No Access Submitted: 06 November 2020 Accepted: 17 December 2020 Published Online: 05 January 2021
Biomicrofluidics 15, 014102 (2021); https://doi.org/10.1063/5.0036585
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  • Julián Mejía Morales
  • Björn Hammarström
  • Gian Luca Lippi
  • Massimo Vassalli
  • Peter Glynne-Jones
A low-cost device for registration-free quantitative phase microscopy (QPM) based on the transport of intensity equation of cells in continuous flow is presented. The method uses acoustic focusing to align cells into a single plane where all cells move at a constant speed. The acoustic focusing plane is tilted with respect to the microscope’s focal plane in order to obtain cell images at multiple focal positions. As the cells are displaced at constant speed, phase maps can be generated without the need to segment and register individual objects. The proposed inclined geometry allows for the acquisition of a vertical stack without the need for any moving part, and it enables a cost-effective and robust implementation of QPM. The suitability of the solution for biological imaging is tested on blood samples, demonstrating the ability to recover the phase map of single red blood cells flowing through the microchip.
The authors would like to thank Dr. Stéphane Barland (UCA Nice) and Dr. Marco Sartore (ElbaTech SRL) for fruitful discussions. J.M.M. acknowledges the funding for international mobility France–Italy provided by the Université Franco Italienne (UFI, Project No. C2-1031) and the Mexican Council of Science and Technology (CONACyT) scholarship (No. 471712). P.G.J. gratefully acknowledges fellowship funding by the UK EPSRC (No. EP/L025035/1). This work has also been supported by the French government through the UCAJEDI Investments in the Future project managed by the National Research Agency (ANR) with Reference No. ANR-15-IDEX-01.
  1. 1. A. Barty, K. A. Nugent, D. Paganin, and A. Roberts, Opt. Lett. 23, 817 (1998). https://doi.org/10.1364/ol.23.000817, Google ScholarCrossref
  2. 2. Y. Park, C. Depeursinge, and G. Popescu, Nat. Photonics 12, 578 (2018). https://doi.org/10.1038/s41566-018-0253-x, Google ScholarCrossref
  3. 3. C. L. Curl, C. J. Bellair, P. J. Harris, B. E. Allman, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, Cell. Physiol. Biochem. 17, 193–200 (2006). https://doi.org/10.1159/000094124, Google ScholarCrossref
  4. 4. W.-J. Zhou, X. Guan, F. Liu, Y. Yu, H. Zhang, T.-C. Poon, and P. P. Banerjee, Appl. Opt. 57, A229–A234 (2018). https://doi.org/10.1364/AO.57.00A229, Google ScholarCrossref
  5. 5. S. Zhang, J. Cheng, and Y.-X. Qin, PLoS ONE 7, e38343 (2012). https://doi.org/10.1371/journal.pone.0038343, Google ScholarCrossref
  6. 6. I. Vasilenko, V. Metelin, M. Nasyrov, V. Belyakov, A. Kuznetsov, and E. Sukhenko, Quant. Phase Imaging 9336, 2078661 (2015). https://doi.org/10.1117/12.2078661, Google ScholarCrossref
  7. 7. C. Martinez Torres, B. Laperrousaz, L. Berguiga, E. Boyer Provera, J. Elezgaray, F. E. Nicolini, V. Maguer-Satta, A. Arneodo, and F. Argoul, Quant. Phase Imaging II 9718, 97182C (2016). https://doi.org/10.1117/12.2211314, Google ScholarCrossref
  8. 8. T. Yamauchi, H. Iwai, and Y. Yamashita, Opt. Express 19, 5536 (2011). https://doi.org/10.1364/oe.19.005536, Google ScholarCrossref
  9. 9. J. Jung, L. E. Matemba, K. Lee, P. E. Kazyoba, J. Yoon, J. J. Massaga, K. Kim, D.-J. Kim, Y. Park, and Y. Park, “Characterizations of erythrocytes from individuals with sickle cell diseases and Malaria infection in Tanzania using a portable quantitative phase imaging unit,” in International Conference on Photonics and Imaging in Biology and Medicine (Optical Society of America, 2017), p. W3A.115. Google Scholar
  10. 10. M. T. Rinehart, H. S. Park, K. A. Walzer, J.-T. A. Chi, and A. Wax, Sci. Rep. 6, 1–9 (2016). https://doi.org/10.1038/srep24461, Google ScholarCrossref
  11. 11. Y. Ma, S. Guo, Y. Pan, R. Fan, Z. J. Smith, S. Lane, and K. Chu, J. Biophotonics 12, e201900011 (2019). https://doi.org/10.1002/jbio.201900011, Google ScholarCrossref
  12. 12. S. S. Kou, L. Waller, G. Barbastathis, and C. J. R. Sheppard, Opt. Lett. 35, 447–449 (2010). https://doi.org/10.1364/OL.35.000447, Google ScholarCrossref
  13. 13. P. K. Poola, V. Jayaraman, K. Chaithanya, D. Rao, and R. John, OSA Contin. 1, 1215 (2018). https://doi.org/10.1364/OSAC.1.001215, Google ScholarCrossref
