Full-Combinatorial Concentration Gradient Array with 3D Micro/Nanofluidics for Antibiotic Susceptibility Testing.

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.