An integrated semiconductor device enabling non-optical genome sequencing

被引:1450
作者
Rothberg, Jonathan M. [1 ]
Hinz, Wolfgang [1 ]
Rearick, Todd M. [1 ]
Schultz, Jonathan [1 ]
Mileski, William [1 ]
Davey, Mel [1 ]
Leamon, John H. [1 ]
Johnson, Kim [1 ]
Milgrew, Mark J. [1 ]
Edwards, Matthew [1 ]
Hoon, Jeremy [1 ]
Simons, Jan F. [1 ]
Marran, David [1 ]
Myers, Jason W. [1 ]
Davidson, John F. [1 ]
Branting, Annika [1 ]
Nobile, John R. [1 ]
Puc, Bernard P. [1 ]
Light, David [1 ]
Clark, Travis A. [1 ]
Huber, Martin [1 ]
Branciforte, Jeffrey T. [1 ]
Stoner, Isaac B. [1 ]
Cawley, Simon E. [1 ]
Lyons, Michael [1 ]
Fu, Yutao [1 ]
Homer, Nils [1 ]
Sedova, Marina [1 ]
Miao, Xin [1 ]
Reed, Brian [1 ]
Sabina, Jeffrey [1 ]
Feierstein, Erika [1 ]
Schorn, Michelle [1 ]
Alanjary, Mohammad [1 ]
Dimalanta, Eileen [1 ]
Dressman, Devin [1 ]
Kasinskas, Rachel [1 ]
Sokolsky, Tanya [1 ]
Fidanza, Jacqueline A. [1 ]
Namsaraev, Eugeni [1 ]
McKernan, Kevin J. [1 ]
Williams, Alan [1 ]
Roth, G. Thomas [1 ]
Bustillo, James [1 ]
机构
[1] Ion Torrent Life Technol, Guilford, CT 06437 USA
关键词
SENSOR ARRAY CHIP; CMOS TECHNOLOGY; DNA; CHARGE; TRANSISTOR; SEA;
D O I
10.1038/nature10242
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:348 / 352
页数:5
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