Cultivating DNA Sequencing Technology After the Human Genome Project.

When the Human Genome Project was completed in 2003, automated Sanger DNA sequencing with fluorescent dye labels was the dominant technology. Several nascent alternative methods based on older ideas that had not been fully developed were the focus of technical researchers and companies. Funding agencies recognized the dynamic nature of technology development and that, beyond the Human Genome Project, there were growing opportunities to deploy DNA sequencing in biological research. Consequently, the National Human Genome Research Institute of the National Institutes of Health created a program-widely known as the Advanced Sequencing Technology Program-that stimulated all stages of development of new DNA sequencing methods, from innovation to advanced manufacturing and production testing, with the goal of reducing the cost of sequencing a human genome first to $100,000 and then to $1,000. The events of this period provide a powerful example of how judicious funding of academic and commercial partners can rapidly advance core technology developments that lead to profound advances across the scientific landscape.

Genome sequencing in microfabricated high-density picolitre reactors.

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.

Application of Computational Fluid Dynamics Techniques to Blood Pumps.

Present-day computational fluid dynamics (CFD) techniques can be used to analyze the behavior of fluid flow in a variety of pumps. CFD can be a powerful tool during the design stage for rapid virtual prototyping of different designs, analyzing performance parameters, and making design improvements. Computational flow solutions provide information such as the location and size of stagnation zones and the local shear rate. These parameters can be correlated to the extent of hemolysis and thrombus formation and are critical to the success of a blood pump. CFD-ACE, an advanced commercial CFD code developed by CFD Research Corporation, has been applied to fluid flows in rotary machines, such as axial flow pumps and inducers. Preprocessing and postprocessing tools for efficient grid generation and advanced graphical flow visualization are integrated seamlessly with CFD-ACE. The code has structured multiblock grid capability, non-Newtonian fluid treatment, a variety of turbulence models, and an Eulerian-Lagrangian particle tracking model. CFD-ACE has been used successfully to study the flow characteristics in an axial flow blood pump. An unstructured flow solver that greatly automates the process of grid generation and speeds up the flow simulation is under development.