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Lensfree Computational Microscopy Tools for On-Chip Imaging of Biochips

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Point-of-Care Diagnostics on a Chip

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

Abstract

The use of optical imaging for medical diagnostics at the point of care (POC) has great potential, but is limited by cost and the need for highly trained personnel. To this end, the cost, complexity, and size of optical microscopy devices can be reduced through the use of computation. These techniques can perform particularly well at specific tasks such as cytometry, water quality management, and disease diagnostics. This chapter focuses on lensfree on-chip imaging techniques that are based on partially coherent digital in-line holography and are especially promising for imaging of biochips toward field-use and telemedicine applications. This emerging imaging platform discards most optical components that are found in traditional microscopes such as lenses and compensates for the lack of physical components in the digital domain. Widely available image sensors and abundant computational power are used to digitally process the acquired raw data to recover traditional microscope-like images with submicron resolution over large sample volumes within biochips.

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References

  1. E. Betzig et al., Imaging intracellular fluorescent proteins at nanometer resolution. Science 313(5793), 1642–1645 (2006)

    Article  ADS  Google Scholar 

  2. E. Chung, D. Kim, Y. Cui, Y.-H. Kim, P.T.C. So, Two-dimensional standing wave total internal reflection fluorescence microscopy: superresolution imaging of single molecular and biological specimens. Biophys. J. 93(5), 1747–1757 (2007)

    Article  ADS  Google Scholar 

  3. K. Goda, K.K. Tsia, B. Jalali, Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena. Nature 458(7242), 1145–1149 (2009)

    Article  ADS  Google Scholar 

  4. M.G.L. Gustafsson, Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution. Proc. Natl. Acad. Sci. 102(37), 13081–13086 (2005)

    Article  ADS  Google Scholar 

  5. S.W. Hell, Toward fluorescence nanoscopy. Nat. Biotechnol. 21(11), 1347–1355 (2003)

    Article  Google Scholar 

  6. S.T. Hess, T.P.K. Girirajan, M.D. Mason, Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys. J. 91(11), 4258–4272 (2006)

    Article  ADS  Google Scholar 

  7. M.J. Rust, M. Bates, X. Zhuang, Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat. Methods 3(10), 793–796 (2006)

    Article  Google Scholar 

  8. W.R. Zipfel, R.M. Williams, W.W. Webb, Nonlinear magic: multiphoton microscopy in the biosciences. Nat. Biotechnol. 21(11), 1369–1377 (2003)

    Article  Google Scholar 

  9. C. Oh, S.O. Isikman, B. Khademhosseini, A. Ozcan, On-chip differential interference contrast microscopy using lensless digital holography. Opt. Exp. 18, 4717–4726 (2010)

    Article  ADS  Google Scholar 

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

    Article  Google Scholar 

  11. D. Tseng, O. Mudanyali, C. Oztoprak, S.O. Isikman, I. Sencan, O. Yaglidere, A. Ozcan, Lensfree microscopy on a cell-phone. Lab Chip 10, 1787–1792 (2010)

    Article  Google Scholar 

  12. S. Seo, S.O. Isikman, I. Sencan, O. Mudanyali, T. Su, W. Bishara, A. Erlinger, A. Ozcan, High-throughput lensfree blood analysis on a chip. Anal. Chem. 82, 4621–4627 (2010)

    Article  Google Scholar 

  13. W. Bishara, T. Su, A.F. Coskun, A. Ozcan, Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution. Opt. Exp. 18, 11181–11191 (2010)

    Article  ADS  Google Scholar 

  14. O. Mudanyali, C. Oztoprak, D. Tseng, A. Erlinger, A. Ozcan, Detection of waterborne parasites using field-portable and cost-effective lensfree microscopy. Lab on a Chip 10, 2419–2423 (2010)

    Article  Google Scholar 

  15. T. Su, A. Erlinger, D. Tseng, A. Ozcan, A compact and light-weight automated semen analysis platform using lensfree on-chip microscopy. Anal. Chem. 82, 8307–8312 (2010)

