Automating crystallization of membrane proteins by robot with soft coordinate measuring

A completely new focus in the area of robotics research has been proposed to enable the automatic handling of nanoliter volumes of highly viscous biomaterials. The robot in question is of immediate need in the proteomics research community following two important recent announcements: the completion of the Human Genome Project (HGP) and the development of the novel in meso method for membrane protein crystallization. The completion of the HGP has sparked off intense activity in the area of protein structure determination. The in meso method introduced a few years ago has helped us get crystals of membrane proteins, such as bacteriorhodopsin, and provides a novel methodology for membrane protein crystallization. The bottleneck to achieve high throughput automation of this, so called in meso method is the handling of nanoliter volumes of the highly viscous cubic phase as part of the crystallization process. The cubic phase sticks to everything that it contacts and has a tendency to disable dispensing robotic tools. In this paper, we discuss the factors that influence the successful delivery of nanoliter volumes of the cubic phase in a controlled and reproducible fashion. An innovative technique of coordinate measurement using the cubic phase as a transducer is proposed and verified. We also describe a robotic system designed and built to address this issue and present the results of crystallization using our in meso robot.