Synthetic aperture-based on-chip microscopy

Wei Luo; Alon Greenbaum; Yibo Zhang; Aydogan Ozcan

doi:10.1038/lsa.2015.34

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Synthetic aperture-based on-chip microscopy

Original Articles

- Synthetic aperture-based on-chip microscopy
- Light: Science & Applications Vol. 4, Issue 2, (2015)
- Affiliations：
  
  1.Electrical Engineering Department, University of California, Los Angeles, CA 90095, USA
  2.Bioengineering Department, University of California, Los Angeles, CA 90095, USA
  3.California NanoSystems Institute (CNSI), University of California, Los Angeles, CA 90095, USA
  4.Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
- Author bio：
  
  A Ozcan, 420 Westwood Plaza, Engr. IV 68-119, UCLA, Los Angeles, CA 90095, USA E-mail: ozcan@ucla.edu
- Funds：
- DOI：10.1038/lsa.2015.34
  CLC：
- Published：2015-06，
  
  Published Online：23 December 2014，
  
  Received：09 August 2014，
  
  Revised：20 December 2014，
  
  Accepted：22 December 2014
- Accepted：
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Luo, W. et al. Synthetic aperture-based on-chip microscopy. Light: Science & Applications, 4, e261 (2015).
DOI：

Luo, W. et al. Synthetic aperture-based on-chip microscopy. Light: Science & Applications, 4, e261 (2015). DOI： 10.1038/lsa.2015.34.

摘要

Abstract

Wide field-of-view (FOV) and high-resolution imaging requires microscopy modalities to have large space-bandwidth products. Lensfree on-chip microscopy decouples resolution from FOV and can achieve a space-bandwidth product greater than one billion under unit magnification using state-of-the-art opto-electronic sensor chips and pixel super-resolution techniques. However

using vertical illumination

the effective numerical aperture (NA) that can be achieved with an on-chip microscope is limited by a poor signal-to-noise ratio (SNR) at high spatial frequencies and imaging artifacts that arise as a result of the relatively narrow acceptance angles of the sensor's pixels. Here

we report

for the first time

a synthetic aperture-based on-chip microscope in which the illumination angle is scanned across the surface of a dome to increase the effective NA of the reconstructed lensfree image to 1.4

achieving e.g.

~250-nm resolution at 700-nm wavelength under unit magnification. This synthetic aperture approach not only represents the largest NA achieved to date using an on-chip microscope but also enables color imaging of connected tissue samples

such as pathology slides

by achieving robust phase recovery without the need for multi-height scanning or any prior information about the sample. To validate the effectiveness of this

synthetic aperture-based

partially coherent

holographic on-chip microscope

we have successfully imaged color-stained cancer tissue slides as well as unstained Papanicolaou smears across a very large FOV of 20.5 mm

. This compact on-chip microscope based on a synthetic aperture approach could be useful for various applications in medicine

physical sciences and engineering that demand high-resolution wide-field imaging.

关键词

Keywords

computational imaginglensfree microscopyon-chip microscopysynthetic aperture

references

Brady DJ.Optical Imaging and Spectroscopy. Hoboken, NJ: Wiley; Massachusetts Ave, NW Washington, DC: Optical Society of America; 2009.

Xu W, Jericho MH, Meinertzhagen, Kreuzer HJ. Digital in-line holography for biological applications.Proc Natl Acad Sci USA2001;98: 11301–11305..

Javidi B, Ferraro P, Hong SH, de Nicola S, Finizio Aet al. Three-dimensional image fusion by use of multiwavelength digital holography.Opt Lett2005;30: 144–146..

Ferraro P, Grilli S, Miccio L, Alfieri D, de Nicola Set al. Full color 3-D imaging by digital holography and removal of chromatic aberrations.J Disp Technol2008;4: 97–100..

Rosen J, Brooker G. Non-scanning motionless fluorescence three-dimensional holographic microscopy.Nat Photonics2008;2: 190–195..

Choi K, Horisaki R, Hahn J, Lim S, Marks DLet al. Compressive holography of diffuse objects.Appl Opt2010;49: H1–H10..

Paturzo M, Merola F, Ferraro P. Multi-imaging capabilities of a 2D diffraction grating in combination with digital holography.Opt Lett2010;35: 1010–1012..

Hahn J, Lim S, Choi K, Horisaki R, Brady DJ. Video-rate compressive holographic microscopic tomography.Opt Express2011;19: 7289–7298..

