Microfluidic device for super-fast evaluation of membrane protein crystallization

Abstract

Membrane proteins embedded in bi-layer lipids of cell membrane have unique functions including inter-cell communication, ions/molecules transport. And there is more than 50% of drug design emphasizes on membrane proteins specifically studying on their structure and formation. Recently we reported the structural and functional studies of membrane protein lipid nanoparticles in native biological membrane. This virus-like nanoparticle formed by a self-assembly crystallization process of membrane protein and lipids is critical to pharmaceutical industrial. These nanoparticles have a variety of potential applications in drug delivery and drug design that can carry specific the membrane protein on aim or release control. The previous studies stay on an inefficient method with a standard dialysis process that has low-throughput, time consumption, and protein sample waste. However, the interdisciplinary cooperation between in biology and Micro electro mechanical systems (MEMS) has been tremendous developed such as Bio-MEMS and Lab-on-achip technologies. Here we demonstrate a new concept with a high-throughput membraneless microfluidic device to fast produce the reconstitution of membrane protein nanoparticles. The reconstitution process in continuous micro flow dominated by convection-diffusion phenomena in microfluidic channel can be completed in seconds to form protein/lipid particles under multiple conditions applied. The controllable syringe pumps is used to test a combination of conditions rather than using inefficient hand pipette. Moreover this novel microfluidic device can save protein sample consumption down to only nanoliter or picoliter. By using this device, we have an ability to rapidly form uniform membrane protein lipid nanoparticles and we believe this new method will make a transformative impact to commercial applications in variety of areas from biology to pharmacology.

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