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The new technology is an advance from a
one-dimensional sieve structure reported by the same MIT group last
year. The key to this new advance, called an anisotropic nanofluidic
sieving structure, is that the researchers have designed the
anisotropic sieve in two orthogonal dimensions (at a right angle),
which enables rapid continuous-flow separation of the biological
sample. This allows continuous isolation and harvesting of subsets of
biomolecules that researchers want to study. And that increases the
probability of detecting even the smallest number of molecules in the
sample.
"With this technology we can isolate interesting
proteins faster and more efficiently. And because it can process such
small biologically relevant entities, it has the potential to be used
as a generic molecular sieving structure for a more complex,
integrated biomolecule preparation and analysis system," said Jongyoon
Han, the Karl Van Tassel Associate Professor of Electrical Engineering
and associate professor of biological engineering at MIT and head of
the MIT team.
Han's coauthors of the Nature Nanotechnology paper
are co-lead authors Jianping Fu, a Ph.D. candidate in the Department
of Mechanical Engineering, and Reto B. Schoch, a postdoctoral
associate in the Research Laboratory of Electronics (RLE). Additional
authors are Anna Stevens, a postdoctoral associate in the Harvard-MIT
Division of Health Sciences and Technology, and Professor Steven
Tannenbaum of MIT's Biological Engineering Division.
Han noted that until the late 1990s, most advances
in biological laboratory equipment were aimed at the Human Genome
Project and discoveries related to DNA, which are larger molecules
compared to proteins. However, because of the vital role proteins play
in almost all biological processes, researchers began to focus their
attention on proteins. But one obstacle has been the lack of good
laboratory tools with which to prepare biological samples to analyze
proteins, said Han, who also has affiliations in MIT's RLE,
Computational and Systems Biology Initiative, Center for Materials
Science and Engineering and Microsystems Technology Laboratories.
"I shifted my attention from DNA into the area of
protein separation around 2002 with the shift to proteomics (the study
of proteins)," Han said. "But the field was using decades-old gel
electrophoresis technology. There is a big gap in the need for
technology in this area."
Han and Fu therefore devised the anisotropic sieve
that is embedded into a silicon chip. A biological sample containing
different proteins is placed in a sample reservoir above the chip. The
sample is then run through the sieve of the chip continuously. The
chip is designed with a network of microfluidic channels surrounding
the sieve, and the anisotropy (directional property) in the sieve
causes proteins of different sizes to follow distinct migration
trajectories, leading to efficient continuous-flow separation. The
current sieve has an array of nanofluidic filters of about 55
nanometers, or billionths of a meter, wide.
"The proteins to be sorted are forced to take two
orthogonal paths. Each path is engineered with different sieving
characters. When proteins of different sizes are injected into the
sieve under applied electric fields, they will separate into different
streams based on size," Han explained. At the bottom of the chip the
separated proteins are collected in individual chambers. Scientists
then can test the proteins.
While other scientists have used similar continuous
flow techniques to separate large molecules like long DNA, the MIT
team succeeded with the tinier proteins. "This is the first time
physiologically relevant molecules like proteins have been separated
in such a manner," said Han. "We can separate the molecules in about a
minute with the current device versus hours for gels."
Another advantage of the microchip is that it can
have so many different pore sizes, and unlike gels, it is possible to
design an exact pore size to increase the separation accuracy. That in
turn can help researchers look for so-called biomarkers, or proteins
that can reveal that disease is present, and thus help researchers
develop diagnostics and treatments for the disease. "Sample
preparation is critical in detecting more biomarker signals," said Han. |
