Abstract

Common-path in-line shearing interferometry, combined with pixel-array imaging, provides a surface metrology that achieves 15 pm surface height resolution. An eighth-wave thermal oxide on silicon generates a reference wave locked in the condition of phase quadrature for phase-to-intensity conversion that makes surface height or index variations directly detectable by an imaging system. The scaling surface mass sensitivity for the surface metrology application is Sscal = 7 fg/mm under 40x magnification with a molecular resolution of approximately 12 IgG molecules within a pixel, limited by the surface roughness of the substrate. When applied to reverse-phase immunoassays in an antibody microarray format under 7x magnification, the current limit of detection is 10 ng/ml for 1 hour incubation, limited by biological and chemical variability. The biosensor is compatible with real-time binding measurements under active flow conditions with a binding dynamic range per well of 103 and a mass sensitivity of 2 pg/mm2.

© 2008 Optical Society of America

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  1. N. L. Anderson and N. G. Anderson, "The human plasma proteome - History, character, and diagnostic prospects," Mol. Cell. Proteomics 1, 845-867 (2002).
    [CrossRef]
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    [CrossRef]
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    [CrossRef]
  4. B. Cunningham, P. Li, and J. Pepper, "Colorimetric resonant reflection as a direct biochemical assay technique," Sens. Actuators B 81, 316-328 (2002).
    [CrossRef]
  5. M. Armani, A. P. Kulkarni, S. E. Fraser, R. C. Flagen, and K. J. Vahala, "Label-free, single-molecule detection with optical microcavities," Science 317, 783-787 (2007).
    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
  14. K. Johansen, H. Arwin, I. Lundstrom, and B. Liedberg, "Imaging surface plasmon resonance sensor based on multiple wavelengths: Sensitivity considerations," Rev. Sci. Instrum. 71, 3530-3538 (2000).
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  17. V. Kiessling and L. K. Tamm, "Measuring distances in supported bilayers by fluorescence interference-contrast microscopy: Polymer supports and SNARE proteins," Biophys. J. 84, 408-418 (2003).
  18. V. Jacobsen, P. Stoller, C. Brunner, V. Vogel, and V. Sandoghdar, "Interferometric optical detection and tracking of very small gold nanoparticles at a water-glass interface," Opt. Express
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2007 (4)

2006 (1)

T. J. Gao, J.H. Lu, and L. J. Rothberg, "Biomolecular sensing using near-null single wavelength arrayed imaging reflectometry," Anal. Chem. 78, 6622-6627 (2006).
[CrossRef]

2005 (1)

G. Gauglitz, "Direct optical sensors: principles and selected applications," Anal. Bioanal. Chem. 381, 141-155 (2005).
[CrossRef]

2004 (3)

M. M. Varma, H. D. Inerowicz, F. E. Regnier, and D. D. Nolte, "High-speed label-free detection by spinning-disk micro-interferometry," Biosens. Bioelectron. 19, 1371-1376 (2004).
[CrossRef]

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

M. M. Varma, D. D. Nolte, H. D. Inerowicz, and F. E. Regnier, "Spinning-disk self-referencing interferometry of antigen-antibody recognition," Opt. Lett. 29, 950-952 (2004).
[CrossRef]

2003 (2)

J. Homola, "Present and future of surface plasmon resonance biosensors," Anal.Bioanal. Chem. 377, 528-539 (2003).
[CrossRef]

V. Kiessling and L. K. Tamm, "Measuring distances in supported bilayers by fluorescence interference-contrast microscopy: Polymer supports and SNARE proteins," Biophys. J. 84, 408-418 (2003).

2002 (2)

B. Cunningham, P. Li, and J. Pepper, "Colorimetric resonant reflection as a direct biochemical assay technique," Sens. Actuators B 81, 316-328 (2002).
[CrossRef]

N. L. Anderson and N. G. Anderson, "The human plasma proteome - History, character, and diagnostic prospects," Mol. Cell. Proteomics 1, 845-867 (2002).
[CrossRef]

2000 (1)

K. Johansen, H. Arwin, I. Lundstrom, and B. Liedberg, "Imaging surface plasmon resonance sensor based on multiple wavelengths: Sensitivity considerations," Rev. Sci. Instrum. 71, 3530-3538 (2000).
[CrossRef]

1957 (1)

Anderson, N. G.

N. L. Anderson and N. G. Anderson, "The human plasma proteome - History, character, and diagnostic prospects," Mol. Cell. Proteomics 1, 845-867 (2002).
[CrossRef]

Anderson, N. L.

N. L. Anderson and N. G. Anderson, "The human plasma proteome - History, character, and diagnostic prospects," Mol. Cell. Proteomics 1, 845-867 (2002).
[CrossRef]

Armani, M.

M. Armani, A. P. Kulkarni, S. E. Fraser, R. C. Flagen, and K. J. Vahala, "Label-free, single-molecule detection with optical microcavities," Science 317, 783-787 (2007).
[CrossRef]

Arwin, H.

