Skip to main content

Advertisement

SpringerLink
Log in

Wide-field pathology imaging using on-chip microscopy

  • Review and Perspectives
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

As the primary imaging tool to assist the examination of pathological samples, the conventional light microscope suffers from limited throughput, relatively high cost, bulky size, lack of portability, and requirement for focus adjustment. All of these drawbacks partially limit the use of light microscopy tools in resource-limited settings. Lens-free on-chip microscopy can help to address these drawbacks and achieve high-throughput pathology slide imaging without using lenses or objectives. Here, we review the performance of this lens-free imaging platform by showing examples of its performance with various samples including normal and sickle-cell disease blood smears and human carcinoma of the breast. This lens-free computational microscopy platform is a promising tool that can serve high-throughput pathology needs especially in resource-poor settings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mills SE (2012) Histology for pathologists. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  2. Chen X, Zheng B, Liu H (2011) Optical and digital microscopic imaging techniques and applications in pathology. Anal Cell Pathol Amst 34:5–18. doi:10.3233/ACP-2011-0006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Mudanyali O, Tseng D, Oh C et al (2010) Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications. Lab Chip 10:1417. doi:10.1039/c000453g

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Greenbaum A, Zhang Y, Feizi A (2014) Wide-field computational imaging of pathology slides using lens-free on-chip microscopy. Sci Transl Med 6:267ra175–267ra175. doi:10.1126/scitranslmed.3009850

    Article  PubMed  Google Scholar 

  5. Luo W, Greenbaum A, Zhang Y, Ozcan A (2015) Synthetic aperture-based on-chip microscopy. Light Sci Appl 4:e261. doi:10.1038/lsa.2015.34

    Article  CAS  Google Scholar 

  6. Greenbaum A, Luo W, Su T-W et al (2012) Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy. Nat Methods 9:889–895. doi:10.1038/nmeth.2114

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Su T-W, Erlinger A, Tseng D, Ozcan A (2010) Compact and light-weight automated semen analysis platform using lensfree on-chip microscopy. Anal Chem 82:8307–8312. doi:10.1021/ac101845q

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Su T-W, Xue L, Ozcan A (2012) High-throughput lensfree 3D tracking of human sperms reveals rare statistics of helical trajectories. Proc Natl Acad Sci 109:16018–16022. doi:10.1073/pnas.1212506109

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Bishara W, Sikora U, Mudanyali O et al (2011) Holographic pixel super-resolution in portable lensless on-chip microscopy using a fiber-optic array. Lab Chip 11:1276. doi:10.1039/c0lc00684j

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Greenbaum A, Luo W, Khademhosseinieh B et al (2013) Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy. Sci Rep. doi:10.1038/srep01717

    PubMed Central  Google Scholar 

  11. Bishara W, Su T-W, Coskun AF, Ozcan A (2010) Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution. Opt Express 18:11181. doi:10.1364/OE.18.011181

    Article  PubMed Central  PubMed  Google Scholar 

  12. Gorocs Z, Ozcan A (2013) On-chip biomedical imaging. IEEE Rev Biomed Eng 6:29–46. doi:10.1109/RBME.2012.2215847

    Article  PubMed Central  PubMed  Google Scholar 

  13. Su T-W, Choi I, Feng J et al (2013) Sperm trajectories form chiral ribbons. Sci Rep. doi:10.1038/srep01664

    Google Scholar 

  14. Greenbaum A, Sikora U, Ozcan A (2012) Field-portable wide-field microscopy of dense samples using multi-height pixel super-resolution based lensfree imaging. Lab Chip 12:1242. doi:10.1039/c2lc21072j

    Article  CAS  PubMed  Google Scholar 

  15. Greenbaum A, Akbari N, Feizi A et al (2013) Field-portable pixel super-resolution colour microscope. PLoS ONE 8:e76475. doi:10.1371/journal.pone.0076475

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Makler TCJ, Palmer AL, Ager M (1998) A review of practical techniques for the diagnosis of malaria. Ann Trop Med Parasitol 92:419–433. doi:10.1080/00034989859401

    Article  CAS  PubMed  Google Scholar 

  17. Orchard G, Nation B (2012) Histopathology. Oxford University Press, Oxford

    Google Scholar 

  18. Verso ML (1964) The evolution of blood-counting technologies. Med Hist 8:149–158. doi:10.1017/S0025727300029392

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Kjeldsberg CR, Perkins SL (1989) Practical diagnosis of hematologic disorders. ASCP Press, Chicago

