Abstract

The space–bandwidth product (SBP) of modern objective lenses is often significantly larger than the pixel count of opto-electronic image sensor chips, and, therefore, much of the information transmitted by the optical system cannot be adequately sampled or digitized. To resolve this mismatch, microscopes are in general designed to maintain the resolution of the optical system while significantly wasting the field of view (FOV) and SBP of the objective lens. We introduce a wide-field and high-resolution coherent imaging method that uses a stack of out-of-focus images to provide much better utilization of the SBP of an objective lens. We demonstrate our approach on a benchtop microscope by using a demagnification camera adapter to match the active area of the image sensor chip to the FOV of an objective lens. We show that the resulting spatial undersampling caused by capturing a large FOV can be mitigated through an iterative pixel super-resolution algorithm that uses e.g., ∼three to five slightly out-of-focus images, yielding an ∼8-fold increase in the SBP of the microscope. Furthermore, the same pixel super-resolution algorithm also achieves phase retrieval, revealing the optical phase information of the specimen. We compared our method against traditional off-axis and phase-shifting digital holographic microscopy modalities and demonstrated at least 3-fold reduction in the number of images required to achieve the same SBP. This technique could be used to maximize the throughput and SBP of lens-based coherent imaging and holography systems and inspire new microscopy designs that benefit from the inherent autofocusing steps of a scanning microscope to increase its SBP.

© 2016 Optical Society of America

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2016 (5)

Y. Zhang, S. Y. C. Lee, Y. Zhang, D. Furst, J. Fitzgerald, and A. Ozcan, “Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis,” Sci. Rep. 6, 28793 (2016).
[Crossref]

E. McLeod and A. Ozcan, “Unconventional methods of imaging: computational microscopy and compact implementations,” Rep. Prog. Phys. 79, 076001 (2016).
[Crossref]

A. Ozcan and E. McLeod, “Lensless imaging and sensing,” Annu. Rev. Biomed. Eng. 18, 77–102 (2016).
[Crossref]

W. Luo, Y. Zhang, Z. Göröcs, A. Feizi, and A. Ozcan, “Propagation phasor approach for holographic image reconstruction,” Sci. Rep. 6, 22738 (2016).
[Crossref]

F. Yi, I. Moon, and B. Javidi, “Cell morphology-based classification of red blood cells using holographic imaging informatics,” Biomed. Opt. Express 7, 2385–2399 (2016).
[Crossref]

2015 (5)

2014 (3)

A. Greenbaum, Y. Zhang, A. Feizi, P.-L. Chung, W. Luo, S. R. Kandukuri, and A. Ozcan, “Wide-field computational imaging of pathology slides using lens-free on-chip microscopy,” Sci. Transl. Med. 6, 267ra175 (2014).
[Crossref]

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

X. Yu, J. Hong, C. Liu, M. Cross, D. T. Haynie, and M. K. Kim, “Four-dimensional motility tracking of biological cells by digital holographic microscopy,” J. Biomed. Opt. 19, 045001 (2014).
[Crossref]

2013 (4)

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, 1717 (2013).
[Crossref]

J. Kostencka, T. Kozacki, and K. Liżewski, “Autofocusing method for tilted image plane detection in digital holographic microscopy,” Opt. Commun. 297, 20–26 (2013).
[Crossref]

A. El Mallahi, C. Minetti, and F. Dubois, “Automated three-dimensional detection and classification of living organisms using digital holographic microscopy with partial spatial coherent source: application to the monitoring of drinking water resources,” Appl. Opt. 52, A68–A80 (2013).
[Crossref]

P. Gao, G. Pedrini, and W. Osten, “Structured illumination for resolution enhancement and autofocusing in digital holographic microscopy,” Opt. Lett. 38, 1328–1330 (2013).
[Crossref]

2012 (5)

J. Min, B. Yao, P. Gao, R. Guo, B. Ma, J. Zheng, M. Lei, S. Yan, D. Dan, T. Duan, Y. Yang, and T. Ye, “Dual-wavelength slightly off-axis digital holographic microscopy,” Appl. Opt. 51, 191–196 (2012).
[Crossref]

