Annals of Biomedical Engineering

, Volume 42, Issue 1, pp 231–240 | Cite as

Optical Systems for Point-of-care Diagnostic Instrumentation: Analysis of Imaging Performance and Cost

  • Mark C. Pierce
  • Shannon E. Weigum
  • Jacob M. Jaslove
  • Rebecca Richards-Kortum
  • Tomasz S. TkaczykEmail author


One of the key elements in point-of-care (POC) diagnostic test instrumentation is the optical system required for signal detection and/or imaging. Many tests which use fluorescence, absorbance, or colorimetric optical signals are under development for management of infectious diseases in resource limited settings, where the overall size and cost of the device is of critical importance. At present, high-performance lenses are expensive to fabricate and difficult to obtain commercially, presenting barriers for developers of in vitro POC tests or microscopic image-based diagnostics. We recently described a compact “hybrid” objective lens incorporating both glass and plastic optical elements, with a numerical aperture of 1.0 and field-of-view of 250 μm. This design concept may potentially enable mass-production of high-performance, low-cost optical systems which can be easily incorporated in the readout path of existing and emerging POC diagnostic assays. In this paper, we evaluate the biological imaging performance of these lens systems in three broad POC diagnostic application areas; (1) bright field microscopy of histopathology slides, (2) cytologic examination of blood smears, and (3) immunofluorescence imaging. We also break down the fabrication costs and draw comparisons with other miniature optical systems. The hybrid lenses provided images with quality comparable to conventional microscopy, enabling examination of neoplastic pathology and infectious parasites including malaria and cryptosporidium. We describe how these components can be produced at below $10 per unit in full-scale production quantities, making these systems well suited for use within POC diagnostic instrumentation.


POC optics Miniature optics Cost assessment Diagnostic imaging performance 



We thank Dr. Nadarajah Vigneswaran at The University of Texas Health Science Center, Dental Branch, Houston, for his help and expertise in reviewing the oral pathology slides. We also thank Dr. Robert Kester at Rice University for his initial editing input of the paper material. This research was supported by the National Cancer Institute (NCI) under Grants R01 CA124319 and R01 CA103830.