    Article  Google Scholar 

  16. B. Khademhosseini, G. Biener, I. Sencan, A. Ozcan, Lensfree color imaging on a nano-structured chip using compressive decoding. Appl. Phys. Lett. 97, 211112–211114 (2010)

    Article  ADS  Google Scholar 

  17. H. Zhu, O. Yaglidere, T. Su, D. Tseng, A. Ozcan, Cost-effective and compact wide-field fluorescent imaging on a cell-phone. Lab Chip 11, 315–322 (2010)

    Article  Google Scholar 

  18. A.F. Coskun, I. Sencan, T. Su, A. Ozcan, Wide-field lensless fluorescent microscopy using a tapered fiber-optic faceplate on a chip. Analyst (2011), 10.1039/C0AN00926A

    Google Scholar 

  19. W. Bishara, U. Sikora, O. Mudanyali, T. Su, O. Yaglidere, S. Luckhart, A. Ozcan, Holographic pixel super-resolution in portable lensless on-chip microscopy using a fiber-optic array. Lab Chip 11, 1276–1279 (2011)

    Article  Google Scholar 

  20. S.O. Isikman, W. Bishara, U. Sikora, O. Yaglidere, J. Yeah, A. Ozcan, Field-portable lensfree tomographic microscope. Lab Chip 11, 2222–2230 (2011)

    Article  Google Scholar 

  21. S.O. Isikman, W. Bishara, H. Zhu, A. Ozcan, Opto-fluidic tomography on a chip. Appl. Phys. Lett. 98, 161109–161111 (2011)

    Article  Google Scholar 

  22. S.O. Isikman, W. Bishara, S. Mavandadi, F.W. Yu, S. Feng, R. Lau, A. Ozcan, Lensfree optical tomographic microscope with a large imaging volume on a chip. Proc. Nat. Acad. Sci. 18, 7296–7301 (2011)

    Article  ADS  Google Scholar 

  23. L.M. Lee, X. Cui, C. Yang, The application of on-chip optofluidic microscopy for imaging Giardia lamblia trophozoites and cysts. Biomed Microdevices 11(5), 951–958 (2009)

    Article  Google Scholar 

  24. X. Cui et al., Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging. Proc. Natl. Acad. Sci. U. S. A. 105(31), 10670–10675 (2008)

    Article  ADS  Google Scholar 

  25. D.N. Breslauer, R.N. Maamari, N.A. Switz, W.A. Lam, D.A. Fletcher, Mobile phone based clinical microscopy for global health applications. PLoS One 4(7), e6320 (2009)

    Google Scholar 

  26. J. Garcia-Sucerquia, W. Xu, S.K. Jericho, P. Klages, M.H. Jericho, H.J. Kreuzer, Digital in-line holographic microscopy. Appl. Opt. 45, 836–850 (2006)

    Article  ADS  Google Scholar 

  27. W. Xu, M.H. Jericho, I.A. Meinertzhagen, H.J. Kreuzer, Digital in-line holography for biological applications. Proc. Natl. Acad. Sci. 98, 11301–11305 (2001)

    Article  ADS  Google Scholar 

  28. D. Gabor, A new microscopic principle. Nature 161, 777–778 (1948)

    Article  ADS  Google Scholar 

  29. J.W. Goodman, Introduction to Fourier optics (Roberts, Greenwood Village, 2005)

    Google Scholar 

  30. I. Yamaguchi, T. Zhang, Phase-shifting digital holography. Opt. Lett. 22, 1268–1270 (1997)

    Article  ADS  Google Scholar 

  31. E.N. Leith, J. Upatnieks, K.A. Haines, Microscopy by wavefront reconstruction. J. Opt. Soc. Am. 55, 981-986 (1965)

    Article  ADS  Google Scholar 

  32. G. Situ, J.T. Sheridan, Holography: an interpretation from the phase-space point of view. Opt. Lett. 32(24), 3492 (2007)