P. Gao, B. Yao, J. Min, R. Guo, B. Ma, J. Zheng, M. Lei, S. Yan, D. Dan, and T. Ye, “Autofocusing of digital holographic microscopy based on off-axis illuminations,” Opt. Lett. 37, 3630–3632 (2012).
[Crossref]

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
[Crossref]

A. Anand, V. K. Chhaniwal, N. R. Patel, and B. Javidi, “Automatic identification of malaria-infected RBC with digital holographic microscopy using correlation algorithms,” IEEE Photon. J. 4, 1456–1464 (2012).
[Crossref]

P. Petruck, R. Riesenberg, and R. Kowarschik, “Optimized coherence parameters for high-resolution holographic microscopy,” Appl. Phys. B 106, 339–348 (2012).
[Crossref]

2011 (3)

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, “Video-rate tomographic phase microscopy,” J. Biomed. Opt. 16, 011005 (2011).
[Crossref]

S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
[Crossref]

P. Memmolo, G. Di Caprio, C. Distante, M. Paturzo, R. Puglisi, D. Balduzzi, A. Galli, G. Coppola, and P. Ferraro, “Identification of bovine sperm head for morphometry analysis in quantitative phase-contrast holographic microscopy,” Opt. Express 19, 23215–23226 (2011).
[Crossref]

2010 (3)

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

W. Bishara, T.-W. Su, A. F. Coskun, and A. Ozcan, “Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution,” Opt. Express 18, 11181–11191 (2010).
[Crossref]

T. Tahara, K. Ito, T. Kakue, M. Fujii, Y. Shimozato, Y. Awatsuji, K. Nishio, S. Ura, T. Kubota, and O. Matoba, “Parallel phase-shifting digital holographic microscopy,” Biomed. Opt. Express 1, 610–616 (2010).
[Crossref]

2009 (2)

2008 (2)

2007 (1)

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
[Crossref]

2006 (2)

2005 (1)

2004 (1)

2002 (1)

1999 (1)

Alfieri, D.

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
[Crossref]

P. Ferraro, S. Grilli, D. Alfieri, S. De Nicola, A. Finizio, G. Pierattini, B. Javidi, G. Coppola, and V. Striano, “Extended focused image in microscopy by digital holography,” Opt. Express 13, 6738–6749 (2005).
[Crossref]

Anand, A.

S. Mahajan, V. Trivedi, P. Vora, V. Chhaniwal, B. Javidi, and A. Anand, “Highly stable digital holographic microscope using Sagnac interferometer,” Opt. Lett. 40, 3743–3746 (2015).
[Crossref]

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

A. Anand, V. K. Chhaniwal, N. R. Patel, and B. Javidi, “Automatic identification of malaria-infected RBC with digital holographic microscopy using correlation algorithms,” IEEE Photon. J. 4, 1456–1464 (2012).
[Crossref]

Ash, W. M.

Awatsuji, Y.

Balduzzi, D.

Bishara, W.

S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
[Crossref]

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

W. Bishara, T.-W. Su, A. F. Coskun, and A. Ozcan, “Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution,” Opt. Express 18, 11181–11191 (2010).
[Crossref]

Charrière, F.

Chhaniwal, V.

Chhaniwal, V. K.

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

A. Anand, V. K. Chhaniwal, N. R. Patel, and B. Javidi, “Automatic identification of malaria-infected RBC with digital holographic microscopy using correlation algorithms,” IEEE Photon. J. 4, 1456–1464 (2012).
[Crossref]

Choi, W.

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, “Video-rate tomographic phase microscopy,” J. Biomed. Opt. 16, 011005 (2011).
[Crossref]

Choi, Y.-S.

Chung, P.-L.

A. Greenbaum, Y. Zhang, A. Feizi, P.-L. Chung, W. Luo, S. R. Kandukuri, and A. Ozcan, “Wide-field computational imaging of pathology slides using lens-free on-chip microscopy,” Sci. Transl. Med. 6, 267ra175 (2014).
[Crossref]

Colomb, T.

Coppola, G.

Coskun, A. F.

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, 1717 (2013).
[Crossref]

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
[Crossref]

W. Bishara, T.-W. Su, A. F. Coskun, and A. Ozcan, “Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution,” Opt. Express 18, 11181–11191 (2010).
[Crossref]

Cross, M.

X. Yu, J. Hong, C. Liu, M. Cross, D. T. Haynie, and M. K. Kim, “Four-dimensional motility tracking of biological cells by digital holographic microscopy,” J. Biomed. Opt. 19, 045001 (2014).
[Crossref]

Cuche, E.

Dai, Q.

Dan, D.

Dasari, R. R.

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, “Video-rate tomographic phase microscopy,” J. Biomed. Opt. 16, 011005 (2011).
[Crossref]

De Nicola, S.

Depeursinge, C.

Devaney, A. J.

Di Caprio, G.

Distante, C.

Duan, T.

Dubey, S. K.

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

Dubois, F.

El Mallahi, A.

Fang-Yen, C.

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, “Video-rate tomographic phase microscopy,” J. Biomed. Opt. 16, 011005 (2011).
[Crossref]

Faridian, A.

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

Feizi, A.

W. Luo, Y. Zhang, Z. Göröcs, A. Feizi, and A. Ozcan, “Propagation phasor approach for holographic image reconstruction,” Sci. Rep. 6, 22738 (2016).
[Crossref]

W. Luo, Y. Zhang, A. Feizi, Z. Göröcs, and A. Ozcan, “Pixel super-resolution using wavelength scanning,” Light Sci. Appl. 5, e16060 (2015).
[Crossref]

A. Greenbaum, Y. Zhang, A. Feizi, P.-L. Chung, W. Luo, S. R. Kandukuri, and A. Ozcan, “Wide-field computational imaging of pathology slides using lens-free on-chip microscopy,” Sci. Transl. Med. 6, 267ra175 (2014).
[Crossref]

Feld, M. S.

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, “Video-rate tomographic phase microscopy,” J. Biomed. Opt. 16, 011005 (2011).
[Crossref]

Feng, S.

S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
[Crossref]

Ferraro, P.

B. Mandracchia, V. Pagliarulo, M. Paturzo, and P. Ferraro, “Surface plasmon resonance imaging by holographic enhanced mapping,” Anal. Chem. 87, 4124–4128 (2015).
[Crossref]

P. Memmolo, G. Di Caprio, C. Distante, M. Paturzo, R. Puglisi, D. Balduzzi, A. Galli, G. Coppola, and P. Ferraro, “Identification of bovine sperm head for morphometry analysis in quantitative phase-contrast holographic microscopy,” Opt. Express 19, 23215–23226 (2011).
[Crossref]

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
[Crossref]

P. Ferraro, S. Grilli, D. Alfieri, S. De Nicola, A. Finizio, G. Pierattini, B. Javidi, G. Coppola, and V. Striano, “Extended focused image in microscopy by digital holography,” Opt. Express 13, 6738–6749 (2005).
[Crossref]

Ferreira, C.

Finizio, A.

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
[Crossref]

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W. Luo, Y. Zhang, A. Feizi, Z. Göröcs, and A. Ozcan, “Pixel super-resolution using wavelength scanning,” Light Sci. Appl. 5, e16060 (2015).
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A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
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A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, 1717 (2013).
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A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
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L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
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X. Yu, J. Hong, C. Liu, M. Cross, D. T. Haynie, and M. K. Kim, “Four-dimensional motility tracking of biological cells by digital holographic microscopy,” J. Biomed. Opt. 19, 045001 (2014).
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A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
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S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
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O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
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A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
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A. Anand, V. K. Chhaniwal, N. R. Patel, and B. Javidi, “Automatic identification of malaria-infected RBC with digital holographic microscopy using correlation algorithms,” IEEE Photon. J. 4, 1456–1464 (2012).
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P. Ferraro, S. Grilli, D. Alfieri, S. De Nicola, A. Finizio, G. Pierattini, B. Javidi, G. Coppola, and V. Striano, “Extended focused image in microscopy by digital holography,” Opt. Express 13, 6738–6749 (2005).
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A. Greenbaum, Y. Zhang, A. Feizi, P.-L. Chung, W. Luo, S. R. Kandukuri, and A. Ozcan, “Wide-field computational imaging of pathology slides using lens-free on-chip microscopy,” Sci. Transl. Med. 6, 267ra175 (2014).
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O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
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A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, 1717 (2013).
[Crossref]

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X. Yu, J. Hong, C. Liu, M. Cross, D. T. Haynie, and M. K. Kim, “Four-dimensional motility tracking of biological cells by digital holographic microscopy,” J. Biomed. Opt. 19, 045001 (2014).
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W. M. Ash, L. Krzewina, and M. K. Kim, “Quantitative imaging of cellular adhesion by total internal reflection holographic microscopy,” Appl. Opt. 48, H144–H152 (2009).
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S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
[Crossref]

Lee, S. Y. C.

Y. Zhang, S. Y. C. Lee, Y. Zhang, D. Furst, J. Fitzgerald, and A. Ozcan, “Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis,” Sci. Rep. 6, 28793 (2016).
[Crossref]

Lee, S.-J.

Lei, M.

Liao, J.

Liu, C.

X. Yu, J. Hong, C. Liu, M. Cross, D. T. Haynie, and M. K. Kim, “Four-dimensional motility tracking of biological cells by digital holographic microscopy,” J. Biomed. Opt. 19, 045001 (2014).
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W. Luo, Y. Zhang, Z. Göröcs, A. Feizi, and A. Ozcan, “Propagation phasor approach for holographic image reconstruction,” Sci. Rep. 6, 22738 (2016).
[Crossref]

W. Luo, Y. Zhang, A. Feizi, Z. Göröcs, and A. Ozcan, “Pixel super-resolution using wavelength scanning,” Light Sci. Appl. 5, e16060 (2015).
[Crossref]

A. Greenbaum, Y. Zhang, A. Feizi, P.-L. Chung, W. Luo, S. R. Kandukuri, and A. Ozcan, “Wide-field computational imaging of pathology slides using lens-free on-chip microscopy,” Sci. Transl. Med. 6, 267ra175 (2014).
[Crossref]

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, 1717 (2013).
[Crossref]

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
[Crossref]

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Mahajan, S.

S. Mahajan, V. Trivedi, P. Vora, V. Chhaniwal, B. Javidi, and A. Anand, “Highly stable digital holographic microscope using Sagnac interferometer,” Opt. Lett. 40, 3743–3746 (2015).
[Crossref]

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

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B. Mandracchia, V. Pagliarulo, M. Paturzo, and P. Ferraro, “Surface plasmon resonance imaging by holographic enhanced mapping,” Anal. Chem. 87, 4124–4128 (2015).
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S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
[Crossref]

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A. Ozcan and E. McLeod, “Lensless imaging and sensing,” Annu. Rev. Biomed. Eng. 18, 77–102 (2016).
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E. McLeod and A. Ozcan, “Unconventional methods of imaging: computational microscopy and compact implementations,” Rep. Prog. Phys. 79, 076001 (2016).
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Miccio, L.

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
[Crossref]

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Mudanyali, O.

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
[Crossref]

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

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L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
[Crossref]

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Oh, C.

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

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A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

P. Gao, G. Pedrini, and W. Osten, “Structured illumination for resolution enhancement and autofocusing in digital holographic microscopy,” Opt. Lett. 38, 1328–1330 (2013).
[Crossref]

Ozcan, A.

