4.8 Article

Label-Free Cancer Stem-like Cell Assay Conducted at a Single Cell Level Using Microfluidic Mechanotyping Devices

Journal

ANALYTICAL CHEMISTRY
Volume 93, Issue 43, Pages 14409-14416

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.1c02316

Keywords

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Funding

  1. JST/PRESTO [JPMJPR16F4, 21H01966, 20H04714]
  2. Fund for the Promotion of Joint International Research (Fostering Joint International Research) [19KK0140]
  3. Shimadzu Science Foundation
  4. Toyota Riken Scholar
  5. Casio Science Promotion Foundation
  6. Grants-in-Aid for Scientific Research [20H04714, 21H01966] Funding Source: KAKEN

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The mechanical phenotype of cells can serve as a label-free, non-destructive, diagnostic marker, and a microfluidic device is a strong candidate for this translational research. The investigation of HT29 cells revealed a high heterogeneity in cell deformability, which may be a potential mechanical marker of CSCs, contributing to cancer diagnosis and treatment development.
The mechanical phenotype of cells is an intrinsic property of individual cells. In fact, this property could serve as a label-free, non-destructive, diagnostic marker of the state of cells owing to its remarkable translational potential. A microfluidic device is a strong candidate for meeting the demand of this translational research as it can be used to diagnose a large population of cells at a single cell level in a high-throughput manner, without the need for off-line pretreatment operations. In this study, we investigated the mechanical phenotype of the human colon adenocarcinoma cell, HT29, which is known to be a heterogeneous cell line with both multipotency and self-renewal abilities. This type of cancer stem-like cell (CSC) is believed to be the unique originators of all tumor cells and may serve as the leading cause of cancer metastasis and drug resistance. By combining consecutive constrictions and microchannels with an ionic current sensing system, we found a high heterogeneity of cell deformability in the population of HT29 cells. Moreover, based on the level of aldehyde dehydrogenase (ALDH) activity and the expression level of CD44s, which are biochemical markers that suggest the multipotency of cells, the high heterogeneity of cell deformability was concluded to be a potential mechanical marker of CSCs. The development of label-free and non-destructive identification and collection techniques for CSCs has remarkable potential not only for cancer diagnosis and prognosis but also for the discovery of a new treatment for cancer.

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