The advent of molecular biology in the 1980s and progress on the Human Genome Project in the 1990s, gave rise to the need for a DNA sequencer capable of decoding base pairs of large quantities of DNA with a high degree of precision and speed. The first DNA sequencers, known as"slab gel" sequencers, consisted of a gel substance sandwiched between two flat panels of glass through which DNA fragments were migrated via electrophoresis. Capillary array DNA sequencers, where DNA fragments undergo electrophoretic migration through narrow, gel-filled glass capillaries, were also developed. Both these early types of DNA sequencers were marred by poor fluorescence detection and inefficiency, requiring a laser to be directly beamed sequentially through each capillary in the array.
Through a number of technological innovations leading to the "Sheath-flow" technique, Dr. Kambara achieved across-the-board improvements in the functionality of the device. These innovations were particularly vital in preventing the scattering of laser light irradiated across the surface of the array, the most vexing issue surrounding parallel analysis in capillary arrays at the time. With this technique, Dr. Kambara succeeded in simultaneously detecting fluorescence in an array of 96 capillaries, while raising the sensitivity of fluorescence detection by more than an order of magnitude. Analytical precision was then vastly increased by fully automating control of the entire process.
Capillary Array DNA Sequencer using multiple Sheath-flow method
Dr. Kambara further discovered that the process could be sped-up by removing much of the heat arising from the electric field used in DNA analysis by adjusting the diameter of, and the distance between individual capillaries, and by air cooling the capillary walls. The end result was a high-throughput capillary array DNA sequencer with a functional capacity nearly 20 to 30 times that of previous devices.
This revolutionary device was soon drafted for use in the Human Genome Project, where it led to groundbreaking results. To make the device viable for use in ordinary research laboratories, Dr. Kambara also developed a "Multiple-Focusing Irradiation" technique that further simplified construction of the sequencer. This new design not only improved device control and maintenance, but made low-cost capillary array DNA sequencers well suited to general purpose tasks a reality.
Development of this latest DNA sequencer has resulted in a fully automated method for decoding DNA base pairs with a level of fluorescence detection sensitivity and throughput capacity more than an order of magnitude higher than previous devices.
Aside from its decisive contribution to the Human Genome Project, this new sequencer is encouraging the advancement of new research in biology and biochemistry, as well as the development of scientific technology in pharmacology, medicine and other research fields utilizing applied genomic data.
