NIST proposed the first DNA sequencer that is based on an electronic nanosensor and able to detect tiny motions of even a single atom. It is a type of electric charge storing capacitor with a tiny ribbon of molybdenum disulfide suspended over a metal electrode which is then immersed in water. The ribbon is 15.5 nanometers (nm, billionths of a meter) long and 4.5 nm wide. The single-stranded DNA contains bits of genetic code and is threaded through a hole of 2.5 nm wide in the thin ribbon. When a DNA base pairs up with and then separates from a complementary base affixed to the hole, the ribbon is able to flex. The motion of the membrane is then recorded as an electrical signal.
79 to 86 percent accuracy was shown in NIST experiments in identifying DNA bases in a single measurement at speeds up to about 70 million bases per second. These experiments show that the sensor can act as a fast, accurate and cost-effective DNA sequencer.
Conventional sequencing comprised of separating, copying, labeling and reassembling pieces of DNA. Automated sequencing of many DNA fragments through “nanopore sequencing” concepts are new and pricy. This sensor, however, is based on a thin film of molybdenum disulfide which is a stable and layered material that conducts electricity. Its main advantage is that it does not stick to DNA which is different from graphene.
DNA has 4 bases. For the simulations, cytosine (C) naturally pairing up with guanine (G) is attached to the inner side of the pore. The electrode is signaled when a piece of DNA passes through the pore. This happens as any of the G in the strand temporarily attaches itself to the embedded C and pulls on the nanoribbon. In order to detect all 4 bases, 4 nanoribbons, each with a different base attached to the pore, can be stacked on top of each other thus creating an integrated DNA sensor. The flexible molybdenum disulfide ribbon deforms as a result of the forces that are required to break up a DNA pair. However, it is still rigid enough not to go through any meaningless movement unlike graphene for example. The unwanted noise thus gets reduced in the sequencing signals. The ribbon deflection is very small, on the order of one angstrom. The pulling force is on the order of 50 piconewtons, enough to break up the extremely delicate chemical bonds between DNA bases.
NIST hopes to build a physical device in the future. It might entail a chip-sized DNA sequencing microfluidic technology along with electronics all combined into a single tiny handheld device.
More information can be found at: National Institute of Standards and Technology.