    Google Scholar 

  20. Greenbaum A, Feizi A, Akbari N, Ozcan A (2013) Wide-field computational color imaging using pixel super-resolved on-chip microscopy. Opt Express 21:12469. doi:10.1364/OE.21.012469

    Article  PubMed Central  PubMed  Google Scholar 

  21. Garcia-Sucerquia J (2012) Color lensless digital holographic microscopy with micrometer resolution. Opt Lett 37:1724–1726. doi:10.1364/OL.37.001724

    Article  PubMed  Google Scholar 

  22. Levin A, Lischinski D, Weiss Y (2004) Colorization using optimization. ACM Trans Graph 23:689. doi:10.1145/1015706.1015780

    Article  Google Scholar 

  23. Gonzalez RC (2008) Digital image processing, 3rd edn. Prentice Hall, Upper Saddle River

    Google Scholar 

  24. Farsiu S, Elad M, Milanfar P (2006) Multiframe demosaicing and super-resolution of color images. IEEE Trans Image Process 15:141–159. doi:10.1109/TIP.2005.860336

    Article  PubMed  Google Scholar 

  25. Hardie RC, Barnard KJ, Bognar JG et al (1998) High-resolution image reconstruction from a sequence of rotated and translated frames and its application to an infrared imaging system. Opt Eng 37:247–260. doi:10.1117/1.601623

    Article  Google Scholar 

  26. Elad M, Hel-Or Y (2001) A fast super-resolution reconstruction algorithm for pure translational motion and common space-invariant blur. IEEE Trans Image Process 10:1187–1193. doi:10.1109/83.935034

    Article  CAS  PubMed  Google Scholar 

  27. Greenbaum A, Ozcan A (2012) Maskless imaging of dense samples using pixel super-resolution based multi-height lensfree on-chip microscopy. Opt Express 20:3129. doi:10.1364/OE.20.003129

    Article  PubMed Central  PubMed  Google Scholar 

  28. Allen LJ, Oxley MP (2001) Phase retrieval from series of images obtained by defocus variation. Opt Commun 199:65–75. doi:10.1016/S0030-4018(01)01556-5

    Article  CAS  Google Scholar 

  29. Almoro P, Pedrini G, Osten W (2006) Complete wavefront reconstruction using sequential intensity measurements of a volume speckle field. Appl Opt 45:8596. doi:10.1364/AO.45.008596

    Article  PubMed  Google Scholar 

  30. Allen LJ, McBride W, O’Leary NL, Oxley MP (2004) Exit wave reconstruction at atomic resolution. Ultramicroscopy 100:91–104. doi:10.1016/j.ultramic.2004.01.012

    Article  CAS  PubMed  Google Scholar 

  31. Zhang Y, Pedrini G, Osten W, Tiziani H (2003) Whole optical wave field reconstruction from double or multi in-line holograms by phase retrieval algorithm. Opt Express 11:3234. doi:10.1364/OE.11.003234

    Article  PubMed  Google Scholar 

  32. Waller L, Tian L, Barbastathis G (2010) Transport of intensity phase-amplitude imaging with higher order intensity derivatives. Opt Express 18:12552–12561. doi:10.1364/OE.18.012552

    Article  PubMed  Google Scholar 

  33. Jingshan Z, Claus RA, Dauwels J et al (2014) Transport of intensity phase imaging by intensity spectrum fitting of exponentially spaced defocus planes. Opt Express 22:10661–10674. doi:10.1364/OE.22.010661

    Article  PubMed  Google Scholar 

  34. Reed Teague M (1983) Deterministic phase retrieval: a Green’s function solution. J Opt Soc Am 73:1434. doi:10.1364/JOSA.73.001434

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Electrical Engineering Department, University of California, Los Angeles, CA, 90095, USA

    Yibo Zhang, Wei Luo & Aydogan Ozcan

  2. Bioengineering Department, University of California, Los Angeles, CA, 90095, USA

    Yibo Zhang, Wei Luo & Aydogan Ozcan

  3. California NanoSystems Institute (CNSI), University of California, Los Angeles, CA, 90095, USA

    Yibo Zhang, Wei Luo & Aydogan Ozcan

  4. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA

    Alon Greenbaum

  5. Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA

    Aydogan Ozcan

Authors
  1. Yibo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alon Greenbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aydogan Ozcan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aydogan Ozcan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Greenbaum, A., Luo, W. et al. Wide-field pathology imaging using on-chip microscopy. Virchows Arch 467, 3–7 (2015). https://doi.org/10.1007/s00428-015-1782-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-015-1782-z

Keywords

Search

Navigation