  1. 1.
    Arpa, A., G. Wetzstein, D. Lanman, and R. Raskar. Single lens off-chip cellphone microscopy. In: IEEE International Workshop on Projector-Camera Systems (PROCAMS), 2012.Google Scholar
  2. 2.
    Barretto, R. P. J., B. Messerschmidt, and M. J. Schnitzer. In vivo fluorescence imaging with high resolution microlenses. Nat. Methods 6:511–512, 2009.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Behr, M. A., E. Kokoskin, T. W. Gyorkos, L. Cédilotte, G. M. Faubert, and J. D. MacLean. Laboratory diagnosis for Giardia lamblia infection: a comparison of microscopy, coprodiagnosis and serology. Can. J. Infect. Dis. 8:33–38, 1996.Google Scholar
  4. 4.
    Bray, F., and B. Møller. Predicting the future burden of cancer. Nat. Rev. Cancer 6:63–74, 2006.PubMedCrossRefGoogle Scholar
  5. 5.
    Breslauer, D. N., R. N. Maamari, N. A. Switz, W. A. Lam, and D. A. Fletcher. Mobile phone based clinical microscopy for global health applications. PLoS ONE 4:e6320, 2009.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Brun, R., J. Blum, F. Chappuis, and C. Burri. Human African trypanosomiasis. Lancet 375:148–159, 2010.PubMedCrossRefGoogle Scholar
  7. 7.
    Camou, S., H. Fujita, and T. Fujii. PDMS 2D optical lens integrated with microfluidic channels: principle and characterization. Lab Chip 3:40–45, 2003.PubMedCrossRefGoogle Scholar
  8. 8.
    Chalmers, R. M., and F. Katzer. Looking for Cryptosporidium: the application of advances in detection and diagnosis. Trends Parasitol. 29:237–251, 2013.PubMedCrossRefGoogle Scholar
  9. 9.
    Chidley, M. D., K. D. Carlson, R. R. Richards-Kortum, and M. R. Descour. Design, assembly, and optical bench testing of a high-numerical-aperture miniature injection-molded objective for fiber-optic confocal reflectance microscopy. Appl. Opt. 45:2545–2554, 2006.PubMedCrossRefGoogle Scholar
  10. 10.
    Chin, C. D., V. Linder, and S. K. Sia. Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip 7:41–57, 2007.PubMedCrossRefGoogle Scholar
  11. 11.
    Chinowsky, T. M., M. S. Grow, K. S. Johnston, K. Nelson, T. Edwards, E. Fu, and P. Yager. Compact, high performance surface plasmon resonance imaging system. Biosens. Bioelectron. 22:2208–2215, 2007.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Farmer, P., J. Frenk, F. M. Knaul, L. N. Shulman, G. Alleyne, L. Armstrong, R. Atun, D. Blayney, L. Chen, R. Feachem, M. Gospodarowicz, J. Gralow, S. Gupta, A. Langer, J. Lob-Levyt, C. Neal, A. Mbewu, D. Mired, P. Piot, K. S. Reddy, J. D. Sachs, M. Sarhan, and J. R. Seffrin. Expansion of cancer care and control in countries of low and middle income: a call to action. Lancet 376:1186–1193, 2010.PubMedCrossRefGoogle Scholar
  13. 13.
    Greenbaum, A., A. Feizi, N. Akbari, and A. Ozcan. Wide-field computational color imaging using pixel super-resolved on-chip microscopy. Opt. Express 10:12469–12483, 2013.CrossRefGoogle Scholar
  14. 14.
    Greenbaum, A., W. Luo, B. Khademhosseinieh, T.-W. Su, A. F. Coskun, and A. Ozcan. Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy. Sci. Rep. 3:1717, 2013.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Greenbaum, A., W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan. Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy. Nat. Methods 9:889–895, 2012.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Industrial Machine Sales, Inc. Personal communication.Google Scholar
  17. 17.
    International Agency for Research on Cancer. In: World Cancer Report, edited by P. Boyle and B. Levin. Lyon. IARC, 2008.Google Scholar
  18. 18.
    Kester, R. T., T. Christenson, R. Richards-Kortum, and T. S. Tkaczyk. Low cost, high performance, self-aligning miniature optical systems. Appl. Opt. 48:3375–3384, 2009.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Kester, R. T., T. Tkaczyk, M. R. Descour, T. Christenson, and R. Richards-Kortum. High numerical aperture microendoscope objective for a fiber confocal reflectance microscope. Opt. Express 15:2409–2420, 2007.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee, M., O. Yaglidere, and A. Ozcan. Field-portable reflection and transmission microscopy based on lensless holography. Biomed. Opt. Express 2:2721–2730, 2011.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Lee-Lewandrowski, E., J. L. Januzzi, S. M. Green, B. Tannous, A. H. Wu, A. Smith, A. Wong, M. M. Murakami, J. Kaczmarek, F. S. Apple, W. L. Miller, K. Hartman, and A. S. Jaffe. Multi-center validation of the Response Biomedical Corporation RAMP® NT-proBNP assay with comparison to the Roche Diagnostics GmbH Elecsys® proBNP assay. Clin. Chim. Acta 386:20–24, 2007.PubMedCrossRefGoogle Scholar
  22. 22.
