An integrated semiconductor device enabling non-optical genome sequencing

Jonathan M. Rothberg (), Wolfgang Hinz, Todd M. Rearick, Jonathan Schultz, William Mileski, Mel Davey, John H. Leamon, Kim Johnson, Mark J. Milgrew, Matthew Edwards, Jeremy Hoon, Jan F. Simons, David Marran, Jason W. Myers, John F. Davidson, Annika Branting, John R. Nobile, Bernard P. Puc, David Light, Travis A. Clark, Martin Huber, Jeffrey T. Branciforte, Isaac B. Stoner, Simon E. Cawley, Michael Lyons, Yutao Fu, Nils Homer, Marina Sedova, Xin Miao, Brian Reed, Jeffrey Sabina, Erika Feierstein, Michelle Schorn, Mohammad Alanjary, Eileen Dimalanta, Devin Dressman, Rachel Kasinskas, Tanya Sokolsky, Jacqueline A. Fidanza, Eugeni Namsaraev, Kevin J. McKernan, Alan Williams, G. Thomas Roth and James Bustillo
Additional contact information
Jonathan M. Rothberg: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Wolfgang Hinz: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Todd M. Rearick: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Jonathan Schultz: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
William Mileski: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Mel Davey: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
John H. Leamon: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Kim Johnson: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Mark J. Milgrew: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Matthew Edwards: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Jeremy Hoon: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Jan F. Simons: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
David Marran: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Jason W. Myers: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
John F. Davidson: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Annika Branting: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
John R. Nobile: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Bernard P. Puc: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
David Light: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Travis A. Clark: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Martin Huber: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Jeffrey T. Branciforte: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Isaac B. Stoner: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Simon E. Cawley: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Michael Lyons: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Yutao Fu: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Nils Homer: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Marina Sedova: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Xin Miao: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Brian Reed: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Jeffrey Sabina: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Erika Feierstein: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Michelle Schorn: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Mohammad Alanjary: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Eileen Dimalanta: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Devin Dressman: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Rachel Kasinskas: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Tanya Sokolsky: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Jacqueline A. Fidanza: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Eugeni Namsaraev: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Kevin J. McKernan: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
Alan Williams: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
G. Thomas Roth: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA
James Bustillo: Ion Torrent by Life Technologies, Suite 100, 246 Goose Lane, Guilford, Connecticut 06437, USA

Nature, 2011, vol. 475, issue 7356, 348-352

Abstract: Abstract The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.

Date: 2011
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DOI: 10.1038/nature10242

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