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Droplet-based dielectrophoresis device for on-chip nanomedicine fabrication and improved gene delivery efficiency

Abstract

In this article, we present the design, fabrication, and experimental verification of a droplet-based microfluidic device for effective on-chip fabrication and separation of polymer-based nanoparticles using dielectrophoresis (DEP) effect. The separated polyplexes nanoparticles were used in cells for improved gene transfection efficiency. By adjusting the flow rate of PEI600-CyD-FA (H1) and DNA plasmids, polyplexes products can be mixed and self-assembled inside droplets within approximately a nanoliter volume. This procedure ensures synthesized particles to have a narrow size distribution. In addition, a new microchannel design was developed to automatically coalesce two moving aqueous droplets and to directly extract aqueous polyplex products from oil. Finally, the H1-DNA polyplexes of ~116 nm diameter were separated via negative DEP force under 8 V peak–peak and 20 MHz conditions by passing three times through a non-uniform electric field. The biological findings demonstrated that the DEP-treated polyplexes still possessed the ability to enter HUVEC cells and that the gene transfection efficiency was raised to 15 %, as opposed to the control group’s 4 % where the polyplexes had no DEP treatment. The quantitative comparison was done by counting the number of cells produced via positive EPFG expression. These hydrodynamic and electrodynamic techniques provide an integrated microfluidic platform for fabricating and screening nanoscale drugs.

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Abbreviations

H :

Height of flow channel

W :

Width of flow channel

F random :

Random force

F deterministic :

Deterministic force

H1 :

Polymer vector, designed for drug/gene delivery

L assembling :

Length of assembling channel

Q blue :

Volume flow rate of blue liquid

Q oil :

Volume flow rate of mineral oil

Q red :

Volume flow rate of red liquid

V droplet :

Droplet velocity

V pp :

Peak-to-peak voltage

FA:

Folic acid

CyD:

Cyclodextrins

DEP:

Dielectrophoresis

PEI:

Polyethylenimine

PCR:

Polymerase chain reaction

EGFP:

Enhanced green fluorescent protein

HUVEC:

Human umbilical vein endothelial cell

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Acknowledgments

This research is supported by project #BME-p3-12 of the Shun Shing Institute of Advanced Engineering, The Chinese University of Hong Kong.

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Correspondence to Shih-Chi Chen.

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Shih-Mo Yang and Hong Yao have contributed equally to this work.

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Yang, SM., Yao, H., Zhang, D. et al. Droplet-based dielectrophoresis device for on-chip nanomedicine fabrication and improved gene delivery efficiency. Microfluid Nanofluid 19, 235–243 (2015). https://doi.org/10.1007/s10404-015-1560-x

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Keywords

  • Droplet
  • Dielectrophoresis
  • Polymeric nanoparticle
  • Gene delivery
  • Particle separation
  • Lab-on-chip