Issue 18, 2021

Simultaneous biochemical and functional phenotyping of single circulating tumor cells using ultrahigh throughput and recovery microfluidic devices

Abstract

Profiling circulating tumour cells (CTCs) in cancer patients' blood samples is critical to understand the complex and dynamic nature of metastasis. This task is challenged by the fact that CTCs are not only extremely rare in circulation but also highly heterogeneous in their molecular programs and cellular functions. Here we report a combinational approach for the simultaneous biochemical and functional phenotyping of patient-derived CTCs, using an integrated inertial ferrohydrodynamic cell separation (i2FCS) method and a single-cell microfluidic migration assay. This combinatorial approach offers unique capability to profile CTCs on the basis of their surface expression and migratory characteristics. We achieve this using the i2FCS method that successfully processes whole blood samples in a tumor cell marker and size agnostic manner. The i2FCS method enables an ultrahigh blood sample processing throughput of up to 2 × 105 cells s−1 with a blood sample flow rate of 60 mL h−1. Its short processing time (10 minutes for a 10 mL sample), together with a close-to-complete CTC recovery (99.70% recovery rate) and a low WBC contamination (4.07-log depletion rate by removing 99.992% of leukocytes), results in adequate and functional CTCs for subsequent studies in the single-cell migration device. For the first time, we employ this new approach to query CTCs with single-cell resolution in accordance with their expression of phenotypic surface markers and migration properties, revealing the dynamic phenotypes and the existence of a high-motility subpopulation of CTCs in blood samples from metastatic lung cancer patients. This method could be adopted to study the biological and clinical value of invasive CTC phenotypes.

Graphical abstract: Simultaneous biochemical and functional phenotyping of single circulating tumor cells using ultrahigh throughput and recovery microfluidic devices

Supplementary files

Article information

Article type
Paper
Submitted
24 May 2021
Accepted
24 Jul 2021
First published
26 Jul 2021

Lab Chip, 2021,21, 3583-3597

Simultaneous biochemical and functional phenotyping of single circulating tumor cells using ultrahigh throughput and recovery microfluidic devices

Y. Liu, W. Zhao, R. Cheng, J. Hodgson, M. Egan, C. N. C. Pope, P. G. Nikolinakos and L. Mao, Lab Chip, 2021, 21, 3583 DOI: 10.1039/D1LC00454A

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