Abstract

Label-free biosensors attempt to overcome the stability and reliability problems of biosensors relying on the detection of labeled molecules. We propose a label-free biosensor based on microring cavities in Silicon-on-Insulator (SOI) that fits in an area below 10x10μm2. The resonance wavelength shift that occurs when the surroundings of a cavity is changed, is used for sensing. While theoretically the performance for bulk refractive index changes is moderate (10-5), this device performs outstanding in terms of absolute molecular mass sensing (theoretical sensitivity of 1fg molecular mass) thanks to its extremely small dimensions. We use the avidin/biotin high affinity couple to demonstrate good repeatability and detection of protein concentrations down to 10ng/ml. Fabrication with Deep UV lithography allows for cheap mass production and integration with electronic functions for complete lab-on-chip devices.

© 2007 Optical Society of America

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References

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  1. J. Homola, "Present and future of Surface Plasmon Resonance Biosensors," Anal. Bioanal. Chem. 377, 528-539 (2003).
    [CrossRef] [PubMed]
  2. P. P. P. Debackere, S. Scheerlinck, P. Bienstman, and R. Baets, Surface Plasmon Interferometer in Silicon-on-Insulator: novel concept for an integrated biosensor," Opt. Express  14, 7063-7072 (2006).
    [CrossRef] [PubMed]
  3. D. Hradetzky, C. Mueller, and H. Reinecke, "Interferometric label-free biomolecular detection system," J. Opt. A: Pure Appl. Opt. 8, S360-S364 (2006).
    [CrossRef]
  4. A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
    [CrossRef] [PubMed]
  5. A. Ksendzov and Y. Lin, "Integrated optics ring-resonator sensors for protein detection," Opt. Lett. 30, 3344-3346 (2005).
    [CrossRef]
  6. C-Y. Chao, W. Fung, and L. J. Guo, "Polymer microring resonators for biochemical sensing applications," IEEE J. Sel. Top. Quantum Electron. 12, 134-142 (2006).
    [CrossRef]
  7. A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
    [CrossRef]
  8. T. Vo-Dinh, ed., Biomedical Photonics Handbook (CRC Press LLC, Boca Raton, 2003).
    [CrossRef]
  9. J. Vörös, "The density and refractive index of adsorbing protein layers," Biophys. J. 87, 553-561 (2004).
    [CrossRef] [PubMed]
  10. C. C. Striemer, T. R. Gaborski, J. L. McGrath, and F. M. Fauchet, "Charge- and size-based separation of macromolecules using ultrathin silicon membranes," Nature 445, 749-753 (2007).
    [CrossRef] [PubMed]
  11. W. Bogaerts, R. Baets, P. Dumon, V. Wiaux, S. Beckx, D. Taillaert, B. Luyssaert, J. Van Campenhout, P. Bienstman, and D. Van Thourhout, "Nanophotonic waveguides in silicon-on-insulator fabricated with CMOS Technology," J. Lightwave Technol. 23, 401-412 (2005).
    [CrossRef]
  12. D. R. Lyde, ed., Handbook of Chemistry and Physics, (CRC press, London, 1997-1998)
  13. F. Zhang, and M. P. Srinivasan, "Self-assembly molecular films of aminosilanes and their immobilization capacities," Langmuir 20, 2309-2314 (2004).
    [CrossRef]
  14. R. Ince and R. Narayanaswamy, "Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors," Analytica Chimica Acta 569, 1-20 (2006).
    [CrossRef]

2007 (2)

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

C. C. Striemer, T. R. Gaborski, J. L. McGrath, and F. M. Fauchet, "Charge- and size-based separation of macromolecules using ultrathin silicon membranes," Nature 445, 749-753 (2007).
[CrossRef] [PubMed]

2006 (5)

D. Hradetzky, C. Mueller, and H. Reinecke, "Interferometric label-free biomolecular detection system," J. Opt. A: Pure Appl. Opt. 8, S360-S364 (2006).
[CrossRef]

C-Y. Chao, W. Fung, and L. J. Guo, "Polymer microring resonators for biochemical sensing applications," IEEE J. Sel. Top. Quantum Electron. 12, 134-142 (2006).
[CrossRef]

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

R. Ince and R. Narayanaswamy, "Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors," Analytica Chimica Acta 569, 1-20 (2006).
[CrossRef]

