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This study introduces a 3D microfluidic device for generating complete combinatorial concentration gradients, advancing combination drug discovery and cellular response studies. The novel system simplifies drug screening and antibiotic susceptibility testing in a high-throughput format.

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Area of Science:

  • Micro/nanofluidics
  • Cellular biology
  • Drug discovery

Background:

  • Micro/nanofluidics enables high-throughput on-chip microscopy of cellular responses.
  • Generating combinatorial concentration gradients for multiple reagents in microfluidic arrays is challenging due to 2D channel limitations.

Purpose of the Study:

  • To present a novel 3D microfluidic device for generating complete combinatorial concentration gradients of two reagents.
  • To overcome the limitations of 2D microfluidic systems in combinatorial drug discovery.

Main Methods:

  • Fabrication of a device using laminated multilayered monolithic films with integrated mixers and cell culture arrays.
  • Utilizing a 3D interconnection of micro/nanochannels.
  • Validation through numerical analysis.

Main Results:

  • Demonstrated reliable generation of a full-combinatorial concentration gradient array for two reagents.
  • Successfully applied the device for one-step antibiotic susceptibility testing of bacterial cells.
  • Showcased potential for screening combinations of two or more drugs.

Conclusions:

  • The 3D microfluidic device effectively generates complete combinatorial concentration gradients, facilitating drug discovery.
  • The laminated object manufacturing method enables versatile 3D micro/nanofluidic system realization.
  • The device offers a streamlined approach for cellular response studies and drug screening.