## Compact and portable low-coherence interferometer with off-axis geometry for quantitative phase microscopy and nanoscopy |

Optics Express, Vol. 21, Issue 5, pp. 5701-5714 (2013)

http://dx.doi.org/10.1364/OE.21.005701

Acrobat PDF (2502 KB)

### Abstract

We present a simple-to-align, highly-portable interferometer, which is able to capture wide-field, off-axis interference patterns from transparent samples under low-coherence illumination. This small-dimensions and low-cost device can be connected to the output of a transmission microscope illuminated by a low-coherence source and measure sub-nanometric optical thickness changes in a label-free manner. In contrast to our previously published design, the

© 2013 OSA

## 1. Introduction

## 2. Off-axis τ interferometer setup

*θ*between the beams, which is described as follows:where

## 3. Data processing

*G*

_{+1}from the zero-order

*I*+

_{s}*I*, and back Fourier transform of the centered temporal coherence function

_{r}*G*

_{+1}. Then, we take the phase argument of the resulting complex function to obtain the wrapped phase. To compensate for aberrations and field curvatures, we perform the same wrapped-phase extraction process for a sample-free interferogram, and the result is subtracted from the first wrapped phase by dividing the sample complex wavefront with sample-free complex wavefront. Finally we apply a quality-guided two-dimensional unwrapping algorithm to remove 2π ambiguities, yielding the unwrapped phase profile which is equal to

*OPD*) can be extracted from

_{s}## 4. Experimental results

### 4.1 Measuring the spatial and temporal OPD sensitivities of the system

### 4.2 Volume holographic grating measurements

### 4.3 Measurements of custom-made phase targets

*n*

_{chrome}= 2.42 and

*n*

_{glass}= 1.515). Note that minimal milling capability of the FIB setups used by us is 10 nm, so it is possible that the inconstant OPD of the letters seen in Fig. 8(a) is caused by the milling process of the glass layer and not due to the spatial interferometric noise. In any case, these results show that the off-axis τ interferometer can be used to perform inexpensive quality checks and imaging during or after the manufacturing of transparent optical elements, as long as the lateral dimensions of the smallest element that needs to be examined is larger than the diffraction-limit spot of the microscope.

### 4.4 Biological cell dynamic measurements

## 5. Discussion and conclusions

## Appendix A

*in vitro*),

*x*,

*y*) [14].

## Acknowledgments

## References and links

1. | G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Erythrocyte structure and dynamics quantified by Hilbert phase microscopy,” J. Biomed. Opt. |

2. | B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A |

3. | B. Kemper, A. Bauwens, A. Vollmer, S. Ketelhut, P. Langehanenberg, J. Müthing, H. Karch, and G. von Bally, “Label-free quantitative cell division monitoring of endothelial cells by digital holographic microscopy,” J. Biomed. Opt. |

4. | N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt. |

5. | P. Girshovitz and N. T. Shaked, “Generalized cell morphological parameters based on interferometric phase microscopy and their application to cell life cycle characterization,” Biomed. Opt. Express |

6. | S. Gawad, M. Giugliano, M. Heuschkel, B. Wessling, H. Markram, U. Schnakenberg, P. Renaud, and H. Morgan, “Substrate arrays of iridium oxide microelectrodes for in vitro neuronal interfacing,” Front Neuroeng |

7. | M. C. Potcoava and M. K. Kim, “Fingerprint biometry applications of digital holography and low-coherence interferography,” Appl. Opt. |

8. | V. Mico, Z. Zalevsky, and J. García, “Common-path phase-shifting digital holographic microscopy: a way to quantitative phase imaging and superresolution,” Opt. Commun. |

9. | V. Micó and J. García, “Common-path phase-shifting lensless holographic microscopy,” Opt. Lett. |

10. | P. Bon, G. Maucort, B. Wattellier, and S. Monneret, “Quadriwave lateral shearing interferometry for quantitative phase microscopy of living cells,” Opt. Express |

11. | M. Lee, O. Yaglidere, and A. Ozcan, “Field-portable reflection and transmission microscopy based on lensless holography,” Biomed. Opt. Express |

12. | R. Chmelík and Z. Harna, “Parallel-mode confocal microscope,” Opt. Eng. |

13. | P. Kolman and R. Chmelík, “Coherence-controlled holographic microscope,” Opt. Express |