    Google Scholar 

  33. J.R. Fienup, Reconstruction of an object from the modulus of its Fourier transform. Opt Lett. 3(1), 27 (1978)

    Google Scholar 

  34. A. Banjanovic, Special report: towards universal global mobile phone coverage. Euromonitor International, 2009

    Google Scholar 

  35. Z.J. Smith, K. Chu, A.R. Espenson, M. Rahimzadeh, A. Gryshuk, M. Molinaro, D.M. Dwyre, S. Lane, D. Matthwes, S.W. Hogiu, Cell-phone-based platform for biomedical device development and education applications. PLos One 6, e17150 (2011)

    Article  ADS  Google Scholar 

  36. S. Tachakra, X.H. Wang, R.S. Istepanian, Y.H. Song, Mobile e-health: the unwired evolution of telemedicine. Telemed. J. E. Health 9, 247–257 (2003)

    Article  Google Scholar 

  37. Y. Granot, A. Ivorra, B. Rubinsky, A new concept for medical imaging centered on cellular phone technology. PLoS One 3, e2075 (2008)

    Article  ADS  Google Scholar 

  38. J.M. Ruano-Lopez, M. Agirregabiria, G. Olabarria, D. Verdoy, D.D. Bang, M. Bu, A. Wolff, A. Voigt, J.A. Dziuban, R. Walczakg, J. Berganzoa, The SmartBioPhone, a point of care vision under development through two European projects: OPTOLABCARD and LABONFOIL. Lab Chip 9, 1495–1499 (2009)

    Article  Google Scholar 

  39. S.C. Park, M.K. Park, M.G. Kang, Super-resolution image reconstruction: a technical overview. IEEE Signal Process. Mag. 20(3), 21–36 (2003)

    Article  ADS  Google Scholar 

  40. R.C. Hardie, High-resolution image reconstruction from a sequence of rotated and translated frames and its application to an infrared imaging system. Opt. Eng. 37(1), 247 (1998)

    Google Scholar 

  41. J. Hahn, S. Lim, K. Choi, R. Horisaki, D.J. Brady, Video-rate compressive holographic microscopic tomography. Opt Exp. 19, 7289–7298 (2011)

    Article  ADS  Google Scholar 

  42. D. J. Brady, K. Choi, D.L. Marks, R. Horisaki, S. Lim, Compressive holography. Opt Exp. 17, 13040–13049 (2009)

    Google Scholar 

  43. H. Meng, F. Hussain, In-line recording and off-axis viewing technique for holographic particle velocimetry. Appl. Opt. 34, 1827–1840 (1995)

    Article  ADS  Google Scholar 

  44. J.B. Pawley (ed.), Handbook of Biological Confocal Microscopy (Plenum, New York, 1995)

    Google Scholar 

  45. J.G. Fujimoto, Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat. Biotech. 21, 1361–1367 (2003)

    Article  Google Scholar 

  46. J.M. Schmitt, Optical coherence tomography (OCT): a review. J. Sel. Top. Quant. Elect. 5, 1205–1215 (1999)

    Article  Google Scholar 

  47. J. Huisken, J. Swoger, F.D. Bene, J. Wittbrodt, E.H.K. Stelzer, Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science 305, 1007–1009 (2004)

    Article  ADS  Google Scholar 

  48. P.J. Keller, A.D. Schmidt, J. Wittbrodt, E.H.K. Stelzer, Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy. Science 322, 1065–1069 (2008)

    Article  ADS  Google Scholar 

  49. J. Sharpe, U. Ahlgren, P. Perry, B. Hill, A. Ross, J. Hecksher-Sørensen, R. Baldock, D. Davidson, Optical projection tomography as a tool for 3D microscopy and gene expression studies. Science 296, 541–545 (2002)

    Article  ADS  Google Scholar 

  50. B. Huang, W. Wang, M. Bates, X. Zhuang, Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science 319, 810–813 (2008)

    Article  ADS  Google Scholar 

  51. M. Fauver, E.J. Seibel, Three-dimensional imaging of single isolated cell nuclei using optical projection tomography. Opt Exp. 13, 4210–4223 (2005)

