Abstract

A self-calibration technique for lensless compact chip-microscopes based on inline holography with pinhole illumination is presented. The pinhole illumination wave acts as reference and is needed for the reconstruction process. This reference wave is assumed to be spherical, so that its phase is already determined by the position of the pinhole in relation to the image sensor. It is shown that the reconstructed spatial resolution is strongly dependent on the estimation for the pinhole to sensor distance. A precision in the range of tens of microns was reached for microscopic imaging with a spatial resolution in the range of one micron. Therefore additional reference crosses are prepared lithographically on the sample holder. The hologram, which contains the optical information about the sample as well as the reference crosses, is used for calibration and image reconstruction at the same time. The presented technique was tested to allow the reconstruction of a spatial resolution corresponding to the limit of detection apertures of about 0.66. The technique was applied to holograms of test beads and blood smear samples.

© 2014 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. D. Gabor, Nature 161, 777 (1948).
    [CrossRef]
  2. W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, Proc. Natl. Acad. Sci. USA 98, 11301 (2001).
    [CrossRef]
  3. J. Garcia-Sucerquia, W. Xu, S. K. Jericho, P. Klages, M. H. Jericho, and H. J. Kreuzer, Appl. Opt. 45, 836 (2006).
    [CrossRef]
  4. D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
    [CrossRef]
  5. M. Kanka, R. Riesenberg, P. Petruck, and C. Graulig, Opt. Lett. 36, 3651 (2011).
    [CrossRef]
  6. Z. Gorocs and A. Ozcan, IEEE Rev. Biomed. Eng. 6, 29 (2013).
  7. A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
    [CrossRef]
  8. A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).
  9. V. Micó and Z. Zalevsky, J. Biomed. Opt. 15, 046027 (2010).
    [CrossRef]
  10. M. Kanka, A. Wuttig, C. Graulig, and R. Riesenberg, Opt. Lett. 35, 217 (2010).
    [CrossRef]
  11. A. Wuttig, M. Kanka, H. J. Kreuzer, and R. Riesenberg, Opt. Express 18, 27036 (2010).
    [CrossRef]

2013

Z. Gorocs and A. Ozcan, IEEE Rev. Biomed. Eng. 6, 29 (2013).

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).

2012

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

2011

2010

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

V. Micó and Z. Zalevsky, J. Biomed. Opt. 15, 046027 (2010).
[CrossRef]

M. Kanka, A. Wuttig, C. Graulig, and R. Riesenberg, Opt. Lett. 35, 217 (2010).
[CrossRef]

A. Wuttig, M. Kanka, H. J. Kreuzer, and R. Riesenberg, Opt. Express 18, 27036 (2010).
[CrossRef]

2006

2001

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, Proc. Natl. Acad. Sci. USA 98, 11301 (2001).
[CrossRef]

1948

D. Gabor, Nature 161, 777 (1948).
[CrossRef]

Coskun, A. F.

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

Gabor, D.

D. Gabor, Nature 161, 777 (1948).
[CrossRef]

Garcia-Sucerquia, J.

Gorocs, Z.

Z. Gorocs and A. Ozcan, IEEE Rev. Biomed. Eng. 6, 29 (2013).

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

Graulig, C.

Greenbaum, A.

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

Isikman, S. O.

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

Jericho, M. H.

J. Garcia-Sucerquia, W. Xu, S. K. Jericho, P. Klages, M. H. Jericho, and H. J. Kreuzer, Appl. Opt. 45, 836 (2006).
[CrossRef]

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, Proc. Natl. Acad. Sci. USA 98, 11301 (2001).
[CrossRef]

Jericho, S. K.

Kanka, M.

Khademhosseinieh, B.

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).

Klages, P.

Kreuzer, H. J.

Luo, W.

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

Meinertzhagen, I. A.

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, Proc. Natl. Acad. Sci. USA 98, 11301 (2001).
[CrossRef]

Micó, V.

V. Micó and Z. Zalevsky, J. Biomed. Opt. 15, 046027 (2010).
[CrossRef]

Mudanyali, O.

