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 journalArticlepeer-review

20 Citations (Scopus)


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
Issue number13
Publication statusPublished - 2016

Bibliographical note

Publisher Copyright:
© The Royal Society of Chemistry 2016.

All Science Journal Classification (ASJC) codes

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


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