Memmolo P, Iannone M, Ventre M, Netti PA, Finizio Aet al. On the holographic 3D tracking ofin vitrocells characterized by a highly-morphological change.Opt Express2012;20: 28485–28493..

Zhu H, Mavandadi S, Coskun AF, Yaglidere O, Ozcan A. Optofluidic fluorescent imaging cytometry on a cell phone.Anal Chem2011;83: 6641–6647..

Greenbaum A, Luo W, Su TW, Göröcs Z, Xue Let al. Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy.Nat Methods2012;9: 889–895..

Mudanyali O, McLeod E, Luo W, Greenbaum A, Coskun AFet al. Wide-field optical detection of nanoparticles using on-chip microscopy and self-assembled nanolenses.Nat Photonics2013;7: 247–254..

Su TW, Xue L, Ozcan A. High-throughput lensfree 3D tracking of human sperms reveals rare statistics of helical trajectories.Proc Natl Acad Sci USA2012;109: 16018–16022..

Isikman SO, Bishara W, Mavandadi S, Yu FW, Feng Set al. Lens-free optical tomographic microscope with a large imaging volume on a chip.Proc Natl Acad Sci USA2011;108: 7296–7301..

Khademhosseinieh B, Biener G, Sencan I, Su TW, Coskun AFet al. Lensfree sensing on a microfluidic chip using plasmonic nanoapertures.Appl Phys Lett2010;97: 221107..

Coskun AF, Sencan I, Su TW, Ozcan A. Lensless wide-field fluorescent imaging on a chip using compressive decoding of sparse objects.Opt Express2010;18: 10510–10523..

Zheng G, Lee SA, Antebi Y, Elowitz MB, Yang C. The ePetri dish, an on-chip cell imaging platform based on subpixel perspective sweeping microscopy (SPSM).Proc Natl Acad Sci USA2011;108: 16889–16894..

Bishara W, Sikora U, Mudanyali O, Su TW, Yaglidere Oet al. Holographic pixel super-resolution in portable lensless on-chip microscopy using a fiber-optic array.Lab Chip2011;11: 1276–1279..

Isikman SO, Bishara W, Sikora U, Yaglidere O, Yeah Jet al. Field-portable lensfree tomographic microscope.Lab Chip2011;11: 2222–2230..

Greenbaum A, Zhang Y, Feizi A, Chung PL, Luo Wet al. Wide-field computational imaging of pathology slides using lens-free on-chip microscopy.Sci Transl Med2014;6: 267ra175..

Bishara W, Su TW, Coskun AF, Ozcan A. Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution.Opt Express2010;18: 11181–11191..

Mudanyali O, Oztoprak C, Tseng D, Erlinger A, Ozcan A. Detection of waterborne parasites using field-portable and cost-effective lensfree microscopy.Lab Chip2010;10: 2419–2423..

Greenbaum A, Luo W, Khademhosseinieh B, Su TW, Coskun AFet al. Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy.Sci Rep2013;3: 1717..

McLeod E, Luo W, Mudanyali O, Greenbaum A, Ozcan A. Toward giga-pixel nanoscopy on a chip: a computational wide-field look at the nano-scale without the use of lenses.Lab Chip2013;13: 2028–2035..

Fienup JR. Reconstruction of an object from the modulus of its Fourier transform.Opt Lett1978;3: 27–29..

Fienup JR. Phase retrieval algorithms: a comparison.Appl Opt1982;21: 2758–2769..

Allen LJ, Oxley MP. Phase retrieval from series of images obtained by defocus variation.Opt Commun2001;199: 65–75..

Zhang Y, Pedrini G, Osten W, Tiziani HJ. Whole optical wave field reconstruction from double or multi in-line holograms by phase retrieval algorithm.Opt Express2003;11: 3234–3241..

Almoro P, Pedrini G, Osten W. Complete wavefront reconstruction using sequential intensity measurements of a volume speckle field.Appl Opt2006;45: 8596–8605..

Kanka M, Riesenberg R, Petruck P, Graulig C. High resolution (NA=0.8) in lensless in-line holographic microscopy with glass sample carriers.Opt Lett2011;36: 3651–3653..

Schwarz CJ, Kuznetsova Y, Brueck SRJ. Imaging interferometric microscopy.Opt Lett2003;28: 1424–1426..

Mico V, Zalevsky Z, Garcia-Martinez P, Garcia J. Single-step superresolution by interferometric imaging.Opt Express2004;12: 2589–2596..

