogation,” Opt. Commun. 356, 41–48 (2015).
[Crossref]

Opt. Express (1)

Opt. Lett. (2)

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

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108(15), 5976–5979 (2011).
[Crossref] [PubMed]

Proc. SPIE (1)

L. Jin, M. Li, and J.-J. He, “Highly sensitive optical sensor based on two cascaded micro-ring resonators with an LED light source,” Proc. SPIE 7943, 794307 (2011).
[Crossref]

Prostate (1)

J. Brolin, L. Skoog, and P. Ekman, “Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue,” Prostate 20(4), 281–295 (1992).
[Crossref] [PubMed]

Talanta (1)

J. V. Samsonova, V. A. Safronova, and A. P. Osipov, “Pretreatment-free lateral flow enzyme immunoassay for progesterone detection in whole cows’ milk,” Talanta 132, 685–689 (2015).
[Crossref] [PubMed]

Other (1)

A. Densomore, D. X. Xu, P. Waldron, S. Janz, A. Delâge, and P. Cheben, “Silicon Microphotonic Waveguides for Biological Sensing,” in Proceedings of IEEE Conference on Biophotonics, Nanophotonics and Metamaterials (IEEE, 2006), pp. 15–18.

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Figures (6)

Fig. 1
Fig. 1 (a) Schematic image of the CMRR sensor; (b) SEM image of the grating coupler; (c) SEM image of sensing ring; (d) SEM image of the directional coupler.
Fig. 2
Fig. 2 Progesterone-MIPs synthesized on the chip and the MIPs principle
Fig. 3
Fig. 3 (a, b) Multi-channels valve and injection pump will be controlled by computer; (c) long ring pipe for liquid storage; (d) microfluidic channel constructed by PMMA and TEC; (e) chip; (f) fiber array; (g, h, i) glass bottle for DI water, sample, waste liquid storage; (j) PMMA lid (k) rubber channel; (l) the packaged chip; (m) metal block integrated with a temperature controller.
Fig. 4
Fig. 4 (a) Electric field intensity of the waveguide for TM mode; (b) Group refractive index as a function of wavelength for the waveguide with H2O and SU8 upper cladding respectively; (c) Simulated and experimental FSR of the CMRR; (d) Experimental transmission spectral of the drop port when the analyte is 1.1% and 1.5% NaCl aqueous solution respectively; (e) Experimental transmission spectral of the drop port for the reference ring and sensing ring; (f) Zoom in view of Fig. 4(e), the Q factor of sensing ring and reference ring is about 10336.06 at 1540.41 nm and 17225.11 at 1550.26 nm.
Fig. 5
Fig. 5 (a) Time-dependent response of the output power with different concentrations of NaCl aqueous solution; (b) The function curve of the output power with the concentration of the NaCl aqueous solutions.
Fig. 6
Fig. 6 (a) Time-dependent power change due to the affinity binding of progesterone at concentrations of 1 pg/mL, 10 pg/mL, 0.1 ng/mL,1 ng/mL, 10 ng/mL and 100 ng/mL in water; (b) Three groups of repeated experiments at concentrations of 1 ng/mL; (c) The response of different solution for the progesterone-MIPs CMRR chip (progesterone and testosterone) and NIPs (progesterone) at 500 seconds; (d) The linear fitting of power with the log values of the different concentrations of progesterone.

Equations (1)

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FSR = λ 2 2 π r × n g ,

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