Y. Zhang, S. Y. C. Lee, Y. Zhang, D. Furst, J. Fitzgerald, and A. Ozcan, “Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis,” Sci. Rep. 6, 28793 (2016).
[Crossref]

A. Ozcan and E. McLeod, “Lensless imaging and sensing,” Annu. Rev. Biomed. Eng. 18, 77–102 (2016).
[Crossref]

W. Luo, Y. Zhang, Z. Göröcs, A. Feizi, and A. Ozcan, “Propagation phasor approach for holographic image reconstruction,” Sci. Rep. 6, 22738 (2016).
[Crossref]

E. McLeod and A. Ozcan, “Unconventional methods of imaging: computational microscopy and compact implementations,” Rep. Prog. Phys. 79, 076001 (2016).
[Crossref]

W. Luo, Y. Zhang, A. Feizi, Z. Göröcs, and A. Ozcan, “Pixel super-resolution using wavelength scanning,” Light Sci. Appl. 5, e16060 (2015).
[Crossref]

A. Greenbaum, Y. Zhang, A. Feizi, P.-L. Chung, W. Luo, S. R. Kandukuri, and A. Ozcan, “Wide-field computational imaging of pathology slides using lens-free on-chip microscopy,” Sci. Transl. Med. 6, 267ra175 (2014).
[Crossref]

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, 1717 (2013).
[Crossref]

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
[Crossref]

S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
[Crossref]

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

W. Bishara, T.-W. Su, A. F. Coskun, and A. Ozcan, “Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution,” Opt. Express 18, 11181–11191 (2010).
[Crossref]

Oztoprak, C.

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

Pagliarulo, V.

B. Mandracchia, V. Pagliarulo, M. Paturzo, and P. Ferraro, “Surface plasmon resonance imaging by holographic enhanced mapping,” Anal. Chem. 87, 4124–4128 (2015).
[Crossref]

Patel, N. R.

A. Anand, V. K. Chhaniwal, N. R. Patel, and B. Javidi, “Automatic identification of malaria-infected RBC with digital holographic microscopy using correlation algorithms,” IEEE Photon. J. 4, 1456–1464 (2012).
[Crossref]

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Pavillon, N.

Pedrini, G.

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

P. Gao, G. Pedrini, and W. Osten, “Structured illumination for resolution enhancement and autofocusing in digital holographic microscopy,” Opt. Lett. 38, 1328–1330 (2013).
[Crossref]

Petrocellis, L. D.

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
[Crossref]

Petruck, P.

P. Petruck, R. Riesenberg, and R. Kowarschik, “Optimized coherence parameters for high-resolution holographic microscopy,” Appl. Phys. B 106, 339–348 (2012).
[Crossref]

Pierattini, G.

Puglisi, R.

Rappaz, B.

Riesenberg, R.

P. Petruck, R. Riesenberg, and R. Kowarschik, “Optimized coherence parameters for high-resolution holographic microscopy,” Appl. Phys. B 106, 339–348 (2012).
[Crossref]

Sencan, I.

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

Seo, S.

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

Shimozato, Y.

Striano, V.

Su, T.-W.

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, 1717 (2013).
[Crossref]

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
[Crossref]

W. Bishara, T.-W. Su, A. F. Coskun, and A. Ozcan, “Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution,” Opt. Express 18, 11181–11191 (2010).
[Crossref]

Sung, Y.

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, “Video-rate tomographic phase microscopy,” J. Biomed. Opt. 16, 011005 (2011).
[Crossref]

Tahara, T.

Tian, L.

Trivedi, V.

S. Mahajan, V. Trivedi, P. Vora, V. Chhaniwal, B. Javidi, and A. Anand, “Highly stable digital holographic microscope using Sagnac interferometer,” Opt. Lett. 40, 3743–3746 (2015).
[Crossref]

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

Tseng, D.

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

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Verrier, N.

von Bally, G.

Vora, P.

Waller, L.

Wang, H.-T.

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A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
[Crossref]

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Yang, Y.

Yao, B.

Ye, T.

Yi, F.

Yu, F. W.

S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
[Crossref]

Yu, X.