    Liang, C., K. B. Sung, R. R. Richards-Kortum, and M. R. Descour. Design of a high-numerical-aperture miniature microscope objective for an endoscopic fiber confocal reflectance microscope. Appl. Opt. 41:4603–4610, 2002.PubMedCrossRefGoogle Scholar
  23. 23.
    McLeod, E., W. Luo, O. Mudanyali, A. Greenbaum, and A. Ozcan. Toward giga-pixel nanoscopy on a chip: a computational wide-field look at the nano-scale without the use of lenses. Lab Chip 13:2028–2035, 2013.PubMedCrossRefGoogle Scholar
  24. 24.
    Miller, A. R., G. L. Davis, Z. M. Oden, M. R. Razavi, A. Fateh, M. Ghazanfari, F. Abdolrahimi, S. Poorazar, F. Sakhaie, R. J. Olsen, A. R. Bahrmand, M. C. Pierce, E. A. Graviss, and R. Richards-Kortum. Portable, battery-operated, low-cost, bright field and fluorescence microscope. PLoS ONE 5:e11890, 2010.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Minion, J., H. Sohn, and M. Pai. Light-emitting diode technologies for TB diagnosis: what is on the market? Expert Rev. Med. Devices 6:341–345, 2009.PubMedCrossRefGoogle Scholar
  26. 26.
    Myers, F. B., and L. P. Lee. Innovations in optical microfluidic technologies for point-of-care diagnostics. Lab Chip 8:2015–2031, 2008.PubMedCrossRefGoogle Scholar
  27. 27.
    Rodriguez, W. R., N. Christodoulides, P. N. Floriano, S. Graham, S. Mohanty, M. Dixon, M. Hsiang, T. Peter, S. Zavahir, I. Thior, D. Romanovicz, B. Bernard, A. P. Goodey, B. D. Walker, and J. T. McDevitt. A microchip CD4 counting method for HIV monitoring in resource-poor settings. PLoS Med. 2:663–672, 2005.CrossRefGoogle Scholar
  28. 28.
    Seo, J., and L. P. Lee. Disposable integrated microfluidics with self-aligned planar microlenses. Sens. Actuators B 99:615–622, 2004.CrossRefGoogle Scholar
  29. 29.
    Shirley, D. A., S. N. Moonah, and K. L. Kotloff. Burden of disease from cryptosporidiosis. Curr. Opin. Infect. Dis. 25:555–563, 2012.PubMedCrossRefGoogle Scholar
  30. 30.
    Sia, S. K., V. Linder, B. A. Parviz, A. Siegel, and G. M. Whitesides. An integrated approach to a portable and low-cost immunoassay for resource-poor settings. Angew. Chem. Int. Ed. 43:498–502, 2004.CrossRefGoogle Scholar
  31. 31.
    Smith, Z. J., K. Chu, A. R. Espenson, M. Rahimzadeh, A. Gryshuk, M. Molinaro, D. M. Dwyre, S. Lane, D. Mathews, and S. Wachsmann-Hogiu. Cell-phone-based platform for biomedical device development and education applications. PLoS ONE 6:e17150, 2011.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Weigum, S. E., P. N. Floriano, S. W. Redding, C. K. Yeh, S. D. Westbrook, H. S. McGuff, A. Lin, F. R. Miller, F. Villarreal, S. D. Rowan, N. Vigneswaran, M. D. Williams, and J. T. McDevitt. Nano-bio-chip sensor platform for examination of oral exfoliative cytology. Cancer Prev. Res. 3:518–528, 2010.CrossRefGoogle Scholar
  33. 33.
    World Health Organization. Laboratory Services in TB Control, Microscopy Part II. Geneva: WHO, 1998.Google Scholar
  34. 34.
    World Health Organization. Basic Malaria Microscopy: Part I. Learner’s Guide, 2nd ed. Geneva: WHO, 2010.Google Scholar
  35. 35.
    Wu, A. H., A. Smith, R. H. Christenson, M. M. Murakami, and F. S. Apple. Evaluation of a point-of-care assay for cardiac markers for patients suspected of acute myocardial infarction. Clin. Chim. Acta 346:211–219, 2004.PubMedCrossRefGoogle Scholar
  36. 36.
    Yacoub-George, E., W. Hell, L. Meixner, F. Wenninger, K. Bock, P. Lindner, H. Wolf, T. Kloth, and K. A. Feller. Automated 10-channel capillary chip immunodetector for biological agents detection. Biosens. Bioelectron. 22:1368–1375, 2007.PubMedCrossRefGoogle Scholar
  37. 37.
    Ymeti, A., J. Greve, P. V. Lambeck, T. Wink, S. W. van Hovell, T. A. Beumer, R. R. Wijn, R. G. Heideman, V. Subramaniam, and J. S. Kanger. Fast, ultrasensitive virus detection using a Young interferometer sensor. Nano Lett. 7:394–397, 2007.PubMedCrossRefGoogle Scholar
  38. 38.
    Zhu, H., S. O. Isikman, O. Mudanyali, A. Greenbaum, and A. Ozcan. Optical imaging techniques for point-of-care diagnostics. Lab Chip 13:51–67, 2012.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Zhu, H., O. Yaglidere, T. Su, D. Tseng, and A. Ozcan. Cost-effective and compact wide-field fluorescent imaging on a cell-phone. Lab Chip 11:315–322, 2010.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2013

Authors and Affiliations

  • Mark C. Pierce
    • 1
  • Shannon E. Weigum
    • 2
  • Jacob M. Jaslove
    • 1
  • Rebecca Richards-Kortum
    • 2
    • 3
  • Tomasz S. Tkaczyk
    • 2
    • 4
    Email author
  1. 1.Department of Biomedical EngineeringRutgers, The State University of New JerseyPiscatawayUSA
  2. 2.Department of BioengineeringRice UniversityHoustonUSA
  3. 3.Rice 360° - Institute for Global Health TechnologiesRice UniversityHoustonUSA
  4. 4.Department of Electrical and Computer EngineeringRice UniversityHoustonUSA

Personalised recommendations