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A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion.
Carl L Hansen1, Emmanuel Skordalakes, James M Berger
1Department of Applied Physics, California Institute of Technology, MS 128-95, Pasadena, CA 91125, USA.
Summary
We developed a novel microfluidic device for precise picoliter-scale fluid metering, enabling efficient protein crystallization screening with minimal sample. This technology significantly improves detection rates and reduces sample volume requirements.
Area of Science:
- Biotechnology
- Chemical Engineering
- Structural Biology
Background:
- Microfluidic devices face challenges in robust and scalable fluid metering.
- Accurate fluid handling is crucial for high-throughput screening applications.
Purpose of the Study:
- To develop a scalable, fluid-property-independent microfluidic system for picoliter-scale fluid metering.
- To apply this technology for efficient screening of protein crystallization conditions.
Main Methods:
- Fabrication and testing of a microfluidic chip with 480 active valves.
- Performing 144 parallel reactions, each utilizing 10 nl of protein sample.
- Leveraging microfluidic mixing for optimized crystallization kinetics.
Main Results:
- The microfluidic device demonstrated robust picoliter-scale fluid metering.
- It successfully screened protein crystallization conditions, detecting more conditions than conventional methods.
- Achieved diffraction-quality crystals from nanoliter-volume reactions.
Conclusions:
- The developed microfluidic scheme offers a scalable solution for precise fluid metering.
- This technology significantly reduces protein sample consumption for crystallization screening.
- It enables efficient growth and harvesting of diffraction-quality crystals.