X. Yu, J. Hong, C. Liu, M. Cross, D. T. Haynie, and M. K. Kim, “Four-dimensional motility tracking of biological cells by digital holographic microscopy,” J. Biomed. Opt. 19, 045001 (2014).
[Crossref]

Zalevsky, Z.

Zhang, L.

Zhang, Y.

Y. Zhang, S. Y. C. Lee, Y. Zhang, D. Furst, J. Fitzgerald, and A. Ozcan, “Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis,” Sci. Rep. 6, 28793 (2016).
[Crossref]

Y. Zhang, S. Y. C. Lee, Y. Zhang, D. Furst, J. Fitzgerald, and A. Ozcan, “Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis,” Sci. Rep. 6, 28793 (2016).
[Crossref]

W. Luo, Y. Zhang, Z. Göröcs, A. Feizi, and A. Ozcan, “Propagation phasor approach for holographic image reconstruction,” Sci. Rep. 6, 22738 (2016).
[Crossref]

Y. Zhang, W. Jiang, L. Tian, L. Waller, and Q. Dai, “Self-learning based Fourier ptychographic microscopy,” Opt. Express 23, 18471–18486 (2015).
[Crossref]

W. Luo, Y. Zhang, A. Feizi, Z. Göröcs, and A. Ozcan, “Pixel super-resolution using wavelength scanning,” Light Sci. Appl. 5, e16060 (2015).
[Crossref]

A. Greenbaum, Y. Zhang, A. Feizi, P.-L. Chung, W. Luo, S. R. Kandukuri, and A. Ozcan, “Wide-field computational imaging of pathology slides using lens-free on-chip microscopy,” Sci. Transl. Med. 6, 267ra175 (2014).
[Crossref]

Zheng, J.

Zhu, Y. Y.

Anal. Chem. (1)

B. Mandracchia, V. Pagliarulo, M. Paturzo, and P. Ferraro, “Surface plasmon resonance imaging by holographic enhanced mapping,” Anal. Chem. 87, 4124–4128 (2015).
[Crossref]

Annu. Rev. Biomed. Eng. (1)

A. Ozcan and E. McLeod, “Lensless imaging and sensing,” Annu. Rev. Biomed. Eng. 18, 77–102 (2016).
[Crossref]

Appl. Opt. (7)

Appl. Phys. B (1)

P. Petruck, R. Riesenberg, and R. Kowarschik, “Optimized coherence parameters for high-resolution holographic microscopy,” Appl. Phys. B 106, 339–348 (2012).
[Crossref]

Appl. Phys. Lett. (2)

A. Anand, A. Faridian, V. K. Chhaniwal, S. Mahajan, V. Trivedi, S. K. Dubey, G. Pedrini, W. Osten, and B. Javidi, “Single beam Fourier transform digital holographic quantitative phase microscopy,” Appl. Phys. Lett. 104, 103705 (2014).
[Crossref]

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. D. Petrocellis, and S. D. Nicola, “Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram,” Appl. Phys. Lett. 90, 041104 (2007).
[Crossref]

Biomed. Opt. Express (2)

IEEE Photon. J. (1)

A. Anand, V. K. Chhaniwal, N. R. Patel, and B. Javidi, “Automatic identification of malaria-infected RBC with digital holographic microscopy using correlation algorithms,” IEEE Photon. J. 4, 1456–1464 (2012).
[Crossref]

J. Biomed. Opt. (2)

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, “Video-rate tomographic phase microscopy,” J. Biomed. Opt. 16, 011005 (2011).
[Crossref]

X. Yu, J. Hong, C. Liu, M. Cross, D. T. Haynie, and M. K. Kim, “Four-dimensional motility tracking of biological cells by digital holographic microscopy,” J. Biomed. Opt. 19, 045001 (2014).
[Crossref]

Lab Chip (1)

O. Mudanyali, D. Tseng, C. Oh, S. O. Isikman, I. Sencan, W. Bishara, C. Oztoprak, S. Seo, B. Khademhosseini, and A. Ozcan, “Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications,” Lab Chip 10, 1417–1428 (2010).
[Crossref]

