Научная статья на тему 'Classification of label-free cancerous cells in blood sample during flow based on interferometric phase microscopy (IPM)'

Classification of label-free cancerous cells in blood sample during flow based on interferometric phase microscopy (IPM) Текст научной статьи по специальности «Биотехнологии в медицине»

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Текст научной работы на тему «Classification of label-free cancerous cells in blood sample during flow based on interferometric phase microscopy (IPM)»

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Classification of label-free cancerous cells in blood sample during flow based on interferometric phase microscopy (IPM)

N. Nissim1, N. Tzvi Shaked1

1Tel-Aviv University, Biomedical Engineering, Tel-Aviv, Israel

The initiation and progression of acute diseases such as cancer and immune deficiencies, as well as wound repair and other regenerative processes often depend on the physiology of a small number of highly specialized cells. These cells can be obtained from biopsies including body fluids, such as blood and urine in easily taken routine lab tests [1]. In cell biology and medical research, in targeted diagnostics and in personalized therapeutic interventions, the identification and isolation of intact, disease-associated cell subsets from complex tissues or heterogeneous cell populations is of utmost importance [2].

Various strategies have been developed for the detection of cell types, the most widely used rely on antibody-based capturing of the cells like fluorescence-activated cell sorting (FACS) [3]. However, for many cell types, antigen combinations are missing that would allow for their unambiguous identification. Moreover, the inherent modification of the cell surface chemistry makes label-based approaches incompatible with noninvasive cell processing and, therefore, disqualifies them for usage in many cell therapeutic applications [4].

The refractive index (RI) of the cell interior is related to the optical interaction of the light field with cellular organelles and their chemical composition and, therefore, is easy accessible by optical techniques without affecting the cell physiology. Label-free interferometric phase microscopy (IPM) is able to measure the cell optical thickness profile in sub-nanometer sensitivity [5-8].

We propose an application for the noninvasive and automated cell processing, with high discriminative power on the level of the individual cell. By acquiring holograms of each cell using IPM and achieving its OPD profile, we extract features that highly differentiate cancerous cells from heterogeneous blood sample.

References

[1] Alix-Panabieres, C. & Pantel, K. Circulating Tumor Cells: Liquid Biopsy of Cancer. Clin. Chem. 59, 110-118 (2013).

[2] Chen, Y. et al. Rare cell isolation and analysis in microfluidics. Lab. Chip 14, 626-645 (2014).

[3] Watanabe, M. et al. Multicolor detection of rare tumor cells in blood using a novel flow cytometry-based system. Cytom. Part J. Int. Soc. Anal. Cytol. 85, 206-213 (2014).

[4] Chen, C. L. et al. Deep Learning in Label-free Cell Classification. Sci. Rep. 6, 21471 (2016).

[5] Girshovitz, P. & Shaked, N. T. Generalized cell morphological parameters based on interferometric phase microscopy and their application to cell life cycle characterization. Biomed. Opt. Express 3, 1757-1773 (2012).

[6] Haifler, M. et al. Interferometric phase microscopy for label-free morphological evaluation of sperm cells. Fertil. Steril. 104, 43-47.e2 (2015).

[7] Balberg, M. et al. Localized measurements of physical parameters within human sperm cells obtained with wide-field interferometry. J. Biophotonics n/a-n/a (2017). doi:10.1002/jbio.201600186

[8] Habaza, M. et al. Rapid 3D Refractive-Index Imaging of Live Cells in Suspension without Labeling Using Dielectrophoretic Cell Rotation. Adv. Sci. n/a-n/a (2016). doi: 10.1002/advs.201600205

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