Abstract: A greedy method for designing combinatorial arrays. An array of reagents are initially selected from a list of candidate reagents in a combinatorial library. The reagents in the array that maximize a design objective are determined in an iterative manner, by examining each variation site in the combinatorial library in a strictly alternating sequence. During each step, each candidate reagent at a given variation site is evaluated by constructing and evaluating the sub-array resulting from the systematic combination of that reagent with the selected reagents at all the other variation sites in the library. The candidate reagents at that variation site are ranked according to the fitness of their respective sub-arrays, and the reagents with the highest fitness are selected. The process is repeated for each variation site in the combinatorial library, until the fitness of the full combinatorial array can no longer be improved.