Light Sci. Appl. (1)

W. Luo, Y. Zhang, A. Feizi, Z. Göröcs, and A. Ozcan, “Pixel super-resolution using wavelength scanning,” Light Sci. Appl. 5, e16060 (2015).
[Crossref]

Nat. Methods (1)

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9, 889–895 (2012).
[Crossref]

Opt. Commun. (1)

J. Kostencka, T. Kozacki, and K. Liżewski, “Autofocusing method for tilted image plane detection in digital holographic microscopy,” Opt. Commun. 297, 20–26 (2013).
[Crossref]

Opt. Express (6)

Opt. Lett. (6)

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

S. O. Isikman, W. Bishara, S. Mavandadi, F. W. Yu, S. Feng, R. Lau, and A. Ozcan, “Lens-free optical tomographic microscope with a large imaging volume on a chip,” Proc. Natl. Acad. Sci. USA 108, 7296–7301 (2011).
[Crossref]

Rep. Prog. Phys. (1)

E. McLeod and A. Ozcan, “Unconventional methods of imaging: computational microscopy and compact implementations,” Rep. Prog. Phys. 79, 076001 (2016).
[Crossref]

Sci. Rep. (3)

A. Greenbaum, W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan, “Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy,” Sci. Rep. 3, 1717 (2013).
[Crossref]

Y. Zhang, S. Y. C. Lee, Y. Zhang, D. Furst, J. Fitzgerald, and A. Ozcan, “Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis,” Sci. Rep. 6, 28793 (2016).
[Crossref]

W. Luo, Y. Zhang, Z. Göröcs, A. Feizi, and A. Ozcan, “Propagation phasor approach for holographic image reconstruction,” Sci. Rep. 6, 22738 (2016).
[Crossref]

Sci. Transl. Med. (1)

A. Greenbaum, Y. Zhang, A. Feizi, P.-L. Chung, W. Luo, S. R. Kandukuri, and A. Ozcan, “Wide-field computational imaging of pathology slides using lens-free on-chip microscopy,” Sci. Transl. Med. 6, 267ra175 (2014).
[Crossref]

Other (3)

“Microscope digital camera DP80,” http://www.olympus-lifescience.com/en/camera/color/dp80/#!cms[tab]=%2Fcamera%2Fcolor%2Fdp80%2Fresources .

J. W. Goodman, Introduction to Fourier Optics (Roberts, 2005).

“Olympus IX83 inverted microscope,” http://www.olympus-lifescience.com/en/microscopes/inverted/ix83/#!cms[tab]=%2Fmicroscopes%2Finverted%2Fix83%2Ffeaturesca50677bd9a5846f8deb5d96a828969 .

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Figures (7)

Fig. 1.
Fig. 1. SBP gap between microscope objectives and image sensors that are employed in coherent imaging experiments. Coherent microscopy and digital holographic imaging fields have been using CCD/CMOS image sensors typically with less than 4 million pixels during the past decade (green highlighted area), while the existing objective lenses can achieve a SBP of ∼ 8 – 25 million (solid lines). We term this practical mismatch between the pixel counts of camera sensor chips and the SBPs of conventional objective lenses the SBP gap in coherent microscopic imaging. Each blue point refers to the pixel count of the image sensor reported in a publication indicated by the reference number next to it. The SBPs reported for these objective lenses include both the phase and amplitude channels and assume a coherent illumination at 532 nm wavelength.

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Fig. 2.
Fig. 2. Our out-of-focus coherent microscopy setup. (a) Quasi-monochromatic illumination at 532 nm wavelength with ∼ 2    nm bandwidth is used for illumination. We introduced a 0.35 × demagnification camera adapter to increase the FOV by ∼ 8 -fold, getting close to the FOV limit of the objective lens. (b) A stack of out-of-focus images is captured by vertically moving the objective lens, which is then used to digitally recover a wide-field and high-resolution complex image of the sample, including both phase and amplitude channels. Typically, N ∼ 3 – 5 .

