Abstract

We combine the differential height measurement concept with structured illumination microscopy to develop wide-field optical nanoprofilometry. Sub-diffraction-limit lateral resolution and axially sectioning imaging are achieved with structured illumination using a liquid-crystal spatial light modulator. As the sample surface is placed into the linear region of the sectioning axial response curve, the signal change owing to topographic variations provides nanometer depth sensitivity. The lateral resolution and the depth profiling accuracy are about 0.3 wavelengths and 6 nm, respectively. Depth profiling on solid-state specimens and label-free superresolution imaging of living cells are demonstrated.

© 2009 Optical Society of America

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J.-Y. Lin, R.-P. Huang, P.-S. Tsai, and C.-H. Lee, J. Opt. A 11, 015301 (2009).
[CrossRef]

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M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

2007

I. Ilev, R. Waynant, I. Gannot, and A. Gandjbakhche, Rev. Sci. Instrum. 78, 093703 (2007).
[CrossRef] [PubMed]

2006

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2003

J. K. H. Horber and M. J. Miles, Science 302, 1002 (2003).
[CrossRef] [PubMed]

2002

2001

J. T. Frohn, H. F. Knapp, and A. Stemmer, Opt. Lett. 26, 828 (2001).
[CrossRef]

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

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J. T. Frohn, H. F. Knapp, and A. Stemmer, Proc. Natl. Acad. Sci. USA 97, 7232 (2000).
[CrossRef] [PubMed]

M. G. L. Gustafsson, J. Microsc. 198, 82 (2000).
[CrossRef] [PubMed]

1997

Agard, D. A.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

Agero, U.

J. C. Neto, U. Agero, R. T. Gazzinelli, and O. N. Mesquita, Biophys. J. 91, 1108 (2006).
[CrossRef]

Ando, T.

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

Cande, W. Z.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

Carlton, P. M.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

Chang, Y. -L.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Chen, H. -C.

Chen, J. J. W.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Dasari, R. R.

Feld, M. S.

Frohn, J. T.

J. T. Frohn, H. F. Knapp, and A. Stemmer, Opt. Lett. 26, 828 (2001).
[CrossRef]

J. T. Frohn, H. F. Knapp, and A. Stemmer, Proc. Natl. Acad. Sci. USA 97, 7232 (2000).
[CrossRef] [PubMed]

Gandjbakhche, A.

I. Ilev, R. Waynant, I. Gannot, and A. Gandjbakhche, Rev. Sci. Instrum. 78, 093703 (2007).
[CrossRef] [PubMed]

Gannot, I.

I. Ilev, R. Waynant, I. Gannot, and A. Gandjbakhche, Rev. Sci. Instrum. 78, 093703 (2007).
[CrossRef] [PubMed]

Gazzinelli, R. T.

J. C. Neto, U. Agero, R. T. Gazzinelli, and O. N. Mesquita, Biophys. J. 91, 1108 (2006).
[CrossRef]

Golubovskaya, I. N.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

Gustafsson, M. G. L.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

M. G. L. Gustafsson, J. Microsc. 198, 82 (2000).
[CrossRef] [PubMed]

Hong, T. -M.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Horber, J. K. H.

J. K. H. Horber and M. J. Miles, Science 302, 1002 (2003).
[CrossRef] [PubMed]

Huang, R. -P.

J.-Y. Lin, R.-P. Huang, P.-S. Tsai, and C.-H. Lee, J. Opt. A 11, 015301 (2009).
[CrossRef]

Ikeda, T.

Ilev, I.

I. Ilev, R. Waynant, I. Gannot, and A. Gandjbakhche, Rev. Sci. Instrum. 78, 093703 (2007).
[CrossRef] [PubMed]

Juskaitis, R.

Knapp, H. F.

J. T. Frohn, H. F. Knapp, and A. Stemmer, Opt. Lett. 26, 828 (2001).
[CrossRef]

J. T. Frohn, H. F. Knapp, and A. Stemmer, Proc. Natl. Acad. Sci. USA 97, 7232 (2000).
[CrossRef] [PubMed]

Kodera, N.

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

Lee, C. -H.

Lee, Y. -C.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Lin, J. -Y.

Lin, W. -C.

Mesquita, O. N.

J. C. Neto, U. Agero, R. T. Gazzinelli, and O. N. Mesquita, Biophys. J. 91, 1108 (2006).
[CrossRef]

Miles, M. J.

J. K. H. Horber and M. J. Miles, Science 302, 1002 (2003).
[CrossRef] [PubMed]

Miyagi, A.

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

Mong, H. -Y.

Neil, M. A. A.

Neto, J. C.

J. C. Neto, U. Agero, R. T. Gazzinelli, and O. N. Mesquita, Biophys. J. 91, 1108 (2006).
[CrossRef]

Peck, K.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Popescu, G.

Sedat, J. W.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

Shao, L.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

Shih, J. -Y.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Stemmer, A.

