A capillary-based fluid handling system bas been developed to process 5000 samples in 8 hours. The system takes deoxyribonucleic acid (DNA) or other chemical samples and automatically processes them as specified in a user-defined protocol with aspiration, dispensing, mixing, thermal cycling, and imaging steps. A serial pipeline process is used to provide flexibility, reproducibility, and reliability for the samples prepared. This laboratory automation system dispenses 40-100 pL droplet volumes using piezoelectric reagent dispensers and prepares 1 or 2-μL final reaction volumes, a 3 to 5-fold reduction in reagent usage over current (2003) state-of-the-art manual and automated instrumentation. Extensive testing of the system has been performed with the University of Washington Genome Center. Applications for ACAPELLA-5K include DNA sequencing, diagnostics, minimal residual disease quantification, drug discovery, environmental testing, forensics, protein crystallography, Polymerase Chain Reaction (PCR) and so on.