An integrated semiconductor device enabling non-optical genome sequencing

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 c...

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Bibliographic Details
Published in:	Nature (London) Vol. 475; no. 7356; pp. 348 - 352
Main Authors:	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, Sabina, Jeffrey, Feierstein, Erika, Schorn, Michelle, Alanjary, Mohammad, Dimalanta, Eileen, Dressman, Devin, Kasinskas, Rachel, Sokolsky, Tanya, Fidanza, Jacqueline A., Namsaraev, Eugeni, McKernan, Kevin J., Williams, Alan, Roth, G. Thomas, Bustillo, James
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 21-07-2011 Nature Publishing Group
Subjects:	631/1647/1888 631/61/514/1948 639/301/119/1000 Arrays Biological and medical sciences Biotechnology Deoxyribonucleic acid Diverse techniques DNA DNA sequencing Electronics industry Escherichia coli - genetics Fundamental and applied biological sciences. Psychology Genome, Bacterial - genetics Genome, Human - genetics Genomes Genomics - instrumentation Genomics - methods Humanities and Social Sciences Humans Integrated circuits Light Male Molecular and cellular biology multidisciplinary Nucleotide sequencing Physiological aspects Rhodopseudomonas - genetics Science Science (multidisciplinary) Semiconductors Sensors Sequence Analysis, DNA - instrumentation Sequence Analysis, DNA - methods Signal processing Vibrio - genetics United States Costs Semiconductor device Robustness Scalability Genome Sequencing
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Summary:	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. 'Post-light' genome sequencing chips Progress towards cheaper and more compact DNA sequencing devices is limited by a number of factors, including the need for imaging technology. A new DNA sequencing technology that does away with optical readout, instead gathering sequence data by directly sensing hydrogen ions produced by template-directed DNA synthesis, offers a route to low cost and scalable sequencing on a massively parallel semiconductor-sensing device or ion chip. The reactions are performed using all natural nucleotides, and the individual ion-sensitive chips are disposable and inexpensive. The system has been used to sequence three bacterial genomes and a human genome: that of Gordon Moore of Moore's law fame.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0028-0836 1476-4687
DOI:	10.1038/nature10242