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Related Experiment Video

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Microfluidic Buffer Exchange for Interference-free Micro/Nanoparticle Cell Engineering
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Interference-free Micro/nanoparticle Cell Engineering by Use of High-Throughput Microfluidic Separation.

David C Yeo1, Christian Wiraja1, Yingying Zhou1

  • 1School of Chemical & Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, Singapore 637459.

ACS Applied Materials & Interfaces
|September 11, 2015
PubMed
Summary

Dean flow fractionation (DFF) microfluidics efficiently separates unbound micro/nanoparticles from engineered cells. This method prevents off-target effects, improving cell therapy safety and efficacy for clinical applications.

Keywords:
Dean flow fractionationcell engineeringcell separationmicrofluidicsnanoparticle

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Area of Science:

  • Biotechnology and Biomedical Engineering
  • Cellular Engineering
  • Microfluidics

Background:

  • Cellular engineering with micro/nanoparticles is vital for imaging and therapeutics.
  • Unbound particles cause off-target signals and unintended cellular effects.
  • Efficient separation of unbound particles from labeled cells remains a challenge.

Purpose of the Study:

  • To demonstrate Dean flow fractionation (DFF) for separating unbound micro/nanoparticles from engineered cells.
  • To evaluate DFF's efficiency and scalability for cell therapy applications.
  • To minimize off-target effects in nanoparticle-engineered cells.

Main Methods:

  • Developed and implemented a fast, continuous, high-throughput Dean flow fractionation (DFF) microfluidic device.
  • Applied DFF for buffer exchange to sort labeled THP-1 cells from unbound fluorescent dye and micro/nanoparticles.
  • Adapted the DFF device for heterogeneous-sized mesenchymal stem cells (MSCs).

Main Results:

  • DFF achieved a 20-fold improvement in depletion efficiency of free dyes/particles compared to centrifugation.
  • Minimized mislabeling of nontarget bystander cells by unbound particles.
  • Complete removal of unbound nanoparticles enabled engineered MSCs to function without off-target effects on endothelial cells.

Conclusions:

  • DFF is an effective, efficient, and scalable method for separating unbound micro/nanoparticles from engineered cells.
  • This technology significantly reduces off-target effects, enhancing the safety of cell-based therapies.
  • DFF can process high cell concentrations, paving the way for interference-free clinical applications.