Abstract

We developed an oblique-incidence reflectivity difference (OI-RD) scanning microscope for label-free imaging of microarrays of biomolecules upon solid substrates. We demonstrate that hybridization reactions in an oligonucleotide microarray fabricated upon a glass slide can be detected by such an OI-RD microscope.

© 2004 Optical Society of America

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References

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  1. M. Schena, Microarray Analysis (Wiley, Hoboken, N.J., 2003), pp. 1–23.
  2. S. P. Gygi, Y. Rochon, B. R. Franza, and R. Aebersold, Mol. Cell Biol. 19, 1720 (1999).
    [PubMed]
  3. G. MacBeath, Nature Genet. 32, 526 (2002).
    [CrossRef]
  4. P. Mitchell, Nature Biotech. 20, 225 (2002).
    [CrossRef]
  5. A. Wong and X. D. Zhu, Appl. Phys. A 63, 1 (1996).
    [CrossRef]
  6. X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
    [CrossRef]
  7. R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (Elsevier, New York, 1987), p. 305.
  8. J. Gray, P. Thomas, and X. D. Zhu, Rev. Sci. Instrum. 72, 3714 (2001).
    [CrossRef]
  9. S. V. Lemeshko, T. Powdrill, Y. Y. Belosludtsev, and M. Hogan, Nucl. Acids Res. 29, 3051 (2001).
    [CrossRef]
  10. M. D. Eisen and P. O. Brown, Methods Enzymol. 303, 179 (1999).
    [CrossRef]
  11. D. E. Gray, S. C. Case-Green, T. S. Fell, P. J. Dobson, and E. M. Southern, Langmuir 13, 2833 (1997).
    [CrossRef]
  12. J. M. Brockman, B. P. Nelson, and R. M. Corn, Annu. Rev. Phys. Chem. 51, 41 (2000).
  13. E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
    [CrossRef] [PubMed]

2003 (1)

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

2002 (2)

G. MacBeath, Nature Genet. 32, 526 (2002).
[CrossRef]

P. Mitchell, Nature Biotech. 20, 225 (2002).
[CrossRef]

2001 (2)

J. Gray, P. Thomas, and X. D. Zhu, Rev. Sci. Instrum. 72, 3714 (2001).
[CrossRef]

S. V. Lemeshko, T. Powdrill, Y. Y. Belosludtsev, and M. Hogan, Nucl. Acids Res. 29, 3051 (2001).
[CrossRef]

2000 (1)

J. M. Brockman, B. P. Nelson, and R. M. Corn, Annu. Rev. Phys. Chem. 51, 41 (2000).

1999 (2)

M. D. Eisen and P. O. Brown, Methods Enzymol. 303, 179 (1999).
[CrossRef]

S. P. Gygi, Y. Rochon, B. R. Franza, and R. Aebersold, Mol. Cell Biol. 19, 1720 (1999).
[PubMed]

1998 (1)

X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
[CrossRef]

1997 (1)

D. E. Gray, S. C. Case-Green, T. S. Fell, P. J. Dobson, and E. M. Southern, Langmuir 13, 2833 (1997).
[CrossRef]

1996 (1)

A. Wong and X. D. Zhu, Appl. Phys. A 63, 1 (1996).
[CrossRef]

Aebersold, R.

S. P. Gygi, Y. Rochon, B. R. Franza, and R. Aebersold, Mol. Cell Biol. 19, 1720 (1999).
[PubMed]

Azzam, R. M. A.

R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (Elsevier, New York, 1987), p. 305.

Barry, R.

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Bashara, N. M.

R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (Elsevier, New York, 1987), p. 305.

Belosludtsev, Y. Y.

S. V. Lemeshko, T. Powdrill, Y. Y. Belosludtsev, and M. Hogan, Nucl. Acids Res. 29, 3051 (2001).
[CrossRef]

Brockman, J. M.