    Article  ADS  Google Scholar 

  52. T.C. Poon, M.H. Wu, K. Shinoda, Y. Suzuki, Optical scanning holography. Proc. IEEE 84(5), 753–764 (1996)

    Article  Google Scholar 

  53. Y. Sung, W. Choi, C. Fang-Yen, K. Badizadegan, R.R. Dasari, M.S. Feld, Optical diffraction tomography for high resolution live cell imaging. Opt. Exp. 17, 266–277 (2009)

    Article  ADS  Google Scholar 

  54. M. Debailleul, B. Simon, V. Georges, O. Haeberle, V. Lauer, Holographic microscopy and diffractive microtomography of transparent samples. Meas. Sci. Technol. 19, 074009 (2008)

    Article  ADS  Google Scholar 

  55. F. Charrière, N. Pavillon, T. Colomb, C. Depeursinge, T.J. Heger, E.A.D. Mitchell, P. Marquet, B. Rappaz, Living specimen tomography by digital holographic microscopy: morphometry of testate amoeba. Opt. Exp. 14, 7005–7013 (2006)

    Article  ADS  Google Scholar 

  56. L. Yu, M.K. Kim, Wavelength-scanning digital interference holography for tomographic three-dimensional imaging by use of the angular spectrum method. Opt. Lett. 30, 2092–2094 (2005)

    Article  ADS  Google Scholar 

  57. J. Jang, B. Javidi, Formation of orthoscopic three-dimensional real images in direct pickup one-step integral imaging. Opt. Eng. 42, 1869–1870 (2003)

    Article  ADS  Google Scholar 

  58. O. Haeberle, K. Belkebir, H. Giovaninni, A. Sentenac, Tomographic diffractive microscopy: basics, techniques and perspectives. J. Mod. Optic 57, 686–699 (2010)

    Article  ADS  MATH  Google Scholar 

  59. M. Radermacher, Weighted Back-Projection Methods. Electron Tomography: Methods for Three Dimensional Visualization of Structures in the Cell, 2nd edn. (Springer, New York, 2006)

    Google Scholar 

  60. M. Born, E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, 7th edn. (Cambridge University Press, Cambridge, UK, 1999). ch. XIII

    Google Scholar 

  61. G.M. Whitesides, The origins and the future of microfluidics. Nature 442(7101), 368–373 (2006)

    Article  ADS  Google Scholar 

  62. D. Psaltis, S.R. Quake, and C. Yang, Developing optofluidic technology through the fusion of microfluidics and optics. Nature 442(7101), 381–386 (2006)

    Article  ADS  Google Scholar 

  63. W. Bishara, H. Zhu, A. Ozcan, Holographic opto-fluidic microscopy. Opt. Exp. 18(26), 27499 (2010)

    Google Scholar 

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Author information

Authors and Affiliations

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

    Serhan O. Isikman, Waheb Bishara, Onur Mudanyali, Ting-Wei Su, Derek Tseng & Aydogan Ozcan

  2. California NanoSystems Institute, Bioengineering Department, Department of Surgery, University of California, Los Angeles, USA

    Aydogan Ozcan

Authors
  1. Serhan O. Isikman
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  2. Waheb Bishara
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  3. Onur Mudanyali
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  4. Ting-Wei Su
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  5. Derek Tseng
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  6. Aydogan Ozcan
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Correspondence to Aydogan Ozcan .

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Editors and Affiliations

  1. , Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, 19104-6321, Pennsylvania, USA

    David Issadore

  2. , School of Engineering, Applied Sciences, Harvard University, Oxford Street 29, Cambridge, 02138, Massachusetts, USA

    Robert M. Westervelt

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Isikman, S.O., Bishara, W., Mudanyali, O., Su, TW., Tseng, D., Ozcan, A. (2013). Lensfree Computational Microscopy Tools for On-Chip Imaging of Biochips. In: Issadore, D., Westervelt, R. (eds) Point-of-Care Diagnostics on a Chip. Biological and Medical Physics, Biomedical Engineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29268-2_4

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  • DOI: https://doi.org/10.1007/978-3-642-29268-2_4

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