J. T. Frohn, H. F. Knapp, and A. Stemmer, Opt. Lett. 26, 828 (2001).
[CrossRef]

J. T. Frohn, H. F. Knapp, and A. Stemmer, Proc. Natl. Acad. Sci. USA 97, 7232 (2000).
[CrossRef] [PubMed]

Taniguchi, M.

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

Tsai, P. -S.

J.-Y. Lin, R.-P. Huang, P.-S. Tsai, and C.-H. Lee, J. Opt. A 11, 015301 (2009).
[CrossRef]

Uchihashi, T.

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

Wang, C. -C.

Wang, C. J. R.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

Wang, J.

C.-H. Lee and J. Wang, Opt. Commun. 135, 233 (1997).
[CrossRef]

Waynant, R.

I. Ilev, R. Waynant, I. Gannot, and A. Gandjbakhche, Rev. Sci. Instrum. 78, 093703 (2007).
[CrossRef] [PubMed]

Wilson, T.

Wu, C. -W.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Yamamoto, D.

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

Yamashita, H.

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

Yang, P. -C.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Yang, S. -C.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Yu, C. -J.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Yuan, A.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

Biophys. J.

J. C. Neto, U. Agero, R. T. Gazzinelli, and O. N. Mesquita, Biophys. J. 91, 1108 (2006).
[CrossRef]

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, Biophys. J. 94, 4957 (2008).
[CrossRef] [PubMed]

Eur. J. Phys.

T. Ando, T. Uchihashi, N. Kodera, D. Yamamoto, A. Miyagi, M. Taniguchi, and H. Yamashita, Eur. J. Phys. 456, 211 (2008).
[CrossRef]

J. Microsc.

M. G. L. Gustafsson, J. Microsc. 198, 82 (2000).
[CrossRef] [PubMed]

J. Natl. Cancer Inst.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, J. Natl. Cancer Inst. 93, 1392 (2001).
[CrossRef] [PubMed]

J. Opt. A

J.-Y. Lin, R.-P. Huang, P.-S. Tsai, and C.-H. Lee, J. Opt. A 11, 015301 (2009).
[CrossRef]

Opt. Commun.

C.-H. Lee and J. Wang, Opt. Commun. 135, 233 (1997).
[CrossRef]

Opt. Express

Opt. Lett.

Proc. Natl. Acad. Sci. USA

J. T. Frohn, H. F. Knapp, and A. Stemmer, Proc. Natl. Acad. Sci. USA 97, 7232 (2000).
[CrossRef] [PubMed]

Rev. Sci. Instrum.

I. Ilev, R. Waynant, I. Gannot, and A. Gandjbakhche, Rev. Sci. Instrum. 78, 093703 (2007).
[CrossRef] [PubMed]

Science

J. K. H. Horber and M. J. Miles, Science 302, 1002 (2003).
[CrossRef] [PubMed]

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Figures (4)

Fig. 1
Fig. 1

(a) (i) and (ii) Spectra of the sectioned images as depicted in Eq. (2). We cut the spectra along the ±45° dashed lines, pick the left and right portions in (i), top and bottom portions in (ii), and assemble them together to obtain the enlarged OTF in (iii). The dashed circle represents the original OTF. (b) Measured linear region of the axial response curve.

Fig. 2
Fig. 2

(a) Conventional bright-field image of four 80 nm gold particles on glass substrate. (b) Superresolution image obtained by using the enlarged OTF in Fig. 1a. (c) Line profiles along the dashed–dotted lines in (a) (gray solid curve) and (b) (black solid curve). (d) Line profiles along the dashed lines in (a) (gray solid curve) and (b) (black solid curve). The dashed curve is the summation of two Airy formulas separated by 190 nm.

Fig. 3
Fig. 3

(a) AFM topography of a gold wire on silicon substrate. (b) Bright-field image of the wire. (c) Topography measured by SINAP. The gray levels represent a 0–200 nm height span. A super-Gaussian low-pass filter is used to suppress the graining noise in the raw image (d). (e) Line profiles of the gold wire from (a) (dashed curve), (b) (gray solid curve), and (c) (black solid curve).

Fig. 4
Fig. 4

Label-free observation of filopodium dynamics of a lung cancer cell. (a) Conventional bright-field reflection image. (b) and (d) are magnified views of the region in the dashed square in (a). (c) and (e) are SINAP images. The arrows indicate two thin filopodia that appear in consecutive 2 s.

Tables (1)

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Table 1 Comparisons between SINAP and Related Techniques

Equations (2)

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

M ϕ m n = 2 M 0 + M X e i 2 m π / 3 + M X + e i 2 m π / 3 + M Y e i 2 n π / 3 + M Y + e i 2 n π / 3 ,
M X ( Y ) = 1 3 | M ϕ 00 + M ϕ 10 ( 01 ) e i 2 π / 3 + M ϕ 20 ( 02 ) e ± i 2 π / 3 | .

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