OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 3, Iss. 5 — May. 1, 2012
  • pp: 991–1005

Toward fast malaria detection by secondary speckle sensing microscopy

Dan Cojoc, Sara Finaurini, Pavel Livshits, Eran Gur, Alon Shapira, Vicente Mico, and Zeev Zalevsky  »View Author Affiliations

Biomedical Optics Express, Vol. 3, Issue 5, pp. 991-1005 (2012)

View Full Text Article

Enhanced HTML    Acrobat PDF (2200 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



Diagnosis of malaria must be rapid, accurate, simple to use, portable and low cost, as suggested by the World Health Organization (WHO). Despite recent efforts, the gold standard remains the light microscopy of a stained blood film. This method can detect low parasitemia and identify different species of Plasmodium. However, it is time consuming, it requires well trained microscopist and good instrumentation to minimize misinterpretation, thus the costs are considerable. Moreover, the equipment cannot be easily transported and installed. In this paper we propose a new technique named “secondary speckle sensing microscopy” (S3M) based upon extraction of correlation based statistics of speckle patterns generated while illuminating red blood cells with a laser and inspecting them under a microscope. Then, using fuzzy logic ruling and principle component analysis, good quality of separation between healthy and infected red blood cells was demonstrated in preliminary experiments. The proposed technique can be used for automated high rate detection of malaria infected red blood cells.

© 2012 OSA

OCIS Codes
(120.6160) Instrumentation, measurement, and metrology : Speckle interferometry
(170.0180) Medical optics and biotechnology : Microscopy
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(170.1530) Medical optics and biotechnology : Cell analysis
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine
(170.6480) Medical optics and biotechnology : Spectroscopy, speckle

ToC Category:
Cell Studies

Original Manuscript: February 3, 2012
Revised Manuscript: March 15, 2012
Manuscript Accepted: March 23, 2012
Published: April 18, 2012

