This research addresses new robotic technologies and systems which enable the automated handling of nanoliter volumes of highly viscous bio-materials. The robotic system is urgently needed by the proteomics community following on the announcement in 2001 that the human genome had been sequenced. This landmark event has led to intense activity in structural biology aimed at determining the 3-dimensional structure of the proteins coded for by the genome. About a third of these proteins are integral to the cell's membranes and x-ray crystallography is the only reliable method for structure determination. A method that uses the lipid cubic mesophase (in meso) has recently been introduced for producing diffraction quality crystals of several important membrane proteins and a protein complex. The in meso method requires the controlled and reproducible handling in high-throughput fashion of accurate, nanoliter volumes of precious, highly viscous protein/lipid cubic phase mixtures of defined shape. Three approaches will be used to facilitate the development of such a system as follows: a) efficient-motion planning of the dispensing tool for effective delivery of viscous materials, b) utilization of the cubic phase for coordinate measuring, and c) computer vision verification of successful dispensing. For efficient-motion planning the PIs will study the motion trajectory of the dispensing tool with respect to the receiving container to assure delivery of accurate cubic phase volumes in the nanoliter range of predetermined shape. To locate the bottom surface of the container for accurate dispensing, the PIs will use the cubic phase itself for coordinate measurement to obviate the need for expensive and complex coordinate measuring machines. Computer vision verification provides a cost effective way to monitor delivery since failure may occur occasionally when the viscous material refuses to leave the dispensing tool.
The intellectual merits of this research are in the creation of new robotic technologies and systems for the automatic handling of nanoliter volumes of highly viscous bio-materials which have never been studied before. The development of the three new technologies related to motion planning, coordinates measuring, and computer-vision inspection will be the primary intellectual merits of this activity.
The broader impacts of this research include the following: a) the project will produce a fully functional robotic system that will enable the screening of thousands of crystallization conditions daily to expedite the better understanding of the structure of membrane proteins, b) the results will create a knowledge base for the automatic handling of generic viscous materials, and c) the educational plan seeks to train students in an interdisciplinary area encompassing engineering and biochemistry.
