A team of researchers from Columbia Engineering and the University of Pennsylvania has figured out a way to measure nanopores — tiny holes in a thin membrane that can detect single biological molecules such as DNA and proteins — with less error than can be achieved with commercial instruments. The researchers have miniaturized the measurement by designing a custom integrated circuit using commercial semiconductor technology, building the nanopore measurement around the new amplifier chip.

Nanopores may lead to extremely low-cost and fast DNA sequencing, but because their signals are very weak it is critically important to measure them as cleanly as possible. “We put a tiny amplifier chip directly into the liquid chamber next to the nanopore, and the signals are so clean that we can see single molecules passing through the pore in only one microsecond,” says Jacob Rosenstein, a Ph.D. candidate in electrical engineering at Columbia. “Previously, scientists could only see molecules that stay in the pore for more than 10 microseconds.”

Many single-molecule measurements are currently made using optical techniques, which use fluorescent molecules that emit photons at a particular wavelength. But, while fluorescence is very powerful, its major limitation is that each molecule usually produces only a few thousand photons per second.

Rosenstein designed the new electronics and did much of the lab work. Marija Drndic, a professor of physics at the University of Pennsylvania, led her group in fabricating the nanopores that the team then measured in their new system. “It’s very exciting to be able to make purely electronic measurements of single molecules,” says Rosenstein. “You can easily imagine nanopore technology having a major impact on DNA sequencing and other medical applications within the next few years.”

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