A design and optimization of a high throughput valve based microfluidic device for single cell compartmentalization...

Area of Science:

• Biotechnology
• Microfluidics
• Cellular Biology

Background:

• Advancements in genomics and proteomics necessitate high-throughput single-cell screening.
• Valve-based microfluidics offer on-demand fluid exchange for assays but are limited by compartment numbers.
• Scaling microfluidic devices to thousands of microvalves for picoliter compartmentalization is a significant challenge.

Purpose of the Study:

• To design and optimize a microfluidic platform for high-throughput single-cell compartmentalization.
• To apply this platform to single-cell enzymatic assays for protein expression quantification.
• To overcome throughput limitations in current single-cell analysis technologies.

Main Methods:

• Utilized COMSOL Multiphysics for design modeling and optimization of circular microvalves.
• Fabricated a microfluidic device with up to 5000 hydrodynamic traps and microvalves.
• Investigated the impact of geometry, actuation media, and fabrication techniques on sealing pressure.

Main Results:

• Optimized microvalve parameters to achieve low sealing pressure (as low as 0.04 MPa).
• Successfully fabricated a microfluidic device capable of high-throughput single-cell compartmentalization.
• Demonstrated variations in granzyme B activity in different cell types using the platform.

Conclusions:

• The developed microfluidic platform significantly enhances throughput for single-cell analysis.
• This technology holds promise for applications in drug discovery and personalized medicine.
• Optimized microvalve design is crucial for achieving high-density microfluidic compartmentalization.