Abstract

Here we report a low-cost and simple wide field-of-view (FOV) on-chip fluorescence-imaging platform, termed fluorescence Talbot microscopy (FTM), which utilizes the Talbot self-imaging effect to enable efficient fluorescence imaging over a large and directly scalable FOV. The FTM prototype has a resolution of 1.2 μm and an FOV of 3.9mm×3.5mm. We demonstrate the imaging capability of FTM on fluorescently labeled breast cancer cells (SK-BR-3) and human embryonic kidney 293 (HEK) cells expressing green fluorescent protein.

© 2012 Optical Society of America

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    [CrossRef]

2012 (2)

S. A. Arpali, C. Arpali, A. Coskun, H. H. Chiang, and A. Ozcan, Lab Chip 12, 4968 (2012).
[CrossRef]

A. Orth and K. Crozier, Opt. Express 20, 13522 (2012).
[CrossRef]

2011 (4)

J. G. Wu, G. A. Zheng, Z. Li, and C. H. Yang, Opt. Lett. 36, 2179 (2011).
[CrossRef]

A. F. Coskun, I. Sencan, T. W. Su, and A. Ozcan, Analyst 136, 3512 (2011).
[CrossRef]

S. Pang, C. Han, L. M. Lee, and C. H. Yang, Lab Chip 11, 3698 (2011).
[CrossRef]

G. A. Zheng, S. A. Lee, Y. Antebi, M. B. Elowitz, and C. H. Yang, Proc. Natl. Acad. Sci. USA 108, 16889 (2011).
[CrossRef]

2009 (1)

S. R. Collins, J. S. Weissman, and N. J. Krogan, Nat. Methods 6, 721 (2009).
[CrossRef]

2008 (1)

K. H. Chung, M. M. Crane, and H. Lu, Nat. Methods 5, 637 (2008).
[CrossRef]

2006 (1)

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

1971 (1)

A. W. Lohmann and D. E. Silva, Opt. Commun. 2, 413 (1971).
[CrossRef]

1967 (1)

Antebi, Y.

G. A. Zheng, S. A. Lee, Y. Antebi, M. B. Elowitz, and C. H. Yang, Proc. Natl. Acad. Sci. USA 108, 16889 (2011).
[CrossRef]

Arpali, C.

S. A. Arpali, C. Arpali, A. Coskun, H. H. Chiang, and A. Ozcan, Lab Chip 12, 4968 (2012).
[CrossRef]

Arpali, S. A.

S. A. Arpali, C. Arpali, A. Coskun, H. H. Chiang, and A. Ozcan, Lab Chip 12, 4968 (2012).
[CrossRef]

Chiang, H. H.

S. A. Arpali, C. Arpali, A. Coskun, H. H. Chiang, and A. Ozcan, Lab Chip 12, 4968 (2012).
[CrossRef]

Chung, K. H.

K. H. Chung, M. M. Crane, and H. Lu, Nat. Methods 5, 637 (2008).
[CrossRef]

Collins, S. R.

S. R. Collins, J. S. Weissman, and N. J. Krogan, Nat. Methods 6, 721 (2009).
[CrossRef]

Coskun, A.

S. A. Arpali, C. Arpali, A. Coskun, H. H. Chiang, and A. Ozcan, Lab Chip 12, 4968 (2012).
[CrossRef]

Coskun, A. F.

A. F. Coskun, I. Sencan, T. W. Su, and A. Ozcan, Analyst 136, 3512 (2011).
[CrossRef]

Crane, M. M.

K. H. Chung, M. M. Crane, and H. Lu, Nat. Methods 5, 637 (2008).
[CrossRef]

Crozier, K.

Ellenberg, J.

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

Elowitz, M. B.

G. A. Zheng, S. A. Lee, Y. Antebi, M. B. Elowitz, and C. H. Yang, Proc. Natl. Acad. Sci. USA 108, 16889 (2011).
[CrossRef]

Erfle, H.

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

Goodman, J. W.

J. W. Goodman, Introduction to Fourier Optics (Roberts, 1996).

Han, C.

S. Pang, C. Han, L. M. Lee, and C. H. Yang, Lab Chip 11, 3698 (2011).
[CrossRef]

Held, M.

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

Krogan, N. J.

S. R. Collins, J. S. Weissman, and N. J. Krogan, Nat. Methods 6, 721 (2009).
[CrossRef]

Lee, L. M.

S. Pang, C. Han, L. M. Lee, and C. H. Yang, Lab Chip 11, 3698 (2011).
[CrossRef]

Lee, S. A.

G. A. Zheng, S. A. Lee, Y. Antebi, M. B. Elowitz, and C. H. Yang, Proc. Natl. Acad. Sci. USA 108, 16889 (2011).
[CrossRef]

Li, Z.

Liebel, U.

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

Lohmann, A. W.

A. W. Lohmann and D. E. Silva, Opt. Commun. 2, 413 (1971).
[CrossRef]

Lu, H.

K. H. Chung, M. M. Crane, and H. Lu, Nat. Methods 5, 637 (2008).
[CrossRef]

Montgomery, W. D.

Neumann, B.

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

Orth, A.

Ozcan, A.