K. Johansen, H. Arwin, I. Lundstrom, and B. Liedberg, "Imaging surface plasmon resonance sensor based on multiple wavelengths: Sensitivity considerations," Rev. Sci. Instrum. 71, 3530-3538 (2000).
[CrossRef]

Bessueille, F.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Bras, M.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Brunner, C.

V. Jacobsen, P. Stoller, C. Brunner, V. Vogel, and V. Sandoghdar, "Interferometric optical detection and tracking of very small gold nanoparticles at a water-glass interface," Opt. Express

Cabrera, M.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Chauvet, J. P.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Cho, W.

Cho, W. R.

Cloared, J. P.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Cunningham, B.

B. Cunningham, P. Li, and J. Pepper, "Colorimetric resonant reflection as a direct biochemical assay technique," Sens. Actuators B 81, 316-328 (2002).
[CrossRef]

Dugas, V.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Dyson, J.

Flagen, R. C.

M. Armani, A. P. Kulkarni, S. E. Fraser, R. C. Flagen, and K. J. Vahala, "Label-free, single-molecule detection with optical microcavities," Science 317, 783-787 (2007).
[CrossRef]

Fraser, S. E.

M. Armani, A. P. Kulkarni, S. E. Fraser, R. C. Flagen, and K. J. Vahala, "Label-free, single-molecule detection with optical microcavities," Science 317, 783-787 (2007).
[CrossRef]

Gao, T. J.

T. J. Gao, J.H. Lu, and L. J. Rothberg, "Biomolecular sensing using near-null single wavelength arrayed imaging reflectometry," Anal. Chem. 78, 6622-6627 (2006).
[CrossRef]

Garrigues, M.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Gauglitz, G.

G. Gauglitz, "Direct optical sensors: principles and selected applications," Anal. Bioanal. Chem. 381, 141-155 (2005).
[CrossRef]

Homola, J.

J. Homola, "Present and future of surface plasmon resonance biosensors," Anal.Bioanal. Chem. 377, 528-539 (2003).
[CrossRef]

Inerowicz, H. D.

M. M. Varma, D. D. Nolte, H. D. Inerowicz, and F. E. Regnier, "Spinning-disk self-referencing interferometry of antigen-antibody recognition," Opt. Lett. 29, 950-952 (2004).
[CrossRef]

M. M. Varma, H. D. Inerowicz, F. E. Regnier, and D. D. Nolte, "High-speed label-free detection by spinning-disk micro-interferometry," Biosens. Bioelectron. 19, 1371-1376 (2004).
[CrossRef]

Jacobsen, V.

V. Jacobsen, P. Stoller, C. Brunner, V. Vogel, and V. Sandoghdar, "Interferometric optical detection and tracking of very small gold nanoparticles at a water-glass interface," Opt. Express

Johansen, K.

K. Johansen, H. Arwin, I. Lundstrom, and B. Liedberg, "Imaging surface plasmon resonance sensor based on multiple wavelengths: Sensitivity considerations," Rev. Sci. Instrum. 71, 3530-3538 (2000).
[CrossRef]

Kiessling, V.

V. Kiessling and L. K. Tamm, "Measuring distances in supported bilayers by fluorescence interference-contrast microscopy: Polymer supports and SNARE proteins," Biophys. J. 84, 408-418 (2003).

Kulkarni, A. P.

M. Armani, A. P. Kulkarni, S. E. Fraser, R. C. Flagen, and K. J. Vahala, "Label-free, single-molecule detection with optical microcavities," Science 317, 783-787 (2007).
[CrossRef]

Li, P.

B. Cunningham, P. Li, and J. Pepper, "Colorimetric resonant reflection as a direct biochemical assay technique," Sens. Actuators B 81, 316-328 (2002).
[CrossRef]

Liedberg, B.

K. Johansen, H. Arwin, I. Lundstrom, and B. Liedberg, "Imaging surface plasmon resonance sensor based on multiple wavelengths: Sensitivity considerations," Rev. Sci. Instrum. 71, 3530-3538 (2000).
[CrossRef]

Lu, J.H.

T. J. Gao, J.H. Lu, and L. J. Rothberg, "Biomolecular sensing using near-null single wavelength arrayed imaging reflectometry," Anal. Chem. 78, 6622-6627 (2006).
[CrossRef]

Lundstrom, I.

K. Johansen, H. Arwin, I. Lundstrom, and B. Liedberg, "Imaging surface plasmon resonance sensor based on multiple wavelengths: Sensitivity considerations," Rev. Sci. Instrum. 71, 3530-3538 (2000).
[CrossRef]

Martin, J. R.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Nolte, D.

Nolte, D. D.

Peng, L.

Pepper, J.

B. Cunningham, P. Li, and J. Pepper, "Colorimetric resonant reflection as a direct biochemical assay technique," Sens. Actuators B 81, 316-328 (2002).
[CrossRef]

Regnier, F.

Regnier, F. E.

Rothberg, L. J.

T. J. Gao, J.H. Lu, and L. J. Rothberg, "Biomolecular sensing using near-null single wavelength arrayed imaging reflectometry," Anal. Chem. 78, 6622-6627 (2006).
[CrossRef]

Sandoghdar, V.

V. Jacobsen, P. Stoller, C. Brunner, V. Vogel, and V. Sandoghdar, "Interferometric optical detection and tracking of very small gold nanoparticles at a water-glass interface," Opt. Express

Souteyrand, E.

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Stoller, P.

V. Jacobsen, P. Stoller, C. Brunner, V. Vogel, and V. Sandoghdar, "Interferometric optical detection and tracking of very small gold nanoparticles at a water-glass interface," Opt. Express

Tamm, L. K.

V. Kiessling and L. K. Tamm, "Measuring distances in supported bilayers by fluorescence interference-contrast microscopy: Polymer supports and SNARE proteins," Biophys. J. 84, 408-418 (2003).

Vahala, K. J.

M. Armani, A. P. Kulkarni, S. E. Fraser, R. C. Flagen, and K. J. Vahala, "Label-free, single-molecule detection with optical microcavities," Science 317, 783-787 (2007).
[CrossRef]

Varma, M. M.

Vogel, V.

V. Jacobsen, P. Stoller, C. Brunner, V. Vogel, and V. Sandoghdar, "Interferometric optical detection and tracking of very small gold nanoparticles at a water-glass interface," Opt. Express

Wang, X. F.

Zhao, M.

Anal. Bioanal. Chem. (1)

G. Gauglitz, "Direct optical sensors: principles and selected applications," Anal. Bioanal. Chem. 381, 141-155 (2005).
[CrossRef]

Anal. Chem. (1)

T. J. Gao, J.H. Lu, and L. J. Rothberg, "Biomolecular sensing using near-null single wavelength arrayed imaging reflectometry," Anal. Chem. 78, 6622-6627 (2006).
[CrossRef]

Anal.Bioanal. Chem. (1)

J. Homola, "Present and future of surface plasmon resonance biosensors," Anal.Bioanal. Chem. 377, 528-539 (2003).
[CrossRef]

Appl. Opt. (3)

Biophys. J. (1)

V. Kiessling and L. K. Tamm, "Measuring distances in supported bilayers by fluorescence interference-contrast microscopy: Polymer supports and SNARE proteins," Biophys. J. 84, 408-418 (2003).

Biosens. and Bioelectron. (1)

M. Bras, V. Dugas, F. Bessueille, J. P. Cloared, J. R. Martin, M. Cabrera, J. P. Chauvet, E. Souteyrand, and M. Garrigues, "Optimization of a silicon/silicon dioxide substrate for fluorescence DNA microarray," Biosens. and Bioelectron. 20, 797-806 (2004).

Biosens. Bioelectron. (1)

M. M. Varma, H. D. Inerowicz, F. E. Regnier, and D. D. Nolte, "High-speed label-free detection by spinning-disk micro-interferometry," Biosens. Bioelectron. 19, 1371-1376 (2004).
[CrossRef]

J. Opt. Soc. Am. (1)

Mol. Cell. Proteomics (1)

N. L. Anderson and N. G. Anderson, "The human plasma proteome - History, character, and diagnostic prospects," Mol. Cell. Proteomics 1, 845-867 (2002).
[CrossRef]

Opt. Lett. (1)

Rev. Sci. Instrum. (1)

K. Johansen, H. Arwin, I. Lundstrom, and B. Liedberg, "Imaging surface plasmon resonance sensor based on multiple wavelengths: Sensitivity considerations," Rev. Sci. Instrum. 71, 3530-3538 (2000).
[CrossRef]

Science (1)

M. Armani, A. P. Kulkarni, S. E. Fraser, R. C. Flagen, and K. J. Vahala, "Label-free, single-molecule detection with optical microcavities," Science 317, 783-787 (2007).
[CrossRef]

Sens. Actuators B (1)

B. Cunningham, P. Li, and J. Pepper, "Colorimetric resonant reflection as a direct biochemical assay technique," Sens. Actuators B 81, 316-328 (2002).
[CrossRef]

Other (4)

D. D. Nolte and M. Zhao, "Scaling mass sensitivity of the BioCD at 0.25 pg/mm," Proc. SPIE 6380, 63800J (2006).

P. Hariharan, Optical Interferometry (Elsevier, 2003).

V. Jacobsen, P. Stoller, C. Brunner, V. Vogel, and V. Sandoghdar, "Interferometric optical detection and tracking of very small gold nanoparticles at a water-glass interface," Opt. Express

O. S. Heavens, Optical Properties of Thin Solid Films (Dover, 1991).

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