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Fig. 3.
Fig. 3. Schematic diagram of the OFI-PSR algorithm.

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Fig. 4.
Fig. 4. OFI-PSR reconstruction results of a resolution test target using N = 5 out-of-focus images. Microscope objective lens, 10 × / 0.3    NA ; camera adapter, 0.35 × ; illumination wavelength, 532 nm. (a) Full FOV OFI-PSR reconstruction of ∼ 4.6    mm 2 FOV. (b) Zoom-in of (a). (c) Single-height in-focus image of ROI 1 indicates severe spatial undersampling with a lateral half-pitch resolution of ∼ 2.2    μm . (d) OFI-PSR reconstruction result for the same ROI 1 shows a significantly improved half-pitch resolution of 1.1 μm.

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Fig. 5.
Fig. 5. OFI-PSR reconstruction results for a human blood smear sample using N = 5 out-of-focus images. Microscope objective lens, 20 × / 0.45    NA ; camera adapter, 0.35 × ; illumination wavelength, 532 nm. (a) Full FOV reconstruction of the OFI-PSR algorithm. (b) In-focus image with a 0.35 × camera adapter shows undersampling. (c) OFI-PSR achieves a significant improvement in image quality.

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Fig. 6.
Fig. 6. Demonstration of phase retrieval and pixel super-resolution by imaging an unstained Pap smear. Microscope objective lens, 20 × / 0.45    NA ; camera adapter, 0.35 × ; illumination wavelength, 532 nm. (a)–(c) In-focus and slightly out-of-focus intensity images of an unstained Pap smear sample. These images do not reveal much information about the sample since it is, by and large, a phase-only object. (d) The phase image recovered by the OFI-PSR algorithm clearly reveals the structure and sub-cellular morphology of the cells. (e) Digital phase contrast image using the OFI-PSR reconstructed complex field. (f) Phase contrast image obtained using the same microscope with a 1 × camera adapter shows good agreement with our digitally reconstructed phase image, except it has an ∼ 8 -fold smaller FOV compared to OFI-PSR.

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Fig. 7.
Fig. 7. Reconstruction quality of the OFI-PSR method with different numbers of out-of-focus measurements ( N ). Microscope objective lens, 20 × / 0.45    NA ; camera adapter, 0.35 × ; illumination wavelength, 532 nm. We used an axial scanning step size of ∼ 30    μm , and each reconstruction has 100 iterations. The reconstruction time of each OFI-PSR image is shown at the left-bottom corner of each sub-figure. (a) In-focus undersampled image of a human blood smear sample. (b)–(e) OFI-PSR reconstructions of the same blood smear sample with N = 3 , 5, 8, and 15 out-of-focus intensity images used as input. (f) In-focus undersampled image of an unstained Pap smear sample. (g)–(j) Digital phase contrast images of OFI-PSR reconstructions of the same Pap smear sample with N = 3 , 5, 8, and 15 out-of-focus intensity measurements used as input.

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Tables (1)

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Table 1. Comparison of OFI-PSR Method with Some of the Traditional Holographic Imaging Configurationsa

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Equations (5)

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I sampled , k = ∑ u , v = 0 , ± 1 , ± 2 , … [ δ u v + H k * ( 0,0 ) · H u v , k · S u v + H k ( 0,0 ) · ( H u v , k − · S u v − ) * + S S u v , k ] · P u v ,
H k ( f x , f y ) = { exp [ j · 2 π n · z k λ 1 − ( λ n f x ) 2 − ( λ n f y ) 2 ] ( f x 2 + f y 2 ≤ ( NA λ ) 2 ) 0 Otherwise .
F u v = F ( f x − u Δ x , f y − v Δ y ) ,
1 N ∑ k = 1 N | z k ( i + 1 ) − z k ( i ) | < ϵ ,
N I = 2 · FOV · r 2 · ( NA λ ) 2 ,

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