A Microfluidic Droplet Array System for Cell-Based Drug Combination Screening

  • Guan-Sheng Du
  • Jian-Zhang Pan
  • Shi-Ping Zhao
  • Ying Zhu
  • Jaap M. J. den Toonder
  • Qun Fang
Part of the Methods in Molecular Biology book series (MIMB, volume 1771)


In the last few decades, drug combination therapy has been widely applied in oncology and in other complex diseases. Due to its potential advantage of lower drug toxicity and higher therapeutic efficacy, drug combination treatment has been more and more studied in fundamental labs and pharmacy companies. In this chapter, we report cell-based drug combination screening using a microfluidic droplet system based on a sequential operation droplet array (SODA) technique. In this system, an oil-covered two-dimensional droplet array chip was used as the platform for cell culture and analysis. This chip was fixed in an x–y–z translation stage under control of a computer program. A tapered capillary connected with a syringe pump was coupled with the droplet array chip to achieve multiple droplet manipulations including liquid metering, aspirating, depositing, mixing, and transferring. Complex multistep operations for drug combination screening involving long-term cell culture, medium changing, schedule-dependent drug dosage and stimulation, and cell viability testing were achieved in parallel using the present system. The drug consumption for each screening test was substantially decreased to 5 ng–5 μg, corresponding to 10- to 1000-fold reductions compared with traditional drug screening systems with 96- or 384-well plates.

Key words

Droplet-based microfluidics High-throughput screening Drug combination Cell-based assay 



We greatly appreciate the financial support of the Natural Science Foundation of China (Grants 20825517, 20890020, and 21227007), Major National Science and Technology Programs (Grant 2013ZX09507005), and the BrainBridge program funded by Philips Research.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemistry, Institute of Microanalytical SystemsZhejiang UniversityHangzhouChina
  2. 2.Materials Technology Institute and Institute for Complex Molecular SystemsEindhoven University of TechnologyEindhovenThe Netherlands
  3. 3.Biomillenia SAS6 rue Jean CalvinParisFrance

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