Double-exclusive liquid repellency (double-ELR): An enabling technology for rare phenotype analysis

Chao Li, Jiaquan Yu, Paxton Paine, Duane S. Juang, Scott M. Berry, David J. Beebe

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Double-exclusive liquid repellency (double-ELR) is an extreme wettability phenomenon in which adjacent regions selectively and completely repel immiscible liquids with different surface chemistries on a non-textured substrate (i.e., a substrate in absence of micro/nano-structures). Under double-ELR conditions, each liquid exhibits no physical contact (contact angle of 180°) with its non-preferred surface chemistry, thus enabling complete partitioning of adjacent fluidic volumes (e.g., between water and oil). This enables a new type of cell culture-based assay, where cell loss from common failure modes (e.g., biofouling from inadvertent cell adhesion, detrimental moisture loss/gain, and liquid handling dead volumes) is significantly mitigated. Importantly, the principles of double-ELR were leveraged to achieve underoil sweep patterning, a no-loss, robust and high-throughput distribution of sub-microliter volumes of aqueous media (and cells). In addition to high-efficiency distribution via sweep patterning, double-ELR can be used to construct "modular" (i.e., easily implemented and/or linked together with spatial and temporal control) higher-order architectures for in vitro imitation of physiologically relevant microenvironments that are of particular interest within the cell assay community, including multi-phenotype cultures with excellent spatial and temporal control, three-dimensional layered multi-phenotype cultures, cultures with selective mechanical cues of extracellular matrix (i.e., collagen fiber alignment), and spheroid cultures. Together, these features of double-ELR uniquely facilitate culture and high content analysis of limited cellular samples (e.g., a few hundred to a few thousand cells).

Original languageEnglish
Pages (from-to)2710-2719
Number of pages10
JournalLab on a Chip
Issue number18
StatePublished - Sep 21 2018

Bibliographical note

Funding Information:
This work is funded by National Science Foundation grant (EFRI-MKIS), Prostate Cancer Foundation Challenge Award, University of Wisconsin Carbone Cancer Center Cancer Center Support Grant P30 CA014520, NIH R01 EB010039 BRG, NIH R01 CA185251, NIH R01 CA186134, NIH R01 CA181648, and EPA H-MAP 83573701. We thank Dr. Max Gong for the discussion and insightful suggestions on the writing of Module III. Author contributions: C. L. and J. Y. designed the research. We especially thank Prof. Joshua Lang for his inspiring discussion on the clinical significance of rare cell isolation and analysis. C. L., J. Y., P. P., and D. J. conducted experiments, and all authors interpreted the data; all authors wrote the manuscript and revised it.

Publisher Copyright:
© 2018 The Royal Society of Chemistry.

ASJC Scopus subject areas

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


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