Skip to main content
SpringerLink
Log in
Book cover

Artificial Intelligence in Label-free Microscopy pp 33–41Cite as

Label-Free High-Throughput Phenotypic Screening

  • Chapter
  • First Online:

  • 1248 Accesses

Abstract

Flow cytometry is a powerful tool for cell counting and biomarker detection in biotechnology and medicine especially with regards to blood analysis. Standard flow cytometers perform cell type classification both by estimating size and granularity of cells using forward- and side-scattered light signals and through the collection of emission spectra of fluorescently labeled cells. However, cell surface labeling as a means of marking cells is often undesirable as many reagents negatively impact cellular viability or provide activating/inhibitory signals, which can alter the behavior of the desired cellular subtypes for downstream applications or analysis. To eliminate the need for labeling, we introduce a label-free imaging-based flow cytometer that measures size and cell protein concentration simultaneously either as a stand-alone instrument or as an add-on to conventional flow cytometers. Cell protein concentration adds a parameter to cell classification, which improves the specificity and sensitivity of flow cytometers without the requirement of cell labeling. This system uses coherent dispersive Fourier transform to perform phase imaging at flow speeds as high as a few meters per second.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Goda, K., & Jalali, B. (2013). Dispersive fourier transformation for fast continuous single-shot measurements. Nature Photonics, 7(2), 102–112.

    Article  Google Scholar 

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

    Article  Google Scholar 

  3. Mahjoubfar, A., Goda, K., Ayazi, A., Fard, A., Kim, S. H., & Jalali, B. (2011). High-speed nanometer-resolved imaging vibrometer and velocimeter. Applied Physics Letters, 98(10), 101107.

    Article  Google Scholar 

  4. Goda, K., Mahjoubfar, A., Wang, C., Fard, A., Adam, J., Gossett, D. R., Ayazi, A., Sollier, E., Malik, O., Chen, E., et al. (2012). Hybrid dispersion laser scanner. Scientific Reports, 2, 445.

    Article  Google Scholar 

  5. Mahjoubfar, A., Goda, K., Wang, C., Fard, A., Adam, J., Gossett, D. R., Ayazi, A., Sollier, E., Malik, O., Chen, E., et al. (2013). 3d ultrafast laser scanner. In SPIE LASE (pp. 86110N–86110N). Washington, DC: International Society for Optics and Photonics.

    Google Scholar 

  6. Goda, K., Ayazi, A., Gossett, D. R., Sadasivam, J., Lonappan, C. K., Sollier, E., Fard, A. M., Hur, S. C., Adam, J., Murray, C., et al. (2012). High-throughput single-microparticle imaging flow analyzer. Proceedings of the National Academy of Sciences, 109(29), 11630–11635.

    Article  Google Scholar 

  7. Carpenter, A. E., Jones, T. R., Lamprecht, M. R., Clarke, C., Kang, I. H., Friman, O., Guertin, D. A., Chang, J. H., Lindquist, R. A., Moffat, J., et al. (2006). Cellprofiler: Image analysis software for identifying and quantifying cell phenotypes. Genome Biology, 7(10), R100.

    Article  Google Scholar 

  8. Popescu, G., Ikeda, T., Goda, K., Best-Popescu, C. A., Laposata, M., Manley, S., Dasari, R. R., Badizadegan, K., & Feld, M. S. (2006). Optical measurement of cell membrane tension. Physical Review Letters, 97(21), 218101.

    Article  Google Scholar 

  9. Grover, W. H., Bryan, A. K., Diez-Silva, M., Suresh, S., Higgins, J. M., & Manalis, S. R. (2011). Measuring single-cell density. Proceedings of the National Academy of Sciences, 108(27), 10992–10996.

    Article  Google Scholar 

  10. Mrema, J. E., Campbell, G. H., Miranda, R., Jaramillo, A. L., & Rieckmann, K. H. (1979). Concentration and separation of erythrocytes infected with plasmodium falciparum by gradient centrifugation. Bulletin of the World Health Organization, 57(1), 133.

    Google Scholar 

  11. Chun, J., Zangle, T. A., Kolarova, T., Finn, R. S., Teitell, M. A., & Reed, J. (2012). Rapidly quantifying drug sensitivity of dispersed and clumped breast cancer cells by mass profiling. Analyst, 137(23), 5495–5498.

    Article  Google Scholar 

  12. Martin, S. J., Bradley, J. G., & Cotter, T. G. (1990). Hl-60 cells induced to differentiate towards neutrophils subsequently die via apoptosis. Clinical & Experimental Immunology, 79(3), 448–453.

    Google Scholar 

  13. Wyllie, A. H., & Morris, R. G. (1982). Hormone-induced cell death. purification ad properties of thymocytes undergoing apoptosis after glucocorticoid treatment. The American Journal of Pathology, 109(1), 78.

    Google Scholar 

  14. Wolff, D. A., & Pertoft, H. (1972). Separation of hela cells by colloidal silica density gradient centrifugation i. separation and partial synchrony of mitotic cells. The Journal of Cell Biology, 55(3), 579–585.