Dan Cojoc, Sara Finaurini, Pavel Livshits, Eran Gur, Alon Shapira, Vicente Mico, and Zeev Zalevsky, "Toward fast malaria detection by secondary speckle sensing microscopy," Biomed. Opt. Express 3, 991-1005 (2012)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. WHO, ed., “World Malaria Report: 2010,” in WHO Library Cataloguing in Publication Data, http://www.who.int/malaria/world_malaria_report_2010/en/index.html .
  2. WHO, “Microscopy Quality Assurance Manual” (2009), http://www.searo.who.int/LinkFiles/Malaria_MalariaMicroscopyManual .
  3. C. K. Murray, R. A. Gasser, A. J. Magill, and R. S. Miller, “Update on rapid diagnostic testing for malaria,” Clin. Microbiol. Rev.21(1), 97–110 (2008). [CrossRef] [PubMed]
  4. C. Wongsrichanalai, M. J. Barcus, S. Muth, A. Sutamihardja, and W. H. Wernsdorfer, “A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT),” Am. J. Trop. Med. Hyg.77(6Suppl), 119–127 (2007). [PubMed]
  5. Centers for Disease Control and Prevention, “Malaria,” www.cdc.gov/malaria .
  6. A. Fontaine, S. Bourdon, M. Belghazi, M. Pophillat, P. Fourquet, S. Granjeaud, M. Torrentino-Madamet, C. Rogier, T. Fusai, and L. Almeras, “Plasmodium falciparum infection-induced changes in erythrocyte membrane proteins,” Parasitol. Res.110(2), 545–556 (2012). [CrossRef] [PubMed]
  7. A. G. Maier, B. M. Cooke, A. F. Cowman, and L. Tilley, “Malaria parasite proteins that remodel the host erythrocyte,” Nat. Rev. Microbiol.7(5), 341–354 (2009). [CrossRef] [PubMed]
  8. J. P. Shelby, J. White, K. Ganesan, P. K. Rathod, and D. T. Chiu, “A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes,” Proc. Natl. Acad. Sci. U.S.A.100(25), 14618–14622 (2003). [CrossRef] [PubMed]
  9. J. P. Mills, M. Diez-Silva, D. J. Quinn, M. Dao, M. J. Lang, K. S. W. Tan, C. T. Lim, G. Milon, P. H. David, O. Mercereau-Puijalon, S. Bonnefoy, and S. Suresh, “Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.104(22), 9213–9217 (2007). [CrossRef] [PubMed]
  10. A. M. Dondorp, K. T. Chotivanich, S. Fucharoen, K. Silamut, J. Vreeken, P. A. Kager, and N. J. White, “Red cell deformability, splenic function and anaemia in thalassaemia,” Br. J. Haematol.105(2), 505–508 (1999). [CrossRef] [PubMed]
  11. A. M. Dondorp, P. A. Kager, J. Vreeken, and N. J. White, “Abnormal blood flow and red blood cell deformability in severe malaria,” Parasitol. Today (Regul. Ed.)16(6), 228–232 (2000). [CrossRef] [PubMed]
  12. F. Omodeo-Salè, A. Motti, N. Basilico, S. Parapini, P. Olliaro, and D. Taramelli, “Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum,” Blood102(2), 705–711 (2003). [CrossRef] [PubMed]
  13. F. Omodeo-Salè, A. Motti, A. Dondorp, N. J. White, and D. Taramelli, “Destabilisation and subsequent lysis of human erythrocytes induced by Plasmodium falciparum haem products,” Eur. J. Haematol.74(4), 324–332 (2005). [CrossRef] [PubMed]
  14. C. A. Moxon, G. E. Grau, and A. G. Craig, “Malaria: modification of the red blood cell and consequences in the human host,” Br. J. Haematol.154(6), 670–679 (2011). [CrossRef] [PubMed]
  15. M. G. Millholland, R. Chandramohanadas, A. Pizzarro, A. Wehr, H. Shi, C. Darling, C. T. Lim, and D. C. Greenbaum, “The malaria parasite progressively dismantles the host erythrocyte cytoskeleton for efficient egress,” Mol. Cell. Proteomics10(12), M111.010678 (2011). [CrossRef] [PubMed]
  16. S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, “Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria,” Acta Biomater.1(1), 15–30 (2005). [CrossRef] [PubMed]
  17. L. Gervais, N. de Rooij, and E. Delamarche, “Microfluidic chips for point-of-care immunodiagnostics,” Adv. Mater. (Deerfield Beach Fla.)23(24), H151–H176 (2011). [CrossRef] [PubMed]
  18. R. Fan, O. Vermesh, A. Srivastava, B. K. H. Yen, L. Qin, H. Ahmad, G. A. Kwong, C.-C. Liu, J. Gould, L. Hood, and J. R. Heath, “Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood,” Nat. Biotechnol.26(12), 1373–1378 (2008). [CrossRef] [PubMed]
  19. R. Lima, T. Ishikawa, Y. Imai, M. Takeda, S. Wada, and T. Yamaguchi, “Radial dispersion of red blood cells in blood flowing through glass capillaries: the role of hematocrit and geometry,” J. Biomech.41(10), 2188–2196 (2008). [CrossRef] [PubMed]
  20. H. W. Hou, A. A. S. Bhagat, A. G. L. Chong, P. Mao, K. S. W. Tan, J. Han, and C. T. Lim, “Deformability based cell margination--a simple microfluidic design for malaria-infected erythrocyte separation,” Lab Chip10(19), 2605–2613 (2010). [CrossRef] [PubMed]
  21. H. Bow, I. V. Pivkin, M. Diez-Silva, S. J. Goldfless, M. Dao, J. C. Niles, S. Suresh, and J. Han, “A microfabricated deformability-based flow cytometer with application to malaria,” Lab Chip11(6), 1065–1073 (2011). [CrossRef] [PubMed]
  22. G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, “Diffraction phase microscopy for quantifying cell structure and dynamics,” Opt. Lett.31(6), 775–777 (2006). [CrossRef] [PubMed]
  23. G. Popescu, Y. Park, W. Choi, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Imaging red blood cell dynamics by quantitative phase microscopy,” Blood Cells Mol. Dis.41(1), 10–16 (2008). [CrossRef] [PubMed]
  24. G. Popescu, Y. K. Park, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Diffraction phase and fluorescence microscopy,” Opt. Express14(18), 8263–8268 (2006). [CrossRef] [PubMed]
  25. Y. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008). [CrossRef] [PubMed]
  26. N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A113(47), 13327–13330 (2009). [CrossRef] [PubMed]
  27. C. S. Yelleswarapu, M. Tipping, S. R. Kothapalli, A. Veraksa, and D. V. Rao, “Common-path multimodal optical microscopy,” Opt. Lett.34(8), 1243–1245 (2009). [CrossRef] [PubMed]
  28. N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J Biophotonics3(7), 432–436 (2010). [CrossRef] [PubMed]
  29. Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010). [CrossRef] [PubMed]
  30. Z. Zalevsky and J. Garcia, “Motion detection system and method,” Israeli Patent Application No. 184868 (July 2007); WO/2009/013738 International Application No. PCT/IL2008/001008 (July 2008).
  31. Y. Beiderman, A. D. Amsel, Y. Tzadka, D. Fixler, V. Mico, J. Garcia, M. Teicher, and Z. Zalevsky, “A microscope configuration for nanometer 3-D movement monitoring accuracy,” Micron42(4), 366–375 (2011). [CrossRef] [PubMed]
  32. Y. Beiderman, I. Horovitz, N. Burshtein, M. Teicher, J. Garcia, V. Mico, and Z. Zalevsky, “Remote estimation of blood pulse pressure via temporal tracking of reflected secondary speckles pattern,” J. Biomed. Opt.15(6), 061707 (2010). [CrossRef] [PubMed]
  33. Y. Beiderman, R. Blumenberg, N. Rabani, M. Teicher, J. Garcia, V. Mico, and Z. Zalevsky, “Demonstration of remote optical measurement configuration that correlates to glucose concentration in blood,” Biomed. Opt. Express2(4), 858–870 (2011). [CrossRef] [PubMed]
  34. W. Trager and J. B. Jensen, “Human malaria parasites in continuous culture,” Science193(4254), 673–675 (1976). [CrossRef] [PubMed]
  35. L. A. Zadeh, “Fuzzy sets,” Inf. Control8(3), 338–353 (1965). [CrossRef]
  36. M. Schneider, A. Kandel, G. Langholz, and G. Chew, Fuzzy Expert System Tools (Wiley, 1996).
  37. E. Gur, D. Mendlovic, and Z. Zalevsky, “Optical implementation of fuzzy-logic controllers. Part I,” Appl. Opt.37(29), 6937–6945 (1998). [CrossRef] [PubMed]
  38. K. Pearson, “On lines and planes of closest fit to systems of points in space,” Philos. Mag.2, 559–572 (1901).
  39. S. Wold, K. Esbensen, and P. Geladi, “Principal component analysis,” Chemom. Intell. Lab. Syst.2(1-3), 37–52 (1987). [CrossRef]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited