Abstract

Detecting the existence of biomarkers is one of the most important issues in molecular diagnosis. This Letter presents a label-free decoding and detection method for biomarker tests based on hyperspectral imaging and interferometry. The decoding and detection results were extracted from a single hyperspectral image with different spectrum-to-thickness reconstructing algorithms, which made the testing procedure extremely fast and simple. The coding capacity of this method is more than 400, and the detection sensitivity can reach 2ng/mm2 without fluorescent labeling.

© 2013 Optical Society of America

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2012

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

A. Kussrow, C. S. Enders, and D. J. Bornhop, Anal. Chem. 84, 779 (2012).
[CrossRef]

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

2010

2009

C. Joo, E. Ozkumur, M. S. Unlu, and J. F. Boer, Biosens. Bioelectron. 25, 275 (2009).
[CrossRef]

2008

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

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

2004

S. M. Varnum, R. L. Woodbury, and R. C. Zangar, Methods Mol. Biol. 264, 161 (2004).
[CrossRef]

2002

Bergstein, D. A.

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

Boer, J. F.

C. Joo, E. Ozkumur, M. S. Unlu, and J. F. Boer, Biosens. Bioelectron. 25, 275 (2009).
[CrossRef]

Bornhop, D. J.

A. Kussrow, C. S. Enders, and D. J. Bornhop, Anal. Chem. 84, 779 (2012).
[CrossRef]

Cabodi, M.

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

Cheben, P.

Chen, S.

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

De Groot, P.

De Lega, X. C.

Delâge, A.

Deng, C.

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

Deng, T.

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

Densmore, A.

Enders, C. S.

A. Kussrow, C. S. Enders, and D. J. Bornhop, Anal. Chem. 84, 779 (2012).
[CrossRef]

Gershoni, J.

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

Goldberg, B. B.

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

Gonzalez, R.

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

Han, C.

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

Huang, G.

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

Janz, S.

Joo, C.

C. Joo, E. Ozkumur, M. S. Unlu, and J. F. Boer, Biosens. Bioelectron. 25, 275 (2009).
[CrossRef]

Kramer, J.

Kussrow, A.

A. Kussrow, C. S. Enders, and D. J. Bornhop, Anal. Chem. 84, 779 (2012).
[CrossRef]

Lapointe, J.

Li, Q.

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Li, W.

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

Li, X.

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Li, Y.

Lin, H.

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Liu, Q. Y.

Lopinski, G.

Lu, Y.

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Ma, R.

Needham, J.

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

Ozkumur, E.

C. Joo, E. Ozkumur, M. S. Unlu, and J. F. Boer, Biosens. Bioelectron. 25, 275 (2009).
[CrossRef]

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

Schmid, J. H.

Song, X.

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

Turzhitsky, M.

Unlu, M. S.

C. Joo, E. Ozkumur, M. S. Unlu, and J. F. Boer, Biosens. Bioelectron. 25, 275 (2009).
[CrossRef]

Ünlü, M. S.

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

Vachon, M.

Varnum, S. M.

S. M. Varnum, R. L. Woodbury, and R. C. Zangar, Methods Mol. Biol. 264, 161 (2004).
[CrossRef]

Wang, C.

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Wang, J.

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

Wang, T.

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Woodbury, R. L.

S. M. Varnum, R. L. Woodbury, and R. C. Zangar, Methods Mol. Biol. 264, 161 (2004).
[CrossRef]

Xu, D. X.

Xu, S.

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

Yang, X.

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

Zangar, R. C.

S. M. Varnum, R. L. Woodbury, and R. C. Zangar, Methods Mol. Biol. 264, 161 (2004).
[CrossRef]

Zhang, D.

Zhang, K.

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Zhou, X.

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Zhu, J.

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

Anal. Chem.

A. Kussrow, C. S. Enders, and D. J. Bornhop, Anal. Chem. 84, 779 (2012).
[CrossRef]

Analyst

Q. Li, K. Zhang, T. Wang, X. Zhou, J. Wang, C. Wang, H. Lin, X. Li, Y. Lu, and G. Huang, Analyst 137, 3760(2012).
[CrossRef]

Appl. Opt.

Biosens. Bioelectron.

C. Joo, E. Ozkumur, M. S. Unlu, and J. F. Boer, Biosens. Bioelectron. 25, 275 (2009).
[CrossRef]

J. Biomed. Opt.

G. Huang, C. Deng, J. Zhu, S. Xu, C. Han, X. Song, and X. Yang, J. Biomed. Opt. 13, 034006 (2008).
[CrossRef]

S. Chen, T. Deng, T. Wang, J. Wang, X. Li, W. Li, and G. Huang, J. Biomed. Opt. 17, 015005 (2012).
[CrossRef]

Methods Mol. Biol.

S. M. Varnum, R. L. Woodbury, and R. C. Zangar, Methods Mol. Biol. 264, 161 (2004).
[CrossRef]

Opt. Lett.

Proc. Natl. Acad. Sci. USA

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

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Figures (5)

Fig. 1.
Fig. 1.

Decoding the bioprobes and detecting biomarkers with interferometry.

Fig. 2.
Fig. 2.

Interference spectrum for different thicknesses of SiO2 film and its fringe location measurement result. Orders for peaks and valleys are marked in the graph.

Fig. 3.
Fig. 3.

(a) Relationship between M(Δ) and Δ. (b) Comparison of the thicknesses reconstructed from a hyperspectral image and measured by an ellipsometer.

Fig. 4.
Fig. 4.

Comparison between spectrum-shifting and fringe location algorithm. (a) and (b) are the thicknesses resolved from a hyperspectral image without pixel overlapping. (c) and (d) are the thicknesses resolved from a hyperspectral image with pixel overlapping. (e)–(g) are reflective spectrums of pixels in the hyperspectral image.

Fig. 5.
Fig. 5.

Workflow for probe decoding and biomarker detection. (a) Mix the chip and sample serum, incubate, and capture a hyperspectral image. (b) The coding information extracted by the fringe location algorithm. (c) The biomarker binding information extracted by the spectrum-shifting algorithm (background suppressed). (d) Test result generated by merging the coding information and the binding information.

Equations (8)

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

d=K×λpeakK2n=k0.5×λvalleyk2n.
Δavr=pixelF(S⃗)·dxdypixeldxdy=F(pixelS⃗·dxdy)pixeldxdy.
S(λ)=|I1(λ)|2+|I2(λ)|22|I1(λ)||I2(λ)|cos(4πndλ),
|S(λ)|d=d0+ΔS(λ)|d=d0|=2|I1(λ)|·|I2(λ)|·|[cos(4πnd0λ)cos(4πnd0+Δλ)]|=4|I1(λ)||I2(λ)|·|sin(4πnd0λ+2πnΔλ)·sin(2πnΔλ)|.
(S(λ)|d=d1S(λ)|d=d0)·dλ=4|I1(λ)||I2(λ)|dλ·|sin(4πnd0λ+2πnΔλ)|dλ·|sin(2πnΔλ)|dλ.
M(Δ)P·Δ(|Δ|<50nm).
(S(λ)|d=d0+ΔS(λ)|d=d0)·dλC1C2P·Δ,
Δ=S⃗|d=d0+ΔS⃗|d=d0C1C2P.

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