    Article  Google Scholar 

  15. Bista, R. K., Uttam, S., Wang, P., Staton, K., Choi, S., Bakkenist, C. J., Hartman, D.J., Brand, R. E., & Liu, Y. (2011). Quantification of nanoscale nuclear refractive index changes during the cell cycle. Journal of Biomedical Optics, 16(7), 070503–070503.

    Article  Google Scholar 

  16. Bosslet, K., Ruffmann, R., Altevogt, P., & Schirrmacher, V. (1981). A rapid method for the isolation of metastasizing tumour cells from internal organs with the help of isopycnic density-gradient centrifugation in percoll. British Journal of Cancer, 44(3), 356.

    Article  Google Scholar 

  17. Phillips, K. G., Velasco, C. R., Li, J., Kolatkar, A., Luttgen, M., Bethel, K., Duggan, B., Kuhn, P., & McCarty, O. (2012). Optical quantification of cellular mass, volume, and density of circulating tumor cells identified in an ovarian cancer patient. Cancer Molecular Targets and Therapeutics, 2, 72.

    Google Scholar 

  18. Gupta, V., Jafferji, I., Garza, M., Melnikova, V., Hasegawa, D. K., Pethig, R., & Davis, D. W. (2012). ApostreamTM, a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood. Biomicrofluidics, 6(2), 024133.

    Article  Google Scholar 

  19. Tycko, D. H., Metz, M. H., Epstein, E. A., & Grinbaum, A. (1985). Flow-cytometric light scattering measurement of red blood cell volume and hemoglobin concentration. Applied Optics, 24(9), 1355–1365.

    Article  Google Scholar 

  20. Liang, X. J., Liu, A. Q., Lim, C. S., Ayi, T. C., & Yap, P. H. (2007). Determining refractive index of single living cell using an integrated microchip. Sensors and Actuators A: Physical, 133(2), 349–354.

    Article  Google Scholar 

  21. Rappaz, B., Marquet, P., Cuche, E., Emery, Y., Depeursinge, C., & Magistretti, P. (2005). Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy. Optics Express, 13(23), 9361–9373.

    Article  Google Scholar 

  22. Gorthi, S. S., & Schonbrun, E. (2012). Phase imaging flow cytometry using a focus-stack collecting microscope. Optics Letters, 37(4), 707–709.

    Article  Google Scholar 

  23. Vona, G., Sabile, A., Louha, M., Sitruk, V., Romana, S., Schütze, K., Capron, F., Franco, D., Pazzagli, M., Vekemans, M., et al. (2000). Isolation by size of epithelial tumor cells: A new method for the immunomorphological and molecular characterization of circulating tumor cells. The American Journal of Pathology, 156(1), 57–63.

    Article  Google Scholar 

  24. Di Caprio, G., Schaak, D., & Schonbrun, E. F. (2013). Hyperspectral microscopy of flowing cells. In Imaging systems and applications (pp. IM4E–3). Washington, DC: Optical Society of America

    Google Scholar 

  25. Barer, R., & Joseph, S. (1954). Refractometry of living cells part i. Basic principles. Quarterly Journal of Microscopical Science, 3(32), 399–423.

    Google Scholar 

  26. Fard, A. M., Mahjoubfar, A., Goda, K., Gossett, D. R., Di Carlo, D., & Jalali, B. (2011). Nomarski serial time-encoded amplified microscopy for high-speed contrast-enhanced imaging of transparent media. Biomedical Optics Express, 2(12), 3387–3392.

    Article  Google Scholar 

  27. Boyraz, O., Kim, J., Islam, M. N., Coppinger, F., & Jalali, B. (2000). Broadband, high-brightness 10-gbit/s supercontinuum source for a/d conversion. In Conference on Lasers and Electro-Optics, 2000. (CLEO 2000) (pp. 489–490). New York: IEEE.

    Google Scholar 

  28. Ikeda, T., Popescu, G., Dasari, R. R., & Feld, M. S. (2005). Hilbert phase microscopy for investigating fast dynamics in transparent systems. Optics Letters, 30(10), 1165–1167.

    Article  Google Scholar 

  29. Revel, J. P., Hoch, P., & Ho, D. (1974). Adhesion of culture cells to their substratum. Experimental Cell Research, 84(1), 207–218.

    Article  Google Scholar 

  30. Whur, P., Koppel, K., Urquhart, C. M., & Williams, D. C. (1977). Substrate retention of fractured retraction fibres during detachment of trypsinized bhk21 fibroblasts. Journal of Cell Science, 24(1), 265–273.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of California Los Angeles, Los Angeles, CA, USA

    Ata Mahjoubfar, Claire Lifan Chen & Bahram Jalali

Authors
  1. Ata Mahjoubfar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire Lifan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bahram Jalali
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Mahjoubfar, A., Chen, C.L., Jalali, B. (2017). Label-Free High-Throughput Phenotypic Screening. In: Artificial Intelligence in Label-free Microscopy. Springer, Cham. https://doi.org/10.1007/978-3-319-51448-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-51448-2_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-51447-5

  • Online ISBN: 978-3-319-51448-2

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation