Automated, integrated modules for fluid handling, thermal cycling and purification of DNA samples for high throughput sequencing and analysis

Over the past 5 years the Genomation Laboratory at the University of Washington has developed an automated fluid handling system called "Acapella" to prepare microliter reactions for genome analysis. Reactions such as restriction enzyme digests, polymerase chain reactions (PCRs), and sequencing reactions are prepared in glass capillaries, one per sample, with an automated system that can process 5,000 samples in 8 hours. A DNA sample is aspirated from a microplate well with a novel piezoelectric aspirator/mixer actuator, reagents are dispensed into the end of the capillary with piezoelectric reagent dispensers, all fluids inside the capillary are mixed with the piezoelectric aspirator/mixer actuator, and the capillary is off-loaded to a capillary cassette for further processing. On-going development includes new, automated modules for thermal processing of capillaries, real-time DNA quantitation, and purification of DNA inside of capillaries to prepare the samples for DNA sequencing. Applicatio ns of the technology include minimal residual disease quantification and sample preparation for DNA sequencing.