Abstract

In 1995, the rapid fabrication of tens, hundreds, and, eventually, tens of thousands of samples in two-dimensional arrays of discrete microscaled samples (pixels) using lithography methods developed for the electronics industry was reported. Importantly, the team developed technologies for the rapid characterization of entire arrays (library) by using a matrix of sensors that corresponded to the samples deposited on the silicon wafer. The researchers commercialized these methodologies, hardware, and software through the start-up firm Symyx Technologies. Symyx developed and marketed “combinatorial methods,” or high throughput experimentation (HTE), for advanced materials, and created a new paradigm in materials research for the chemical process industry (CPI) and the advanced materials producers. This discontinuity, or step-change, reflected an earlier response by the pharmaceutical industry toward significant market demands for new products—reduced product innovation cycle time, increased return on research and development (R&D) investment, and industry consolidation. Symyx Technologies facilitated implementation efforts throughout the chemicals and advanced materials industries, with the result that the methodology known as “combinatorial chemistry” is now relatively ubiquitous in companies conducting research in advanced materials, catalysts, and polymers.

Many of the methodologies adopted by advanced materials researchers were developed for drug discovery in the pharmaceuticals industry. The major industry driver in pharmaceuticals was to develop new therapeutics with very tight time- and cost constraints. Combinatorial chemists indicated that, in theory, the number of potential drug targets—small organic molecules containing C, H, N, and O atoms—approaches 10⁵⁰, although the number of compounds considered useful is probably closer to 10¹⁰–10¹⁵ (7), and that the only way to screen this diversity was by using massively parallel synthesis and characterization techniques. By 1999, the ability to robotically synthesize and characterize 1 million distinct organic compounds per year was realized by some pharmaceutical companies, driving down R&D costs per sample by two orders of magnitude, to $1 or less per “hit”.

Today, many chemical and advanced materials companies have implemented some form of HTE in their discovery research phases through internal investment, mergers, and acquisitions. The market drivers—global pressures for higher performance specialty materials and higher profits on commodity materials—have pressed these industries to increase productivity in their new product discovery and process development phases. HTE for materials often has little similarity with methods developed in the drug discovery arena, however researchers have quite effectively leveraged many methods and tools from the pharmaceutical applications. This is evident in the area of industrial catalysis, where HTE utilized in the discovery and process development phases have cut concept-to-launch cycle times in half; this represents significant cost savings as well as commercial advantages such as market penetration and intellectual property position.

Application areas, methodologies, library design, and library fabrications for catalysts, polymeric materials, and inorganic materials are discussed.