SBIR PHase I: High-Throughput Purification of Combinatorial Libraries

This Small Business Innovation Research (SBIR)Phase I project will develop a highly-parallel, mass-selected purification system for large pharmaceutical drug libraries. The need for high-throughput purification is driven by the industry recognition that combinatorial chemistry samples must still be purified even after chemical screening. This is a daunting task considering the exponentially increasing number of drug candidates being synthesized by combinatorial and parallel methods. This proposal will examine monolithic parallel flash chromatography and preparative liquid chromatography configurations. The key enabling technology is photoionization mass spectrometry, which permits accurate molecular detection in mixtures of compounds without the problems of competition-for-charge and ion suppressions that plague conventional ionization methods. This will make it possible to monitor several chromatography columns at the same time. The goal of the project is to have a purification system in place that has a practical purification rate of 1 min per sample (16 parallel purifications in about 16 min) corresponding to a potential 16 hr daily rate of 960 sample purifications per day. The commercial application of this project will be in the important niche market of molecular analysis and screening for drug discovery.