SBIR Phase II: High Speed Chemical Analysis of Combinatorial Libraries

Syagen Technology Inc, Tustin CA

Investigators

Abstract

This Small Business Innovation Research Phase II project will develop a high through-put drug screening technology based on the successful Phase I feasibility demonstration. High throughput methods in parallel and combinatorial organic synthesis are revolutionizing the field of drug discovery and biological screening. However, progress is seriously impeded by lack of reliable methods for conducting high throughput chemical analysis (HTCA) for composition and purity assessment. Current approaches rely on liquid chromatography/mass spectrometry (LC/MS). With a cycle time of about 5 min, an LC/MS instrument can analyze about 300 samples in a 24 hr period. We propose an innovative MS concept that reduces cycle time to about 10 sec, raising the potential analysis rate to >5,000 samples/day. The innovation is based on a novel ionization source that achieves (1) near-universal and efficient ionization of drug compounds, (2) minimal fragmentation molecular ion spectra for accurate analysis, (3) minimal interference from air constituents and commonly used solvents, and (4) suppression of competition-for-charge and ion suppression effects experienced by conventional methods. The proposed technology advances analytical and research capabilities to improve fundamental understanding of drug molecules and to build a knowledge base for implementing more rational approaches to lead drug optimization. Market research indicates the potential for exponential growth on the basis of quick penetration of the chemical analysis niche of the rapidly growing field of combinatorial and parallel synthesis methods for drug discovery. The proposed high throughput chemical analysis system has the potential to dominate the market for combinatorial library analysis, which is a rapidly growing field of drug discovery. Our real-time, complex mixture analyzers will also be marketed for applications in drug testing, environmental monitoring, and on-line process monitoring.