Alexandrov SA, Hillman TR, Gutzler T, Sampson DD. Synthetic aperture Fourier holographic optical microscopy.Phys Rev Lett2006;97: 168102..

Mico V, Zalevsky Z, García J. Superresolution optical system by common-path interferometry.Opt Express2006;14: 5168–5177..

Mico V, Zalevsky Z, García-Martínez P, García J. Superresolved imaging in digital holography by superposition of tilted wavefronts.Appl Opt2006;45: 822–828..

Mico V, Zalevsky Z, García-Martínez P, García J. Synthetic aperture superresolution with multiple off-axis holograms.J Opt Soc Am A2006;23: 3162–3170..

Ralston TS, Marks DL, Carney PS, Boppart SA. Interferometric synthetic aperture microscopy.Nat Phys2007;3: 129–134..

Martínez-León L, Javidi B. Synthetic aperture single-exposure on-axis digital holography.Opt Express2008;16: 161–169..

Granero L, Micó V, Zalevsky Z, García J. Synthetic aperture superresolved microscopy in digital lensless Fourier holography by time and angular multiplexing of the object information.Appl Opt2010;49: 845–857..

Micó V, Zalevsky Z. Superresolved digital in-line holographic microscopy forhigh-resolution lensless biological imaging.J Biomed Opt2010;15: 046027..

Rodrigo JA, Alieva T, Cristóbal G, Calvo ML. Wavefield imagingviaiterative retrieval based on phase modulation diversity.Opt Express2011;19: 18621–18635..

Tippie AE, Kumar AK, Fienup JR. High-resolution synthetic-aperture digital holography with digital phase and pupil correction.Opt Express2011;19: 12027–12038..

Pelagotti A, Paturzo M, Locatelli M, Geltrude A, Meucci Ret al. An automatic method for assembling a large synthetic aperture digital hologram.Opt Express2012;20: 4830–4839..

Zheng G, Horstmeyer R, Yang C. Wide-field, high-resolution Fourier ptychographic microscopy.Nat Photonics2013;7: 739–745..

Tian L, Li X, Ramchandran K, Waller L. Multiplexed coded illumination for Fourier Ptychography with an LED array microscope.Biomed Opt Express2014;5: 2376–2389..

Fienup JR. Reconstruction of a complex-valued object from the modulus of its Fourier transform using a support constraint.J Opt Soc Am A1987;4: 118–123..

Mudanyali O, Tseng D, Oh C, Isikman SO, Sencan Iet al. Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications.Lab Chip2010;10: 1417–1428..

Hardie RC, Barnard KJ, Bognar JG, Armstrong EE, Watson EA. High-resolution image reconstruction from a sequence of rotated and translated frames and its application to an infrared imaging system.Opt Eng1998;37: 247–260..

Elad M, Hel-Or Y. A fast super-resolution reconstruction algorithm for pure translational motion and common space-invariant blur.IEEE Trans Image Process2001;10: 1187–1193..

Park SC, Park MK, Kang MG. Super-resolution image reconstruction: a technical overview.IEEE Signal Process Mag2003;20: 21–36..

Farsiu S, Elad M, Milanfar P. Multiframedemosaicing and super-resolution of color images.IEEE Trans Image Process2006;15: 141–159..

Pech-Pacheco JL, Cristobal G, Chamorro-Martinez J, Fernandez-Valdivia J. Diatomautofocusing in brightfield microscopy: a comparative study. Proceedings of the 15thInternational Conference on Pattern Recognition 2000. Barcelona, Spain September3-7, 2000. IEEE Computer Society: Los Alamitos, CA, USA, 2000.

Goodman J.Introduction to Fourier Optics. 3rd ed. Greenwood Village, CO: Roberts and Company Publishers; 2004.

Greenbaum A, Feizi A, Akbari N, Ozcan A. Wide-field computational color imaging using pixel super-resolved on-chip microscopy.Opt Express2013;21: 12469–12483..

Levin A, Lischinski D, Weiss Y. Colorization using optimization.ACM Trans Graph2004;23: 689–694..

Gonzalez RC.Digital Image Processing. 3rd ed. Upper Saddle River, NJ: Prentice Hall; 2008.

Zernike F. Phase contrast, a new method for the microscopic observation of transparent objects.Physica1942;9: 686–698..

Gorocs Z, Ozcan A. On-chip biomedical imaging.IEEE Rev Biomed Eng2013;6: 29–46..

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