J. M. Brockman, B. P. Nelson, and R. M. Corn, Annu. Rev. Phys. Chem. 51, 41 (2000).

Brown, P. O.

M. D. Eisen and P. O. Brown, Methods Enzymol. 303, 179 (1999).
[CrossRef]

Calvert, R.

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Case-Green, S. C.

D. E. Gray, S. C. Case-Green, T. S. Fell, P. J. Dobson, and E. M. Southern, Langmuir 13, 2833 (1997).
[CrossRef]

Corn, R. M.

J. M. Brockman, B. P. Nelson, and R. M. Corn, Annu. Rev. Phys. Chem. 51, 41 (2000).

Dobson, P. J.

D. E. Gray, S. C. Case-Green, T. S. Fell, P. J. Dobson, and E. M. Southern, Langmuir 13, 2833 (1997).
[CrossRef]

Eisen, M. D.

M. D. Eisen and P. O. Brown, Methods Enzymol. 303, 179 (1999).
[CrossRef]

Fell, T. S.

D. E. Gray, S. C. Case-Green, T. S. Fell, P. J. Dobson, and E. M. Southern, Langmuir 13, 2833 (1997).
[CrossRef]

Franza, B. R.

S. P. Gygi, Y. Rochon, B. R. Franza, and R. Aebersold, Mol. Cell Biol. 19, 1720 (1999).
[PubMed]

Gray, D. E.

D. E. Gray, S. C. Case-Green, T. S. Fell, P. J. Dobson, and E. M. Southern, Langmuir 13, 2833 (1997).
[CrossRef]

Gray, J.

J. Gray, P. Thomas, and X. D. Zhu, Rev. Sci. Instrum. 72, 3714 (2001).
[CrossRef]

Gu, B. Y.

X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
[CrossRef]

Gygi, S. P.

S. P. Gygi, Y. Rochon, B. R. Franza, and R. Aebersold, Mol. Cell Biol. 19, 1720 (1999).
[PubMed]

Hextall, P.

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Hogan, M.

S. V. Lemeshko, T. Powdrill, Y. Y. Belosludtsev, and M. Hogan, Nucl. Acids Res. 29, 3051 (2001).
[CrossRef]

Lemeshko, S. V.

S. V. Lemeshko, T. Powdrill, Y. Y. Belosludtsev, and M. Hogan, Nucl. Acids Res. 29, 3051 (2001).
[CrossRef]

Li, Z. Y.

X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
[CrossRef]

Lu, H. B.

X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
[CrossRef]

MacBeath, G.

G. MacBeath, Nature Genet. 32, 526 (2002).
[CrossRef]

Masih, G.

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Mitchell, P.

P. Mitchell, Nature Biotech. 20, 225 (2002).
[CrossRef]

Nelson, B. P.

J. M. Brockman, B. P. Nelson, and R. M. Corn, Annu. Rev. Phys. Chem. 51, 41 (2000).

Platt, A.

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Powdrill, T.

S. V. Lemeshko, T. Powdrill, Y. Y. Belosludtsev, and M. Hogan, Nucl. Acids Res. 29, 3051 (2001).
[CrossRef]

Rochon, Y.

S. P. Gygi, Y. Rochon, B. R. Franza, and R. Aebersold, Mol. Cell Biol. 19, 1720 (1999).
[PubMed]

Schena, M.

M. Schena, Microarray Analysis (Wiley, Hoboken, N.J., 2003), pp. 1–23.

Scrivener, E.

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Soloviev, M.

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Southern, E. M.

D. E. Gray, S. C. Case-Green, T. S. Fell, P. J. Dobson, and E. M. Southern, Langmuir 13, 2833 (1997).
[CrossRef]

Terrett, J.

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Thomas, P.

J. Gray, P. Thomas, and X. D. Zhu, Rev. Sci. Instrum. 72, 3714 (2001).
[CrossRef]

Wong, A.