  14. 14. C. Zuo, Q. Chen, W. Qu, and A. Asundi, Opt. Express 21, 24060–24075 (2013). https://doi.org/10.1364/OE.21.024060, Google ScholarCrossref
  15. 15. K. Lee and Y. Park, Opt. Lett. 39, 3630 (2014). https://doi.org/10.1364/ol.39.003630, Google ScholarCrossref
  16. 16. L. Waller, S. S. Kou, C. J. R. Sheppard, and G. Barbastathis, Opt. Express 18, 22817 (2010). https://doi.org/10.1364/OE.18.022817, Google ScholarCrossref
  17. 17. W. Yu, X. Tian, X. He, X. Song, L. Xue, C. Liu, and S. Wang, Appl. Phys. Lett. 109, 071112 (2016). https://doi.org/10.1063/1.4961383, Google ScholarScitation, ISI
  18. 18. R. Zmijan, U. S. Jonnalagadda, D. Carugo, Y. Kochi, E. Lemm, G. Packham, M. Hill, and P. Glynne-Jones, RSC Adv. 5, 83206 (2015). https://doi.org/10.1039/C5RA19497K, Google ScholarCrossref
  19. 19. O. Jakobsson, M. Antfolk, and T. Laurell, Anal. Chem. 86, 6111 (2014), pMID: 24863098. https://doi.org/10.1021/ac5012602, Google ScholarCrossref
  20. 20. F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. d’Ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, Light Sci. Appl. 6, e16241 (2016). https://doi.org/10.1038/lsa.2016.241, Google ScholarCrossref
  21. 21. P. Glynne-Jones, R. J. Boltryk, and M. Hill, Lab Chip 12, 1417 (2012). https://doi.org/10.1039/C2LC21257A, Google ScholarCrossref
  22. 22. C. Willert, B. Stasicki, J. Klinner, and S. Moessner, Meas. Sci. Technol. 21, 075402 (2010). https://doi.org/10.1088/0957-0233/21/7/075402, Google ScholarCrossref
  23. 23. S. van der Walt, J. L. Schönberger, J. Nunez-Iglesias, F. Boulogne, J. D. Warner, N. Yager, E. Gouillart, and T. Yu, and the scikit-image contributors, PeerJ 2, e453 (2014). https://doi.org/10.7717/peerj.453, Google ScholarCrossref
  24. 24. T. Sun, Z. Zhuo, W. Zhang, J. Lu, and P. Lu, Laser Phys. 28, 125601 (2018). https://doi.org/10.1088/1555-6611/aae036, Google ScholarCrossref
  25. 25. S. S. Gorthi and E. Schonbrun, Opt. Lett. 37, 707 (2012). https://doi.org/10.1364/ol.37.000707, Google ScholarCrossref
  26. 26. E. Bostan, E. Froustey, M. Nilchian, D. Sage, and M. Unser, “Variational phase imaging using the transport-of-intensity equation,” IEEE Trans. Image Process. 25(2), 807–817 (2016). https://doi.org/10.1109/TIP.2015.2509249, Google ScholarCrossref
  27. 27. C. R. Harris, K. J. Millman, S. J. van der Walt, R. Gommers, P. Virtanen, D. Cournapeau, E. Wieser, J. Taylor, S. Berg, N. J. Smith, R. Kern, M. Picus, S. Hoyer, M. H. van Kerkwijk, M. Brett, A. Haldane, J. F. del Río, M. Wiebe, P. Peterson, P. Gérard-Marchant, K. Sheppard, T. Reddy, W. Weckesser, H. Abbasi, C. Gohlke, and T. E. Oliphant, Nature 585, 357 (2020). https://doi.org/10.1038/s41586-020-2649-2, Google ScholarCrossref
  28. 28. B. Hammarström, M. Vassalli, and P. Glynne-Jones, J. Appl. Phycol. 32, 339 (2019). https://doi.org/10.1007/s10811-019-01907-5, Google ScholarCrossref
  29. 29. N. C. Pégard and J. W. Fleischer, J. Biomed. Opt. 18, 040503 (2013). https://doi.org/10.1117/1.jbo.18.4.040503, Google ScholarCrossref
  30. 30. V. K. Jagannadh, M. D. Mackenzie, P. Pal, A. K. Kar, and S. S. Gorthi, Opt. Express 24, 22144 (2016). https://doi.org/10.1364/oe.24.022144, Google ScholarCrossref
  31. 31. N. O. Loewke, S. Pai, C. Cordeiro, D. Black, B. L. King, C. H. Contag, B. Chen, T. M. Baer, and O. Solgaard, IEEE. Trans. Med. Imaging 37, 929 (2018). https://doi.org/10.1109/tmi.2017.2775604, Google ScholarCrossref
  32. 32. N. R. Patel, V. K. Chhaniwal, B. Javidi, and A. Anand, Advanced Microscopy Techniques IV; and Neurophotonics II (OSA, 2015). Google Scholar
  33. 33. V. Bianco, P. Memmolo, P. Carcagnì, F. Merola, M. Paturzo, C. Distante, and P. Ferraro, Adv. Intel. Syst. 2, 1900153 (2020). https://doi.org/10.1002/aisy.201900153, Google ScholarCrossref
  34. 34. T. Go, J. H. Kim, H. Byeon, and S. J. Lee, J. Biophotonics 11, e201800101 (2018). https://doi.org/10.1002/jbio.201800101, Google ScholarCrossref
  35. 35. F. A. M. Ramírez, E. M. Rodriguez, C. A. O. Castelblanco, and M. Camacho, in Optical Methods for Inspection, Characterization, and Imaging of Biomaterials III, edited by P. Ferraro, M. Ritsch-Marte, S. Grilli, and C. K. Hitzenberger (SPIE, 2017). Google Scholar
  36. 36. B. Rappaz, B. Breton, E. Shaffer, and G. Turcatti, Comb. Chem. High Throughput Screen. 17, 80 (2014). https://doi.org/10.2174/13862073113166660062, Google ScholarCrossref
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