Microfluidic device for super‐fast evaluation of membrane protein nanoparticle formation

Abstract

Membrane proteins embedded in bilayer lipids of cell membrane have unique functions including inter-cell communication and ionic/molecular transport. To understand the structure and function of the membrane protein embedded in a native biological bilayer lipid environment is a major research area in biology. A reconstitution/crystallisation process of membrane proteins and lipids can form virus-like nanoparticles, and have important potential applications in drug design and drug delivery. Earlier studies used a standard dialysis process that is inherently low-throughput, time consuming (days to weeks) and costly in protein materials. In this reported work a new microfluidic device is demonstrated to rapidly form membrane protein lipid nanoparticles in an extremely short period (seconds). The reconstitution process occurs using a continuous flow dominated by convection-diffusion phenomena in the microfluidic channel, which can form protein/lipid nanoparticles using only nanolitres or picolitres of protein sample. Moreover, a controllable syringe pump is used to test a combination of conditions, rather than using inefficient hand pipetting. Therefore this novel microfluidic device has an ability to rapidly form uniform membrane protein/lipid nanoparticles, and the authors believe that this new method will make a transformative impact on commercial applications in a variety of areas from biology to pharmacology.