The revolution in modern biology and medicine can be attributed in large part to the inventions of innovative technologies for the identification and quantitative measurement of biomolecules (DNA, RNA and proteins). For example, the development of polymerase chain reaction (PCR) for DNA amplification and automated DNA sequencer for DNA sequencing, has made possible the sequencing of the human genome. The availability of complete genome sequences and the free dissemination of genome sequence data have dramatically changed the nature of biomedical research. Sequence and other genomic data have the potential to lead to remarkable improvement in many facets of human life and society, including understanding, diagnosis, treatment and prevention of disease. With current technologies, however, the cost of sequencing a mammalian-sized genome is on the order of 10-50 million US dollars. To be able to perform comprehensive studies of human genetic variations, to elucidate the molecular etiology of cancer and the genetic basic of complex human traits/diseases, new technologies will be needed for the rapid, low-cost and routine sequencing of the genomes of many individuals and populations. One of the major thrusts of our research and engineering efforts is to develop the scientific and technological knowledge underpinning such a major advance.