Human leucocytes processed by fast-rate inertial microfluidics retain conventional functional characteristics

Area of Science:

• Biotechnology
• Microfluidics
• Cellular Therapy Manufacturing

Background:

• Clinical cell therapy manufacturing involves complex steps like cell manipulation and buffer exchange.
• Current methods use low-throughput centrifugation or costly closed-system alternatives.
• Inertial focusing (IF) microfluidics offers a potential high-throughput, cost-effective solution for closed-system cell processing.

Purpose of the Study:

• To assess the efficacy and cellular impact of a novel inertial focusing (IF) microfluidic device for cell therapy manufacturing.
• To evaluate the device's ability to perform simultaneous leukocyte separation, buffer exchange, and volume reduction.
• To investigate the effects of IF processing on human cell viability, immunophenotype, and metabolic activity.

Main Methods:

• A custom-designed IF microfluidic device was utilized for cell processing.
• Peripheral blood mononuclear cells and isolated monocytes were used for characterization.
• Multi-parameter flow cytometry was employed to analyze post-processing cell viability, function, and fate.

Main Results:

• The IF device achieved high efficiency in separating CD14+ monocytes (approx. 97%) and performing buffer exchange (approx. 60%) at high flow rates (15 ml/min).
• Leukocyte processing using the IF device was well-tolerated.
• No significant differences were observed in downstream cell viability, immunophenotype, or metabolic activity compared to conventional methods.

Conclusions:

• IF microfluidic devices demonstrate high efficiency and safety for cell therapy manufacturing applications.
• The developed IF device offers a promising alternative to current methods for leukocyte separation and buffer exchange.
• This technology has the potential to significantly benefit clinical cell therapy production by providing a high-throughput, closed-system solution.