Issue 18, 2022

Label-free detection and enumeration of rare circulating tumor cells by bright-field image cytometry and multi-frame image correlation analysis

Abstract

Identification and enumeration of circulating tumor cells (CTCs) in peripheral blood are proved to correlate with the progress of metastatic cancer and can provide valuable information for diagnosis and monitoring of cancer. Here, we introduce a bright-field image cytometry (BFIC) technique, assisted by a multi-frame image correlation (MFIC) algorithm, as a label-free approach for tumor cell detection in peripheral blood. For this method, images of flowing cells in a wide channel were continuously recorded and cell types were determined simultaneously using a deep neural network of YOLO-V4 with an average precision (AP) of 98.63%, 99.04%, and 98.95% for cancer cell lines HT29, A549, and KYSE30, respectively. The use of the wide microfluidic channel (400 μm width) allowed for a high throughput of 50 000 cells per min without clogging. Then erroneous or missed cell classifications caused by imaging angle differences or accidental misinterpretations in single frames were corrected by the multi-frame correlation analysis. This further improved the AP to 99.40%, 99.52%, and 99.47% for HT29, A549, and KYSE30, respectively. Meanwhile, cell counting was also accomplished in this dynamic process. Moreover, our imaging cytometry method can readily detect as few as 10 tumor cells from 100 000 white blood cells and was unaffected by the EMT process. Furthermore, CTCs from 8 advanced-stage cancer clinical samples were also successfully detected, while none for 6 healthy control subjects. Although this method is implemented for CTCs, it can also be used for the detection of other rare cells.

Graphical abstract: Label-free detection and enumeration of rare circulating tumor cells by bright-field image cytometry and multi-frame image correlation analysis

Supplementary files

Article information

Article type
Paper
Submitted
25 Feb 2022
Accepted
29 May 2022
First published
31 May 2022

Lab Chip, 2022,22, 3390-3401

Label-free detection and enumeration of rare circulating tumor cells by bright-field image cytometry and multi-frame image correlation analysis

Z. Du, Y. Li, B. Chen, L. Wang, Y. Hu, X. Wang, W. Zhang and X. Yang, Lab Chip, 2022, 22, 3390 DOI: 10.1039/D2LC00190J

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements