4.3 Article

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

Journal

CYTOMETRY PART A
Volume 99, Issue 5, Pages 511-523

Publisher

WILEY
DOI: 10.1002/cyto.a.24227

Keywords

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

Funding

  1. Horizon 2020 European Research Council (ERC) [678316]
  2. European Research Council (ERC) [678316] Funding Source: European Research Council (ERC)

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A method for real-time visualization and automatic processing for detection and classification of untreated cancer cells in blood was presented using digital holographic microscopy and machine learning. The study achieved high accuracy in automatically classifying primary and metastatic cancer cells, as well as blood cells, providing a foundation for further automatic enrichment and cancer cell grading.
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. (c) 2020 International Society for Advancement of Cytometry

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