Performing nucleic acid reactions using predispensed lyophilized reaction mixtures

A system is described in which manipulations of nucleic acids are performed in wells containing predispensed lyophilized reaction mixtures requiring addition of only nucleic acid. This allows increased reproducibility for single-step reactions (e.g., restrictions and ligations), as well as improved productivity for complex reactions (e.g., sequencing). Enzymes, co-factors, nucleotides and buffers can be dried and stored at room temperature without loss of essential function. When used for DNA sequencing, hundreds of templates a day can be sequenced with the potential to determine megabase amounts of sequence per week.