Real-Time Stain-Free Classification of Cancer Cells and Blood Cells Using Interferometric Phase Microscopy and Machine Learning

Noga Nissim, Matan Dudaie, Itay Barnea, Natan T. Shaked*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We present a method for real-time visualization and automatic processing for detection and classification of untreated cancer cells in blood during stain-free imaging flow cytometry using digital holographic microscopy and machine learning in throughput of 15 cells per second. As a preliminary model for circulating tumor cells in the blood, following an initial label-free rapid enrichment stage based on the cell size, we applied our holographic imaging approach, providing the quantitative optical thickness profiles of the cells during flow. We automatically classified primary and metastatic colon cancer cells, where the two types of cancer cells were isolated from the same individual, as well as four types of blood cells. We used low-coherence off-axis interferometric phase microscopy and a microfluidic channel to image cells during flow quantitatively. The acquired images were processed and classified based on their morphology and quantitative phase features during the cell flow. We achieved high accuracy of 92.56% for distinguishing between the cells, enabling further automatic enrichment and cancer-cell grading from blood.

Original languageEnglish
Pages (from-to)511-523
Number of pages13
JournalCytometry. Part A : the journal of the International Society for Analytical Cytology
Volume99
Issue number5
DOIs
StatePublished - May 2021

Funding

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

    Keywords

    • blood cells
    • cancer cells
    • cell classification
    • digital holographic microscopy
    • imaging flow cytometry
    • liquid biopsy
    • machine learning
    • quantitative phase microscopy

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