MIT's molecular sieve advances protein research
September 11, 2006 - 2015
New MIT technology promises to speed up the accurate sorting of
proteins, work that may ultimately aid in the detection and treatment
Separating proteins from complex biological fluids such as blood
is becoming increasingly important for understanding diseases and
developing new treatments. The molecular sieve developed by MIT
engineers is more precise than conventional methods and has the
potential to be much faster.
The team's results appear in recent issues of Physical Review Letters,
the Virtual Journal of Biological Physical Research and the Virtual
Journal of Nanoscale Science and Technology.
The key to the molecular sieve, which is made using microfabrication
technology, is the uniform size of the nanopores through which proteins
are separated from biological fluids. Millions of pores can be spread
across a microchip the size of a thumbnail.
The sieve makes it possible to screen proteins by specific size
In contrast, the current technique used for separating proteins,
gel electrophoresis, is time-consuming and less predictable. Pore
sizes in the gels vary, and the process itself is not well understood
"No one has been able to measure the gel pore sizes accurately,"
said Jongyoon Han, the Karl Van Tassel Associate Professor of Electrical
Engineering and Biological Engineering at MIT. "With our nanopore
system, we control the pore size precisely, so we can control the
sieving process of the protein molecules."
That, in turn, means proteins can be separated more efficiently,
which should help scientists learn more about these crucial molecules,
said Han, who also has appointments in MIT's Research Laboratory
of Electronics, Computational and Systems Biology Initiative, Center
for Materials Science and Engineering and Microsystems Technology
Han and his team, led by Jianping Fu, a graduate student in the
Department of Mechanical Engineering, have devised a sieve that
is embedded into a silicon chip. A biological sample containing
proteins is put through the sieve for separation.
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
Juhwan Yoo, a Caltech undergraduate, also participated in the research
as a summer visiting student. Funding came from the National Science
Foundation, the National Institutes of Health and the Singapore-MIT