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PROTEIN SAMPLE PREP MIT engineer designs nano protein sieving technology

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Jongyoon Han is one significant step closer to his goal of developing a single, automated nanofluidic device that would handle several different aspects of sample prep for protein studies.

Han, an associate professor of electrical and biological engineering at MIT, recently completed work using chip-based microfabricated nanofluidic filters to sieve proteins. The technology is based on research Han began as a graduate student at Cornell, where he developed a nanofilter capable of sorting DNA molecules. At MIT, he “started to apply similar devices to separate smaller molecules, such as proteins,” Han says. He notes that while protein sieving is the basis for widely used tools, such as 2D gels, the actual sieving process has been poorly understood from a biophysical standpoint. 2D gels, for instance, are a “random nanoporous matrix [in which] gel pore sizes are always distributed over a wide range,” Han says. That means there’s little rhyme or reason to the sieving process that takes place on a gel — and with little understanding of what’s actually going on, scientists have been unable to improve the sorting process.

One goal for Han’s research, in addition to finding another way to sieve proteins, was to use “very regularly sized nanofilters” to allow his team to conduct a “well controlled experiment on the sieving process.” The results of his experiments may not stand the field on its head, but they could lay the groundwork for building better, more accurate protein sorting tools. “We basically clearly confirmed” the ideas people have had of sieving, Han says, noting that the results were not a huge surprise. However, they did prove some of the aspects of sieving that have always been counterintuitive: “If you have a protein which is about 10 nm in diameter and you have a nanopore of 50 nm in size, the typical thinking is a 50 nm pore wouldn’t be able to sieve or filter the protein,” Han says. In fact, the 50 nm pore turns out to be sufficient for sorting proteins, he notes, due to the different ways the molecules are acting in nanoscale.

Han and his team will continue to study sieving and to work on the nanofilter technology, he says. He hopes to add other techniques, such as concentrating proteins, to the device’s capabilities.

— Meredith Salisbury

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