As nanotechnology becomes ever more ubiquitous, researchers are using it to make medical diagnostics smaller, faster, and cheaper, in order to better diagnose diseases, learn more about inherited traits, and more. But as sensors get smaller, measuring them becomes more difficult—there is always a tradeoff between how long any measurement takes to make and how precise it is. And when a signal is very weak, the tradeoff is especially big.
A team of researchers at Columbia Engineering, led by Electrical Engineering Professor Ken Shepard, together with colleagues at 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. They have miniaturized the measurement by designing a custom integrated circuit using commercial semiconductor technology, building the nanopore measurement around the new amplifier chip.
published online publication on Nature Methods' website at 2 p.m., March 18, 2012.
Nanopores are exciting scientists because they may lead to extremely low-cost and fast DNA sequencing. But the signals from nanopores are very weak, so 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 Engineering and lead author of the paper. "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.