14. | Z. Monemhaghdoust, F. Montfort, Y. Emery, C. Depeursinge, and C. Moser, “Dual wavelength full field imaging in low coherence digital holographic microscopy,” Opt. Express |

15. | Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette, and G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express |

16. | B. Bhaduri, H. Pham, M. Mir, and G. Popescu, “Diffraction phase microscopy with white light,” Opt. Lett. |

17. | N. T. Shaked, Y. Zhu, N. Badie, N. Bursac, and A. Wax, “Reflective interferometric chamber for quantitative phase imaging of biological sample dynamics,” J. Biomed. Opt. |

18. | J. Jang, C. Y. Bae, J.-K. Park, and J. C. Ye, “Self-reference quantitative phase microscopy for microfluidic devices,” Opt. Lett. |

19. | B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, “Simplified approach for quantitative digital holographic phase contrast imaging of living cells,” J. Biomed. Opt. |

20. | N. T. Shaked, “Quantitative phase microscopy of biological samples using a portable interferometer,” Opt. Lett. |

21. | N. T. Shaked, T. M. Newpher, M. D. Ehlers, and A. Wax, “Parallel on-axis holographic phase microscopy of biological cells and unicellular microorganism dynamics,” Appl. Opt. |

22. | G. Popescu, L. P. Deflores, J. C. Vaughan, K. Badizadegan, H. Iwai, R. R. Dasari, and M. S. Feld, “Fourier phase microscopy for investigation of biological structures and dynamics,” Opt. Lett. |

23. | L. Xue, J. Lai, S. Wang, and Z. Li, “Single-shot slightly-off-axis interferometry based Hilbert phase microscopy of red blood cells,” Biomed. Opt. Express |

24. | B. A. E. Saleh and M. C. Teich, “Fourier optics,” in |

25. | B. A. E. Saleh and M. C. Teich, “Statistical optics,” in |

26. | D. C. Ghiglia and M. D. Pritt, |

27. | S. Reyntjens and R. Puers, “A review of focused ion beam applications in microsystem technology,” J. Micromech. Microeng. |

28. | Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. |

29. | I. Shock, A. Barbul, P. Girshovitz, U. Nevo, R. Korenstein, and N. T. Shaked, “Optical phase nanoscopy in red blood cells using low-coherence spectroscopy,” J. Biomed. Opt. |

30. | J. W. Goodman, “Coherence of optical waves,” in |

**OCIS Codes**

(090.2880) Holography : Holographic interferometry

(110.0180) Imaging systems : Microscopy

(180.3170) Microscopy : Interference microscopy

(090.1995) Holography : Digital holography

(070.2615) Fourier optics and signal processing : Frequency filtering

**ToC Category:**

Microscopy

**History**

Original Manuscript: November 1, 2012

Revised Manuscript: December 24, 2012

Manuscript Accepted: January 1, 2013

Published: March 1, 2013

**Virtual Issues**

Vol. 8, Iss. 4 *Virtual Journal for Biomedical Optics*

**Citation**

Pinhas Girshovitz and Natan T. Shaked, "Compact and portable low-coherence interferometer with off-axis geometry for quantitative phase microscopy and nanoscopy," Opt. Express **21**, 5701-5714 (2013)

