Microfluidics 3D gel-island chip for single cell isolation and lineage-dependent drug responses study

Zhixiong Zhang, Yu Chih Chen, Yu Heng Cheng, Yi Luan, Euisik Yoon

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

3D cell culture in the extracellular matrix (ECM), which not only provides structural support to cellular constituents, but also initiates regulatory biochemical cues for a variety of important cell functions in tissue, has become more and more important in understanding cancer pathology and drug testing. Although the ECM-gel has been used in cell culture both in bulk and on-chip, previous studies focused on collective cell behavior rather than single-cell heterogeneity. To track the behavior of each individual cell, we have developed a gel-island chip, which can form thousands of islands containing single cells encapsulated by the desired ECM. Optimized by Poisson's distribution, the device can attain 34% single cell capture efficiency of the exact number of single cells per island. A good culture media exchange rate and high cell viability can be achieved in the gel-islands. The cells in the islands can be automatically counted for high-throughput analysis. As a proof of concept, we monitored the proliferation and differentiation of single Notch+ (stem-like) T47D breast cancer cells. The 3D collagen gel environment was found to be favorable for the stem-like phenotype through better self-renewal and de-differentiation (Notch- to Notch+ transition). More interestingly, we found that the Notch- de-differentiated cells were more resistant to doxorubicin and cisplatin than the Notch+ cells. Combining the 3D ECM culture and single cell resolution, the presented platform can automatically analyze the individual cell behaviors of hundreds of cells using a small amount of drug and reagents.

Original languageEnglish
Pages (from-to)2504-2512
Number of pages9
JournalLab on a chip
Volume16
Issue number13
DOIs
Publication statusPublished - 2016 Jan 1

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All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

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