A. Wong and X. D. Zhu, Appl. Phys. A 63, 1 (1996).
[CrossRef]

Yang, G. Z.

X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
[CrossRef]

Zhang, D. Z.

X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
[CrossRef]

Zhu, X. D.

J. Gray, P. Thomas, and X. D. Zhu, Rev. Sci. Instrum. 72, 3714 (2001).
[CrossRef]

X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
[CrossRef]

A. Wong and X. D. Zhu, Appl. Phys. A 63, 1 (1996).
[CrossRef]

Annu. Rev. Phys. Chem. (1)

J. M. Brockman, B. P. Nelson, and R. M. Corn, Annu. Rev. Phys. Chem. 51, 41 (2000).

Appl. Phys. A (1)

A. Wong and X. D. Zhu, Appl. Phys. A 63, 1 (1996).
[CrossRef]

Langmuir (1)

D. E. Gray, S. C. Case-Green, T. S. Fell, P. J. Dobson, and E. M. Southern, Langmuir 13, 2833 (1997).
[CrossRef]

Methods Enzymol. (1)

M. D. Eisen and P. O. Brown, Methods Enzymol. 303, 179 (1999).
[CrossRef]

Mol. Cell Biol. (1)

S. P. Gygi, Y. Rochon, B. R. Franza, and R. Aebersold, Mol. Cell Biol. 19, 1720 (1999).
[PubMed]

Nature Biotech. (1)

P. Mitchell, Nature Biotech. 20, 225 (2002).
[CrossRef]

Nature Genet. (1)

G. MacBeath, Nature Genet. 32, 526 (2002).
[CrossRef]

Nucl. Acids Res. (1)

S. V. Lemeshko, T. Powdrill, Y. Y. Belosludtsev, and M. Hogan, Nucl. Acids Res. 29, 3051 (2001).
[CrossRef]

Phys. Rev. B (1)

X. D. Zhu, H. B. Lu, G. Z. Yang, Z. Y. Li, B. Y. Gu, and D. Z. Zhang, Phys. Rev. B 57, 2514 (1998).
[CrossRef]

Proteomics (1)

E. Scrivener, R. Barry, A. Platt, R. Calvert, G. Masih, P. Hextall, M. Soloviev, and J. Terrett, Proteomics 3, 122 (2003).
[CrossRef] [PubMed]

Rev. Sci. Instrum. (1)

J. Gray, P. Thomas, and X. D. Zhu, Rev. Sci. Instrum. 72, 3714 (2001).
[CrossRef]

Other (2)

R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (Elsevier, New York, 1987), p. 305.

M. Schena, Microarray Analysis (Wiley, Hoboken, N.J., 2003), pp. 1–23.

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Figures (3)

Fig. 1
Fig. 1

OI-RD microscope for microarray imaging. The substrate lies upon a pair of translation stages that are movable along the x and y directions: PEM, photoelastic modulator; PC, Pockels cell; A, analyzer; PD, photodiode.

Fig. 2
Fig. 2

OI-RD and fluorescence scans of a microarray of 60-base oligonucleotides before and after hybridization. Columns 1–3 are printed with different oligonucleotides. The top position in column 3 was left blank for alignment. (a) ImΔp-Δs image of the printed microarray before hybridization; (b) ImΔp-Δs image of the microarray after hybridization with an unlabeled oligonucleotide complementary to column 1 and a Cy5-labeled oligonucleotide complementary to column 3; (c) Cy5 fluorescence image after hybridization; (d) differential ImΔp-Δs image obtained by subtraction of (a) from (b), revealing hybridized spots in both column 1 (label free) and column 3 (Cy5 labeled).

Fig. 3
Fig. 3

ImΔp-Δs averaged over the area of a printed spot versus printing concentration: open circles, before hybridization; filled squares, after hybridization.

Equations (1)

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Δp-Δs-i4π01/2s sin2 θ cos θs-0s cos2 θ-0 sin2 θ×d-sd-0ddλ,

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