P. P. P. Debackere, S. Scheerlinck, P. Bienstman, and R. Baets, Surface Plasmon Interferometer in Silicon-on-Insulator: novel concept for an integrated biosensor," Opt. Express  14, 7063-7072 (2006).
[CrossRef] [PubMed]

2005 (2)

2004 (2)

J. Vörös, "The density and refractive index of adsorbing protein layers," Biophys. J. 87, 553-561 (2004).
[CrossRef] [PubMed]

F. Zhang, and M. P. Srinivasan, "Self-assembly molecular films of aminosilanes and their immobilization capacities," Langmuir 20, 2309-2314 (2004).
[CrossRef]

2003 (1)

J. Homola, "Present and future of Surface Plasmon Resonance Biosensors," Anal. Bioanal. Chem. 377, 528-539 (2003).
[CrossRef] [PubMed]

Aldridge, J. C.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Anthes-Washburn, M.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Baets, R.

Beckx, S.

Beumer, T. A. M.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Bienstman, P.

Bogaerts, W.

Chao, C-Y.

C-Y. Chao, W. Fung, and L. J. Guo, "Polymer microring resonators for biochemical sensing applications," IEEE J. Sel. Top. Quantum Electron. 12, 134-142 (2006).
[CrossRef]

Chbouki, N.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Chu, S.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Debackere, P. P .P.

Desai, T. A

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Dumon, P.

Fauchet, F. M.

C. C. Striemer, T. R. Gaborski, J. L. McGrath, and F. M. Fauchet, "Charge- and size-based separation of macromolecules using ultrathin silicon membranes," Nature 445, 749-753 (2007).
[CrossRef] [PubMed]

Fung, W.

C-Y. Chao, W. Fung, and L. J. Guo, "Polymer microring resonators for biochemical sensing applications," IEEE J. Sel. Top. Quantum Electron. 12, 134-142 (2006).
[CrossRef]

Gaborski, T. R.

C. C. Striemer, T. R. Gaborski, J. L. McGrath, and F. M. Fauchet, "Charge- and size-based separation of macromolecules using ultrathin silicon membranes," Nature 445, 749-753 (2007).
[CrossRef] [PubMed]

Gill, D.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Goldberg, B. B.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Greve, J.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Guo, L. J.

C-Y. Chao, W. Fung, and L. J. Guo, "Polymer microring resonators for biochemical sensing applications," IEEE J. Sel. Top. Quantum Electron. 12, 134-142 (2006).
[CrossRef]

Heideman, R. G.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Homola, J.

J. Homola, "Present and future of Surface Plasmon Resonance Biosensors," Anal. Bioanal. Chem. 377, 528-539 (2003).
[CrossRef] [PubMed]

Hradetzky, D.

D. Hradetzky, C. Mueller, and H. Reinecke, "Interferometric label-free biomolecular detection system," J. Opt. A: Pure Appl. Opt. 8, S360-S364 (2006).
[CrossRef]

Hryniewicz, J.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Ince, R.

R. Ince and R. Narayanaswamy, "Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors," Analytica Chimica Acta 569, 1-20 (2006).
[CrossRef]

Kanger, J. S.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

King, O.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Ksendzov, A.

Lambeck, P. V.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Lin, Y.

Little, B. E.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Luyssaert, B.

McGrath, J. L.

C. C. Striemer, T. R. Gaborski, J. L. McGrath, and F. M. Fauchet, "Charge- and size-based separation of macromolecules using ultrathin silicon membranes," Nature 445, 749-753 (2007).
[CrossRef] [PubMed]

Mueller, C.

D. Hradetzky, C. Mueller, and H. Reinecke, "Interferometric label-free biomolecular detection system," J. Opt. A: Pure Appl. Opt. 8, S360-S364 (2006).
[CrossRef]

Narayanaswamy, R.

R. Ince and R. Narayanaswamy, "Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors," Analytica Chimica Acta 569, 1-20 (2006).
[CrossRef]

Popat, K. C.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Reinecke, H.

D. Hradetzky, C. Mueller, and H. Reinecke, "Interferometric label-free biomolecular detection system," J. Opt. A: Pure Appl. Opt. 8, S360-S364 (2006).
[CrossRef]

Scheerlinck, S.

Srinivasan, M. P.

F. Zhang, and M. P. Srinivasan, "Self-assembly molecular films of aminosilanes and their immobilization capacities," Langmuir 20, 2309-2314 (2004).
[CrossRef]

Striemer, C. C.

