Intelligent Imaging Robot for Structural Genomics

DESCRIPTION (provided by applicant): Knowledge of 3-D structure of proteins is essential for understanding how they function and the designing of drugs to influence those functions. The Structural Genomics Initiative of the NIH aims to solve the 3-D structure of thousands of proteins a year by a major scale-up of technology. X-ray crystallography, which requires high-quality protein crystals, is a significant means of deducing 3-D structures. Growing protein crystals is a process of trial and error, and, in high-throughput protein crystallization, essential for the Structural Genomics Initiative to succeed, combinatorial methods are used to set up thousands of crystallization trials and imaging robots inspect each vessel for crystals and crystal-like objects. A bottleneck is the inability of automatic image analysis methods to recognize and flag the presence of protein crystals and microcrystals to the exclusion of all else. During Phase I, an intelligent imaging method based on a spectroscopic marker of the protein was designed and tested and found to be successful in recognizing protein crystals and microcrystals exclusively. An analytical procedure also was developed to facilitate automation of this imaging method. In Phase II of this SBIR project, we propose to build the imager based on a novel design and use it to image entire protein drops rapidly. Criteria for scoring the drops based on the size of protein crystals only will be established. The imager will be automated so that it can be integrated with the rest of an automated crystal growing process. Crystal screens can be set up and the drops containing crystals identified without human intervention speeding up crystal growth and protein structure determination. There is a demand for such an imaging robot among high-throughput laboratories, pharmaceutical companies, drug discovery firms, and contract X-ray crystallography laboratories. The new method is expected to play an important role in the success of the Structural Genomics Initiative and the discovery of new drugs. The imager also will find use in semiconductor wafer inspection and screening for cancer.