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An integrated semiconductor device enabling non-optical genome sequencing

Open access
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·2011·Nature
DOI 10.1038/nature10242
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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. 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.

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Show all 11 references

Research works printed but not linked: 34

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Metadata

Authors
Rothberg, J. M., Hinz, W., Rearick, T. M., Schultz, J., Mileski, W., Davey, M., Leamon, J. H., Johnson, K., Milgrew, M. J., Edwards, M., Hoon, J., Simons, J. F., Marran, D., Myers, J. W., Davidson, J. F., Branting, A., Nobile, J. R., Puc, B. P., Light, D., Clark, T. A., Huber, M., Branciforte, J. T., Stoner, I. B., Cawley, S. E., Lyons, M., Fu, Y., Homer, N., Sedova, M., Miao, X., Reed, B., Sabina, J., Feierstein, E., Schorn, M., Alanjary, M., Dimalanta, E., Dressman, D., Kasinskas, R., Sokolsky, T., Fidanza, J. A., Namsaraev, E., McKernan, K. J., Williams, A., Roth, G. T., & Bustillo, J.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2011-07
Volume
475
Issue
7356
Pages
348-352
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature10242
OpenAlex
W1988929438
Cited by
2,172
References
11
FWCI
125.99
Type
journal article
Language
en
Open access
hybrid
Licence
creativecommons.org/licenses/by-nc-sa/3.0/ (tdm)

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CoChat. (2026). Citation check: An integrated semiconductor device enabling non-optical genome sequencing. https://app.cochat.ai/papers/10.1038/nature10242
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Rothberg, J. M., Hinz, W., Rearick, T. M., Schultz, J., Mileski, W., Davey, M., Leamon, J. H., Johnson, K., Milgrew, M. J., Edwards, M., Hoon, J., Simons, J. F., Marran, D., Myers, J. W., Davidson, J. F., Branting, A., Nobile, J. R., Puc, B. P., Light, D., . . . Bustillo, J. (2011). An integrated semiconductor device enabling non-optical genome sequencing. Nature. https://doi.org/10.1038/nature10242

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