http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-21-5-5701

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### References

- G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Erythrocyte structure and dynamics quantified by Hilbert phase microscopy,” J. Biomed. Opt.10(6), 060503 (2005).
- B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A73A(10), 895–903 (2008).
- B. Kemper, A. Bauwens, A. Vollmer, S. Ketelhut, P. Langehanenberg, J. Müthing, H. Karch, and G. von Bally, “Label-free quantitative cell division monitoring of endothelial cells by digital holographic microscopy,” J. Biomed. Opt.15(3), 036009 (2010).
- N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
- P. Girshovitz and N. T. Shaked, “Generalized cell morphological parameters based on interferometric phase microscopy and their application to cell life cycle characterization,” Biomed. Opt. Express3(8), 1757–1773 (2012).
- S. Gawad, M. Giugliano, M. Heuschkel, B. Wessling, H. Markram, U. Schnakenberg, P. Renaud, and H. Morgan, “Substrate arrays of iridium oxide microelectrodes for in vitro neuronal interfacing,” Front Neuroeng2, 1–7 (2009).
- M. C. Potcoava and M. K. Kim, “Fingerprint biometry applications of digital holography and low-coherence interferography,” Appl. Opt.48(34), H9–H15 (2009).
- V. Mico, Z. Zalevsky, and J. García, “Common-path phase-shifting digital holographic microscopy: a way to quantitative phase imaging and superresolution,” Opt. Commun.281(17), 4273–4281 (2008).
- V. Micó and J. García, “Common-path phase-shifting lensless holographic microscopy,” Opt. Lett.35(23), 3919–3921 (2010).
- P. Bon, G. Maucort, B. Wattellier, and S. Monneret, “Quadriwave lateral shearing interferometry for quantitative phase microscopy of living cells,” Opt. Express17(15), 13080–13094 (2009).
- M. Lee, O. Yaglidere, and A. Ozcan, “Field-portable reflection and transmission microscopy based on lensless holography,” Biomed. Opt. Express2(9), 2721–2730 (2011).
- R. Chmelík and Z. Harna, “Parallel-mode confocal microscope,” Opt. Eng.38(10), 1635–1639 (1999).
- P. Kolman and R. Chmelík, “Coherence-controlled holographic microscope,” Opt. Express18(21), 21990–22003 (2010).
- Z. Monemhaghdoust, F. Montfort, Y. Emery, C. Depeursinge, and C. Moser, “Dual wavelength full field imaging in low coherence digital holographic microscopy,” Opt. Express19(24), 24005–24022 (2011).
- Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette, and G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express19(2), 1016–1026 (2011).
- B. Bhaduri, H. Pham, M. Mir, and G. Popescu, “Diffraction phase microscopy with white light,” Opt. Lett.37(6), 1094–1096 (2012).
- N. T. Shaked, Y. Zhu, N. Badie, N. Bursac, and A. Wax, “Reflective interferometric chamber for quantitative phase imaging of biological sample dynamics,” J. Biomed. Opt.15(3), 030503 (2010).
- J. Jang, C. Y. Bae, J.-K. Park, and J. C. Ye, “Self-reference quantitative phase microscopy for microfluidic devices,” Opt. Lett.35(4), 514–516 (2010).
- B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, “Simplified approach for quantitative digital holographic phase contrast imaging of living cells,” J. Biomed. Opt.16(2), 026014 (2011).
- N. T. Shaked, “Quantitative phase microscopy of biological samples using a portable interferometer,” Opt. Lett.37(11), 2016–2018 (2012).
- N. T. Shaked, T. M. Newpher, M. D. Ehlers, and A. Wax, “Parallel on-axis holographic phase microscopy of biological cells and unicellular microorganism dynamics,” Appl. Opt.49(15), 2872–2878 (2010).
- G. Popescu, L. P. Deflores, J. C. Vaughan, K. Badizadegan, H. Iwai, R. R. Dasari, and M. S. Feld, “Fourier phase microscopy for investigation of biological structures and dynamics,” Opt. Lett.29(21), 2503–2505 (2004).
- L. Xue, J. Lai, S. Wang, and Z. Li, “Single-shot slightly-off-axis interferometry based Hilbert phase microscopy of red blood cells,” Biomed. Opt. Express2(4), 987–995 (2011).
- B. A. E. Saleh and M. C. Teich, “Fourier optics,” in Fundamentals of Photonics, B. A. E. Saleh ed. (Wiley, 1991), pp. 102–149.
- B. A. E. Saleh and M. C. Teich, “Statistical optics,” in Fundamentals of Photonics, B. A. E. Saleh ed. (Wiley, 1991), pp. 403–442.
- D. C. Ghiglia and M. D. Pritt, Two-Dimensional Phase Unwrapping: Theory, Algorithms, and Software (Wiley, 1998).
- S. Reyntjens and R. Puers, “A review of focused ion beam applications in microsystem technology,” J. Micromech. Microeng.11(4), 287–300 (2001).
- Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008).
- I. Shock, A. Barbul, P. Girshovitz, U. Nevo, R. Korenstein, and N. T. Shaked, “Optical phase nanoscopy in red blood cells using low-coherence spectroscopy,” J. Biomed. Opt.17(10), 101509 (2012).
- J. W. Goodman, “Coherence of optical waves,” in Statistical Optics, B. A. E. Saleh ed. (Wiley, 2000), pp. 157–226.

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