A method for parallel, automated, thermal cycling of submicroliter samples

A large fraction of the cost of DNA sequencing and other DNA-analysis proce sses results from the reagent costs incurred during cycle sequencing or PCR . In particular, the high cost of the enzymes and dyes used in these proces ses often results in thermal cycling costs exceeding $0.50 per sample. In t he case of high-throughput DNA sequencing, this is a significant and unnece ssary expense. Improved detection efficiency of new sequencing instrumentat ion allows the reaction volumes for cycle sequencing to be scaled down to o ne-tenth of presently used volumes, resulting in at least a 10-fold decreas e in the cost of this process. However, commercially available thermal cycl ers and automated reaction setup devises have inherent design limitations w hich make handling volumes of <1 <mu>L extremely difficult. In this paper, we describe a method for thermal cycling aimed at reliable, automated cycli ng of submicroliter reaction volumes.