The technologies that make sequencing DNA fast, cheap and widely available have the potential to revolutionize bio-medical research and herald the era of personalized medicine. Being able to sequence human genomes for $1000 will enable comparative studies of variations between individuals in both sickness and health. Ultimately it can improve the quality of medical care by identifying patients who will gain the greatest benefit from a particular medicine, and those who are most at risk of adverse reactions. Nanopore-based sequencing technologies attempt to thread a long DNA molecule through a few nanometer wide nanopore and use physical differences between the four base types to read the sequence of bases in DNA. The two major potential benefits of nanopore sequencing are the high speed and the low price. Nanopore sequencing does not need slow and expensive chemistry, therefore electrical-only sequence readout can proceed at highest rates achievable by modern electronics. At present, the nanopore sequencing is still a promise - no single nucleotide resolution has as yet been achieved experimentally. It is very likely that the ability to localize a DNA molecule inside a nanopore with a single base resolution would provide a sufficient time for read-out electronics to determine the base type. We propose a nano-electro-mechanical device (DNA Transistor) capable of controlling the translocation of a single DNA molecule inside a nanopore with single nucleotide accuracy. This function is based on interaction of discrete charges, localized on phosphate groups along the backbone of a DNA molecule, with the externally controlled electric field confined inside the nanopore. The design of the DNA Transistor relies on well researched thin film deposition techniques from semiconductors industry. The device is a stack of metal and dielectric layers, each a few atoms thin, with a nanopore penetrating through the stack. The electric potentials applied to the metal layers traps the DNA molecule inside the nanopore. Pulsing these potentials allows controlled translocation of the molecule with a single base resolution. IBM Research is uniquely positioned to implement the proposed idea. Our experimental effort will rely on in-house industry leading semiconductor device fabrication facilities. The experimental component of the effort will be complemented by a modeling and simulation component that will rely on in-house Blue Gene supercomputing capabilities.
Our first aim i s to fabricate the DNA transistor and demonstrate its capability to translocate the DNA molecule through the nanopore with a single base resolution.
The second aim i s to electrically differentiate bases of the localized DNA molecule.
The final aim i s to develop cost-effective DNA Transistor fabrication methods suitable for mass production.
IBM proposes the design, characterization and production of a nano-electro-mechanical device (the DNA Transistor) that forms the basis of a fast technology to sequence human genomes for $1000. The widespread availability of this technology will enable comparative studies of variations between individuals in both sickness and health. Ultimately it can improve the quality of medical care by identifying patients who will gain the greatest benefit from a particular medicine, and those who are most at risk of adverse reactions.
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