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

Ozcan, A.

Z. Gorocs and A. Ozcan, IEEE Rev. Biomed. Eng. 6, 29 (2013).

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

Oztoprak, C.

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

Petruck, P.

Riesenberg, R.

Sencan, I.

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

Su, T.-W.

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

Tseng, D.

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

Wuttig, A.

Xu, W.

J. Garcia-Sucerquia, W. Xu, S. K. Jericho, P. Klages, M. H. Jericho, and H. J. Kreuzer, Appl. Opt. 45, 836 (2006).
[CrossRef]

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, Proc. Natl. Acad. Sci. USA 98, 11301 (2001).
[CrossRef]

Xue, L.

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

Yaglidere, O.

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

Zalevsky, Z.

V. Micó and Z. Zalevsky, J. Biomed. Opt. 15, 046027 (2010).
[CrossRef]

Appl. Opt.

IEEE Rev. Biomed. Eng.

Z. Gorocs and A. Ozcan, IEEE Rev. Biomed. Eng. 6, 29 (2013).

J. Biomed. Opt.

V. Micó and Z. Zalevsky, J. Biomed. Opt. 15, 046027 (2010).
[CrossRef]

Lab Chip

D. Tseng, O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan, Lab Chip 10, 1787 (2010).
[CrossRef]

Nat. Methods

A. Greenbaum, W. Luo, T.-W. Su, Z. Gorocs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, Nat. Methods 9, 889 (2012).
[CrossRef]

Nature

D. Gabor, Nature 161, 777 (1948).
[CrossRef]

Opt. Express

Opt. Lett.

Proc. Natl. Acad. Sci. USA

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, Proc. Natl. Acad. Sci. USA 98, 11301 (2001).
[CrossRef]

Sci. Rep.

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, Sci. Rep. 3, 1717 (2013).

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (6)

Fig. 1.
Fig. 1.

Sketch of the experimental setup. A customary cover slip for microscopy acts as a sample holder. On its surface an array of small reference crosses was fixed lithographically.

Fig. 2.
Fig. 2.

Flowchart for determination of optimal spherical reference wavefront.

Fig. 3.
Fig. 3.

Influence of wrongly chosen pinhole distances to the spatial resolution. The simulated pinhole distance is 4 mm. The test sample (A) with a distance of 400 μm to the pinhole consists of two crosses with a distance of 200 μm to each other and an elliptical resolution test chart. The pinhole distances used for reconstruction are (B) 3.92 mm, (C) 3.96 mm, (D) 4 mm, (E) 4.04 mm, and (F) 4.08 mm.

Fig. 4.
Fig. 4.

Conventional reconstructed red blood cells on a sample holder (170 μm thick cover slip). The phase of the spherical reference wave was estimated by the pinhole position. The reconstructed red blood cells are blurred (C, D) because a wrongly assumed pinhole-to-sensor distance. This agrees with the also imaged distance between two reference crosses of 222.8 μm (A, B) instead of the design distance of 200 μm.

Fig. 5.
Fig. 5.

Result of the iterative optimization technique using reference crosses on a sample holder. After three iterations the imaged cross-to-cross distance converged to the real value. The red blood cells are imaged in their natural size and with an detection NA of 0.66 (C, D).

Fig. 6.
Fig. 6.

Improvement of the spatial resolution by the presented technique. A hologram of micro beads (2 μm) on a sample holder with additional reference crosses (distance 200 μm to each other) was recorded. The first approximation for the reference phase leads to a blurred wrongly scaled image (A, B). Using the presented technique, all beads are resolved (D) and the imaged cross-to-cross distance equals the real value.

Equations (9)

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

I=|u+v|2=|u|2+uv*+vu*+|v|2,
ϕexp[ikr]v/|v|,
u˜Cϕu,
o˜TSP[u˜;f],
u˜(z)=Cϕ(z).
f[1f0+1z1z0]1.
z(n+1)d0d(n)z(n).
f(n+1)[1f(n)+1z(n+1)1z(n)]1.
|d(n)/d01|>ϵ

Metrics