Abstract

Diffraction-based molecular detection is achieved by etching optical gratings into thermal oxide on silicon. The gratings perform as a stable common-path diffractive optical balance (DOB) designed to operate near a missing diffraction order. The biosensor is operated in an off-null condition with a phase bias to produce a high-contrast responsivity that is linear in accumulated molecules but with a low background. The DOB linear responsivity is a factor of 20 larger than the reflectometric responsivity of planar thermal oxide.

© 2012 Optical Society of America

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  1. X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
    [CrossRef]
  2. D. D. Nolte, Rev. Sci. Instrum. 80, 101101 (2009).
    [CrossRef]
  3. D. D. Nolte, Optical Interferometry for Biology and Medicine (Springer, 2011).
  4. Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).
  5. J. B. Goh, P. L. Tam, R. W. Loo, and M. C. Goh, Anal. Biochem. 313, 262 (2003).
    [CrossRef]
  6. R. W. Loo, P. L. Tam, J. B. Goh, and M. C. Goh, Anal. Biochem. 337, 338 (2005).
    [CrossRef]
  7. R. M. Ostroff, D. Hopkins, A. B. Haeberli, W. Baouchi, and B. Polisky, Clin. Chem. 45, 1659 (1999).
  8. T. Gao and L. J. Rothberg, Anal. Chem. 79, 7589 (2007).
    [CrossRef]
  9. M. Zhao, X. Wang, and D. D. Nolte, Opt. Express 16, 7102 (2008).
    [CrossRef]
  10. E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
    [CrossRef]
  11. X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Opt. 46, 7836 (2007).
    [CrossRef]
  12. X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Phys. Lett. 93, 223904 (2008).
    [CrossRef]

2009 (1)

D. D. Nolte, Rev. Sci. Instrum. 80, 101101 (2009).
[CrossRef]

2008 (4)

X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
[CrossRef]

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Phys. Lett. 93, 223904 (2008).
[CrossRef]

M. Zhao, X. Wang, and D. D. Nolte, Opt. Express 16, 7102 (2008).
[CrossRef]

2007 (2)

T. Gao and L. J. Rothberg, Anal. Chem. 79, 7589 (2007).
[CrossRef]

X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Opt. 46, 7836 (2007).
[CrossRef]

2005 (1)

R. W. Loo, P. L. Tam, J. B. Goh, and M. C. Goh, Anal. Biochem. 337, 338 (2005).
[CrossRef]

2003 (1)

J. B. Goh, P. L. Tam, R. W. Loo, and M. C. Goh, Anal. Biochem. 313, 262 (2003).
[CrossRef]

1999 (1)

R. M. Ostroff, D. Hopkins, A. B. Haeberli, W. Baouchi, and B. Polisky, Clin. Chem. 45, 1659 (1999).

1991 (1)

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Appelqvist, R.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Baouchi, W.

R. M. Ostroff, D. Hopkins, A. B. Haeberli, W. Baouchi, and B. Polisky, Clin. Chem. 45, 1659 (1999).

Bergstein, D. A.

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Cabodi, M.

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Charlton, D.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Fan, X. D.

X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
[CrossRef]

Gao, T.

T. Gao and L. J. Rothberg, Anal. Chem. 79, 7589 (2007).
[CrossRef]

Gershoni, J. M.

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Goh, J. B.

R. W. Loo, P. L. Tam, J. B. Goh, and M. C. Goh, Anal. Biochem. 337, 338 (2005).
[CrossRef]

J. B. Goh, P. L. Tam, R. W. Loo, and M. C. Goh, Anal. Biochem. 313, 262 (2003).
[CrossRef]

Goh, M. C.

R. W. Loo, P. L. Tam, J. B. Goh, and M. C. Goh, Anal. Biochem. 337, 338 (2005).
[CrossRef]

J. B. Goh, P. L. Tam, R. W. Loo, and M. C. Goh, Anal. Biochem. 313, 262 (2003).
[CrossRef]

Goldberg, B. B.

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Gonzalez, R.

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Gustafson, E. K.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Haeberli, A. B.

R. M. Ostroff, D. Hopkins, A. B. Haeberli, W. Baouchi, and B. Polisky, Clin. Chem. 45, 1659 (1999).

Hopkins, D.

R. M. Ostroff, D. Hopkins, A. B. Haeberli, W. Baouchi, and B. Polisky, Clin. Chem. 45, 1659 (1999).

Lee, J.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Lin, C. I.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Loo, R. W.

R. W. Loo, P. L. Tam, J. B. Goh, and M. C. Goh, Anal. Biochem. 337, 338 (2005).
[CrossRef]

J. B. Goh, P. L. Tam, R. W. Loo, and M. C. Goh, Anal. Biochem. 313, 262 (2003).
[CrossRef]

Magginetti, P.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Needham, J. W.

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Nolte, D. D.

D. D. Nolte, Rev. Sci. Instrum. 80, 101101 (2009).
[CrossRef]

M. Zhao, X. Wang, and D. D. Nolte, Opt. Express 16, 7102 (2008).
[CrossRef]

X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Phys. Lett. 93, 223904 (2008).
[CrossRef]

X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Opt. 46, 7836 (2007).
[CrossRef]

D. D. Nolte, Optical Interferometry for Biology and Medicine (Springer, 2011).

Norton, R.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Ostroff, R. M.

R. M. Ostroff, D. Hopkins, A. B. Haeberli, W. Baouchi, and B. Polisky, Clin. Chem. 45, 1659 (1999).

Ozkumur, E.

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Polisky, B.

R. M. Ostroff, D. Hopkins, A. B. Haeberli, W. Baouchi, and B. Polisky, Clin. Chem. 45, 1659 (1999).

Rothberg, L. J.

T. Gao and L. J. Rothberg, Anal. Chem. 79, 7589 (2007).
[CrossRef]

Shopoua, S. I.

X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
[CrossRef]

Sun, Y. Z.

X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
[CrossRef]

Suter, J. D.

X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
[CrossRef]

Tam, P. L.

R. W. Loo, P. L. Tam, J. B. Goh, and M. C. Goh, Anal. Biochem. 337, 338 (2005).
[CrossRef]

J. B. Goh, P. L. Tam, R. W. Loo, and M. C. Goh, Anal. Biochem. 313, 262 (2003).
[CrossRef]

Teng, N.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Tsay, Y. G.

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

Unlu, M. S.

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Wang, X.

Wang, X. F.

X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Phys. Lett. 93, 223904 (2008).
[CrossRef]

X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Opt. 46, 7836 (2007).
[CrossRef]

White, I. M.

X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
[CrossRef]

Zhao, M.

Zhu, H. Y.

X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
[CrossRef]

Anal. Biochem. (2)

J. B. Goh, P. L. Tam, R. W. Loo, and M. C. Goh, Anal. Biochem. 313, 262 (2003).
[CrossRef]

R. W. Loo, P. L. Tam, J. B. Goh, and M. C. Goh, Anal. Biochem. 337, 338 (2005).
[CrossRef]

Anal. Chem. (1)

T. Gao and L. J. Rothberg, Anal. Chem. 79, 7589 (2007).
[CrossRef]

Anal. Chim. Acta (1)

X. D. Fan, I. M. White, S. I. Shopoua, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal. Chim. Acta 620, 8 (2008).
[CrossRef]

Appl. Opt. (1)

Appl. Phys. Lett. (1)

X. F. Wang, M. Zhao, and D. D. Nolte, Appl. Phys. Lett. 93, 223904 (2008).
[CrossRef]

Clin. Chem. (2)

Y. G. Tsay, C. I. Lin, J. Lee, E. K. Gustafson, R. Appelqvist, P. Magginetti, R. Norton, N. Teng, and D. Charlton, Clin. Chem. 37, 1502 (1991).

R. M. Ostroff, D. Hopkins, A. B. Haeberli, W. Baouchi, and B. Polisky, Clin. Chem. 45, 1659 (1999).

Opt. Express (1)

Proc. Natl. Acad. Sci. USA (1)

E. Ozkumur, J. W. Needham, D. A. Bergstein, R. Gonzalez, M. Cabodi, J. M. Gershoni, B. B. Goldberg, and M. S. Unlu, Proc. Natl. Acad. Sci. USA 105, 7988 (2008).
[CrossRef]

Rev. Sci. Instrum. (1)

D. D. Nolte, Rev. Sci. Instrum. 80, 101101 (2009).
[CrossRef]

Other (1)

D. D. Nolte, Optical Interferometry for Biology and Medicine (Springer, 2011).

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Figures (3)

Fig. 1.
Fig. 1.

DOB grating fabricated on thermal oxide on silicon. (a)  S i O 2 thicknesses on the ridges and the grooves are 205 and 140 nm, respectively; a pseudozero first-order diffraction is achieved when the grating is illuminated by normal-incidence 488 nm wavelength light. (b) A protein layer immobilized on both the ridges and the grooves increases the diffraction; the depth of the grooves is an essential parameter for a strong induced diffraction. (c) Map of linear responsivity per 1 nm protein as a function of ridge and groove thermal oxide thicknesses.

Fig. 2.
Fig. 2.

Common-path laser scanning BioCD system based on first-order diffraction from the DOB chip. The laser is not incident perpendicular to the disc, but it is tilted by half the diffraction angle. This permits the 1 st -order diffraction to counterpropagate through the pinhole, which serves as a spatial filter that automatically demodulates the spatial carrier wave of the grating.

Fig. 3.
Fig. 3.

(a) Optical micrograph of the gratings produced by photolithography. (b) IgG antibody spot immobilized on the grating scanned and automatically demodulated from the carrier frequency in the image. (c) and (d) Spot arrays created on the DOB grating and on a BioCD by a second round of photolithography with precise 1 nm SiO2 thickness to simulate protein spots and calibrate the DOB sensitivity. The linear responsivity is 50% per nm on the DOB and is 2.5% per nm on a reflectometric BioCD.

Equations (2)

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r 1 = r 1 + ( 1 + r 1 ) 2 i δ r 2 = r 2 + e i α ( 1 + r 2 e i α ) 2 i δ ,
I = | r 1 r 2 | 2 = I + η | B ( r 1 , h ) | 2 δ 2 + 2 η Im [ B ( r 1 , h ) * ε ] δ ,

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