Quantitative phase microscopy spatial signatures of cancer cells

Darina Roitshtain, Lauren Wolbromsky, Evgeny Bal, Hayit Greenspan, Lisa L. Satterwhite, Natan T. Shaked*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


We present cytometric classification of live healthy and cancerous cells by using the spatial morphological and textural information found in the label-free quantitative phase images of the cells. We compare both healthy cells to primary tumor cells and primary tumor cells to metastatic cancer cells, where tumor biopsies and normal tissues were isolated from the same individuals. To mimic analysis of liquid biopsies by flow cytometry, the cells were imaged while unattached to the substrate. We used low-coherence off-axis interferometric phase microscopy setup, which allows a single-exposure acquisition mode, and thus is suitable for quantitative imaging of dynamic cells during flow. After acquisition, the optical path delay maps of the cells were extracted and then used to calculate 15 parameters derived from the cellular 3D morphology and texture. Upon analyzing tens of cells in each group, we found high statistical significance in the difference between the groups in most of the parameters calculated, with the same trends for all statistically significant parameters. Furthermore, a specially designed machine learning algorithm, implemented on the phase map extracted features, classified the correct cell type (healthy/cancer/metastatic) with 81–93% sensitivity and 81–99% specificity. The quantitative phase imaging approach for liquid biopsies presented in this paper could be the basis for advanced techniques of staging freshly isolated live cancer cells in imaging flow cytometers.

Original languageEnglish
Pages (from-to)482-493
Number of pages12
JournalCytometry. Part A : the journal of the International Society for Analytical Cytology
Issue number5
StatePublished - May 2017


FundersFunder number
Horizon 2020 European Research Council
Horizon 2020 Framework Programme678316
European Research Council


    • cytometry
    • digital holographic microscopy
    • interferometric imaging
    • machine learning
    • quantitative phase microscopy


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