S. A. Arpali, C. Arpali, A. Coskun, H. H. Chiang, and A. Ozcan, Lab Chip 12, 4968 (2012).
[CrossRef]

A. F. Coskun, I. Sencan, T. W. Su, and A. Ozcan, Analyst 136, 3512 (2011).
[CrossRef]

Pang, S.

S. Pang, C. Han, L. M. Lee, and C. H. Yang, Lab Chip 11, 3698 (2011).
[CrossRef]

Pepperkok, R.

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

Rogers, P.

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

Sencan, I.

A. F. Coskun, I. Sencan, T. W. Su, and A. Ozcan, Analyst 136, 3512 (2011).
[CrossRef]

Silva, D. E.

A. W. Lohmann and D. E. Silva, Opt. Commun. 2, 413 (1971).
[CrossRef]

Su, T. W.

A. F. Coskun, I. Sencan, T. W. Su, and A. Ozcan, Analyst 136, 3512 (2011).
[CrossRef]

Weissman, J. S.

S. R. Collins, J. S. Weissman, and N. J. Krogan, Nat. Methods 6, 721 (2009).
[CrossRef]

Wu, J. G.

Yang, C. H.

J. G. Wu, G. A. Zheng, Z. Li, and C. H. Yang, Opt. Lett. 36, 2179 (2011).
[CrossRef]

S. Pang, C. Han, L. M. Lee, and C. H. Yang, Lab Chip 11, 3698 (2011).
[CrossRef]

G. A. Zheng, S. A. Lee, Y. Antebi, M. B. Elowitz, and C. H. Yang, Proc. Natl. Acad. Sci. USA 108, 16889 (2011).
[CrossRef]

Zheng, G. A.

G. A. Zheng, S. A. Lee, Y. Antebi, M. B. Elowitz, and C. H. Yang, Proc. Natl. Acad. Sci. USA 108, 16889 (2011).
[CrossRef]

J. G. Wu, G. A. Zheng, Z. Li, and C. H. Yang, Opt. Lett. 36, 2179 (2011).
[CrossRef]

Analyst (1)

A. F. Coskun, I. Sencan, T. W. Su, and A. Ozcan, Analyst 136, 3512 (2011).
[CrossRef]

J. Opt. Soc. Am. (1)

Lab Chip (2)

S. A. Arpali, C. Arpali, A. Coskun, H. H. Chiang, and A. Ozcan, Lab Chip 12, 4968 (2012).
[CrossRef]

S. Pang, C. Han, L. M. Lee, and C. H. Yang, Lab Chip 11, 3698 (2011).
[CrossRef]

Nat. Methods (3)

S. R. Collins, J. S. Weissman, and N. J. Krogan, Nat. Methods 6, 721 (2009).
[CrossRef]

B. Neumann, M. Held, U. Liebel, H. Erfle, P. Rogers, R. Pepperkok, and J. Ellenberg, Nat. Methods 3, 385 (2006).
[CrossRef]

K. H. Chung, M. M. Crane, and H. Lu, Nat. Methods 5, 637 (2008).
[CrossRef]

Opt. Commun. (1)

A. W. Lohmann and D. E. Silva, Opt. Commun. 2, 413 (1971).
[CrossRef]

Opt. Express (1)

Opt. Lett. (1)

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

G. A. Zheng, S. A. Lee, Y. Antebi, M. B. Elowitz, and C. H. Yang, Proc. Natl. Acad. Sci. USA 108, 16889 (2011).
[CrossRef]

Other (1)

J. W. Goodman, Introduction to Fourier Optics (Roberts, 1996).

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Figures (4)

Fig. 1.
Fig. 1.

FTM operating principle. (a) The schematic diagram of the FTM system: the microlens grid creates the original focal grid at Zf. The sample on a filter-coated CMOS sensor is located at the Talbot length ZT away from the original focal grid. (b) As the plane wave is tilted by a small angle θ, the Talbot focal grid laterally shifts by Δ. (c) Scan and reconstruction method for the full-field image.

Fig. 2.
Fig. 2.

(a) FTM prototype: the filter coated CMOS sensor is placed beneath the Talbot illuminator. (b) Schematics of the Talbot illuminator (top view). L1, fiber collimator f=13mm; L2, f=10mm; L3, f=50mm; M, 45° mirrors; MLG, microlens grid; PBS, polarizing beam splitter; ¼WP, quarter-wave plate.

Fig. 3.
Fig. 3.

(a) Scalar wave simulations. (a1), (a2) First Talbot focal grid with incident angle of 0 rad and 4.1 mrad, respectively. (a3), (a4) Intensity profile of the spot specified by the square in (a1) and (a2), respectively. (b) Resolution target with the linewidth from 3.0 to 1.0 μm: (b1) an FIB image of the resolution target, (b2) the FTM image. (c) Cross-section line trace of the (c1) horizontal and (c2) vertical marks of 1.2 μm.

Fig. 4.
Fig. 4.

Full-field FTM images. (a) HEK cells expressing GFP in nuclei. (b) Magnified view of (a) corresponding to the FOV of a 20× microscope objective. (c), (d) SK-BR-3 cells with Her2 marker in the membrane labeled by Qdot625. (e), (f) Images of the same sample by on-chip detection using (e) uniform illumination (f) FTM, and (g) a conventional microscope with a 20× objective.

Equations (1)

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Δ=2d2tan(θ)/λ.

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