An integrated semiconductor device enabling non-optical genome sequencing

作者：Rothberg Jonathan M^*; Hinz Wolfgang; Rearick Todd M; Schultz Jonathan; Mileski William; Davey Mel; Leamon John H; Johnson Kim; Milgrew Mark J; Edwards Matthew; Hoon Jeremy; Simons Jan F; Marran David; Myers Jason W; Davidson John F; Branting Annika; Nobile John R; Puc Bernard P; Light David; Clark Travis A; Huber Martin; Branciforte Jeffrey T; Stoner Isaac B; Cawley Simon E; Lyons Michael; Fu Yutao; Homer Nils; Sedova Marina; Miao Xin; Reed Brian

来源：Nature, 2011, 475(7356): 348-352.

DOI：10.1038/nature10242

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.

• 出版日期2011-7-21