[Editors] MIT's molecular sieve advances protein research

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

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MIT's molecular sieve advances protein research
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For Immediate Release
WEDNESDAY, SEP. 13, 2006
Contact: Elizabeth A. Thomson
Phone: 617-258-5402
Email: thomson at mit.edu

IMAGE AVAILABLE

CAMBRIDGE, Mass.--New MIT technology promises to speed up the 
accurate sorting of proteins, work that may ultimately aid in the 
detection and treatment of disease.

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 and shape.
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 by 
scientists.

"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 Laboratories.

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 
disease.

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 Alliance.