C. C. Striemer, T. R. Gaborski, J. L. McGrath, and F. M. Fauchet, "Charge- and size-based separation of macromolecules using ultrathin silicon membranes," Nature 445, 749-753 (2007).
[CrossRef] [PubMed]

Subramaniam, V.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Taillaert, D.

Ünlü, M. S.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Van, V.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Van Campenhout, J.

van Hövell, S. W. F. M.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Van Thourhout, D.

Vörös, J.

J. Vörös, "The density and refractive index of adsorbing protein layers," Biophys. J. 87, 553-561 (2004).
[CrossRef] [PubMed]

Wiaux, V.

Wijn, R. R.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Wink, T.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Yalçin, A.

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

Ymeti, A.

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Zhang, F.

F. Zhang, and M. P. Srinivasan, "Self-assembly molecular films of aminosilanes and their immobilization capacities," Langmuir 20, 2309-2314 (2004).
[CrossRef]

Anal. Bioanal. Chem. (1)

J. Homola, "Present and future of Surface Plasmon Resonance Biosensors," Anal. Bioanal. Chem. 377, 528-539 (2003).
[CrossRef] [PubMed]

Analytica Chimica Acta (1)

R. Ince and R. Narayanaswamy, "Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors," Analytica Chimica Acta 569, 1-20 (2006).
[CrossRef]

Biophys. J. (1)

J. Vörös, "The density and refractive index of adsorbing protein layers," Biophys. J. 87, 553-561 (2004).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (2)

C-Y. Chao, W. Fung, and L. J. Guo, "Polymer microring resonators for biochemical sensing applications," IEEE J. Sel. Top. Quantum Electron. 12, 134-142 (2006).
[CrossRef]

A. Yalçin, K. C. Popat, J. C. Aldridge, T. A Desai, J. Hryniewicz, N. Chbouki, B. E. Little, O. King, V. Van, S. Chu, D. Gill, M. Anthes-Washburn, M. S. Ünlü, and B. B. Goldberg, "Optical sensing of biomolecules using microring resonators," IEEE J. Sel. Top. Quantum Electron. 12, 148-155 (2006).
[CrossRef]

J. Lightwave Technol. (1)

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

D. Hradetzky, C. Mueller, and H. Reinecke, "Interferometric label-free biomolecular detection system," J. Opt. A: Pure Appl. Opt. 8, S360-S364 (2006).
[CrossRef]

Langmuir (1)

F. Zhang, and M. P. Srinivasan, "Self-assembly molecular films of aminosilanes and their immobilization capacities," Langmuir 20, 2309-2314 (2004).
[CrossRef]

Nano Lett. (1)

A. Ymeti, J. Greve, P. V. Lambeck, T. Wink, S. W. F. M. van Hövell, T. A. M. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, J. S. Kanger, "Fast, ultrasensitive virus detection using a young interferometer sensor," Nano Lett. 7, 394-397 (2007).
[CrossRef] [PubMed]

Nature (1)

C. C. Striemer, T. R. Gaborski, J. L. McGrath, and F. M. Fauchet, "Charge- and size-based separation of macromolecules using ultrathin silicon membranes," Nature 445, 749-753 (2007).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (1)

Other (2)

T. Vo-Dinh, ed., Biomedical Photonics Handbook (CRC Press LLC, Boca Raton, 2003).
[CrossRef]

D. R. Lyde, ed., Handbook of Chemistry and Physics, (CRC press, London, 1997-1998)

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Figures (5)

Fig. 1.
Fig. 1.

a) SEM picture of a microring cavity, b) measured spectra, c) measurement setup.

Fig. 2.
Fig. 2.

Resonance wavelength shift versus bulk refractive index change.

Fig. 3.
Fig. 3.

Resonance wavelength shift corresponding to different avidin concentrations for quantitative molecular detection.

Fig. 4.
Fig. 4.

Non-specific binding tests to show a lower output for biotin/BSA interactions.

Fig. 5.
Fig. 5.

Real time interaction measurements for different avidin concentrations.

Equations (3)

Equations on this page are rendered with MathJax. Learn more.

λ resonance = L m n eff
Δ n min = m L ( n eff n bulk ) 1 Δ λ min
Δ M min = ρ S m L ( n eff t ) 1 Δ λ min

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