Abstract

The use of aplanatic solid immersion lenses (ASILs) made of high-refractive-index optical materials provides a route to wide-field high-resolution optical microscopy. Structured illumination microscopy (SIM) can double the spatial bandwidth of a microscope to also achieve high-resolution imaging. We investigate the combination of ASILs and SIM in fluorescence microscopy, which we call structured illumination solid immersion fluorescence microscopy (SISIM), to pursue a microscopic system with very large NA and high lateral resolution. We demonstrate that the combination can produce a wide-field high-resolution microscopic system with bandwidth corresponding to an NA of 3. Future developments of the SISIM system to make it achieve even higher resolution are proposed.

© 2011 Optical Society of America

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References

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    [CrossRef]
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    [CrossRef]
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    [CrossRef] [PubMed]

2010 (2)

2008 (1)

2006 (1)

2000 (2)

M. G. L. Gustafsson, D. A. Agard, and J. W. Sedat. Proc. SPIE 3919, 141 (2000).
[CrossRef]

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

1999 (1)

R. Heintzmann and C. Cremer, Proc. SPIE 3568, 185 (1999).
[CrossRef]

1994 (1)

B. D. Terris, H. J. Mamin, D. Rugar, W. R. Studenmund, and G. S. Kino, Appl. Phys. Lett. 65, 388 (1994).
[CrossRef]

1990 (1)

S. M. Mansfield and G. S. Kino, Appl. Phys. Lett. 57, 2615 (1990).
[CrossRef]

1989 (1)

Agard, D. A.

M. G. L. Gustafsson, D. A. Agard, and J. W. Sedat. Proc. SPIE 3919, 141 (2000).
[CrossRef]

Axelrod, D.

Benedetti, P. A.

Chuang, C.-J.

Cremer, C.

R. Heintzmann and C. Cremer, Proc. SPIE 3568, 185 (1999).
[CrossRef]

Gustafsson, M. G. L.

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

M. G. L. Gustafsson, D. A. Agard, and J. W. Sedat. Proc. SPIE 3919, 141 (2000).
[CrossRef]

Heintzmann, R.

Hsu, K.

Kino, G. S.

B. D. Terris, H. J. Mamin, D. Rugar, W. R. Studenmund, and G. S. Kino, Appl. Phys. Lett. 65, 388 (1994).
[CrossRef]

S. M. Mansfield and G. S. Kino, Appl. Phys. Lett. 57, 2615 (1990).
[CrossRef]

Liu, S.

Mamin, H. J.

B. D. Terris, H. J. Mamin, D. Rugar, W. R. Studenmund, and G. S. Kino, Appl. Phys. Lett. 65, 388 (1994).
[CrossRef]

Mansfield, S. M.

S. M. Mansfield and G. S. Kino, Appl. Phys. Lett. 57, 2615 (1990).
[CrossRef]

Pitter, M. C.

Rugar, D.

B. D. Terris, H. J. Mamin, D. Rugar, W. R. Studenmund, and G. S. Kino, Appl. Phys. Lett. 65, 388 (1994).
[CrossRef]

Sedat, J. W.

M. G. L. Gustafsson, D. A. Agard, and J. W. Sedat. Proc. SPIE 3919, 141 (2000).
[CrossRef]

See, C. W.

Somekh, M. G.

Stout, A. L.

Studenmund, W. R.

B. D. Terris, H. J. Mamin, D. Rugar, W. R. Studenmund, and G. S. Kino, Appl. Phys. Lett. 65, 388 (1994).
[CrossRef]

Terris, B. D.

B. D. Terris, H. J. Mamin, D. Rugar, W. R. Studenmund, and G. S. Kino, Appl. Phys. Lett. 65, 388 (1994).
[CrossRef]

Wang, L.

L. Wang, M. C. Pitter, and M. G. Somekh, Appl. Opt. 49, 6160 (2010).
[CrossRef]

L. Wang, “High-resolution structured illumination solid immersion fluorescence microscopy,” Ph.D thesis (The University of Nottingham, 2010).

Appl. Opt. (4)

Appl. Phys. Lett. (2)

S. M. Mansfield and G. S. Kino, Appl. Phys. Lett. 57, 2615 (1990).
[CrossRef]

B. D. Terris, H. J. Mamin, D. Rugar, W. R. Studenmund, and G. S. Kino, Appl. Phys. Lett. 65, 388 (1994).
[CrossRef]

J. Microsc. (1)

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

J. Opt. Soc. Am. A (1)

Proc. SPIE (2)

R. Heintzmann and C. Cremer, Proc. SPIE 3568, 185 (1999).
[CrossRef]

M. G. L. Gustafsson, D. A. Agard, and J. W. Sedat. Proc. SPIE 3919, 141 (2000).
[CrossRef]

Other (1)

L. Wang, “High-resolution structured illumination solid immersion fluorescence microscopy,” Ph.D thesis (The University of Nottingham, 2010).

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Figures (5)

Fig. 1
Fig. 1

Schematic of the SISIM system. The ASIL configuration is shown in the enlarged inset.

Fig. 2
Fig. 2

Structured illumination patterns (small insets, cropped to 2 μm × 2 μm ) and their BFP images orientated at azimuthal angle of (a)  0 ° , (b)  120 ° , and (c)  240 ° . The ± 1 order diffraction beams from the grating spots are indicated by the arrows.

Fig. 3
Fig. 3

20 nm fluorescent bead image obtained with the SISIM system (left) and the simulated image from a 3 NA system (right) at an emission wavelength of 670 nm .

Fig. 4
Fig. 4

2D correlation coefficient data and cubic fitting curve between the experimental SISIM image and a series of simulated images of a 20 nm bead under different NA at 670 nm ; the peak value is found at ( 3.02 ± 0.01 , 0.8639 ± 0.0005 ).

Fig. 5
Fig. 5

Images of a field of 20 nm fluorescent beads obtained with (a), (c) SIF and (b), (d) SISIM. Scale bar: 0.5 μm . 3D surface plots of the beads close to each other in the middle of the images are shown in the small insets (area: 1000 nm × 1000 nm ).

Equations (1)

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i s ( x ) = { [ 1 + 2 cos ( 2 π m g x ) ] i 1 + [ 1 2 sin ( 2 π m g x ) ] i 2 + [ 1 2 cos ( 2 π m g x ) ] i 3 + [ 1 + 2 sin ( 2 π m g x ) ] i 4 } ,

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