A team of researchers at Columbia Engineering and the University of Pennsylvania have discovered a way to measure nanopores. The research team miniaturized the measurement by designing a custom integrated circuit using commercial semiconductor technology, building the nanopore measurement around the new amplifier chip. Nanopores are 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.
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. However, as sensors become smaller, measuring them becomes more difficult. There is always a tradeoff between how long any measurement takes to make and how precise it is. When a signal is very weak, the tradeoff is especially big.
Nanopores may lead to extremely low-cost and fast DNA sequencing. However, the signals from nanopores are very weak, so it is critically important to measure them as cleanly as possible. The research team placed a tiny amplifier chip directly into the liquid chamber next to the nanopore. The signals were clean to see single molecules passing through the pore in only one microsecond. 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. While fluorescence is very powerful, its major limitation is that each molecule usually produces only a few thousand photons per second. As a result, you can’t see anything that happens faster than a few milliseconds because any image you could take would be too dim. Techniques that measure electrons or ions, on the other hand, can handle billions of signals per second. The problem is that for electronic measurements there is no equivalent to a fluorescent wavelength filter, so even though the signal comes through, it is often buried in background noise.
The research team at Columbia Engineering was led by Electrical Engineering Professor Ken Shepard. Their research was published in the Advance Online Publication on Nature Methods’s website. Jacob Rosenstein, a Ph.D. candidate in electrical engineering at Columbia Engineering, is the lead author of the paper. Rosenstein designed the new electronics and did much of the lab work. The researchers at the University of Pennsylvania fabricated the nanopores that the team then measured in the new system. The research was funded by the National Institutes of Health, the Semiconductor Research Corporation, and the Office of Naval Research.