The sieving process is based on a theoretical model known as the Ogston sieving mechanism. In the model, proteins move through deep and shallow regions that act together to form energy barriers. These barriers separate proteins by size. The smaller proteins go through more quickly, followed by increasingly larger proteins, with the largest passing through last.
Once the proteins are separated, scientists can isolate and capture the proteins of interest. These include the "biomarker" proteins that are present when the body has a disease. By studying changes in these biomarkers, researchers can identify disease early on, even before symptoms show up, and potentially develop new treatments.To date, the Ogston sieving model has been used to explain gel electrophoresis, even though no one has been able to unequivocally confirm this model in gel-based experiments. The MIT researchers were, however, able to confirm Ogston sieving in the nanopore sieves.
"This is the first time anyone was able to experimentally confirm this theoretical idea behind molecular sieving, which has been used for more than 50 years," Han said. "We can precisely control the pore size, so we can do better engineering. We can change the pore shape and engineer a better separation system." The sieve structure is based on work Han did earlier at Cornell University with large strands of DNA.
The performance of the researchers' current one-dimensional sieves matches the state-of-the-art speed of one-dimensional gels, but Han said the sieve's performance can be improved greatly.
"This device can replace gels and give us an ideal physical platform to investigate Ogston sieving," Fu said. The new sieves also potentially could be used to replace 2D gels in the process of discovering disease biomarkers, as well as to learn more about disease.